Diminution of early insulin response to glucose in subjects with normal but minimally elevated fasting plasma glucose. Evidence for early beta-cell dysfunction.

AIM: Systematic analysis of beta-cell function in Japanese health examinees. METHODS: In 938 Japanese health examinees (627 men and 311 women, mean age and body mass index, 54.0 years and 23.6 kg/m2, respectively), plasma specific insulin was measured at fasting and during a 75-g oral glucose tolerance test. The subjects were stratified into six groups based on fasting plasma glucose < or = 5.1 mmol/l, 5.2-6.0 mmol/l, 6.1-6.9 mmol/l, 7.0-7.8 mmol/l, 7.9-8.7 mmol/l, and > or = 8.8 mmol/l as the 1st, 2nd, 3rd, 4th, 5th and 6th groups, respectively. RESULTS: Distribution of fasting insulin showed a very modest 'inverted U' shape, with the peak in the 5th group. Progressive increase from the 1st toward the 5th group was significant. In contrast, the ratio of change in insulin to change in glucose from 0 to 30 min during the glucose tolerance test was greatest in the 1st group and progressively declined in the groups with higher fasting glycaemia. Difference in the ratio was most striking and highly significant between the 1st and 2nd groups. Distribution of the insulin to glucose ratio of subjects with normal glucose tolerance significantly overlapped with that of untreated patients with diabetes. CONCLUSIONS: In a Japanese population, (i) beta-cell starts to deteriorate during normoglycaemia with a minimal elevation of fasting plasma glucose, and (ii) there are glucose-tolerant subjects with beta-cell dysfunction.