Can the onset of type 2 diabetes be delayed by a group-based lifestyle intervention? A randomised control trial The epidemic of obesity and diabetes: trends and treatments. Lifestyle intervention is associated with lower prevalence of urinary incontinence: the Diabetes Prevention Program. The prevention or delay of type 2 diabetes. The Cost-Effectiveness of Lifestyle Modification or Metformin in Preventing Type 2 Diabetes in Adults with Impaired Glucose Tolerance HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial Regression From Pre-Diabetes to Normal Glucose Regulation in the Diabetes Prevention Program Within-trial cost-effectiveness of lifestyle intervention or metformin for the primary prevention of type 2 diabetes. The comparative efficacy of lifestyle intervention and metformin by educational attainment in the Diabetes Prevention Program. Relationship of body size and shape to the development of diabetes in the diabetes prevention program. Screening for Type 2 Diabetes Mellitus: A Cost-Effectiveness Analysis The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up. Costs associated with the primary prevention of type 2 diabetes mellitus in the diabetes prevention program. Lifestyle and Metformin Interventions Have a Durable Effect to Lower CRP and tPA Levels in the Diabetes Prevention Program Except in Those Who Develop Diabetes Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. Effects of Genetic Variants Previously Associated with Fasting Glucose and Insulin in the Diabetes Prevention Program A clinical trial to maintain glycemic control in youth with type 2 diabetes. Effect of Intervention in Subjects with High Risk of Diabetes Mellitus in Pakistan Long-term Effects of Lifestyle Intervention or Metformin on Diabetes Development and Microvascular Complications: the DPP Outcomes Study The diabetes prevention program and its global implications. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. The 10-Year Cost-Effectiveness of Lifestyle Intervention or Metformin for Diabetes Prevention Prevention of type 2 diabetes - where is the evidence? Feasibility and effectiveness of a targeted diabetes prevention program for 18 to 60-year-old South Asian migrants: design and methods of the DH!AAN study Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. The Sydney Diabetes Prevention Program: A community-based translational study A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. A model of translational research for diabetes prevention in low and middle-income countries: The Diabetes Community Lifestyle Improvement Program (D-CLIP) trial. Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study. Preventing type 2 diabetes using combination therapy: design and methods of the CAnadian Normoglycaemia Outcomes Evaluation (CANOE) trial Pleiotropic Action of Short-Term Metformin and Fenofibrate Treatment, Combined With Lifestyle Intervention, in Type 2 Diabetic Patients With Mixed Dyslipidemia PREVENT-DM Comparative Effectiveness Trial of Lifestyle Intervention and Metformin. The cost-effectiveness of diabetes prevention: results from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study General effect on high-risk persons when general practitioners are trained in intensive treatment of type 2 diabetes Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Cluster randomised controlled trial of a peer-led lifestyle intervention program: study protocol for the Kerala diabetes prevention program Cost-Effectiveness of the Interventions in the Primary Prevention of Diabetes Among Asian Indians Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Clinical Outcomes and Cost-Effectiveness of Strategies for Managing People at High Risk for Diabetes Menopause and risk of diabetes in the Diabetes Prevention Program 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Body Size and Shape Changes and the Risk of Diabetes in the Diabetes Prevention Program Diabetes, glycaemia, and cognition-a secondary analysis of the Finnish Diabetes Prevention Study. Let’s prevent diabetes: study protocol for a cluster randomised controlled trial of an educational intervention in a multi-ethnic UK population with screen detected impaired glucose regulation The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin‐naïve people with Type 2 diabetes: the DUAL IV trial 
Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study Slowing Down the Progression of Type 2 Diabetes: We Need Fair, Innovative, and Disruptive Action on Environmental and Policy Levels! A Comprehensive Lifestyle Intervention to Prevent Type 2 Diabetes and Cardiovascular Diseases: the German CHIP Trial A community based primary prevention programme for type 2 diabetes integrating identification and lifestyle intervention for prevention: the Let's Prevent Diabetes cluster randomised controlled trial. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial.
This study was a r and omised control trial with a waiting control group . It was design ed to evaluate the effectiveness of a 6-month , group-based diabetes prevention programme , The Healthy Living Course and assess whether participation in the programme led to changes in modifiable risk factors for type 2 diabetes among an already at-risk pre-diabetic population . Individuals design ated at risk for diabetes by their general practitioners ( GPs ) were screened using an Oral Glucose Tolerance Test . Volunteers ( N = 307 ) with pre-diabetes were assigned to an intervention or wait-control group in the ratio of approximately 2 : 1 . The sample was pre-tested on biochemical , anthropometric and self-report behavioural , cognitive and mood variables and post-tested either at the end of the educational/support-based lifestyle programme or the end of the wait period . The intervention group significantly improved their diabetes knowledge , motivation to change , positive affect , healthy eating and activity levels and showed significantly greater reductions in weight , body mass index , waist circumference , diastolic blood pressure and fasting plasma glucose in comparison with controls . The intervention group also changed their diagnostic status from pre-diabetes to non-diabetes at a greater rate than the wait group ( 43 % vs. 26 % ) who received st and ard care from their GPs Cardiovascular disease remains the leading cause of death in women . Both obesity and diabetes mellitus are important independent risk factors for the development of cardiovascular disease . Obesity is the leading risk factor for type 2 diabetes . The Centers for Disease Control and Prevention report that 32 % of white and 53 % of black women are obese . Women with a body mass index ( BMI ) of 30 kg/m2 have a 28 times greater risk of developing diabetes than do women of normal weight . The risk of diabetes is 93 times greater if the BMI is 35 kg/m2.1 The presence of diabetes can increase a woman 's risk of heart disease 2-fold . In addition , the presence of diabetes overshadows the protective effects of the premenopausal state . In 2007 , 11.5 million of all women over the age of 20 ( 10.2 % ) had diabetes , and rates were slightly higher in ethnic minority groups : 10.4 % in Hispanic women and 11.8 % in non-Hispanic black women.2 The national prevalence rates of diabetes have increased in parallel with the rates of obesity ( Fig. 1 ) . Fig. 1 Age-adjusted percentage of U.S. adults who were obese or who had a diagnosis of diabetes mellitus . Screening Screening for obesity and diabetes is the 1st step to treatment and often reveals individuals who are at risk for but do not yet have overt disease . The United States Preventive Services Task Force ( USPSTF ) recommends that all adults be screened for obesity . Obesity signifies excess adipose tissue . The most widely used method for screening is determination of the BMI . The BMI is weight in kilograms divided by height in meters squared ( BMI = kg/m2 ) ( Table I ) . Most electronic medical records automatically calculate BMI if height and weight are entered . There are also many smart-phone applications and online calculators that can calculate BMI ( for example , http://www.nhlbisupport.com/ bmi ) . Other screening tools include  waist circumference and the waist-to-hip ratio . In women , a waist circumference > 35 in ( 88 cm ) or a waist-to-hip ratio > 0.7 indicates excess visceral fat and increased risk for disease . TABLE I. Body Mass Index ( BMI ) Classification Recommendations for screening for diabetes vary by guideline author . The USPSTF recommends screening asymptomatic patients who have  blood pressures > 135/80 mmHg  . The American Diabetes Association ( ADA ) recommends that individuals who are ≥18 years of age and have a BMI ≥25 kg/m2 and 1 additional risk factor for diabetes should be screened annually ( Table II).3 Individuals over the age of 45 without risk factors should be screened every 3 years . In January 2010 , the ADA released new recommendations for the use of hemoglobin A1C as a screening tool . An A1C greater than 6.5 % indicates diabetes . In addition , the results of screening tests for diabetes can identify individuals with “ prediabetes ” who have a markedly increased risk of developing overt disease.3 TABLE II . American Diabetes Association Recommendations on Screening for Type 2 Diabetes3 Non-Pharmaceutical Treatment Lifestyle-treatment options for diabetes mellitus and excess weight are similar , and 2 recent studies 4,5 have demonstrated the critical components for treating pre-diabetes and diabetes through weight loss , using caloric restriction and physical activity . The 1st study was the Diabetes Prevention Program.4 The purpose of the study was to identify individuals who were at risk for developing diabetes because of elevated fasting plasma glucose or impaired glucose tolerance levels that were not yet in the diagnostic range , in order to determine if metformin or an intensive lifestyle intervention could delay or prevent the onset of diabetes . More than 3,000 individuals with prediabetes were r and omized to receive placebo , metformin , or a 16-session lifestyle-modification program . The intensive lifestyle program set a goal of 7 % weight loss and 150 min/wk of moderate physical activity . Fifty percent of the lifestyle-intervention group lost 7 % of their body weight . The 3-year incidence of diabetes in the metformin group was 31 % lower than that in the placebo group . The incidence was 58 % lower in the lifestyle group than in the placebo group.4 The clinical implication s of this study are that we should 1 ) identify individuals with pre-diabetes and 2 ) recommend lifestyle modifications that result in a 7 % weight loss and include 150 min/wk of moderate physical activity . The 2nd study that examined lifestyle treatment of diabetes and obesity is the Look AHEAD Trial . The purpose of the study was to determine the effect of intentional weight loss on cardiovascular risk factors in individuals with diabetes . Approximately 5,100 individuals with type 2 diabetes and an elevated BMI were r and omized . Study conditions specified a 36-session intensive lifestyle intervention with the option of using partial meal replacements for caloric restriction or 4 sessions of st and ard diabetes support and education ( DSE ) . At 1 year , 55 % of the intensive-lifestyle-intervention group achieved 7 % weight loss . Hemoglobin A1C , systolic and diastolic blood pressure , and lipids improved significantly more in the intensive-lifestyle group than in the DSE group.5 The clinical implication of this study is that intentional weight loss of at least 7 % can improve the cardiovascular risk profile of patients with type 2 diabetes . Conclusions Excess weight affects two thirds of the U.S. adult population and increases risk for cardiovascular disease and diabetes . All patients should be screened for obesity and most should be screened for pre-diabetes and diabetes . The best treatment for diabetes is prevention . Prevention of diabetes can be accomplished through a 7 % weight loss through intensive lifestyle interventions that include caloric reduction and approximately 30 min of daily moderate physical activity . Practitioners will have access to these evidence -based programs soon . The Centers for Disease Control and Prevention are promoting community-based diabetes prevention programs throughout the country OBJECTIVE Diabetes is associated with increased urinary incontinence risk . Weight loss improves incontinence , but exercise may worsen this condition . We examined whether an intensive lifestyle intervention or metformin therapy among overweight pre-diabetic women was associated with a lower prevalence of incontinence . RESEARCH DESIGN AND METHODS We analyzed data from the Diabetes Prevention Program , a r and omized controlled trial in 27 U.S. centers . Of the 1,957 women included in this analysis , 660 ( 34 % ) were r and omized to intensive lifestyle therapy  , 636 ( 32 % ) to metformin  , and 661 ( 34 % ) to placebo with st and ard lifestyle advice . The main outcome measure was incontinence symptoms by frequency and type by a vali date d question naire completed at the end-of-trial visit ( mean 2.9 years ) . RESULTS The prevalence of total ( stress or urge ) weekly incontinence was lower among women in the intensive lifestyle group ( 38.3 % ) than those r and omized to metformin ( 48.1 % ) or placebo ( 45.7 % ) . This difference was most apparent among women with stress incontinence ( 31.3 % for intensive lifestyle group vs. 39.7 % for metformin vs. 36.7 % for placebo , P = 0.006 ) . Changes in weight accounted for most of the protective effect of the intensive lifestyle intervention on stress incontinence . CONCLUSIONS Less-frequent urinary incontinence may be a powerful motivator for women to choose lifestyle modification to prevent diabetes D iabetes is one of the most costly and burdensome chronic diseases of our time and is a condition that is increasing in epidemic proportions in the U.S. and throughout the world ( 1 ) . The complications result ing from the disease are a significant cause of morbidity and mortality and are associated with the damage or failure of various organs such as the eyes , kidneys , and nerves . Individuals with type 2 diabetes are also at a significantly higher risk for coronary heart disease , peripheral vascular disease , and stroke , and they have a greater likelihood of having hypertension , dyslipidemia , and obesity ( 2–6 ) . There is also growing evidence that at glucose levels above normal but below the diabetes threshold diagnostic now referred to as pre-diabetes , there is a substantially increased risk of cardiovascular disease ( CVD ) and death ( 5,7–10 ) . In these individuals , CVD risk factors are also more prevalent ( 5–7,9,11–14 ) , which further increases the risk but is not sufficient to totally explain it . In contrast to the clear benefit of glucose lowering to prevent or retard the progression of microvascular complications associated with diabetes ( 15– 18,21 ) , it is less clear whether the high rate of CVD in people with impaired glucose homeostasis , i.e. , those with impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) , or diabetes , is caused by elevated blood glucose levels or will respond to treatments that lower blood glucose . Epidemiological studies have shown a clear relationship ( 19,20 ) , whereas intervention trials in people with diabetes suggest , but have not demonstrated , a clear benefit of glycemic control ( 15,16,21,22 ) . Additionally , there are no studies that have investigated a benefit of glucose lowering on macrovascular disease in subjects with only pre-diabetes ( IFG or IGT ) but not diabetes . Although the treatment of diabetes has become increasingly sophisticated , with over a dozen pharmacological agents available to lower blood glucose , a multitude of ancillary supplies and equipment available , and a clear recognition by health care professionals and patients that diabetes is a serious disease , the normalization of blood glucose for any appreciable period of time is seldom achieved ( 23 ) . In addition , in well-controlled socalled “ intensively ” treated patients , serious complications still occur ( 15–18,21 ) , and the economic and personal burden of diabetes remains . Furthermore , microvascular disease is already present in many individuals with undiagnosed or newly diagnosed type 2 diabetes ( 11,24– 28 ) . Given these facts , it is not surprising that studies have been initiated in the last decade to determine the feasibility and benefit of various strategies to prevent or delay the onset of  type 2 diabetes .  