Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Effects of Therapeutic Lifestyle Program on Ultrasound‐diagnosed Nonalcoholic Fatty Liver Disease Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. Independent effects of physical activity in patients with nonalcoholic fatty liver disease.
OBJECTIVE Nonalcoholic fatty liver disease ( NAFLD ) and its association with insulin resistance are increasingly recognized as major health burdens . The main objectives of this study were to assess the relation between liver lipid content and serum lipids , markers of liver function and inflammation in healthy overweight subjects , and to determine whether caloric restriction ( CR ) ( which improves insulin resistance ) reduces liver lipids in association with these same measures . METHODS AND PROCEDURES Forty-six white and black overweight men and women ( BMI = 24.7 - 31.3 kg/m(2 ) ) were r and omized to " control ( CO ) " = 100 % energy requirements ; " CR " = 25 % ; " caloric restriction and increased structured exercise (CR+EX)"= 12.5 % CR + 12.5 % increase in energy expenditure through exercise ; or " low-calorie diet ( LCD ) " = 15 % weight loss by liquid diet followed by weight-maintenance , for 6 months . Liver lipid content was assessed by magnetic resonance spectroscopy ( MRS ) and computed tomography ( CT ) . Lipid concentrations , markers of liver function ( alanine aminotransferase ( ALT ) , alkaline phosphatase ( ALK ) ) , and whole-body inflammation ( tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) ) were measured in fasting blood . RESULTS At baseline , increased liver lipid content ( by MRS ) correlated ( P < 0.05 ) with elevated fasting triglyceride ( r = 0.52 ) , ALT ( r = 0.42 ) , and hsCRP ( r = 0.33 ) concentrations after adjusting for sex , race , and alcohol consumption . With CR , liver lipid content was significantly lowered by CR , CR+EX , and LCD ( detected by MRS only ) . The reduction in liver lipid content , however , was not significantly correlated with the reduction in triglycerides ( r = 0.26 ; P = 0.11 ) or with the changes in ALT , high-density lipoprotein (HDL)-cholesterol , or markers of whole-body inflammation . DISCUSSION CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD Exercise training is commonly prescribed for treatment of nonalcoholic fatty liver disease ( NAFLD ) . We sought to determine whether exercise training prevents the development of NAFLD in Otsuka Long-Evans Tokushima Fatty ( OLETF ) rats and to eluci date the molecular mechanisms underlying the effects of exercise on hepatic steatosis . Four-week-old OLETF rats were r and omly assigned to either a sedentary control group ( Sed ) or a group given access to voluntary running wheels for 16 wk ( Ex ) . Wheels were locked 2 days before euthanasia in the Ex animals , and both groups were euthanized at 20 wk old . Voluntary wheel running attenuated weight gain and reduced serum glucose , insulin , free fatty acids , and triglycerides in Ex animals compared with Sed ( P < 0.001 ) . Ex animals exhibited significantly reduced hepatic triglyceride levels and displayed fewer lipid droplets ( Oil Red O staining ) and reduced lipid droplet size compared with Sed . Wheel running increased by threefold the percent of palmitate oxidized completely to CO(2 ) in the Ex animals but did not alter AMP-activated protein kinase-alpha ( AMPKalpha ) or AMPK phosphorylation status . However , fatty acid synthase and acetyl-coenzyme A carboxylase ( ACC ) content were significantly reduced ( approximately 70 and approximately 35 % , respectively ) , and ACC phosphorylation and cytochrome c content were significantly elevated ( approximately 35 and approximately 30 % , respectively ) in the Ex animals . These results unequivocally demonstrate that daily physical activity attenuates hepatic steatosis and NAFLD in an obese rodent model and suggest that this effect is likely mediated , in part , through enhancement of hepatic fatty acid oxidation and reductions in key protein intermediates of fatty acid synthesis Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis Background : To investigate the effects of varied therapeutic lifestyle programs on patients with ultrasound‐diagnosed nonalcoholic fatty liver disease ( NAFLD ) . Methods : A prospect i ve , case‐controlled study was conducted . A total of 54 subjects with NAFLD were subdivided into 3 groups : ( 1 ) diet plus exercise group ( DPE group , n = 16 ) ; ( 2 ) exercise group ( E group , n = 23 ) ; and ( 3 ) control group ( C group , n = 15 ) . The DPE group received a low‐calorie balanced diet and