the majority of japanese patients with type 2 diabetes mellitus are not obese , as reported by kosaka and ogata more than 50 years ago .
eastern asian subjects might share common characteristics of the disease , comparable to those reported in korean people .
it is , therefore , debatable whether we can apply epidemiological evidence obtained from studies of caucasian subjects with type 2 diabetes and obesity to eastern asian people , especially in the fields of diabetic complications , which are influenced not only by hyperglycemia but also by obesity .
for example , type 2 diabetes is a relative risk factor for cardiovascular disease in asians , as in western societies , but the absolute risk differs greatly between these populations [ 47 ] .
recently , the  legacy effect  of intensive glycemic control early after the diagnosis of diabetes was advocated based on the ukpds follow - up study . however , there is no report about the legacy effect of past obesity over a lifetime on diabetic complications .
although there have been inconsistent results as to whether obesity is a risk for diabetic nephropathy [ 912 ] , it was reported that current obesity and maximum past body mass index ( bmi ) were significant risk factors for diabetic nephropathy in the japanese .
although caucasian subjects with type 2 diabetes usually maintain their body weight status during their disease course , the majority of patients of eastern asian ethnicity begin to lose body weight from around the time of diagnosis of diabetes [ 3 , 13 ] .
this was easily overlooked , even if the effect of obesity in the past persisted for a long time , because they were already nonobese at the start of clinical follow - up . to clarify the influence of past obesity on diabetic complications is an important clinical concern in patients of eastern asian ethnicity .
we therefore analyzed the difference in the prevalence of diabetic nephropathy in japanese type 2 diabetics according to their history of body weight status to clarify the effect of past obesity on diabetic nephropathy .
we examined subjects with type 2 diabetes whose estimated glomerular filtration rate ( egfr ) was 30  ml / min/1.73  m or more and who were admitted to saiseikai central hospital from january 1999 to december 2004 ( n = 1834 ) or keio university hospital from april 1998 to september 2010 ( n = 1093 ) for the management of metabolic control . the study protocol was reviewed and approved by the ethics committee of both hospitals . those subjects in whom the etiology of renal disease was strongly suspected to be other than diabetic nephropathy were excluded . according to the history of body weight status and the japanese criteria for obesity , we defined  current obesity  as bmi on hospitalization of 25 or more ,  previous obesity  as bmi on hospitalization of less than 25 and self - reported maximum bmi in the past of 25 or more , and  continuously lean  as maximum bmi of less than 25 .
hba1c level on admission was determined by high - performance liquid chromatography ( hplc : arkray inc . ,
kyoto , japan ) according to the recommended method by the japan diabetes society ( jds ) at that time and converted to the national glycohemoglobin standardization program ( ngsp ) value .
egfr ( ml / min/1.73  m ) was calculated as 194  cr  age ( with further multiplication by 0.739 for female subjects ) using the equation provided by the japanese society of nephrology .
subjects with albumin excretion rate ( aer ) of 20  g / min or more in 24-hour urine were considered to have diabetic nephropathy .
hypertension was defined as systolic blood pressure > 140  mmhg , diastolic blood pressure > 90  mmhg , or the prescription of antihypertensive medication .
< 1.04  mmol / l , or the prescription of lipid - lowering medication .
continuous variables are expressed as mean  sd . differences in baseline characteristics among the obesity categories were analyzed by anova and chi - squared test . chi - squared test was also performed to evaluate differences in prevalence , with bonferroni 's correction for post hoc multiple comparisons . as a result ,
logistic regression analysis with forced entry method was performed to detect significant independent predictors of diabetic nephropathy .
we adopted as covariates factors such as sex , age , disease duration , hypertension , dyslipidemia , hba1c , and obesity status ( current obesity , past obesity , and continuously lean ) in this study .
we analyzed a total of 2927 persons ( males 2038 , females 889 , age 59.3  10.6 years , bmi 24.0  4.0 , duration of diabetes 10.4  28.0 years , hba1c 9.3  2.8% ) .
the prevalence of current obesity in the total subjects was 33.6% , previous obesity 41.5% , and a continuous lean state 24.8% .
the prevalence of nephropathy was significantly different among the categories , and both currently obese ( 40.6% ) and previously obese ( 35.6% ) patients had a significantly higher prevalence of diabetic nephropathy than that in continuously lean patients ( 24.3% ) ( p < 0.017 ) .  
when we divided the patients into quartiles according to current bmi , the prevalence of nephropathy significantly increased as current bmi increased ( figure 1 , p < 0.001 ) .