Two early reports ( 29,30 ) suggested that changes in lifestyle can prevent diabetes , but weaknesses in study design limited their general relevance . Recently , however , four well- design ed r and omized controlled trials have been reported ( 31–35 ) . In the Finnish study ( 31 ) , 522 middleaged ( mean age 55 years ) obese ( mean BMI 31 kg/m ) subjects with IGT were r and omized to receive either brief diet and exercise counseling ( control group ) or intensive individualized instruction on weight reduction , food intake , and guidance on increasing physical activity ( intervention group ) . After an average follow-up of 3.2 years , there was a 58 % relative reduction in the incidence of diabetes in the intervention group compared with the control subjects . A strong correlation was also seen between the ability to stop the progression to diabetes and the degree to which subjects were able to achieve one or more of the following : lose weight ( goal of 5.0 % weight reduction ) , reduce fat intake ( goal of 30 % of calories ) , reduce saturated fat intake ( goal of 10 % of calories ) , increase fiber intake ( goal of 15 g/1,000 kcal ) , and exercise ( goal of 150 min/week ) . No untoward effects of the lifestyle interventions were observed . In the Diabetes Prevention Program ( DPP ) ( 32–34 ) , the 3,234 enrolled subjects were slightly younger ( mean age 51 years ) and more obese ( mean BMI 34 kg/m ) but had nearly identical glucose intolerance compared with subjects in the Finnish study . About 45 % of the participants were from minority groups ( e.g , AfricanAmerican , Hispanic ) , and 20 % were 60 years of age . Subjects were r and omized to one of three intervention groups , which included the intensive nutrition and exercise counseling ( “ lifestyle ” ) group or either of two masked medication treatment groups : the biguanide metformin group or the placebo group . The latter interventions were combined with st and ard diet and exercise recommendations . After an average follow-up of 2.8 years ( range 1.8–4.6 years ) , a 58 % relative reduction in the progression to diabetes was observed in the lifestyle group ( absolute incidence 4.8 % ) , and a 31 % relative reduction in the progression of diabetes was observed in the metformin group ( absolute incidence 7.8 % ) compared with control subjects ( absolute incidence 11.0 % ) . ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Context The Diabetes Prevention Program ( DPP ) showed that lifestyle changes or metformin effectively decreased the development of  type 2 diabetes in adults with impaired glucose tolerance . The economics of these interventions is important to policymakers . Contribution This cost-effectiveness model estimates that the DPP life-style intervention would cost society about $ 8800 and metformin would cost about $ 29900 per quality -adjusted life-year saved . While lifestyle intervention had a favorable cost-effectiveness profile at any adult age , metformin was not cost-effective after age 65 years . Implication s The cost-effectiveness of lifestyle intervention to prevent type 2 diabetes  in high-risk individuals is within the range that American society typically finds acceptable for health care interventions . The Editors During the past half century , the number of persons with diagnosed diabetes in the United States has increased 4- to 6-fold ( 1 ) . Recent large clinical trials from Asia , Europe , and North America have demonstrated that behavioral and medication interventions can delay or prevent the development of type 2 diabetes in persons with impaired glucose tolerance , which is defined by a plasma glucose level between 7.77 mmol/L ( 140 mg/dL ) and 11.04 mmol/L ( 199 mg/dL ) 2 hours after a 75-g oral glucose load ( 2 - 6 ) . The Diabetes Prevention Program ( DPP ) r and omly assigned 3234 nondiabetic persons 25 years of age or older with impaired glucose tolerance and fasting glucose levels between 5.27 mmol/L ( 95 mg/dL ) and 6.94 mmol/L ( 125 mg/dL ) to placebo ; a lifestyle-modification program with the goals of at least a 7 % weight loss and 150 minutes of physical activity per week ; or metformin , 850 mg twice daily ( 4 ) . The mean age of participants was 51 years , and the mean body mass index was 34.0 kg/m2 ; 68 % were women and 45 % were members of minority groups ( 4 ) . The average follow-up was 2.8 years . Compared with the placebo intervention , the lifestyle intervention reduced the incidence of type 2 diabetes by 58 % and the metformin intervention reduced the incidence of type 2 diabetes by 31 % ( 4 ) . We have previously described the costs of the DPP interventions and their cost-effectiveness within the 3-year trial period ( 7 , 8) . In this analysis , we project the costs , health outcomes , and cost-effectiveness of the DPP lifestyle and metformin interventions over a lifetime relative to the placebo intervention . Methods Clinical Trial The lifestyle intervention involved a healthy , low-calorie , low-fat diet and moderate physical activity , such as brisk walking . The lifestyle intervention was implemented with a 16-lesson core curriculum covering diet , exercise , and behavior modification that was taught by case managers on a one-on-one basis , followed by individual sessions ( usually monthly ) and group sessions with case managers ( 9 ) . At the end of the study , 38 % of participants in the lifestyle intervention group had lost at least 7 % of their initial body weight .  The metformin and placebo interventions were initiated at a dosage of 850 mg once a day . At 1 month , the dosage of metformin or placebo was increased to 850 mg twice daily . Case managers reinforced adherence during individual quarterly sessions ( 10 ) . At the end of the study , 72 % of participants in the metformin intervention group and 77 % of participants in the placebo intervention group took at least 80 % of the prescribed dose . All participants received st and ard lifestyle recommendations through written information and an annual 20- to 30-minute individual session that emphasized the importance of a healthy lifestyle ( 10 ) . Simulation Model We assessed the progression from impaired glucose tolerance to onset of diabetes to clinical ly diagnosed diabetes to diabetes with complications and death by using a lifetime simulation model originally developed by the Centers for Disease Control and Prevention and Research Triangle Institute International . The model has a Markov structure and includes annual transition probabilities between disease states ( 11 ) . In addition to disease progression , the model tracks costs and quality -adjusted life-years ( QALYs ) . The model has been described elsewhere ( 11 ) . For our analyses , we modified the model to include data from the DPP on progression , costs , and quality of life associated with impaired glucose tolerance , data from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) on diabetes progression and complications , and new data on cost and quality of life associated with diabetes . A technical report describing the model is available . Supplement . Technical Report Disease Progression , Complications , and Comorbid Conditions Impaired Glucose Tolerance to Onset of Type 2 Diabetes We analyzed data from the DPP to assess the annual hazard of diabetes onset in the lifestyle , metformin , and placebo intervention groups . For patients receiving the placebo intervention , the annual hazard of diabetes onset was 10.8 per 100 person-years . At 3 years of follow-up , the risk reductions for the lifestyle and metformin interventions were 55.8 % and 29.9 % , respectively . In the base-case analysis , we assumed that the lifestyle and metformin interventions would be applied until diabetes onset and that the health and quality -of-life benefits associated with the interventions persisted until diabetes onset . Complications and Comorbid Conditions Associated with Impaired Glucose Tolerance We analyzed data from the DPP and other published sources to assess the prevalence of complications and comorbid conditions in participants with impaired glucose tolerance . At baseline , 6.0 % of DPP participants had microalbuminuria and 0.4 % had nephropathy .  The DPP did not measure peripheral neuropathy , but previous studies found that the prevalence of neuropathy in persons with impaired glucose tolerance was 74 % of that in persons with newly diagnosed type 2 diabetes ( 12 ) and 12.3 % of persons with newly diagnosed type 2 diabetes have neuropathy ( 13 ) . Therefore , we assumed that at baseline , 8.5 % of DPP participants had clinical neuropathy . At baseline , 28 % of DPP participants had hypertension , 45 % had dyslipidemia , 7 % were smokers , 1.1 % had a history of cerebrovascular disease , and 2.0 % had a history of myocardial infa rct ion . No other complications were present . We assumed that during impaired glucose tolerance , microvascular or neuropathic complications would not progress . We assumed that hypertension and dyslipidemia developed at the rates observed in the DPP . On the basis of 2 large studies ( 14 , 15 ) , we assumed that the incidences of coronary heart disease and cerebrovascular disease in patients with impaired glucose tolerance were 58 % and 56 % , respectively , of those observed in patients with type 2 diabetes . We further assumed that nondiabetes-related mortality for persons with impaired glucose tolerance was the same as for persons with diabetes ( 16 ) . Onset of Type 2 Diabetes to Clinical Diagnosis of Type 2 Diabetes In the DPP , participants were tested for diabetes every 6 months ; diabetes was diagnosed at onset . In routine clinical practice , type 2 diabetes is estimated to develop 8 to 12 years before its clinical diagnosis ( 17 , 18 ) . In our base-case analysis , we therefore assumed that a 10-year delay occurred between the onset and clinical diagnosis of diabetes . Participants in the DPP  had a mean hemoglobin A1c level of 6.4 % at the onset of diabetes . Participants in the UKPDS had a mean hemoglobin A1c of 7.1 % after a dietary run-in period but before r and omization ( 13 ) . Both DPP placebo participants and UKPDS participants received st and ard lifestyle recommendations . Accordingly , we assumed that during the 10-year interval between onset and clinical diagnosis of diabetes , patients were treated for type 2 diabetes and that hemoglobin A1c level increased at 0.07 % per year from 6.4 % to 7.1 % . Complications and Comorbid Conditions Associated with Undiagnosed Diabetes We further assumed that between onset and clinical diagnosis of diabetes , microvascular and neuropathic complications progressed slowly , such that by clinical diagnosis of type 2 diabetes , their prevalence reached the level observed in the UKPDS cohort at r and omization ( 13 , 19 , 20 ) . We assumed that blood pressure and lipid levels progressed as they did in DPP participants and that cardiovascular complications occurred as they would in type 2 diabetes according to risk factors and hemglobin A1c level ( 21 , 22 ) . Clinical Diagnosis of Type 2 Diabetes to Diabetes with Complications and Death We assumed that after clinical diagnosis , all persons with type 2 diabetes received intensive glycemic management as described in the UKPDS ( 13 ) . We modeled changes in hemoglobin A1c and diabetes treatments to reflect those observed in the UKPDS intensive therapy group . We based risk for retinopathy progression on UKPDS 38 ( 23 ) , risk for nephropathy progression on UKPDS 64 ( 20 ) , and risk for neuropathy progression on UKPDS 33 ( 13 ) . We based risk for cerebrovascular disease on UKPDS 60 ( 22 ) and risk for coronary heart disease on UKPDS 56 ( 21 ) . Costs Costs of Impaired Glucose Tolerance To estimate the total direct medical costs of impaired glucose tolerance , we considered the costs of the DPP interventions ( the cost of identifying participants , implementing and maintaining the interventions , and monitoring and treating the side effects of the interventions ) and the costs of the medical care outside the DPP ( 7 ) . In analyses from the perspective of society , we included both direct medical costs and direct nonmedical costs . We did not include indirect costs because they are captured in the assessment of QALYs ( 24 ) . Table 1 shows the total direct medical costs by treatment group , sex , and year in the DPP ( 7 ) . Costs were higher in the lifestyle and metformin interventions than in the placebo intervention and higher in women than in men . Costs decreased over time in all 3 intervention groups but after year 1 tended to decrease more in the lifestyle than OBJECTIVE Glycated hemoglobin ( HbA1c ) , a st and ard measure of chronic glycemia for managing diabetes , has been proposed to diagnose diabetes and identify people at risk . The Diabetes Prevention Program ( DPP ) was a 3.2-year r and omized clinical trial of preventing type 2 diabetes with a 10-year follow-up study , the DPP Outcomes Study ( DPPOS ) . We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5 % ( 48 mmol/mol ) . RESEARCH DESIGN AND METHODS We r and omized 3,234 nondiabetic adults at high risk of diabetes to placebo , metformin , or intensive lifestyle intervention  and followed them for the development of diabetes as diagnosed by fasting plasma glucose ( FPG ) and 2-h postload glucose ( 2hPG ) concentrations ( 1997 American Diabetes Association [ ADA ] criteria ) . HbA1c was measured but not used for study eligibility or outcomes . We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG , 2hPG , or HbA1c ( 2010 ADA criteria ) .  RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups . Diabetes incidence defined by HbA1c ≥6.5 % was reduced by 44 % by metformin and 49 % by lifestyle during the DPP and by 38 % by metformin and 29 % by lifestyle throughout follow-up . Unlike the primary DPP and DPPOS findings based on glucose criteria , metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c . CONCLUSIONS HbA1c predicted incident diabetes . In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes , metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes . The long-term implication s for other health outcomes remain to be determined OBJECTIVE Participants in the Diabetes Prevention Program ( DPP ) r and omized to intensive lifestyle modification  ( ILS ) or metformin had a significantly reduced incidence of diabetes compared with those r and omized to placebo , yet most were still at risk because they had pre-diabetes . We explored the effect of baseline characteristics , weight change , ILS , and metformin on regression from pre-diabetes to the lowest-risk state of normal glucose regulation ( NGR ) defined by American Diabetes Association criteria . RESEARCH DESIGN AND METHODS The DPP was a prospect i ve r and omized trial . Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up . RESULTS Lower baseline fasting ( hazard ratio 1.52 , P < 0.01 ) and 2-h ( 1.24 , P < 0.01 ) glucose predicted regression to NGR , as did younger age ( 1.07 , P < 0.01 ) and greater insulin secretion ( 1.09 , P = 0.04 ) .  