FOR THE JAPAN DIABETES COMPLICATIONS STUDY GROUP AND THE JAPANESE ELDERLY DIABETES INTERVENTION TRIAL

OBJECTIVEdTo develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes. RESEARCHDESIGNANDMETHODSdWe 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 pro-gression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for pre-diction. The predictive accuracy of the calculated 5-year risks was cross-validated. RESULTSdSex, 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 incor-porated 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 over-estimated 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). CONCLUSIONSdThe risk engine accurately predicts macro- andmicrovascular complications and would provide helpful information in risk classification and health economic simulations