A 2-STEP STRATEGY FOR IDENTIFICATION OF HIGH-RISK SUBJECTS FOR A CLINICAL-TRIAL OF PREVENTION OF NIDDM

OBJECTIVE - To evaluate 2-h plasma glucose (2HPG), fasting plasma gluc ose (FPG), glycosylated hemoglobin (HbA(1)), a combination of FPG and HbA(1) (FPG-HbA(1)), and other factors as screening tests for identify ing high-risk subjects for a clinical trial of prevention of NIDDM and to identify strategies to minimize the total number of oral glucose t olerance tests (OGTTs) required to reemit eligible subjects to the tri al. RESEARCH DESIGN END METHODS - One thousand, one hundred and eight nondiabetic Pima Indians aged 25-64 years were followed for up to 5 ye ars, and factors predicting NIDDM, defined by World Health Organizatio n criteria (2HPG greater than or equal to 11.1 mmol/l), were assessed using Cox's proportional hazards analysis. Various threshold values of FPG, HbA(1), and FPG-HbA(1) were determined, which, when combined wit h an OGTT, identified subjects with impaired glucose tolerance (IGT) ( 2HPG greater than or equal to 7.8 and <11.1 mmol/l) at a number of spe cified risks for developing NIDDM in 5 years. The value of each of the three tests was then assessed by calculating (for each threshold) the numbers To be screened, the numbers requiring an OGTT, and the sample size of IGT subjects needed to detect a 33% reduction in NIDDM by an experimental intervention at a power of 80%. RESULTS - During a median of 4.3 years of follow-up, 91 (8.2%) of the 1,108 nondiabetic subject s developed NIDDM. The estimated 5-year cumulative incidence rate was 13.5%. Each of the variables, 2HPG, FPG, HbA(1), FPG-HbA(1), BMI, IGT, and systolic (sBP), diastolic (dBP), and mean (MBP) blood pressures, predicted NIDDM (P < 0.05 for each) when controlled for age and sex. I n a stepwise proportional hazards analysis model, 2HPG and FPG-HbA, (P < 0.001 for each) were selected as the best set of predictors of NIDD M and of fasting hyperglycemia (FPG greater than or equal to 7.8 mmol/ l). CONCLUSIONS - A two-step strategy, in which high-risk individuals are first identified by FPG or FPG-HbA, and then the OGTT is used to s elect subjects with IGT, requires fewer OGTTs than when using 2HPG as the initial screening test without substantially increasing the number s that would need to be screened. Such a strategy also offers the adva ntage of reducing the necessary sample size and is therefore an effect ive, efficient, and convenient method of identifying eligible subjects for a clinical trial of prevention of NIDDM.