ILS  ( 2.05 , P < 0.01 ) and weight loss ( 1.34 , P < 0.01 ) had significant and independent effects on regression . A nonsignificant trend for regression was also observed for metformin ( 1.25 , P = 0.06 ) , male sex ( 1.17 , P = 0.08 ) , and insulin sensitivity ( 1.07 , P = 0.09 ) . In those entering the study with both impaired fasting glucose ( IFG ) and impaired glucose tolerance ( IGT ) , male sex and insulin sensitivity predicted regression to isolated IFG , whereas ILS , metformin , female sex , and greater insulin secretion predicted regression to isolated IGT . CONCLUSIONS Insulin secretion , and other biologic processes retained with younger age , are key in restoring NGR in people with pre-diabetes . However , NGR may also be attained through weight loss and additional aspects of ILS OBJECTIVE The Diabetes Prevention Program ( DPP ) demonstrated that intensive lifestyle and metformin interventions reduced the incidence of type 2 diabetes compared with a placebo intervention . The aim of this study was to assess the cost-effectiveness of the lifestyle and metformin interventions relative to the placebo intervention . RESEARCH DESIGN AND METHODS Analyses were performed from a health system perspective that considered direct medical costs only and a societal perspective that considered direct medical costs , direct nonmedical costs , and indirect costs . Analyses were performed with the interventions as implemented in the DPP and as they might be implemented in clinical practice . RESULTS The lifestyle and metformin interventions required more re sources than the placebo intervention from a health system perspective , and over 3 years they cost approximately US dollars 2250 more per participant . As implemented in the DPP and from a societal perspective , the lifestyle and metformin interventions cost US dollars 24400 and US dollars 34500 , respectively , per case of diabetes delayed or prevented and US dollars 51600 and US dollars 99200 per quality -adjusted life-year ( QALY ) gained . As the interventions might be implemented in routine clinical practice and from a societal perspective , the lifestyle and metformin interventions cost US dollars 13200 and US dollars 14300 , respectively , per case of diabetes delayed or prevented and US dollars 27100 and US dollars 35000 per QALY gained . From a health system perspective , costs per case of diabetes delayed or prevented and costs per QALY gained tended to be lower . CONCLUSIONS Over 3 years , the lifestyle and metformin interventions were effective and were cost-effective from the perspective of a health system and society . Both interventions are likely to be affordable in routine clinical practice , especially if implemented in a group format and with generic medication pricing OBJECTIVE Educational attainment is inversely associated with type 2 diabetes risk , but it is unknown whether education impacts individuals ' diabetes prevention efforts . We examined the comparative efficacy of intensive lifestyle intervention and metformin by educational attainment among participants in the Diabetes Prevention Program ( DPP ) , an ongoing U.S. multi-site trial beginning in 1996 . METHODS We studied 2,910 DPP participants r and omized to receive lifestyle intervention , metformin , or placebo .  Stratifying by educational attainment , diabetes incidence and relative risk reductions by treatment assignment were estimated using Cox proportional hazards regression . RESULTS 47 % of participants had completed college and 53 % had not . Compared to placebo , lifestyle participants who had completed college demonstrated a 68 % reduction in diabetes incidence ( 95 % CI=56 , 77 ) , whereas those with less education experienced a 47 % risk reduction ( 95 % CI=29 , 61 ) . For metformin participants , college graduates experienced a 49 % relative risk reduction ( 95 % CI=33 , 62 ) , compared to 23 % ( 95 % CI=1 , 41 ) among those with lower educational attainment . There was a statistically significant education-by-treatment interaction with incident diabetes ( p=0.03 ) . CONCLUSIONS Intensive lifestyle intervention and metformin have greater efficacy among highly educated individuals . Future efforts to deliver these treatments and study their dissemination may be more effective if tailored to individuals ' educational background OBJECTIVE We report the effects of several different measures of body size at baseline on the subsequent development of diabetes . High levels of body fat predict the onset of diabetes , but this association has not been previously reported in a large multiethnic population of overweight or obese people with impaired glucose tolerance . RESEARCH METHODS AND PROCEDURES Height , weight , waist circumference , hip circumference , and skinfolds were measured at baseline in 3234 participants enrolled in a r and omized clinical trial to treat individuals with impaired glucose tolerance with placebo , metformin , or a lifestyle modification program .  Cox proportional hazards models were used to assess the effect of baseline body size variables on the development of diabetes . RESULTS Over an average of 3.2 years in both the placebo and lifestyle groups , baseline waist circumference had the highest or second highest R(2 ) value for predicting diabetes in both sexes . Cox hazard ratios per 1 st and ard deviation were 1.43 and 1.49 for men in the placebo or lifestyle groups , respectively , and 1.29 and 1.53 for women in the placebo and lifestyle groups , respectively , adjusted for age and self-reported race/ethnicity . The c-statistic from the receiver operating characteristic curves also favored the waist circumference in men and women in the lifestyle group and men in the placebo group . No components of body size were predictive in the metformin-treated group , and metformin compared with the placebo group was effective in preventing diabetes only in individuals with a BMI > or = 35 kg/m(2 ) or a waist circumference > or = 98.0 cm . DISCUSSION Large waist circumference was a better predictor of risk for developing diabetes than most other measures in the placebo and lifestyle groups . No baseline measure of body size or shape predicted risk of diabetes in the metformin-treated group Context In 2003 , the U.S. Preventive Services Task Force recommended screening for type 2 diabetes in adults with hypertension or hyperlipidemia . The economic implication s of this recommendation are unclear . Contribution Diabetes screening for 55-year-old hypertensive persons would cost the U.S. health care system $ 34 375 per quality -adjusted life-year gained . Exp and ing screening to all adults regardless of the presence of hypertension would cost an additional $ 360 966 per quality -adjusted life-year . Implication s The cost-effectiveness of targeting diabetes screening to hypertensive adults older than 55 years of age is similar to the cost-effectiveness of many accepted health care interventions . Universal diabetes screening is far more costly . The Editors Although many adults who meet criteria for type 2 diabetes ( hereafter , diabetes ) have not been identified ( 1 ) , screening for diabetes remains controversial ( 2 - 11 ) . Direct evidence indicates that various treatments to reduce complications are effective among people with clinical ly detected diabetes ( 12 - 14 ) , but no direct evidence tells us the magnitude of any further benefit from starting these treatments earlier , after detection by screening ( 15 ) . In the absence of direct evidence , research ers have applied mathematical models of diabetes progression to the issue of screening . One analysis found that the cost per quality -adjusted life-year ( QALY ) gained by universal diabetes screening was lower for younger than for older people : $ 13 376 at age 25 to 34 years , increasing to $ 116 908 at age 55 to 64 years ( 16 ) . This conclusion followed from the model 's focus on the provision of glycemic control after screening to prevent microvascular complications . The analysis did not consider treatments to reduce the risks for complications of cardiovascular disease ( CVD ) . More recent research suggests that the benefits of CVD risk reduction may be substantial for people with diabetes . The Hypertension Optimal Treatment ( HOT ) trial found that the optimal blood pressure target is lower for people with hypertension and diabetes than for people with hypertension without diabetes ( 14 ) . Other research supports the finding that intensive control of hypertension is beneficial among people with diabetes ( 15 , 17 - 19 ) . Because the benefit may be greater for older people ( at greater risk for CVD ) , the conclusion of the previous analysis , that diabetes screening is most cost-effective among younger people , needs to be reconsidered . We performed a new cost-effectiveness analysis to compare universal diabetes screening ( universal screening ) and diabetes screening targeted to  patients with hypertension ( targeted screening ) . When an up date d version of the model used in the previous analysis that includes benefits from intensive treatment of hypertension was applied , we estimated the incremental cost-effectiveness of these 2 strategies for people in different age groups . Our analysis considers a one-time opportunistic screening for men and women of all races and ethnicities . Methods The Model We used a Markov model of diabetes disease progression to simulate lifetime diabetes-related health care costs and QALYs for people with diabetes ( Appendix Figure 1 ) . Demographic characteristics of the simulated cohort are based on 1997 population estimates projected from the 1990 U.S. Census and data on the distribution of people with diabetes by hypertension , cholesterol level , and smoking status ( 20 ) . As people progress through the simulation model from the onset of diabetes to death , they can develop 5 types of complications : nephropathy , neuropathy , retinopathy , coronary heart disease ( CHD ) , and stroke . People can die of some of these complications or of other causes . The model includes transition probabilities between disease stages on each of the 5 complication paths . The basic model structure has been described previously ( 16 , 21 ) . Key model parameters are presented in the Appendix Tables 1 to 10 . To incorporate screening into the model , we first added a screening module in which some patients with diabetes are identified earlier than they would usually have been in the absence of screening . Second , we made assumptions about the transition probabilities between disease stages from the onset of diabetes to the time of usual clinical diagnosis of diabetes on the basis of the knowledge that progression is relatively slow during this period ( 15 ) . After clinical diagnosis , disease progression depends on the number of years after normal diagnosis . Screening allows for earlier diagnosis , which in turn allows for earlier treatment interventions , such as intensive glycemic control and intensive hypertension control . These interventions decrease the transition probabilities , thereby delaying or preventing progression to diabetes complications . Costs are incurred for screening and diagnostic testing ; st and ard glycemic control and , if the person is hypertensive , st and ard hypertension control ; interventions ( intensive glycemic control and , if the person is hypertensive , intensive hypertension control ) ; and complications over the remaining lifetime of each person with diabetes . The sum of these costs and the model 's estimate of the expected QALYs for each screening strategy are used to calculate the incremental cost-effectiveness ratio of screening relative to no screening . We discounted future costs and QALYs at a 3 % annual rate . Costs are measured in 1997 U.S. dollars . Interventions We assumed that , in the absence of screening , diabetes would be diagnosed 10 years after its onset ( 15 ) . With one-time opportunistic screening , diabetes would be diagnosed on average 5 years after onset and therefore patients would begin treatment 5 years earlier . After diabetes diagnosis , all patients are treated with intensive glycemic control and , if they have hypertension , with intensive hypertension control . With targeted screening , only people with hypertension are screened . Those who screen positive and receive a diagnosis of diabetes begin intensive glycemic control and intensive hypertensive control 5 years earlier than they would in the absence of screening . With universal screening , all people , regardless of hypertension status , are screened . Those who screen positive and receive a diagnosis of diabetes begin intensive glycemic control 5 years earlier than in the absence of screening and begin intensive hypertension control 5 years earlier if they have hypertension . We defined hypertension as a blood pressure of 140/90 mm Hg or higher . We assumed that 19 % of people age 25 to 44 years , 47 % of people age 45 to 64 years , and 60 % of people age 65 to 74 years had hypertension and therefore were included in targeted screening ( 20 ) . Treatment of hypertension is modeled as st and ard ( with a target diastolic blood pressure of 90 mm Hg ) or intensive ( with a target diastolic blood pressure of 80 mm Hg ) , as in the HOT trial ( 14 ) . All persons with hypertension receive st and ard hypertension treatment until they receive a diagnosis of diabetes , after which they receive intensive hypertension treatment . The incremental cost of intensive hypertension control relative to st and ard control is $ 149 per year . In the HOT trial , the relative risk reduction for CHD events ( fatal and nonfatal myocardial infa rct ion ) was 51 % , and the relative risk reduction for stroke was about 30 % . Although neither of these separate relative risk reductions was statistically significant , the relative risk reduction ( 51 % ) for the aggregate outcome of major CVD events was statistically significant ( P = 0.005 ) . We initially modeled the relative risk reduction for CHD events for intensive hypertension control to be 51 % , with no risk reduction for stroke . We conducted a sensitivity analysis that included a 30 % relative risk reduction for stroke on the basis of other studies showing that intensive hypertension control reduces risk among people with diabetes ( 17 , 19 ) . Model estimates of the effects of glycemic control are based on the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , a 10-year r and omized , controlled trial of intensive versus conventional glycemic control ( 12 ) . On the basis of the UKPDS , the reduction in hemoglobin A1c from intensive glycemic treatment is modeled as slowing the progression of microvascular complications ( 12 ) . The incremental cost of intensive glycemic control ( relative to st and ard control ) ranges from $ 900 to $ 1100 per year , depending on the number of years since diagnosis . Screening and Diagnostic Tests The Figure illustrates the screening and diagnostic testing process and shows where costs are incurred . Figure . Progression of persons screened for diabetes . Appendix Figure 1 . Markov model of diabetes disease progression . LEA CA MI Screening Tests We assume a one-time opportunistic screening during a regularly scheduled physician office visit . The model assumes screening by a fasting capillary blood glucose ( CBG ) test ( 22 ) and an extra 10 minutes over the usual 15 minutes for the physician visit , incurring a cost of $ 24.40 per person screened . Costs for the CBG test are derived from the Medicare Clinical Diagnostic Laboratory Fee Schedule ( 23 ) ; physician visit costs are derived from Relative Values for Physicians ( 24 ) . Table 1 shows prevalence ( from the National Health and Nutrition Examination Survey III data tape ) , CBG sensitivity and specificity values ( 22 ) with exact data points clarified via personal communication ( Rolka DB , 18 January 2002 ) , and the number needed to screen to detect one previously undiagnosed person with diabetes by sex , hypertension status , and age . Table 1 . Number of Screenings and Diagnostic Tests  Needed To Identify One Undiagnosed Diabetes Case Diagnostic Tests All people who screen ( true or false ) positive receive a diagnostic test , the fasting plasma glucose test , which is repeated if the result is positive . Because 2 consecutive elevated fasting plasma glucose test results define diabetes ( 11 ) , we assume CONTEXT Gestational diabetes ( GDM ) confers a high risk of  type 2 diabetes .  