regular high‐intensity stationary bicycle exercise program for 10 weeks , while the E group received the same exercise protocol as the DPE group but without any changes in diet . Anthropometric indices , biochemical data , physical fitness data and liver ultrasound findings were recorded . A generalized estimating equation method was used to determine the differences among groups . Results : Compared with the C group , the DPE group demonstrated significant improvements in anthropometric indices , total cholesterol , insulin sensitivity , liver biochemistry , ultrasound finding and physical fitness , while the E group showed significant improvements in anthropometric indices , insulin sensitivity status , ultrasound finding and physical fitness but not liver biochemistry . Compared with the E group , the DPE group showed greater reduction in anthropometric indices ( body mass index , body weight , abdominal circumference , hip circumference ) , total cholesterol , alanine aminotransferase , and γ‐glutamyltransferase . Conclusion : Our data suggest that both 10‐week diet‐plus‐exercise and exercise‐only therapeutic lifestyle programs are effective for improving anthropometric indices , insulin sensitivity , ultrasound findings and physical fitness in ultrasound‐diagnosed NAFLD patients . However , the range of improvement in patients on the diet‐plus‐exercise program is more obvious than that in patients on the exercise‐only program . Moreover , the diet‐plus‐exercise program result ed in significant improvement in liver biochemistry , but the exercise‐only program did not . In summary , diet plus exercise is more efficacious than exercise alone in the lifestyle modification treatment of NAFLD Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postpr and ial energy storage . We conducted a study to examine this hypothesis by reversing muscle insulin resistance with a single bout of exercise and measuring hepatic de novo lipogenesis and hepatic triglyceride synthesis after a carbohydrate-rich meal . We studied 12 healthy , young , lean , insulin resistant individuals in an interventional , r and omized cross-over trial . The response to the ingestion of a carbohydrate-rich meal was studied at rest and after one 45-min bout of exercise on an elliptical trainer .  Hepatic de novo lipogenesis was assessed by using 2H2O , and changes in glycogen and fat content in liver and muscle were measured by 13C and 1H magnetic resonance spectroscopy , respectively . Exercise result ed in a greater than threefold increase in postpr and ial net muscle glycogen synthesis ( P < 0.001 ) , reflecting improved muscle insulin responsiveness , and a ≈40 % reduction ( P < 0.05 ) in net hepatic triglyceride synthesis . These changes in whole body energy storage were accompanied by a ≈30 % decrease in hepatic de novo lipogenesis ( P < 0.01 ) and were independent of changes in fasting or postpr and ial plasma glucose and insulin concentrations . These data demonstrate that skeletal muscle insulin resistance is an early therapeutic target for the treatment and prevention of atherogenic dyslipidemia and NAFLD in young insulin resistant individuals who are prone to develop the metabolic syndrome and type 2 diabetes BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies . Currently , only limited data are available on the effects of exercise programs on insulin resistance , and visceral , hepatic , and intramyocellular fat accumulation . We hypothesized that a 12-week controlled aerobic exercise program without weight loss reduces visceral , hepatic , and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents . Twenty-nine postpubertal ( Tanner stage IV and V ) , Hispanic adolescents , 15 obese ( 7 boys , 8 girls ; 15.6 + /- 0.4 years ; 33.7 + /- 1.1 kg/m(2 ) ; 38.3 + /- 1.5 % body fat ) and 14 lean ( 10 boys , 4 girls ; 15.1 + /- 0.3 years ; 20.6 + /- 0.8 kg/m(2 ) ; 18.9 + /- 1.5 % body fat ) , completed a 12-week aerobic exercise program ( 4 x 30 min/week at > or = 70 % of peak oxygen consumption ( VO(2)peak ) ) . Measurements of cardiovascular fitness , visceral , hepatic , and intramyocellular fat content ( magnetic resonance imaging (MRI)/magnetic resonance spectroscopy ( MRS ) ) , and insulin resistance were obtained at baseline and postexercise . In both groups , fitness increased ( obese : 13 + /- 2 % , lean : 16 + /- 4 % ; both P < 0.01 ) . In obese participants , intramyocellular fat remained unchanged , whereas hepatic fat content decreased from 8.9 + /- 3.2 to 5.6 + /- 1.8 % ; P < 0.05 and visceral fat content from 54.7 + /- 6.0 to 49.6 + /- 5.5 cm(2 ) ; P < 0.05 . Insulin resistance decreased indicated by decreased fasting insulin ( 21.8 + /- 2.7 to 18.2 + /- 2.4 microU/ml ; P < 0.01 ) and homeostasis model assessment of insulin resistance ( HOMA(IR ) ) ( 4.9 + /- 0.7 to 4.1 + /- 0.6 ; P < 0.01 ) . The decrease in visceral fat correlated with the decrease in fasting insulin ( R(2 ) = 0.40 ; P < 0.05 ) . No significant changes were observed in any parameter in lean participants except a small increase in lean body mass ( LBM ) . Thus , a controlled aerobic exercise program , without weight loss , reduced hepatic and visceral fat accumulation , and decreased insulin resistance in obese adolescents OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity AIM To investigate the effect of lifestyle intervention on  non-alcoholic fatty liver disease ( NAFLD ) in Chinese obese children . METHODS Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided r and omly into three groups . Group1 , consisting of 38 obese children , was an untreated control group without any intervention . Group 2 , consisting of 19 obese children in summer camp , was strictly controlled only by life style intervention . Group 3 , consisting of 19 obese children , received oral vitamin E therapy at a dose of 100 mg/d . The height , weight , fasting blood glucose ( FBG ) , fasting serum insulin ( FINS ) , plasma alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , triglyceride ( TG ) , total cholesterol ( TCHO ) and homeostasis model assent-insulin resistance ( HOMA-IR ) were measured at baseline and after one month . All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups . RESULTS The monitor indices of BMI , ALT , AST , TG , TCHO and HOMA-IR were successfully improved except in group 1 . BMI and ALT in group 2 were reduced more significantly than in group 3 ( 2.44 + /- 0.82 vs 1.45 + /- 0.80 , P = 0.001 ; 88.58 + /- 39.99 vs 63.69 + /- 27.05 , P = 0.040 , respectively ) . CONCLUSION Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children . Compared with vitamin E , lifestyle intervention is more effective . Therefore , lifestyle intervention should represent the first step in the management of children with NAFLD UNLABELLED Information on the long-term prognosis of nonalcoholic fatty liver disease ( NAFLD ) is limited . We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospect ively study ing 247 such patients from four international centers ( in Australia , USA , UK and Italy ) . Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment . Both cohorts were Child-Pugh class A and had advanced fibrosis ( stage 3 ) or cirrhosis ( stage 4 ) confirmed by liver biopsy at enrollment . In the NAFLD cohort , followed up for a mean of 85.6 months ( range , 6 - 297 ) , there were 48 ( 19.4 % ) liver-related complications and 33 ( 13.4 % ) deaths or liver transplants . In the HCV cohort , followed up for 74.9 months ( mean ; range , 6 - 238 ) , there were 47 ( 16.7 % ) liver-related complications and 25 ( 9.4 % ) deaths or liver transplants . When adjusting for baseline differences in age and gender , the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort ( P = 0.03 ) , including incident hepatocellular cancer ( 6 versus 18 ; P = 0.03 ) , but that of cardiovascular events ( P = 0.17 ) and overall mortality ( P = 0.6 ) were similar in both groups . In the NAFLD cohort , platelet count , stage 4 fibrosis , lowered platelet count , and lowered serum cholesterol and alanine aminotransferase ( ALT ) levels were associated with liver-related complications ; an aspartate aminotransferase/ALT ratio > 1 and older age were associated with overall mortality , and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality . CONCLUSIONS Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection , but similar overall mortality . Some clinical and laboratory features predict liver-related complications and other outcomes in patients with NAFLD Unexplained abnormalities on liver function tests are common and often perplexing . Fatty liver , or hepatic steatosis , is a common clinical and histologic finding . When hepatic steatosis does not coexist with alcoholic hepatitis or steatohepatitis , it is a benign condition ( 1 , 2 ) . Fatty liver is usually attributed to alcohol abuse . Although the hepatotoxicity of ethanol has been well established , only 8 % to 20 % of persons with chronic alcoholism develop cirrhosis ( 3 ) . In the Dionysos Study , a survey of the prevalence of chronic liver disease in the general population that included 6917 participants ( 3 , 4 ) , the risk threshold for ethanol-induced liver disease