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Objective: To develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes.Research Design and Methods: We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated.Results: Sex, age, HbA1c, years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02).Conclusions: The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations. [ABSTRACT FROM AUTHOR]

The Japan Diabetes Complications Study, a randomised lifestyle intervention study of type 2 diabetes conducted at 59 institutes throughout Japan that enrolled 2033 eligible patients from January 1995 to March 1996, was directed at: (i) determining the incidence and progression rates of complications of diabetes; (ii) exploring clinical risk factors for complications of diabetes; and (iii) determining the association between lifestyle factors, including diet and physical activity, and complications of diabetes, in addition to comparing, in a randomised manner, the effects on type 2 diabetes of an extensive lifestyle intervention and conventional treatment. The protocol for the study originally specified four study populations according to primary outcomes, consisting of: (1) a macroangiopathy group (N = 1771); (ii) a nephropathy group (N = 1607); (iii) a retinopathy-incident group (N = 1221); and (iv) a retinopathy-progression group (N = 410). The primary outcomes were: (i) development of retinopathy; (ii) progression of retinopathy; (iii) development of overt nephropathy; and (iv) occurrence of macroangiopathic events including proven coronary heart disease and stroke. The study was originally planned to follow patients for 8 years, and an extended follow-up is ongoing. Information about primary outcomes, laboratory tests, and other clinical variables for each patient was collected at a central data centre through an annual report from each investigator. Additionally, extensive lifestyle surveys were conducted at baseline and 5 years after the beginning of the study intervention in both the intervention and conventional treatment groups. A description of the occurrence of complications of diabetes and of all-cause mortality, provided in this paper, demonstrated a clear gender-based difference in cardiovascular disease and all-cause mortality. [ABSTRACT FROM AUTHOR]

Objective: To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.Research Design and Methods: We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.Results: Annual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups.Conclusions: In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists. [ABSTRACT FROM AUTHOR]

Objective: To determine the best lipid variable to predict coronary heart disease (CHD) in Japanese patients with type 2 diabetes.Research Design and Methods: Eligible Japanese men and women (1,771) aged 40-70 years with type 2 diabetes from 59 institutes nationwide were followed for a planned 8-year period. The performance of eight conventional lipid variables, i.e., total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC), triglycerides (TGs), non-HDLC, TC/HDLC ratio, LDLC/HDLC ratio, and TG/HDLC ratio, as predictors of incident CHD were evaluated by four methods: hazard ratio (HR) per one SD increment by multivariate Cox analysis, χ(2) likelihood ratio test, area under the receiver operating characteristic curve (AUC), and tertile analysis.Results: Although all variables significantly predicted CHD events in men, non-HDLC (HR per one SD 1.78 [95% CI 1.43-2.21]; AUC 0.726) and TC/HDLC (HR 1.63 [1.36-1.95]; AUC 0.718) had the better predictive performances among the variables, including LDLC. In women, TGs (log-transformed; HR 1.72 [1.21-2.43]; AUC 0.708) were the best predictor according to results of tertile analysis (HR of the top tertile versus the bottom tertile 4.31 [1.53-12.16]). The associations with incident CHD were linear and continuous.Conclusions: For Japanese diabetic men, non-HDLC and TC/HDLC were the best predictors, whereas TGs were most predictive for women. These findings, which included prominent sex differences, should be considered among clinical approaches to risk reduction among East Asians with diabetes. [ABSTRACT FROM AUTHOR]

Objective: The metabolic syndrome (MetS) is believed to be associated with an increased risk of cardiovascular disease (CVD). Although its prevalence is extremely high among diabetic patients, its prevalence in those with no history of CVD has not been determined. Moreover, prospective studies published on the association between MetS and cardiovascular events in diabetic populations have used only the World Health Organization (WHO) definition of MetS and included only white European subjects. The aim of this study was to determine the prevalence of MetS, as defined by both the WHO and the National Cholesterol Education Program (NCEP), and its predictive value for CVD in Asian diabetic patients in a long-term, prospective setting.Research Design and Methods: The baseline characteristics and incidence/hazard ratio of cardiovascular events (coronary heart disease and stroke) were determined in 1,424 Japanese type 2 diabetic patients with and without MetS, as defined by WHO (WHO-MetS) or the NCEP.Results: A high prevalence (38-53%, depending on sex and definition) of MetS was found among diabetic patients, even those with no history of CVD. During the 8-year study period, only WHO-MetS was a predictor for CVD in female patients. In male patients, although both definitions of MetS were significant predictors for CVD, individual components of MetS, such as hyperlipidemia or hypertension, were equivalent or better predictors.Conclusions: We found that MetS is relatively common in diabetic patients with no history of CVD. We suggest that the commonly used definitions of MetS, at least in their present forms, have limited clinical usefulness for Asian diabetic patients and may need some ethnic group-specific modifications for global use. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to examine the associations between possible indices of obesity based on information on weight history and the incidence of microvascular complications.Methods: A cohort of individuals with type 2 diabetes from 59 institutes in Japan was followed for 8years. Patients were classified into three categories according to weight at entrance and past maximum weight: normal (BMI at baseline <25kg/m(2) and maximum BMI <25kg/m(2)), past obesity (BMI at baseline <25kg/m(2) and maximum BMI ≥25kg/m(2)), and current obesity (BMI at baseline ≥25kg/m(2)) groups. The outcomes were diabetic retinopathy and overt nephropathy.Results: BMI at maximum and baseline of the 1809 patients was 26.5±3.5 and 23.1±3.0kg/m(2) (p<0.01), respectively (23.0±1.6 and 20.6±1.9kg/m(2) for normal, 27.4±2.0 and 22.8±1.4kg/m(2) for past obesity, and 30.1±2.9 and 27.0±1.8kg/m(2) for current obesity). The hazard ratios of past and current obesity compared to normal were 1.92 (95% CI, 1.08-3.41; p=0.03) and 2.21 (1.16-4.22; p=0.02), respectively, for overt nephropathy and 1.38 (1.05-1.83; p=0.02) and 1.64 (1.18-2.28; p<0.01), respectively, for diabetic retinopathy after adjustment for confounders.Conclusions: Past obesity as well as current obesity were associated with increased risks of microvascular complications. Further identification of high-risk populations may be possible by classifying normal weight patients by past obesity. [ABSTRACT FROM AUTHOR]