In the Diabetes Prevention Program ( DPP ) , intensive lifestyle ( ILS ) and metformin prevented or delayed diabetes in women with a history of GDM . OBJECTIVE The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study . DESIGN This was a r and omized controlled clinical trial with an observational follow-up . SETTING The study was conducted at 27 clinical centers . PARTICIPANTS Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study . The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry . INTERVENTIONS Interventions included placebo , ILS , or metformin . OUTCOMES MEASURE Outcomes measure was diabetes mellitus . RESULTS Over 10 years , women with a history of GDM assigned to placebo had a 48 % higher risk of developing diabetes compared with women without a history of GDM . In women with a history of GDM , ILS and metformin reduced progression to diabetes compared with placebo by 35 % and 40 % , respectively . Among women without a history of GDM , ILS reduced the progression to diabetes by 30 % , and metformin did not reduce the progression to diabetes . CONCLUSIONS Women with a history of GDM are at an increased risk of developing diabetes . In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study , both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period . Among women without a history of GDM , lifestyle but not metformin reduced progression to diabetes OBJECTIVE To describe the costs of the Diabetes Prevention Program ( DPP ) interventions to prevent or delay type 2 diabetes . RESEARCH DESIGN AND METHODS We describe the direct medical costs , direct nonmedical costs , and indirect costs of the placebo , metformin , and intensive lifestyle interventions over the 3-year study period of the DPP . Re source use and cost are summarized from the perspective of a large health system and society . Research costs are excluded . RESULTS The direct medical cost of laboratory tests to identify one subject with impaired glucose tolerance ( IGT ) was $ 139 . Over 3 years , the direct medical costs of the interventions were $ 79 per participant in the placebo group , $ 2,542 in the metformin group , and $ 2,780 in the lifestyle group . The direct medical costs of care outside the DPP were $ 272 less per participant in the metformin group and $ 432 less in the lifestyle group compared with the placebo group . Direct nonmedical costs were $ 9 less per participant in the metformin group and $ 1,445 greater in the lifestyle group compared with the placebo group . Indirect costs were $ 230 greater per participant in the metformin group and $ 174 less in the lifestyle group compared with the placebo group . From the perspective of a health system , the cost of the metformin intervention relative to the placebo intervention was $ 2,191 per participant and the cost of the lifestyle intervention was $ 2,269 per participant over 3 years . From the perspective of society , the cost of the metformin intervention relative to the placebo intervention was $ 2,412 per participant and the cost of the lifestyle intervention was $ 3,540 per participant over 3 years . CONCLUSIONS The metformin and lifestyle interventions are associated with modest incremental costs compared with the placebo intervention . The evaluation of costs relative to health benefits will determine the value of these interventions to health systems and society OBJECTIVE We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes . RESEARCH DESIGN AND METHODS The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were r and omized to lifestyle , metformin , or placebo interventions for 3.4 years . Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing . In addition to baseline testing , anthropometry was performed every 6 months ; fasting insulin yearly ; and hs-CRP , tissue plasminogen activator ( tPA ) , and fibrinogen at 1 year and end of study ( EOS ) . RESULTS CRP and tPA levels were unchanged in the placebo group but fell in the lifestyle and metformin groups at 1 year and remained lower at EOS . These reductions were not seen in those who developed diabetes over the course of the study despite intervention . Fibrinogen was lower at 1 year in the lifestyle group . Differences in weight and weight change explained most of the influence of diabetes on the CRP response in the lifestyle group , but only partly in the placebo and metformin groups . Weight , insulin sensitivity , and hyperglycemia differences each accounted for the influence of diabetes on the tPA response . CONCLUSIONS Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA . Incident diabetes prevented these improvements , and this was accounted for by differences in weight , insulin resistance , and glucose levels CONTEXT A past history of gestational diabetes mellitus ( GDM ) confers a very high risk of postpartum development of diabetes , particularly type 2 diabetes . OBJECTIVE The Diabetes Prevention Program ( DPP ) sought to identify individuals with impaired glucose tolerance ( IGT ) and intervene in an effort to prevent or delay their progression to diabetes . This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM . DESIGN The DPP was a r and omized , controlled clinical trial . SETTING The study was a multicenter , National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites . PATIENTS A total of 2190 women were r and omized into the DPP and provided information for past history of GDM . This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM . INTERVENTIONS Subjects were r and omized to either st and ard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention . MAIN OUTCOMES The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing . Assessment s of insulin secretion and insulin sensitivity were also performed . RESULTS Whereas entering the study with similar glucose levels , women with a history of GDM r and omized to placebo had a crude incidence rate of diabetes 71 % higher than that of women without such a history . Among women reporting a history of GDM , both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50 % compared with the placebo group , whereas this reduction was 49 and 14 % , respectively in parous women without GDM . These data suggest that metformin may be more effective in women with a GDM history as compared with those without . CONCLUSIONS Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline . Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM Common genetic variants have been recently associated with fasting glucose and insulin levels in white population s. Whether these associations replicate in pre-diabetes is not known . We extended these findings to the Diabetes Prevention Program , a clinical trial in which participants at high risk for diabetes were r and omized to placebo , lifestyle modification or metformin for diabetes prevention . We genotyped previously reported polymorphisms ( or their proxies ) in/near G6PC2 , MTNR1B , GCK , DGKB , GCKR , ADCY5 , MADD , CRY2 , ADRA2A , FADS1 , PROX1 , SLC2A2 , GLIS3 , C2CD4B , IGF1 , and IRS1 in 3,548 Diabetes Prevention Program participants . We analyzed variants for association with baseline glycemic traits , incident diabetes and their interaction with response to metformin or lifestyle intervention . We replicated associations with fasting glucose at MTNR1B ( P<0.001 ) , G6PC2 ( P = 0.002 ) and GCKR ( P = 0.001 ) . We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B ( P<0.001 ) , and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 ( P<0.001 ) . The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait , indicating a sustained deleterious effect at this locus . We also replicated the association of MADD with fasting proinsulin levels ( P<0.001 ) . We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions . The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons . These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth , there are few data to guide treatment . We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes . METHODS Eligible patients 10 to 17 years of age were treated with metformin ( at a dose of 1000 mg twice daily ) to attain a glycated hemoglobin level of less than 8 % and were r and omly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone ( 4 mg twice a day ) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors . The primary outcome was loss of glycemic control , defined as a glycated hemoglobin level of at least 8 % for 6 months or sustained metabolic decompensation requiring insulin . RESULTS Of the 699 r and omly assigned participants ( mean duration of diagnosed type 2 diabetes , 7.8 months ) , 319 ( 45.6 % ) reached the primary outcome over an average follow-up of 3.86 years . Rates of failure were 51.7 % ( 120 of 232 participants ) , 38.6 % ( 90 of 233 ) , and 46.6 % ( 109 of 234 ) for metformin alone , metformin plus rosiglitazone , and metformin plus lifestyle intervention , respectively . Metformin plus rosiglitazone was superior to metformin alone ( P=0.006 ) ; metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone . Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness , with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls . Serious adverse events were reported in 19.2 % of participants . CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes . The addition of rosiglitazone , but not an intensive lifestyle intervention , was superior to metformin alone . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; TODAY Clinical Trials.gov number , NCT00081328 . ) Aims . To observe the rate of conversion from impaired glucose tolerance ( IGT ) to diabetes following lifestyle modification ( LSM ) or a combination of lifestyle and metformin compared to a control population with 18-month followup . Methods . Forty screening camps were organized , which 5000 people attended . Around 2300 persons filled the question naire and 1825 subjects were identified as high risk . Of 1739 subjects who took the oral glucose tolerance test , 317 subjects were identified as IGT . The 317 IGT subjects were r and omized into three groups : control group was given st and ard medical advice , LSM group was given intensive lifestyle modification advice , while LSM + drug group was given intensive lifestyle advice and metformin 500 mg twice daily . Results . At the end , 273 subjects completed the study , giving a compliance rate of 86 % . Total of 47 incident cases of diabetes were diagnosed ( overall incidence was 4 cases per 1000 person-months with the incidence of 8.6 cases in control group , 2.5 cases in the LSM , and 2.3 cases in the LSM + drug groups ) . Conclusions . Study showed that lifestyle intervention had a major impact in preventing diabetes among IGT subjects in this region . Adding drug did not show any improved results . We recommend lifestyle advice and followup should be incorporated in primary health care Background The worldwide epidemic of type 2 diabetes requires effective prevention . We determined the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention , originally demonstrated during the 3-year Diabetes Prevention Program ( DPP ) , and whether diabetes-associated microvascular complications are reduced . Methods The DPP ( 1996–2001 ) was a r and omized trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk to develop diabetes . All participants were offered lifestyle training at DPP-end . 2776 ( 88 % ) of the surviving DPP cohort were followed in the DPP Outcome Study ( DPPOS 2002–2013 ) and analyzed by intention-to-treat based on original DPP assignment . During DPPOS , the lifestyle group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin . Findings During 15 years of average follow-up , lifestyle intervention and metformin  reduced diabetes incidence rates by 27 % ( p<0.0001 ) and 18 % ( p=0.001 ) , respectively , compared with the placebo group , with declining between group differences over time . At year 15 , the cumulative incidences of diabetes were 55 , 56 and 62 % , respectively . The prevalences at study -end of the aggregate microvascular outcome , composed of nephropathy , neuropathy , and retinopathy , were not significantly different among the treatment groups ( 11–13 % ) in the total cohort . However , in women ( n=1887 ) lifestyle intervention was associated with a lower prevalence ( 8.7 % ) than in the placebo ( 11 % ) and metformin ( 11.2 % ) groups , with 21 % ( p=0.03 ) and 22 % ( p=0.02 ) reductions with lifestyle compared with placebo and metformin , respectively . Compared with participants who progressed to diabetes , those who did n’t progress had a 28 % lower prevalence of microvascular complications ( p<0.0001 ) . Interpretation Lifestyle intervention or metformin significantly reduce diabetes development over 15 years . There were no overall differences in the aggregate microvascular outcome among treatment groups ; however , those who did not progress to diabetes had a lower prevalence of microvascular complications than those who progressed . Funding National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK Type 2 diabetes affects over 150 million adults worldwide and this figure is expected to double over the next 25 yr . This increase will be accompanied by a marked increase in the number of patients with ESRD due to diabetes . We hypothesized that a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes We r and omly assigned 3234 nondiabetic persons with elevated fasting and postload plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 % weight loss and at least 150 min of physical activity per week . The mean age of the participants was 51 yr , and the mean body mass index was 34.0 kg/m(2 ) ; 68 % were women , and 45 % were members of non-Caucasian racial/ethnic groups . The average follow-up was 2.8 yr . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence of diabetes by 58 % ( 95 % CI : 48 to 66 % ) and metformin by 31 % ( 95 % CI : 17 to 43 % ) , compared with placebo ; the lifestyle intervention was significantly more effective than metformin . In conclusion , lifestyle changes and treatment with  metformin  both reduced the incidence of diabetes in persons at high risk and the lifestyle intervention was more effective than metformin . Because the lifestyle changes worked equally in all racial/ethnic groups in the Diabetes Prevention Program , they should be applicable to high-risk population s worldwide and may be able to reduce the projected progressive rise in the incidence of diabetes and the expected increase in ESRD BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program  with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin OBJECTIVE The Diabetes Prevention Program ( DPP ) and its Outcomes Study ( DPPOS ) demonstrated that either intensive lifestyle intervention or metformin could prevent type 2 diabetes in high-risk adults for at least 10 years after r and omization . We report the 10-year within-trial cost-effectiveness of the interventions . RESEARCH DESIGN AND METHODS Data on re source utilization , cost , and quality of life were collected prospect ively . Economic analyses were performed from health system and societal perspectives . RESULTS Over 10 years , the cumulative , undiscounted per capita direct medical costs of the interventions , as implemented during the DPP , were greater for lifestyle ( $ 4,572 ) than metformin ( $ 2,281 ) or placebo ( $ 752 ) . The cumulative direct medical costs of care outside the DPP/DPPOS were least for lifestyle ( $ 26,810 lifestyle vs. $ 27,384 metformin vs. $ 29,007 placebo ) . The cumulative , combined total direct medical costs were greatest for lifestyle and least for metformin ( $ 31,382 lifestyle vs. $ 29,665 metformin vs. $ 29,759 placebo ) . The cumulative quality -adjusted life-years ( QALYs ) accrued over 10 years were greater for lifestyle ( 6.89 ) than metformin ( 6.79 ) or placebo ( 6.74 ) . When costs and outcomes were discounted at 3 % and adjusted for survival , lifestyle cost $ 12,878 per QALY , and metformin had slightly lower costs and nearly the same QALYs as placebo . CONCLUSIONS Over 10 years , from a payer perspective , lifestyle was cost-effective and metformin was marginally cost-saving compared with placebo . Investment in lifestyle and metformin interventions for diabetes prevention in high-risk adults provides good value for the money spent Diabetes is an “ old disease ” . The first description of diabetes written on papyrus about 3500 years ago is found in the Ebers papyrus  , which was discovered in Egypt in 1873 by the German archeologist Georg Ebers . Humans , like most mammals , may develop diabetes , if sufficient environmental exposure to physical inactivity , unhealthy diet and obesity are present . Genetic effects are important for the individual risk of type 2 diabetes ( T2D ) but twin studies have shown that the genetic effects combined explain less than 50 % of the risk of T2D ( 1 ) . Today we know almost 100 susceptibility genes associated with T2D but the relative importance of each of these genes is low ( 2 ) , and together they explain only a small part of the disease risk . Thus , genetic screening can not be used for the prediction of T2D for individuals . On the other h and , healthy lifestyle can also prevent T2D in people who are genetically at high risk , e.g. those with positive family history ( 3 ) . Thus , the importance of lifestyle factors for the development and prevention of T2D is overwhelming . The strongest evidence in medicine is considered to come from r and omized controlled trials ( RCTs ) . They are also important in providing the link to causal inference that in most observational studies can not be derived . At the same time , observational studies are necessary for the identification of factors associated with an increased or decreased