was the ingestion of more than 30 g of alcohol per day . However , only 74 of 1349 participants at risk ( 5.5 % ) showed persistent signs of alcoholic liver damage ( 4 ) . Steatosis can also occur in association with other conditions , such as obesity , hypernutritional support , drug- or toxin-induced hepatitis , type 2 diabetes mellitus , and cachexia , and it can occur after jejunoileal bypass surgery for refractory obesity ( 1 , 5 - 12 ) . The role of obesity compared with that of alcohol in inducing fatty liver or abnormal results on liver function tests is still controversial . Although the presence of excess weight for at least 10 years has been cl aim ed to be a potential additional risk factor for acute alcoholic hepatitis and cirrhosis ( 13 ) , most data have been collected from selected series or retrospectively . To explore the relative roles of obesity and alcohol abuse , alone and in combination , in inducing steatosis , we performed an intracohort study in the general population of two towns of northeastern Italy ( Campogalliano , in the province of Modena , and Cormons , in the province of Gorizia ) that participated in the Dionysos Study ( 3 ) . Data indicate that obesity plays a greater role than excessive alcohol intake in inducing fatty liver . Methods Patients The details of the overall design of the Dionysos Study have been described elsewhere ( 3 , 4 ) . Briefly , 6917 of the 10 150 inhabitants ( age range , 12 to 65 years ) of two northern Italian communities were screened . For each participant , an extensive medical history was obtained that included history of chronic liver disease in first-degree relatives ; a detailed history of acute hepatitis , gallstone disease , surgical operations , blood transfusions , drug abuse , dental procedures , dog or other domestic animal bites , homosexual sex , or tattooing ; previous diagnosis of chronic hepatitis , cirrhosis , hemochromatosis , Wilson disease , primary biliary cirrhosis , other congenital liver diseases , diabetes , hyperlipoproteinemia , pericarditis , or heart diseases ; careful question ing for any current symptoms of liver or biliary diseases , including biliary colic , anorexia , pruritus , jaundice , dark urine , and ascites ; and personal habits , including tobacco and coffee consumption and type and duration of past and present professions and duties . Each participant also underwent a detailed physical examination aim ed at detecting liver diseases or physical signs related to chronic liver disease , including jaundice , excoriation of skin , ascites , pretibial edema , flapping tremor , spider nevi , palmar erythema , liver enlargement , and palpable spleen ; measurement of height , weight , body mass index ( calculated as weight in kg/height in square meters ) , and left wrist circumference ; and assay for serum levels of alanine aminotransferase , aspartate aminotransferase , -glutamyltransferase , glucose , mean corpuscular volume of erythrocytes , platelet count , and presence of hepatitis B surface antigen and antibody to hepatitis C virus . The current study involves 257 persons 19 to 70 years of age from the Dionysos cohort who tested negative for infection with hepatitis B virus or hepatitis C virus and had no evidence of chronic liver disease . Design The intracohort study began in March 1997 . The study was approved by the ethical committee of Fondo Studio Malattie del Fegato , Trieste , Italy . Of 6917 participants in the initial Dionysos Study cohort ( 3 ) , 3618 were excluded : Three hundred twelve tested positive for hepatitis B surface antigen ( n=86 ) or antibody to hepatitis C virus ( n=226 ) , 2 had histologically proven hemochromatosis or primary biliary cirrhosis , 19 had histologically proven cryptogenetic cirrhosis , and 3285 of them were overweight but not obese ( body mass , 25 kg/m2 to 30 kg/m2 ) or were obese but drank less than 60 g of alcohol per day . The remaining 3299 participants were divided into four groups according to body mass index and daily ( g/d ) and lifetime ( kg ) alcohol intake . The control group consisted of 2753 persons of normal weight ( body mass index<25 kg/m2 ) who drank less than 100 kg of alcohol over a lifetime and did not drink more than 30 g of alcohol per day . The obese group included 283 obese persons ( body mass index>30 kg/m2 ) who drank less than 100 kg of alcohol over a lifetime and did not drink more than 30 g of alcohol per day . The heavy drinker group comprised 168 persons of normal weight who drank more than 100 kg of alcohol over a lifetime and drank more than 60 g of alcohol