On the pathogenesis of type II diabetes with special reference to diminished insulin response and obesity: a 5-12 year follow-up study of subjects with borderline glucose tolerance.

In a 5-12 year follow-up study of 288 subjects with borderline glucose tolerance, 56 of them worsened to overt noninsulin dependent diabetes mellitus (NIDDM). Multivariate analysis indicated that a high level of fasting and 2-hour blood glucose values at the initial 100 g oral glucose tolerance test, a large maximal body weight index (Max. BWI) and a diminished insulin response to glucose load were significant independent risk factors for worsening to diabetes. Deterioration to diabetes was observed 4.5 times, 6.1 times and 2.1 times more frequently in subjects with fasting blood glucose greater than or equal to 100 mg/100 ml, 2-hour blood glucose greater than or equal to 180 mg/100 ml and Max. BWI greater than or equal to 130%, respectively, as compared with those having lower values of each variable. Diabetes developed almost exclusively from low insulin responders in 253 non- or mildly obese subjects, while in 35 severely obese subjects a certain number of 'normal or high' insulin responders did develop diabetes. In conclusion, the majority of cases of NIDDM develop on the basis of low insulin secretion, with an additional precipitating factor of obesity, and, in some with higher insulin responses diabetes develops when extreme obesity exists, though these cases form a minor group in Japan today.