risk of a disease , and for generation of hypotheses on potential means for prevention based on modifiable risk factors . Observational studies have by now identified a large number of factors that are associated with the development of T2D or with the protection against it . Most of them are related to physical activity , diet and obesity . It has also been shown unequivocally that exposures ( poor nutrition , infections , smoking , etc . ) during fetal life and early infancy result ing in insufficient development ( often shown as low birth weight ) also predict T2D later in life ( 4 ) . Traditionally , T2D has been considered to be a disease of the elderly . However , with increasing obesity and sedentary lifestyle in children , there are increasing numbers of cases of T2D already occurring at a young age in many population s ( 5 ) . In the past two decades several innovative RCTs have repeatedly shown that interventions on modifiable risk factors can reduce the incidence of diabetes in high-risk groups . The evidence has been summarized in several systematic review s and meta-analyses ( 6,7 ) . There is compelling scientific evidence from RCTs that T2D can be prevented or its onset delayed . The key for prevention is a multimodal package of lifestyle changes that is a sum outcome of dietary and physical activity behaviours . The power of lifestyle was dramatically illustrated by the Finnish Diabetes Prevention Study ( DPS ) that explicitly showed that when the study participants with impaired glucose tolerance reached all five modest lifestyle intervention targets , none of them progressed to T2D ( 8) . Importantly , lifestyle intervention lasting for 3–6 years has been shown to have a carry-over effect on T2D incidence that lasts for several years ; up to 15 in the Finnish Diabetes Prevention Study ( 9 ) and 20 years in the China Da Qing Diabetes Prevention Study ( 10 ) . The observed sustained risk reduction seems to be a result of sustained lifestyle changes , but the legacy effect of improved glycaemia during the early intervention may also have contributed to the long-term effect . The follow-up data from the Chinese study indicate moreover that vascular risks are also reduced by lifestyle management . Several prognostic question naires exist for detecting people at risk of T2D ( 11 ) . One of the screening tools with an adequately high sensitivity and specificity is the Finnish Diabetes Risk Score ( FINDRISC ) developed in Finl and ( 12 ) . The FINDRISC has been successfully implemented in the Finnish primary health care system and used also in many other countries . The FINDRISC was also tested in the Omani population and as a result a slightly modified Omani Diabetes Risk Score was developed ( 13 ) which may be a suitable screening tool for the Arab population s in the Middle East . Lifestyle interventions aim ing at translating evidence from efficacy RCTs on T2D prevention into “ real world ” intervention programmes have also been carried out in various population s. Such data were recently combined in a meta- analysis considering the relationship between intervention effectiveness and adherence to guidelines ( 14 ) . The primary meta- analysis included 22 studies with outcome data for weight loss at 12 months . The pooled result of the direct pairwise meta- analysis shows that Background South Asian migrants are at particularly high risk of type 2 diabetes . Previous studies have shown that intensive lifestyle interventions may prevent the onset of diabetes . Such interventions have not been culturally adapted and evaluated among South Asians in industrialized countries . Therefore , we have set up a r and omized controlled trial to study the effectiveness of a targeted lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk factors among 18 to 60-year-old Hindustani Surinamese ( South Asians ) in The Hague , the Netherl and s. Here we present the study design and describe the characteristics of those recruited . Methods Between May 18 , 2009 and October 11 , 2010 , we screened 2307 Hindustani Surinamese ( 18–60 years old ) living in The Hague . We sent invitations to participate to those who had an impaired fasting glucose of 5.6 - 6.9 mmol/l , an impaired glucose tolerance of 7.8 - 11.0 mmol/L , a glycated hemoglobin level of 6.0 % or more and /or a value of 2.39 or more for the homeostasis model assessment of estimated insulin resistance . In total , 536 people ( 56.1 % of those eligible ) participated . People with a higher level of education and a family history of type 2 diabetes were more likely to participate . The control and intervention groups were similar with regard to important background characteristics . The intervention group will receive a culturally targeted intervention consisting of dietary counseling using motivational interviewing and a supervised physical activity program . The control group will receive generic lifestyle advice . To determine the effectiveness , a physical examination ( anthropometrics , cardiorespiratory test , lipid profile , and measures of oral glucose tolerance , glycated hemoglobin , and insulin ) and interview ( physical activity , diet , quality of life , and intermediate outcomes ) were carried out at baseline and will be repeated at 1 year and 2 years . The process and the costs will be evaluated . Discussion This trial will provide insight into the feasibility and effectiveness of a targeted , intensive , lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk factors among 18 to 60-year-old South Asians . Trial registration Dutch Trial Register : The Diabetes Prevention Program ( DPP ) was a r and omized clinical trial of prevention of type 2 diabetes in high-risk people .  Troglitazone , an insulin-sensitizing agent , was used initially but was discontinued during the trial . Troglitazone therapy was compared with other DPP interventions , considering both the short-term " in-trial " results and the longer-term results after troglitazone were discontinued . From 1996 to 1998 , participants were r and omly assigned to treatment with metformin ( n = 587 ) , troglitazone ( n = 585 ) , double placebo ( n = 582 ) , or intensive lifestyle intervention ( ILS ) ( n = 589 ) . Because of concern regarding its liver toxicity , the troglitazone arm was discontinued in June 1998 , after which follow-up of all participants continued . During the mean 0.9 year ( range 0.5 - 1.5 years ) of troglitazone treatment , the diabetes incidence rate was 3.0 cases/100 person-years , compared with 12.0 , 6.7 , and 5.1 cases/100 person-years in the placebo , metformin , and ILS participants ( P < 0.001 , troglitazone vs. placebo ; P = 0.02 , troglitazone vs. metformin ; P = 0.18 , troglitazone vs. ILS ) . This effect of troglitazone was in part due to improved insulin sensitivity with maintenance of insulin secretion . During the 3 years after troglitazone withdrawal , the diabetes incidence rate was almost identical to that of the placebo group . Troglitazone , therefore , markedly reduced the incidence of diabetes during its limited period of use , but this action did not persist . Whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes remains to be determined Background Type 2 diabetes is a major public health problem in Australia with prevalence increasing in parallel with increasing obesity . Prevention is an essential component of strategies to reduce the diabetes burden . There is strong and consistent evidence from r and omised controlled trials that type 2 diabetes can be prevented or delayed through lifestyle modification which improves diet , increases physical activity and achieves weight loss in at risk people . The current challenge is to translate this evidence into routine community setting s , determine feasible and effective ways of delivering the intervention and providing on-going support to sustain successful behavioural changes . Methods / Design The Sydney Diabetes Prevention Program ( SDPP ) is a translational study which will be conducted in 1,550 participants aged 50 - 65 years ( including 100 indigenous people aged 18 years and older ) at high risk of future development of diabetes . Participants will be identified through a screening and recruitment program delivered through primary care and will be offered a community-based lifestyle modification intervention . The intervention comprises an initial individual session and three group sessions based on behaviour change principles and focuses on five goals : 5 % weight loss , 210 min/week physical activity ( aerobic and strength training exercise ) , limit dietary fat and saturated fat to less than 30 % and 10 % of energy intake respectively , and at least 15 g/1000 kcal dietary fibre . This is followed by 3-monthly contact with participants to review progress and offer ongoing lifestyle advice for 12 months . The effectiveness and costs of the program on diabetes-related risk factors will be evaluated . Main outcomes include changes in weight , physical activity , and dietary changes ( fat , saturated fat and fibre intake ) . Secondary outcomes include changes in waist circumference , fasting plasma glucose , blood pressure , lipids , quality of life , psychological well being , medication use and health service utilization . Discussion This translational study will ascertain the reach , feasibility , effectiveness and cost-effectiveness of a lifestyle modification program delivered in a community setting through primary health care . If demonstrated to be effective , it will result in recommendations for policy change and practical methods for a wider community program for preventing or delaying the onset of type 2 diabetes in high risk people OBJECTIVE Therapies with metformin , sulfonylureas , or insulin improve glycemic control in the short term but do not prevent progressive islet beta-cell failure or long-term deterioration in glycemia . Our goal was to evaluate , in patients recently diagnosed with type 2 diabetes ( <3 years ) , the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy . RESEARCH DESIGN AND METHODS A Diabetes Outcome Progression Trial ( ADOPT ) is a r and omized , double-blind , parallel-group study consisting of a screening visit , a 4-week placebo run-in , a 4-year treatment period , and an observational follow-up of approximately 3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years . After run-in , patients will be r and omized to rosiglitazone , glyburide , or metformin titrated to the maximum effective daily doses ( 8 mg rosiglitazone , 15 mg glyburide , or 2 g metformin ) . The primary outcome is time to monotherapy failure , defined as the time following titration to the maximal effective or tolerated dose when fasting plasma glucose exceeds 180 mg/dl ( 10 mmol/l ) . Secondary outcomes include measures of islet beta-cell function , insulin sensitivity , dyslipidemia , changes in urinary albumin excretion , plasminogen activator inhibitor-1 antigen , fibrinogen , and C-reactive protein . Safety and tolerability will also be evaluated . Patient-reported outcomes and re source utilization data will be collected and analyzed . CONCLUSIONS ADOPT will provide data on the effect of mechanistically differing treatment options on metabolic control , beta-cell function , and markers of macrovascular disease risk in type 2 diabetes AIMS The Diabetes Community Lifestyle Improvement Program ( D-CLIP ) aims to implement and evaluate in a controlled , r and omized trial the effectiveness , cost-effectiveness , and sustainability of a culturally appropriate , low-cost , and sustainable lifestyle intervention for the prevention of type 2 diabetes mellitus in India . METHODS D-CLIP , a translational research project adapted from the methods and curriculum developed and tested for efficacy in the Diabetes Prevention Program , utilizes innovated methods ( a step-wise model of diabetes prevention with lifestyle and metformin added when needed ; inclusion of individuals with isolated glucose tolerance , impaired fasting glucose , and both ; classes team-taught by professionals and trained community educators ) with the goals of increasing diabetes prevention , community acceptability , and long-term dissemination and sustainability of the program . The study outcomes are : diabetes incidence ( primary measure of effectiveness ) , cost-effectiveness , changes in anthropometric measures , plasma lipids , blood pressure , blood glucose , and HbA(1c , ) Program acceptability and sustainability will be assessed using a mixed methods approach . CONCLUSION D-CLIP , a low-cost , community-based , research program , addresses the key components of translational research and can be used as a model for prevention of chronic diseases in other low and middle-income country setting BACKGROUND Lifestyle interventions can delay the onset of type 2 diabetes in people with impaired glucose tolerance , but whether this leads subsequently to fewer complications or to increased longevity is uncertain . We aim ed to assess the long-term effects of lifestyle interventions in people with impaired glucose tolerance on the incidence of diabetes , its complications , and mortality . METHODS The original study was a cluster r and omised trial , started in 1986 , in which 33 clinics in Da Qing , China , were r and omly assigned to either be a control clinic or provide one of three interventions ( diet , exercise , or diet plus exercise ) for 6 years for 577 adults with impaired glucose tolerance who usually receive their medical care from the clinics . Subsequently , participants were followed for up to 30 years to assess the effects of intervention on the incidence of diabetes , cardiovascular disease events , composite microvascular complications , cardiovascular disease death , all-cause mortality , and life expectancy . FINDINGS Of the 577 participants , 438 were assigned to an intervention group and 138 to the control group  ( one refused baseline examination ) . After 30 years of follow-up , 540 ( 94 % ) of 576 participants were assessed for outcomes ( 135 in the control group , 405 in the intervention group ) . During the 30-year follow-up , compared with control , the combined intervention group had a median delay in diabetes onset of 3·96 years ( 95 % CI 1·25 to 6·67 ; p=0·0042 ) , fewer cardiovascular disease events ( hazard ratio 0·74 , 95 % CI 0·59 - 0·92 ; p=0·0060 ) , a lower incidence of microvascular complications ( 0·65 , 0·45 - 0·95 ; p=0·025 ) , fewer cardiovascular disease deaths ( 0·67 , 0·48 - 0·94 ; p=0·022 ) , fewer all-cause deaths ( 0·74 , 0·61 - 0·89 ; p=0·0015 ) , and an average increase in life expectancy of 1·44 years ( 95 % CI 0·20 - 2·68 ; p=0·023 ) . INTERPRETATION Lifestyle intervention in people with impaired glucose tolerance delayed the onset of type 2 diabetes and reduced the incidence of cardiovascular events , microvascular complications , and cardiovascular and all-cause mortality , and increased life expectancy . These findings provide strong justification to continue to implement and exp and the use of such interventions to curb the global epidemic of type 2 diabetes and its consequences . FUNDING US Centers for Disease Control and Prevention , WHO , Chinese Center for Disease Control and Prevention , World Bank , Ministry of Public Health of the People 's Republic of China , Da Qing First Hospital , China-Japan Friendship Hospital , and National Center for Cardiovascular Diseases & Fuwai Hospital Several studies have demonstrated that type 2 diabetes mellitus ( DM ) can be prevented/delayed in subjects with impaired glucose tolerance ( IGT ) by using pharmacologic agents and /or lifestyle interventions . However , a number of challenges remain , including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches . IGT , like DM , is characterized by insulin resistance , β‐cell dysfunction and increased hepatic glucose production . We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy . In this context , we initiated the Canadian Normoglycemia Outcomes Evaluation ( CANOE ) study , a moderately sized , r and omized , double‐blind , controlled trial . The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone , in addition to a healthy living lifestyle programme , will prevent the development of DM . The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT . A total of 200 patients will be recruited in Toronto and London , Ontario , and followed for an average of 4 years ( range 3–5 years ) . Active treatment with metformin ( 500 mg ) plus rosiglitazone ( 2 mg ) , administered as one capsule twice daily , will be compared to matched placebo .  