per day . Finally , the obese and heavy drinker group consisted of 95 obese persons who drank more than 100 kg of alcohol over a lifetime and drank more than 60 g of alcohol per day . The definition of heavy drinker as consumption of 30 g of alcohol per day or 100 kg of alcohol over a lifetime was based on previous data indicating these amounts of alcohol as the risk threshold for alcoholic liver disease in both sexes ( 4 ) . Alcohol intake was calculated by using data from a semi-quantitative , color food question naire ( 14 , 15 ) that included detailed questions on the use of alcoholic beverages ( 16 , 17 ) . Each participant was asked , in multiple-choice form , whether he or she drank beer , red wine , white wine , alcoholic aperitifs , or hard liquors daily , weekly , monthly , or hardly ever or never . For each type of alcoholic beverage , a color picture of a glass containing a st and ard unit of the beverage ( 200 mL for beer , 100 mL for wine , 70 mL for aperitif , and 40 mL for hard liquor ) was printed in the question naire . Each participant was asked if he or she usually drank a glass like the one reported in the picture , a smaller one , or a larger one . If the participant answered that he or she usually drank a glass that was smaller or larger than the one pictured , the amount of the beverage consumed per day was reduced or increased by 25 % . To calculate accurately the amount of alcohol in grams for each unit ( glass ) , the br and of beverage was also recorded . Daily alcohol intake was computed by multiplying the frequency of consumption of each unit of beverage by the alcohol content of the specified portions , according to st and ard procedures ( 14 - 17 ) . Total lifetime intake of alcohol was computed by multiplying the daily alcohol intake by years of alcohol intake . As described in detail elsewhere ( 4 ) , alcohol consumption was vali date d by monitoring wine intake ( liters per year per person ) from purchase records of wine sellers in the two participating towns and by cross-checking the alcohol consumption declared by the participant with family members . Among the participants who fit the inclusion criteria , 300 ( 150  residents of Campogalliano and 150 residents of Cormons , pair-matched for age ) were r and omly selected from the four groups by using the r and om procedure of the SPSS software package ( SPSS , Inc. , Chicago , Illinois ) . Informed consent to participate was obtained from 285 participants . Twenty-eight persons were excluded : Nineteen stated that they had reduced their daily alcohol intake to less than 30 g/d for at least 2 years or that their body mass index was less than 30 kg/m2 from 1993 to 1997 ; 6 who had type 2 diabetes mellitus ( 3 women and 1 man ) or hyperlipoproteinemia type 2b ( 2 men ) took oral antidiabetic drugs or cholestyramine , and 3 regularly took drugs . The remaining 257 participants , who were 19 to 70 years of age and had taken no drugs in the past 6 months , were enrolled in the study . Sixty-seven were assigned to the control group , 66 to the obese group , 69 to the heavy drinker group , and 55 to the obese and heavy drinker group . Two consecutive blood sample s were obtained 15 days apart from all of the enrolled participants , and the following were measured : serum levels of alanine aminotransferase , aspartate aminotransferase , and -glutamyltransferase ; mean corpuscular volume of erythrocytes ; platelet count ; and levels of glucose , cholesterol , and triglycerides All participants also underwent hepatobiliarysplenic ultrasonography , which was performed by two operators ( one in each center ) . The ultrasonograph operators were unaware of the participants ' clinical and biochemical profiles and the aim of the study . Steatosis was defined as the presence of an ultrasonographic pattern consistent with bright liver , with evident ultrasonographic contrast between hepatic and renal parenchyma , vessel blurring , focal sparing , and narrowing of the lumen of the hepatic veins , according to international guidelines ( 18 , 19 ) . Previous studies indicated that ultrasonography can detect and quantitate hepatic fat accumulation with an accuracy similar to that of computed tomography and liver biopsy ( 20 ) . The biochemical and ultrasonographic findings ( presence or absence of steatosis and gallstones ) were reported to the physician of the study participant . Statistical Analysis Statistical analysis was performed by using the SPSS statistical package , version 7.1 ( SPSS , Inc. ) . Data are expressed as the mean SD or the median with 95 % CIs for