when we similarly divided them into quartiles according to previous maximum bmi , the prevalence of nephropathy significantly increased as previous maximum bmi increased ( figure 1 , p < 0.001 ) .
current bmi and previous maximum bmi were highly correlated with each other ( r = 0.785 , p < 0.001 ) .  
in logistic regression analysis , both current obesity and previous obesity revealed a significant odds ratio for nephropathy , as well as diabetic retinopathy , independent of sex , age , disease duration , hypertension , dyslipidemia , and hba1c ( table 2 ) .
we confirmed that previous obesity , as well as present obesity , was closely associated with nephropathy in type 2 diabetes .
the notable finding of this study was that obesity is an independent risk factor , not only if it is present , but also if it was present in the past .
the mechanism is the theme for investigation of how obesity in the past can influence diabetic complications over time .
both current bmi and previous maximum bmi were associated with the nephropathy , as demonstrated in figure 1 . however ,
so , generally , the higher the previous bmi , the higher the current bmi .
when we analyzed the effects of previous obesity , we had to separate the effects of current obesity from those of previous obesity .
this was the reason we analyzed the effect of previous obesity according to the categories defined as previous maximum bmi and current bmi .
as a result , we could elucidate the effect of previous obesity on diabetic nephropathy .
whether nephropathy in type 2 diabetes really derives from diabetes has always been a point of discussion .
however , type 2 diabetes per se is a disease so closely linked with obesity and the metabolic syndrome that we can not strictly distinguish the cause among the components of the syndrome .
we here found that the effect of obesity was independent of the existence of diabetic retinopathy , and we expect this result can be applied to all type 2 diabetes patients .  
several groups , including us , have reported that albuminuria was the strongest predictor of the progression of diabetic nephropathy [ 1822 ] .
we did not chronologically follow the decline of glomerular filtration rate ( gfr ) in this study
. however , as we defined diabetic nephropathy by albuminuria , obesity , either current or past , might relate to the gfr decline through albuminuria .
although this concept is strictly defined with exclusion of both nephrosclerosis and diabetic nephropathy , the suspected mechanisms , including the contraction of efferent glomerular arterioles by the activated renin - angiotensin system ( ras ) and glomerular hyperfiltration , as well as glomerular hypertrophy due to insulin resistance , are very similar to those of diabetic nephropathy .
the border between the concepts of diabetic nephropathy and obesity - related nephropathy is unclear , and they can not be distinguished clinically if a patient has both .
vivante et al . reported that overweight state and obesity in adolescents were associated with significantly increased risk for both diabetic and nondiabetic esrd during a 25-year period . if obesity even before the diagnosis of diabetes influences kidney function later , these concepts are continuous and indivisible .   there are some limitations of this study .
one is that this study was retrospective , based on self - reported body weight in the past . as for the other limitation
, we might have to consider how they lost their body weight because the study subjects required metabolic interventions for poor glycemic status .
however , we only have the data of maximum body weight and the body weight on admission but not the duration .
so the hypothesis needs to be confirmed in a future large cohort study with more detailed information . in spite of these limitations ,
we therefore believe it includes important suggestions on the effect of obesity on diabetic nephropathy .
our study indicated that obesity in the past , as well as present obesity , was a risk factor for diabetic nephropathy .
we should consider the effect of earlier obesity on diabetic nephropathy even if it has been present before the diagnosis of diabetes .
 
 aims . we analyzed the prevalence of nephropathy according to past body weight status in japanese subjects with type 2 diabetes because the influence of past obesity on diabetic complications is not certain 
 . methods . 
 we examined the prevalence of nephropathy in 2927 subjects with type 2 diabetes mellitus according to current bmi and maximum bmi in the past . 
 we defined  current obesity  as bmi on hospitalization of 25 or more ,  previous obesity  as bmi on hospitalization of less than 25 and self - reported maximum bmi in the past of 25 or more , and  continuously lean  as maximum bmi of less than 25 . 
 results . 
 the prevalence of nephropathy was significantly higher in subjects with current obesity ( 40.6% ) or previous obesity ( 35.6% ) than in those who were continuously lean ( 24.3% ) ( p < 0.017 ) . 
 in logistic regression analysis , previous obesity , as well as current obesity , was a significant risk factor for nephropathy , independent of sex , age , disease duration , hypertension , dyslipidemia , hba1c , and diabetic retinopathy . conclusions . 
 obesity in the past , as well as the present body weight status , was a risk factor for diabetic nephropathy . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion 
5. Conclusion