Subjects will be eligible for r and omization if they have IGT and are between the ages of 30–75 years . The primary outcome will be the development of new‐onset DM , diagnosed by either two fasting plasma glucose values of ≥7 mmol/l or one positive oral glucose tolerance test with a 2‐h plasma glucose value of > 11.0 mmol/l during the active drug phase of the trial . With a sample size of 100 participants per group , we will be able to detect a relative risk reduction of 45 % , with a two‐sided log‐rank test with a significance level of 0.05 and 80 % power , assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years . In conclusion , the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high‐risk Canadians OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment , administered alone or in sequence , on glucose and lipid metabolism , cardiovascular risk factors , and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia . RESEARCH DESIGN AND METHODS We studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were r and omized twice , initially to either  metformin or placebo  , and then to micronized fenofibrate or placebo . RESULTS Fenofibrate alleviated diabetic dyslipidemia – induced changes in plasma high-sensitivity C-reactive protein , fibrinogen , and plasminogen activator inhibitor (PAI)-1 and in monocyte cytokine release , whereas metformin or lifestyle intervention improved mainly glucose and lipid metabolism . The strongest pleiotropic effect was observed when fenofibrate was added to metformin . CONCLUSIONS Fenofibrate , particularly administered together with metformin , is superior to metformin and lifestyle intervention in exhibiting beneficial effects on systemic inflammation , hemostasis , and monocyte secretory function in type 2 diabetic patients with mixed dyslipidemia INTRODUCTION Although the Diabetes Prevention Program and other clinical trials demonstrated the efficacy of intensive lifestyle interventions ( ILI ) and metformin to prevent type 2 diabetes , no studies have tested their comparative effects in pragmatic setting s. This study was design ed to compare the real-world effectiveness of ILI , metformin , and st and ard care among Hispanic women ( Latinas ) with prediabetes . STUDY DESIGN RCT . SETTING / PARTICIPANTS Ninety-two Latinas , who had a mean hemoglobin A1c of 5.9 % , BMI of 33.3 kg/m2 , and waist circumference of 97.4 cm ( 38.3 inches ) , were recruited from an urban community and r and omly assigned to ILI , metformin , or st and ard care using 1:1:1 allocation . Data were collected from 2013 - 2015 and analyzed in 2016 . INTERVENTION The 12-month ILI was adapted from the Diabetes Prevention Program 's ILI and delivered by community health workers ( promotoras ) over 24 sessions . Metformin participants received 850 mg twice daily . Those r and omized to st and ard care continued their regular medical care . MAIN OUTCOME MEASURES Weight and secondary outcomes ( waist circumference , blood pressure , hemoglobin A1c , fasting plasma glucose , insulin , and lipids ) were assessed at baseline and 12 months . RESULTS ILI participants demonstrated significantly greater mean weight loss ( -4.0 kg , 5.0 % ) than metformin ( -0.9 kg , 1.1 % ) and st and ard care participants ( + 0.8 kg , 0.9 % ) ( p<0.001 ) . The difference in weight loss between metformin and st and ard care was not significant . The ILI group experienced a greater reduction in waist circumference than st and ard care ( p=0.001 ) , and a marginal improvement in hemoglobin A1c compared with metformin and st and ard care ( p=0.063 ) . CONCLUSIONS In the first comparative effectiveness trial of diabetes prevention treatments , a 12-month ILI produced significantly greater weight loss than metformin and st and ard care among Latinas with prediabetes . These data suggest that ILI delivered by promotoras is an effective strategy for preventing diabetes in this high-risk group , which may be superior to metformin . Future pragmatic trials involving larger sample s should examine differences in diabetes incidence associated with these treatments Background The Diabetes Prevention Program ( DPP ) was a r and omized , controlled clinical trial . It demonstrated that among high-risk individuals with impaired glucose tolerance , diabetes incidence was reduced by 58 % with lifestyle intervention and 31 % with metformin compared to placebo . During the Diabetes Prevention Program Outcomes Study ( DPPOS ) , all DPP participants were unmasked to their treatment assignments , the original lifestyle intervention group was offered additional lifestyle support , the metformin group continued metformin , and all three groups were offered a group-implemented lifestyle intervention . Over the 10 years of combined DPP/DPPOS follow-up , diabetes incidence was reduced by 34 % in the lifestyle group and 18 % in the metformin group compared to placebo . The purpose of this article is to review and synthesize analyses published by the DPP/DPPOS Research Group that have described the cost-effectiveness of diabetes prevention . Methods We describe the re source utilization and costs of the DPP and DPPOS interventions , the costs of non-intervention-related medical care , the impact of the interventions on diabetes progression and quality -of-life , and the cost-effectiveness of the interventions from health system and societal perspectives . Cost-effectiveness analyses were performed with a 3-year time horizon using DPP data , a lifetime time horizon that simulated 3-year DPP data , and a 10-year time horizon using combined DPP/DPPOS data . Results Although more expensive than the placebo intervention , the greater costs of the lifestyle and metformin interventions were offset by reductions in the costs of nonintervention-related medical care . Every year after r and omization , quality -of-life was better for participants in the lifestyle intervention compared to those in the metformin or placebo intervention . In both the simulated lifetime analysis and the 10-year within trial economic analysis , lifestyle and metformin were extremely cost-effective ( that is , improved outcomes at a low incremental cost ) or even cost-saving ( that is , improved outcomes and reduced total costs ) compared to the placebo intervention . Conclusions The implementation of diabetes prevention programs in high-risk individuals will result in important health benefits and represents a good value for money . Trial registration NCT00004992 ( DPP ) and NCT00038727 ( DPPOS ) Objective . Within the frame of a r and omized clinical trial to examine whether training of general practitioners ( the intervention group ) in intensive lifestyle modification and pharmacological treatment of patients with type 2 diabetes has a spillover effect on individuals with impaired fasting glycaemia ( IFG ) or impaired glucose tolerance ( IGT ) . Design . A high-risk screening study for type 2 diabetes with an intervention programme , where general practice s were r and omized to provide st and ard treatment versus intensive lifestyle modification and pharmacological treatment to newly diagnosed diabetic patients . Setting . General practice s in Denmark . Subjects . Of 1821 individuals identified with IFG or IGT , results from oral glucose tolerance tests after one and three years were available in 1510 individuals . Main outcome measures . Progression rates from IFG and IGT to diabetes and effect of intervention were estimated in a regression model using interval censoring . Results . A total of 442 persons developed diabetes .  There was no significant overall effect of intervention on progression rates . For risk factors , no difference in rate of change was found between r and omization groups , but a difference was found between general practice s within the same r and omization groups . Conclusion . General practitioners identify a high number of incident diabetes cases in individuals with IFG or IGT found by high-risk screening . Intervention at the general practitioner 's level in intensive treatment type 2 diabetes does not have a significant spillover effect reducing the risk of diabetes from pre-diabetic conditions . This could indicate that intervention strategies should be specifically targeted at individuals with IFG or IGT , either by training general practitioners or directly at the individual level Insulin resistance and beta-cell dysfunction , two factors central to the pathogenesis of type 2 diabetes , were studied in relation to the development of diabetes in a group of participants with impaired glucose tolerance in the Diabetes Prevention Program ( DPP ) at baseline and after specific interventions design ed to prevent diabetes . Participants were r and omly assigned to  placebo ( n = 1,082 ) , metformin ( 850 mg twice a day ) ( n = 1,073 ) , or intensive lifestyle intervention  ( n = 1,079 ) . The diabetes hazard rate was negatively associated with baseline insulin sensitivity ( hazard rate ratio = 0.62 - 0.94 per SD difference , depending on treatment group and measure of sensitivity ) and with baseline insulin secretion ( hazard rate ratio = 0.57 - 0.76 per SD ) . Improvements in insulin secretion and insulin sensitivity were associated with lower hazard rates in all treatment arms ( hazard rate ratio = 0.46 - 0.95 per SD increase and 0.29 - 0.79 per SD increase , respectively ) . In multivariate models that included the three metabolic variables ( changes in body weight , insulin sensitivity , and insulin secretion ) each significantly and independently predicted progression to diabetes when adjusted for the other two variables . The intensive lifestyle intervention , which elicited the greatest reduction in diabetes incidence , produced the greatest improvement in insulin sensitivity and the best preservation of beta-cell function after 1 year , whereas the placebo group , which had the highest diabetes incidence , had no significant change in insulin sensitivity and beta-cell function after 1 year . In the metformin group , diabetes risk , insulin sensitivity , and beta-cell function at 1 year were intermediate between those in the intensive lifestyle and placebo groups . In conclusion , higher insulin secretion and sensitivity at baseline and improvements in response to treatment were associated with lower diabetes risk in the DPP . The better preventive effectiveness of intensive lifestyle may be due to improved insulin sensitivity concomitant with preservation of beta-cell function Background India currently has more than 60 million people with Type 2 Diabetes Mellitus ( T2DM ) and this is predicted to increase by nearly two-thirds by 2030 . While management of those with T2DM is important , preventing or delaying the onset of the disease , especially in those individuals at ‘ high risk ’ of developing T2DM , is urgently needed , particularly in re source -constrained setting s. This paper describes the protocol for a cluster r and omised controlled trial of a peer-led lifestyle intervention program to prevent diabetes in Kerala , India . Methods / design A total of 60 polling booths are r and omised to the intervention arm or control arm in rural Kerala , India . Data collection is conducted in two steps . Step 1 ( Home screening ) : Participants aged 30–60 years are administered a screening question naire . Those having no history of T2DM and other chronic illnesses with an Indian Diabetes Risk Score value of ≥60 are invited to attend a mobile clinic ( Step 2 ) . At the mobile clinic , participants complete question naires , undergo physical measurements , and provide blood sample s for biochemical analysis . Participants identified with T2DM at Step 2 are excluded from further study participation . Participants in the control arm are provided with a health education booklet containing information on symptoms , complications , and risk factors of T2DM with the recommended levels for primary prevention . Participants in the intervention arm receive : ( 1 ) eleven peer-led small group sessions to motivate , guide and support in planning , initiation and maintenance of lifestyle changes ; ( 2 ) two diabetes prevention education sessions led by experts to raise awareness on T2DM risk factors , prevention and management ; ( 3 ) a participant h and book containing information primarily on peer support and its role in assisting with lifestyle modification ; ( 4 ) a participant workbook to guide self-monitoring of lifestyle behaviours , goal setting and goal review ; ( 5 ) the health education booklet that is given to the control arm . Follow-up assessment s are conducted at 12 and 24 months . The primary outcome is incidence of T2DM . Secondary outcomes include behavioural , psychosocial , clinical , and biochemical measures . An economic evaluation is planned . Discussion Results from this trial will contribute to improved policy and practice regarding lifestyle intervention programs to prevent diabetes in India and other re source -constrained setting s . Trial registration Australia and New Zeal and Clinical Trials Registry : ACTRN12611000262909 OBJECTIVE —In the Indian Diabetes Prevention Programme ( IDPP ) , a 3-year r and omized , controlled trial , lifestyle modification ( LSM ) and metformin helped to prevent type 2 diabetes in subjects with impaired glucose tolerance ( IGT ) . The direct medical costs and cost-effectiveness of the interventions relative to the control group are reported here . RESEARCH DESIGN AND METHODS —Relative effectiveness and costs of interventions ( LSM , metformin , and LSM and metformin ) in the IDPP were estimated from the health care system perspective . Costs of intervention considered were only the direct medical costs . Direct nonmedical , indirect , and research costs were excluded . The cost-effectiveness of interventions was measured as the amount spent to prevent one case of diabetes within the 3-year trial period . RESULTS —The direct medical cost to identify one subject with IGT was Indian rupees ( INR ) 5,278 ( $ 117 ) . Direct medical costs of interventions over the 3-year trial period were INR 2,739 ( $ 61 ) per subject in the control group , INR 10,136 ( $ 225 ) with LSM , INR 9,881 ( $ 220 ) with metformin , and INR 12,144 ( $ 270 ) with LSM and metformin . The number of individuals needed to treat to prevent a case of diabetes was 6.4 with LSM , 6.9 with metformin , and 6.5 with LSM and metformin . Cost-effectiveness to prevent one case of diabetes with LSM was INR 47,341 ( $ 1,052 ) , with metformin INR 49,280 ( $ 1,095 ) , and with LSM and metformin INR 61,133 ( $ 1,359 ) . CONCLUSIONS —Both LSM and metformin were cost-effective interventions for preventing diabetes among high risk-individuals in India and perhaps may be useful in other developing countries as well . The long-term cost-effectiveness of the interventions needs to be assessed OBJECTIVE The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance ( IGT ) . Participants with IGT are at high risk for cardiovascular disease ( CVD ) , with a marked increase in the number and severity of CVD risk factors . We prospect ively assessed the impact of our interventions on hypertension , dyslipidemia , and CVD events . RESEARCH DESIGN AND METHODS The study group consisted of 3,234 individuals with IGT r and omly assigned to receive intensive lifestyle intervention , metformin , or placebo . Annual assessment of blood pressure , lipids , electrocardiogram , and CVD events was undertaken . RESULTS Hypertension was present in 30 % of participants at study entry and then increased in the placebo and metformin groups , although it significantly decreased with intensive lifestyle intervention . Triglyceride levels fell in all treatment groups , but fell significantly more with intensive lifestyle intervention . Total cholesterol and LDL cholesterol levels were similar among treatment groups . Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up , the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27 - 28 % less for hypertension and 25 % less for hyperlipidemia compared with placebo and metformin groups . Over an average of 3 years , 89 CVD events from 64 participants were positively adjudicated study wide , with no differences among treatment groups . CONCLUSIONS Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy . Although no differences in CVD events were noted after 3 years , achieved risk factor modifications suggest that longer intervention may reduce CVD event rates Context A previous Markov modelbased analysis estimated that use of the Diabetes Prevention Program diet and exercise intervention to forestall diabetes in high-risk people would be cost-effective from a societal perspective . Contribution Using a vali date d model design ed to be more complete and realistic than previous models , the authors estimated that the intervention would cost society about $ 62600 per quality -adjusted life-year saved . It would be cost-saving if the annual cost of the intervention decreased from $ 672 to $ 100 . Implication s This model suggests that the Diabetes Prevention Program intervention costs more per quality -adjusted life-year saved than previously estimated , and health plans and insurers may consider it too expensive to cover . The Editors Recent r and omized , controlled studies have shown that diabetes can be prevented or delayed in high-risk individuals by intensive lifestyle modification programs ( 1 , 2 ) or glucose-lowering drugs ( 2 - 4 ) . For example , in the Diabetes Prevention Program ( DPP ) , the relative reductions in the 2.8-year incidence of diabetes were 58 % in the lifestyle modification group and 31 % in the metformin group ( 2 ) . This raises hopes of substantially reducing the morbidity , mortality , and cost of this important disease . However , the trial was too short to observe the effects on microvascular or macrovascular outcomes , and the programs cost several hundred dollars a year ( 5 ) . These findings generate obvious questions : What are the long-term effects of trying to prevent diabetes in high-risk people ? Does lifestyle modification truly prevent or just postpone diabetes ? Is such a prevention program cost-effective ? What is the best strategy ? A previous analysis has suggested that lifestyle modification would be cost-effective over 75 years from a societal perspective ( 6 ) . We used a more thorough , clinical ly realistic , and independently vali date d model to estimate the short- and intermediate-term health and economic effects of different prevention programs for high-risk individuals and health plans , as well as for society . Methods We conducted the analysis by using the Archimedes model , which has been described elsewhere ( 7 - 9 ) . Briefly , it is a simulation model written at a relatively high level of anatomic , physiologic , clinical , and administrative detail . It uses object-oriented programming to create in the model objects that correspond to objects in reality , one-to-one . Among the hundreds of objects are  people , pancreases , cells , plasma glucose levels , coronary arteries , plaque , chest pain , emergency departments , electrocardiograms , aspirin , and angioplasties  . Helpful analogies might be a flight simulator ( in which the objects include the plane and its wings , airports , runways , buildings , and the wind ) , or the SimCity computer game . In the Archimedes model , each individual is simulated down to the level of hepatic glucose production , insulin resistance , -cell fatigue , and similar biological variables . The core of the model is a set of differential equations that represent the anatomy and physiology pertinent to diseases and their complications . Currently , the model includes diabetes , congestive heart failure , coronary artery disease , stroke , hypertension , and asthma in a single integrated model . The structure and equations of the model pertinent to diabetes and its complications are described elsewhere ( 8 , 9 ) . The Appendix and a technical report available through our Web site ( 10 ) describe additional aspects of the model and its validations that are pertinent to this analysis . Calculations are performed by using a distributed computing network . Clinical Events The model includes the biological variables and outcomes relevant to diabetes and its complications . Examples are basal hepatic glucose production ; insulin amount ; insulin resistance ; fasting plasma glucose ; hemoglobin A1c ( HbA1c ) ; 2-hour oral glucose tolerance ; high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , and total cholesterol ; triglycerides ; systolic and diastolic blood pressures and their determinants ( for example , cardiac output , arterial compliance , peripheral resistance ) ; weight and body mass index ( BMI ) ; stenosis of coronary arteries ; retinopathy ( assessed by the Early Treatment of Diabetic Retinopathy scale ) ; urine protein ; creatinine ; peripheral neuropathy ; foot ulcers of varying degrees of severity ; and amputations . The use of differential equations preserves the continuous nature of biological variables as well as the interactions between them . Clinical outcomes are defined in terms of the underlying variables , as occurs in reality . For example , a person is said to have diabetes if his or her fasting plasma glucose level exceeds 6.9375 mmol/L ( 125 mg/dL ) or results on a 2-hour oral glucose tolerance test exceed 11.0445 mmol/L ( 199 mg/dL ) . This enables the model to incorporate different definitions and changes in definitions . The model is continuous : Biological variables are changing and interacting continuously , the natural histories and severity of conditions progress smoothly , any clinical event can occur at any time , and the timing of events is as condensed or drawn out as occurs in reality . The model also includes a detailed representation of the processes and logistics of clinical care and their related costs . Interventions , both to prevent diabetes and to manage it when it occurs , are modeled at the level of the underlying biology . Pertinent to this analysis is that in the model , diet and exercise reduce weight ( 2 ) ; reduce blood pressure ( 11 ) ; improve LDL cholesterol , HDL cholesterol , and total cholesterol levels ( 12 ) ; and decrease fasting plasma glucose levels ( 2 ) . The effects of metformin in the model are to reduce fasting plasma glucose and 2-hour oral glucose tolerance test results ( 2 ) ( by reducing basal hepatic glucose production ) , decrease LDL cholesterol and triglyceride levels ( 13 ) , and retard weight gain . Data used to build the model were derived from basic physiologic studies , surveys , epidemiologic studies , and clinical trials using methods described in the technical report ( 10 ) . Every variable in the model is estimated from at least 1 empirical source ; no variables are simply assumed . We identified specific sources by search ing MEDLINE from 1970 to 28 February 2005 and by consulting textbooks and clinical experts . Because the model includes scores of continuously valued , interacting variables , it does not have simplified states , transitions , or events at discrete time intervals that can be tabulated , as is commonly done for a Markov-type model . The equations themselves are in the technical report ( 10 ) . For nonmathematical readers , we have calculated annualized rates of change of representative biological variables and annualized rates of occurrence of representative clinical events , and compared them with rates for comparable events observed in epidemiologic studies and clinical trials . The Appendix reports those results . Costs The DPP measured the direct medical costs of delivering the lifestyle and metformin interventions  ( for example , personnel , health education material s , medications , and laboratory tests ) . Compared with the placebo group 's costs , costs in the lifestyle group were $ 1356 more per person in the first year , with approximately $ 672 in annual costs thereafter ; for the metformin group , costs were $ 977 in the first year and averaged $ 742 per year thereafter ( 5 ) . Following the completion of the DPP , metformin became generic . When this is considered , the cost of the metformin program is reduced to about $ 780 for 3 years , or about $ 260 a year . In the DPP study , costs apply to the year 2000 . To calculate the routine costs of providing health care to high-risk people before they develop diabetes , as well as to people with diabetes and its complications , the model includes a detailed mathematical representation of a health care system , including such elements as facilities , personnel , tests and treatments , protocol s , and provider behaviors . For the base-case analysis , we obtained itemized costs from Kaiser Permanente , a nonprofit , group- practice , integrated managed care organization that provides comprehensive care ( with no deductibles or copayments ) . The facilities , personnel , protocol s , and costs in the model are based on that organization 's records , at the level of detail at which actual accounts are kept ( for example , 37 different kinds of office visits ) . The model calculates costs by keeping track of the occurrence of every event that has cost implication s and adding them up . The costs assigned to any event or item were calculated by Kaiser Permanente 's cost-accounting department using micro-costing methods ( 14 ) , and they represent the real costs to the organization , not charges , reimbursements , or diagnosis-related groups . Because costs vary from setting to setting , the implication s of different cost structures are examined in the sensitivity analysis . Calculation of costs applies to the year 2000 . Indirect costs , such as lost time from work and decreased productivity , are included in the cost-effectiveness analysis through the Quality of Well-Being Index ( 14 ) . We calculated the effects of lifestyle and metformin interventions  on quality of life . For people who do not yet have diabetes , we used utility weights reported for the participants of the DPP study ( 15 ) . For people who have diabetes and its complications , we used the results of a published survey by Coffey and colleagues ( 16 ) . Both surveys used the Quality of Well-Being Index . The decrements in quality of life were assumed to be additive for people who have 2 or more complications , with a limit that quality of life could not be less than 0 . Use of an additive rule biases the calculation of cost/ quality -adjusted life-year ( QALY ) in favor of a prevention program , making the program appear more cost-effective than would occur if a multiplicative model were used . We discuss the Objective : The study objectives were to examine the association between menopause status and diabetes risk  among women with glucose intolerance and to determine if menopause status modifies response to diabetes prevention interventions . Methods : The study population included women in premenopause ( n = 708 ) , women in natural postmenopause ( n = 328 ) , and women with bilateral oophorectomy ( n = 201 ) in the Diabetes Prevention Program , a r and omized placebo-controlled trial of  lifestyle intervention and metformin  among glucose-intolerant adults . Associations between menopause and diabetes risk were evaluated using Cox proportional hazard models that adjusted for demographic variables ( age , race/ethnicity , family history of diabetes , history of gestational diabetes mellitus ) , waist circumference , insulin resistance , and corrected insulin response . Similar models were constructed after stratification by menopause type and hormone therapy use . Results : After adjustment for age , there was no association between natural menopause or bilateral oophorectomy and diabetes risk . Differences by study arm were observed in women who reported bilateral oophorectomy . In the lifestyle arm , women with bilateral oophorectomy had a lower adjusted hazard for diabetes ( hazard ratio [ HR ] , 0.19 ; 95 % CI , 0.04 - 0.94 ) , although observations were too few to determine if this was independent of hormone therapy use . No significant differences were seen in the metformin ( HR , 1.29 ; 95 % CI , 0.63 - 2.64 ) or placebo arms ( HR , 1.37 ; 95 % CI , 0.74 - 2.55 ) . Conclusions : Among women at high risk for diabetes , natural menopause was not associated with diabetes risk and did not affect response to diabetes prevention interventions . In the lifestyle intervention , bilateral oophorectomy was associated with a decreased diabetes risk BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial ,  diabetes incidence  in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups .  On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) The research ers conducted this study to test the hypothesis that risk of  type 2 diabetes  is less following reductions in body size and central adiposity . The Diabetes Prevention Program ( DPP ) recruited and r and omized individuals with impaired glucose tolerance to treatment with placebo , metformin , or lifestyle modification .  Height , weight , waist circumference , and subcutaneous and visceral fat at L2-L3 and L4-L5 by computed tomography were measured at baseline and at 1 year . Cox proportional hazards models assessed by sex the effect of change in these variables over the 1st year of intervention upon development of diabetes over subsequent follow-up in a subset of 758 participants . Lifestyle reduced visceral fat at L2-L3 ( men −24.3 % , women −18.2 % ) and at L4-L5 ( men −22.4 % , women −17.8 % ) , subcutaneous fat at L2-L3 ( men −15.7 % , women −11.4 % ) and at L4-L5 ( men −16.7 % , women −11.9 % ) , weight ( men −8.2 % , women −7.8 % ) , BMI ( men −8.2 % , women −7.8 % ) , and waist circumference ( men −7.5 % , women −6.1 % ) . Metformin  reduced weight ( −2.9 % ) and BMI ( −2.9 % ) in men and subcutaneous fat ( −3.6 % at L2-L3 and −4.7 % at L4-L5 ) , weight ( −3.3 % ) , BMI ( −3.3 % ) , and waist circumference ( −2.8 % ) in women . Decreased diabetes risk by lifestyle intervention was associated with reductions of body weight , BMI , and central body fat distribution after adjustment for age and self-reported ethnicity . Reduced diabetes risk with lifestyle intervention may have been through effects upon both overall body fat and central body fat but with metformin appeared to be independent of body fat BACKGROUND Type 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies , but these observations are limited by lack of data on the exact timing of diabetes onset . We investigated diabetes , dysglycaemia , and cognition in the Finnish Diabetes Prevention Study , in which the timing and duration of diabetes are well documented . METHODS The Finnish Diabetes Prevention Study comprised middle-aged , overweight participants with impaired glucose tolerance but no diabetes at baseline ( n = 522 ) , r and omized to lifestyle intervention or a control group .  After an intervention period ( mean duration 4 years ) and follow-up ( additional 9 years ) ,  cognitive assessment with the CERAD test battery and Trail Making Test A ( TMT ) was executed twice within a 2-year interval . Of the 364 ( 70 % ) participants with cognitive assessment s , 171 ( 47 % ) had developed diabetes . RESULTS Cognitive function did not differ between those who developed diabetes and those who did not . Lower mean 2-h glucose at an oral glucose tolerance test ( OGTT ) and HbA1C during the intervention period predicted better performance in the TMT ( p = 0.012 and 0.024 , respectively ) . Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessment s ( p = 0.001 ) whereas those with long duration of diabetes did not ( p = 0.844 ) . CONCLUSIONS Better glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9 years later in this secondary analysis of the Finnish Diabetes Prevention Study population . In addition , learning effects in cognitive testing were not evident in people with long diabetes duration . Copyright © 2015 John Wiley & Sons , Background The prevention of type 2 diabetes is a globally recognised health care priority , but there is a lack of rigorous research investigating optimal methods of translating diabetes prevention programmes , based on the promotion of a healthy lifestyle , into routine primary care . The aim of the study is to establish whether a pragmatic structured education programme targeting lifestyle and behaviour change in conjunction with motivational maintenance via the telephone can reduce the incidence of type 2 diabetes in people with impaired glucose regulation ( a composite of impaired glucose tolerance and /or impaired fasting glucose ) identified through a vali date d risk score screening programme in primary care . Design Cluster r and omised controlled trial undertaken at the level of primary care practice s. Follow-up will be conducted at 12 , 24 and 36 months . The primary outcome is the incidence of type 2 diabetes . Secondary outcomes include changes in HbA1c , blood glucose levels , cardiovascular risk , the presence of the Metabolic Syndrome and the cost-effectiveness of the intervention . Methods The study consists of screening and intervention phases within 44 general practice s coordinated from a single academic research centre . Those at high risk of impaired glucose regulation or type 2 diabetes are identified using a risk score and invited for screening using a 75 g-oral glucose tolerance test . Those with screen detected impaired glucose regulation will be invited to take part in the trial . Practice s will be r and omised to st and ard care or the intensive arm . Participants from intensive arm practice s will receive a structured education programme with motivational maintenance via the telephone and annual refresher sessions . The study will run from 2009–2014 . Discussion This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme conducted within routine primary care in the United Kingdom . Trial registration Clinical trials.gov The Diabetes Prevention Program is a r and omized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk individuals with elevated fasting plasma glucose concentrations and impaired glucose tolerance . The 27 clinical centers in the U.S. are recruiting at least 3,000 participants of both sexes , approximately 50 % of whom are minority patients and 20 % of whom are > or = 65 years old , to be assigned at r and om to one of three intervention groups : an intensive lifestyle intervention focusing on a healthy diet and exercise and two masked medication treatment groups -- metformin or placebo -- combined with st and ard diet and exercise recommendations .  Participants are being recruited during a 2 2/3-year period , and all will be followed for an additional 3 1/3 to 5 years after the close of recruitment to a common closing date in 2002 . The primary outcome is the development of diabetes , diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria . The 3,000 participants will provide 90 % power to detect a 33 % reduction in an expected diabetes incidence rate of at least 6.5 % per year in the placebo group . Secondary outcomes include cardiovascular disease and its risk factors ; changes in glycemia , beta-cell function , insulin sensitivity , obesity , diet , physical activity , and health-related quality of life ; and occurrence of adverse events . A fourth treatment group -- troglitazone combined with st and ard diet and exercise recommendations --was included initially but discontinued because of the liver toxicity of the drug . This r and omized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in individuals at high risk Aim To investigate the safety and efficacy of insulin degludec/liraglutide ( IDegLira ) , a novel combination product , as add‐on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy . Methods In this 26‐week , double‐blind trial , adults with Type 2 diabetes [ HbA1c 53–75 mmol/mol ( 7.0–9.0 % ) ] were r and omized to IDegLira ( n = 289 ) or placebo ( n = 146 ) as add‐on to pre‐trial sulphonylurea ± metformin , titrating to a fasting glycaemic target of 4.0–6.0 mmol/l . Treatment initiation was at 10 dose steps , and maximum dose was 50 dose steps ( 50 units insulin degludec/1.8 mg liraglutide ) . Results The mean HbA1c decreased from 63 mmol/mol ( 7.9 % ) to 46 mmol/mol ( 6.4 % ) with IDegLira and to 57 mmol/mol ( 7.4 % ) with placebo [ estimated treatment difference –11 mmol/mol ( 95 % CI –13 ; –10 ) or –1.02 % ( 95 % CI –1.18 ; –0.87 ) ; P < 0.001 ] . The HbA1c target of 53 mmol/mol ( < 7 % ) was achieved by 79.2 % of participants in the IDegLira group vs 28.8 % in the placebo group [ estimated odds ratio 11.95 ( 95 % CI 7.22 ; 19.77 ) ; P < 0.001 ] . Mean weight change was + 0.5 kg with IDegLira vs –1.0 kg with placebo [ estimated treatment difference 1.48 kg ( 95 % CI 0.90 ; 2.06 ) ; P < 0.001 ] . Confirmed hypoglycaemia occurred in 41.7 and 17.1 % of IDegLira‐ and placebo‐treated participants , respectively , with rates of 3.5 vs 1.4 events/patient‐years of exposure [ estimated rate ratio 3.74 ( 95 % CI 2.28 ; 6.13 ) ; P < 0.001 ] . IDegLira was generally well tolerated . The rates of serious adverse events were 20.3 and 8.0 per 100 patient‐years of exposure with IDegLira and placebo , respectively , without obvious patterns in the type of events . Conclusions IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials . What 's new?IDegLira is a combination of insulin degludec and liraglutide . Basal insulins and glucagon‐like peptide‐1 ( GLP‐1 ) receptor agonists have complementary effects in a Type 2 diabetes treatment regimen , with GLP‐1 receptor agonists also being insulin‐sparing . Treatment guidelines often advocate discontinuing sulphonylureas on basal insulin initiation , but widespread concomitant use of these drugs continues in current clinical practice . It is therefore anticipated that many  sulphonylurea‐treated people will have IDegLira added to their therapy , yet this combination has not previously been studiedThis r and omized controlled trial shows that IDegLira can be used in people uncontrolled  with sulphonylureas ± metformin  to improve efficacy with a favourable benefit – risk profile Purpose The purpose of this study is to assess if diagnosis of type 2 diabetes affected health-related quality of life ( HRQoL ) among participants in the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study and changes with treatment or diabetes duration . Methods 3,210 participants with pre-diabetes were r and omized to  metformin ( MET ) , intensive lifestyle intervention ( ILS ) , or placebo ( PLB ) .  HRQoL was assessed using the SF-36 including : ( 1 ) 8 SF-36 subscales ; ( 2 ) the physical component ( PCS ) and mental component summary ( MCS ) scores ; and ( 3 ) the SF-6D . The sample was categorized by diabetes free versus diagnosed . For diagnosed subgroup , mean scores in the diabetes-free period , at 6 months , 2 , 4 and 6 years post-diagnosis , were compared . Results PCS and SF-6D scores declined in all participants in all treatment arms ( P < .001 ) . MCS scores did not change significantly in any treatment arm regardless of diagnosis . ILS participants reported a greater decrease in PCS scores at 6 months post-diagnosis ( P < .001 ) and a more rapid decline immediately post-diagnosis in SF-6D scores ( P = .003 ) than the MET or PLB arms . ILS participants reported a significant decrease in the social functioning subscale at 6 months ( P < .001 ) and two years ( P < .001 ) post-diagnosis . Conclusions Participants reported a decline in measures of overall health state ( SF-6D ) and overall physical HRQoL , whether or not they were diagnosed with diabetes during the study . There was no change in overall mental HRQoL. Participants in the ILS arm with diabetes reported a more significant decline in some HRQoL measures than those in the MET and PLB arms that developed diabetes Over the past decades , we have observed an increase of prevalence of diabetes  in many countries along with significant differences in prevalence trends between countries worldwide ( 1 ) . In Europe and other Western countries , the prevalence rate reaches a plateau or has slowed down on the level of ∼8–10 % . In Asia , a continuous rise in prevalence has been monitored , similar to that in Africa , and an explosion of diabetes prevalence can be observed in the Arabic region . Surprisingly , in each of the countries , there is a significant number of people who do not develop  diabetes  during their lives despite living unhealthy lifestyles in similar environments — in Europe , an estimated 10 % of the population ( 2 ) . These people might be the secret answer to successful individual diabetes prevention , but we still do not underst and the detailed mechanisms of why some people develop diabetes— and why others do not . What we can do is observe individual lifestyle and environment as determinants for the development or prevention of diabetes and the respective risk factors including genetic susceptibility . The interplay between these determinants , influencing the probability of the individual staying healthy or how a person learns or chooses a healthy lifestyle , will define success in diabetes prevention ( 3 ) . Innovative actions are needed to slow down the progression of type 2 diabetes . The purpose of this article is to offer innovative policy and environmental strategic activities design ed to enable sustainable diabetes prevention with scalability on national level . # # # Why Do We Need Environmental and Policy Changes in Diabetes Prevention ? Diabetes prevention is a success story , but it generates new challenges . Throughout the past 15 years , a number of r and omized controlled trials have sought to test various interventions to prevent diabetes ( 4 ) . The results are overwhelmingly positive on an individual level , with a significant relative diabetes risk reduction attributed to lifestyle and pharmacological intervention ( 5 The prevalence of type 2 diabetes is continuously increasing . This chronic metabolic disorder is difficult to treat and imposes a considerable economic burden on the healthcare system . In view of the fact that type 2 diabetes is primarily caused by behavioral factors , effective preventive strategies are urgently needed . We examined the effects of a holistic lifestyle intervention on clinical and laboratory parameters as well as on the long-term diabetes risk in patients at risk to develop diabetes . We conducted a r and omized controlled trial in a primary care setting in Hannover , Germany , with 83 patients diagnosed as (pre)diabetic or at risk for diabetes . CHIP Germany is a 40-hour coaching lifestyle intervention program for the primary and secondary prevention of type 2 diabetes and cardiovascular diseases . The intervention included a comprehensive nutrition and health educational program based on the American CHIP approach . The primary outcome parameter was the body mass index ( BMI ) . Secondary outcome parameters included body weight , blood pressure , fasting glucose , HbA1c , blood lipids , and the FINDRISK score , which assesses long-term diabetes risk . At the final measurement after 12 months , in the intervention group the BMI was reduced by 1.4 versus 0.2 kg/m2 in controls ( p = .119 ) . The mean sustained weight loss after 12 months was −4.1 kg in the intervention group versus −0.8 kg in controls . Furthermore , we found a trend toward a stronger reduction in blood pressure , fasting glucose , and HbA1c as well as an improved FINDRISK score in the intervention group , compared to controls . Although failing to reach statistical significance at the final assessment , this comprehensive lifestyle intervention showed a noticeable reduction in several cardiometabolic risk factors which may facilitate the prevention of diabetes OBJECTIVES Prevention of type 2 diabetes ( T2DM ) is a priority in healthcare , but there is a lack of evidence investigating how to effectively translate prevention research into a UK primary care setting . We assessed whether a structured education programme targeting lifestyle and behaviour change was effective at preventing progression to T2DM  in people with pre-diabetes . MATERIAL S AND METHODS Forty-four general practice s were r and omised to receive either st and ard care or a 6hour group structured education programme with an annual refresher course , and regular phone contact . Participants were followed up for 3years . The primary outcome was progression to T2DM . RESULTS Eight hundred and eighty participants were included ( 36 % female , mean age 64years , 16 % ethnic minority group ) ; 131 participants developed T2DM . There was a non-significant 26 % reduced risk of developing T2DM in the intervention arm compared to st and ard care ( HR 0.74 , 95 % CI 0.48 , 1.14 , p=0.18 ) . The reduction in T2DM risk when excluding those who did not attend the initial education session was also non-significant ( HR 0.65 , 0.41 , 1.03 , p=0.07 ) . There were statistically significant improvements in HbA1c ( -0.06 , -0.11 , -0.01 ) , LDL cholesterol ( -0.08 , -0.15 , -0.01 ) , sedentary time ( -26.29 , -45.26 , -7.32 ) and step count ( 498.15 , 162.10 , 834.20 ) when data were analysed across all time points . CONCLUSIONS This study suggests that a relatively low re source , pragmatic diabetes prevention programme result ed in modest benefits to biomedical , lifestyle and psychosocial outcomes , however the reduction to the risk of T2DM did not reach significance . The findings have important implication s for future research and primary care BACKGROUND Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes , at least as long as the intervention continues . In the extended follow-up of the Finnish Diabetes Prevention Study , we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling . METHODS Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omly assigned to intensive lifestyle intervention or control group . After a median of 4 years of active intervention period , participants who were still free of diabetes were further followed up for a median of 3 years , with median total follow-up of 7 years . Diabetes incidence , bodyweight , physical activity , and dietary intakes of fat , saturated fat , and fibre were measured . FINDINGS During the total follow-up , the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group , respectively ( log-rank test p=0.0001 ) , indicating 43 % reduction in relative risk . The risk reduction was related to the success in achieving the intervention goals of weight loss , reduced intake of total and saturated fat and increased intake of dietary fibre , and increased physical activity . Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention , and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 ( p=0.0401 ) , indicating 36 % reduction in relative risk . INTERPRETATION Lifestyle intervention in people at high risk for type 2 diabetes result ed in sustained lifestyle changes and a reduction in diabetes incidence , which remained after the individual lifestyle counselling was stopped AIMS To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin . METHODS This double-blind , placebo-controlled trial , r and omly allocated people with Type 2 diabetes aged 18 - 77 years and inadequate glycaemic control on diet and exercise [ HbA1c 53 - 86 mmol/mol ( 7.0 - 10.0 % ) ] to receive placebo ( n = 75 ) or dapagliflozin monotherapy 2.5 mg ( n = 65 ) , 5 mg ( n = 64 ) or 10 mg ( n = 70 ) once daily in the morning . After 24 weeks , low-dose double-blind metformin 500 mg/day was added to the placebo group regimen ( placebo+low-dose metformin group ) . Changes in HbA1c level , fasting plasma glucose and body weight , as well as adverse events , were assessed over 102 weeks . RESULTS Of the 274 participants r and omized , 167 completed the study ( 60.9 % ) . At 102 weeks , significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c ( -5.8 mmol/mol [ -0.53 % ] , P = 0.018 ; and -4.8 mmol/mol [ -0.44 % ] , P = 0.048 ) , respectively ) ; and for FPG ( -0.69 mmol/L , P = 0.044 ; and -1.12 mmol/l , P = 0.001 , respectively ) . For body weight , the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant ( -2.60 kg ; P = 0.016 ) . Hypoglycaemic events were uncommon , with rates of 5.3 % for placebo+low-dose metformin group and 0 - 4.6 % for the dapagliflozin groups . Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group . CONCLUSIONS Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks . Dapagliflozin may provide an alternative initial pharmacotherapy in such people
Conclusions HbA1c is neither sensitive nor specific for detecting pre‐diabetes ; fasting glucose is specific but not sensitive .
Interventions in people classified through screening as having pre‐diabetes have some efficacy in preventing or delaying onset of type 2 diabetes in trial population s. As screening is inaccurate , many people will receives an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention .
These findings suggest that “ screen and treat ” policies alone are unlikely to have substantial impact on the worsening epidemic of type 2 diabetes .
& NA ; Objectives To assess diagnostic accuracy of screening tests for  pre‐diabetes  and efficacy of interventions ( lifestyle or metformin ) in preventing onset of type 2 diabetes in people with pre‐diabetes .