continuous variables . Statistical comparison was done by using the F-test ( analysis of variance ) ( 21 ) . Bivariate risk ratios ( 22 , 23 ) with 95 % CIs ( StatXact 3 for Windows , CYTEL Software Co. , Cambridge , Massachusetts ) and positive predictive values were calculated . Role of the Funding Source The funding source did not have any role in the analysis or 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 Both obesity and aging increase intrahepatic fat ( IHF ) content , which leads to nonalcoholic fatty liver disease ( NAFLD ) and metabolic abnormalities such as insulin resistance . We evaluated the effects of diet and diet in conjunction with exercise on IHF content and associated metabolic abnormalities in obese older adults . Eighteen obese ( BMI > or=30 kg/m(2 ) ) older ( > or=65 years old ) adults completed a 6-month clinical trial . Participants were r and omized to diet ( D group ; n = 9 ) or diet + exercise ( D+E group ; n = 9 ) . Primary outcome was IHF quantified by magnetic resonance spectroscopy ( MRS ) . Secondary outcomes included insulin sensitivity ( assessed by oral glucose tolerance ) , body composition ( assessed by dual-energy X-ray absorptiometry ) , physical function ( VO(2 peak ) and strength ) , glucose , lipids , and blood pressure ( BP ) . Body weight ( D : -9 + /- 1 % , D+E : -10 + /- 2 % , both P < 0.05 ) and fat mass ( D : -13 + /- 3 % , D+E -16 + /- 3 % , both P < 0.05 ) decreased in both groups but there was no difference between groups . IHF decreased to a similar extent in both groups ( D : -46 + /- 11 % , D+E : -45 + /- 8 % , both P < 0.05 ) , which was accompanied by comparable improvements in insulin sensitivity ( D : 66 + /- 25 % , D+E : 68 + /- 28 % , both P < 0.05 ) . The relative decreases in IHF correlated directly with relative increases in insulin sensitivity index ( ISI ) ( r = -0.52 ; P < 0.05 ) . Improvements in VO(2 peak ) , strength , plasma triglyceride ( TG ) , and low-density lipoprotein-cholesterol concentration , and diastolic BP occurred in the D+E group ( all P < 0.05 ) but not in the D group . Diet with or without exercise results in significant decreases in IHF content accompanied by considerable improvements in insulin sensitivity in obese older adults . The addition of exercise to diet therapy improves physical function and other obesity- and aging-related metabolic abnormalities UNLABELLED Nonalcoholic fatty liver disease , characterized by elevated liver enzymes , central obesity , and insulin resistance , is becoming increasingly prevalent . The effects of changes in physical activity on the metabolic profile of this group have not been reported . We assessed at 3 months the impact of a behavior change-based lifestyle intervention on physical activity  and the effects of this change on the metabolic profile of people with fatty liver disease . In all , 141 participants with nonalcoholic fatty liver disease were prospect ively enrolled into either a low- or moderate-intensity lifestyle intervention or to a control group . Physical activity  was assessed using a vali date d reporting tool and  physical fitness  was measured using the YMCA protocol on a cycle ergometer . Individualized counseling to increase physical activity  was provided . Overall , 96 % of participants attended the 3-month follow-up assessment . Participants in the moderate- and low-intensity intervention groups were 9 times more likely to increase physical activity by an hour or more per week compared to controls . Patients increasing or maintaining their reported physical activity to > or = 150 minutes/week , and those who increased their objective levels of fitness , had the greatest improvements in liver enzymes and other metabolic indices compared to those who were least active . This effect was independent of weight loss and was corroborated by an objective measure of fitness . There was no dose-response effect on liver enzymes with incremental increases in physical activity above 60 minutes/week . CONCLUSION Lifestyle counseling interventions are effective in improving physical activity behavior . Maintaining or increasing physical activity provides health benefits for patients with fatty liver , independent of changes in weight
BACKGROUND & AIMS Exercise is an integral component of lifestyle intervention aim ed at weight loss , but an independent benefit of exercise in NAFLD has also been suggested .
METHODS We aim ed to evaluate the efficacy of aerobic exercise and /or progressive resistance training for the modulation of  liver fat and alanine aminotransferase ( ALT ) levels in adults .