POOR PHYSICAL-FITNESS, AND IMPAIRED EARLY INSULIN-RESPONSE BUT LATE HYPERINSULINEMIA, AS PREDICTORS OF NIDDM IN MIDDLE-AGED SWEDISH MEN

In a prospective population-based study of middle-aged Caucasian men, performed in Malmo, Sweden, specifically designed to evaluate physical fitness, early and late insulin response as predictors of non-insulin -dependent diabetes mellitus (NIDDM), 4,637 non-diabetic men underwent oral glucose tolerance tests at the ages of 48 and 54 years. At the b ase-line examination, physical fitness was measured in terms of lung v ital capacity and oxygen uptake during ergometry; early insulin respon se in terms of the 40-min insulin increment during an oral glucose tol erance test (a correlate of acute insulin response to an intravenous g lucose tolerance test), and late insulin response were measured in ter ms of the 2-h insulin value during the oral glucose tolerance test (a correlate of glucose disposal during euglycaemic clamp testing). Of th e subjects studied 116 developed NIDDM (0.4% annually), and when compa red with non-diabetic men at baseline, they were found to have an 11% higher mean body mass index (p < 0.001), a higher frequency of family history of diabetes (31 vs 18%, p < 0.001), 16% lower mean physical ac tivity index (p < 0.05), 16% lower mean estimated maximal oxygen uptak e (p < 0.001), 10% lower mean vital capacity (p < 0.001), 26% lower 40 -min to total insulin response ratio (p < 0.001), and a 2.7 times high er mean 2-h insulin value during an oral glucose tolerance test (p < 0 .001). Regression analysis (using Cox's proportional hazards model) sh owed both low vital capacity, and impaired early insulin response but late hyperinsulinaemia to be independent predictors of NIDDM, in addit ion to body mass index and fasting blood glucose level (p=0.05-0.0001) . Among subjects with impaired glucose tolerance at baseline (44 of 27 8 developed NIDDM), fasting glucose level alone predicted diabetes in this model. The findings suggest that in this age group in a Caucasian population, not only does insulin resistance precede glucose intolera nce and NIDDM, but also loss of early insulin response indicating impa ired beta-cell function to be an early feature of the process culminat ing in diabetes. As both physical fitness [which correlates inversely with late insulin response (r = -0.42, p < 0.0001)], and the level of physical activity were shown to correlate with diabetes development in this large series, measures to correct these adverse features should be included in future strategies for preventing NIDDM.