Serum proinsulin is disproportionately elevated both in the basal state and after an oral glucose load in non-insulin dependent diabetes mellitus (NIDDM). However, there is no detailed information about the effect of glycemic control on this abnormality. We investigated the effect of glycemic control by dietary treatment on serum proinsulin level in the basal state and in response to an oral glucose load. Ten NIDDM patients (7 men and 3 women), aged 19–60 yr, with mean (± SD) body mass index of 28 ± 6 kg/m2 (range 21–42 kg/m2) and normal renal and liver function were studied. Before and after dietary therapy (25–30 kcal/kg ideal body wt), 100-g oral glucose tolerance tests were performed. Proinsulin was measured with our proinsulin-specific antiserum, which recognizes the connecting site of the B-chain of insulin and C-peptide. After dietary treatment, fasting plasma glucose decreased from 197 ± 35 to 113 ± 18 mg/dl (P < .001). Both serum insulin and proinsulin decreased (insulin from 15 ± 8 to 10 ± 4 μU/ml, P < .02; proinsulin from 31 ± 18 to 13 ± 5 pM, P < .02), and the molar ratio of proinsulin to insulin also tended to decrease (from 0.31 ± 0.08 to 0.24 ± 0.10, P < .10). Insulin response to oral glucose increased after dietary treatment, whereas proinsulin response did not change, resulting in a significant decrease in the molar ratio of the area under the curve of proinsulin to insulin after glucose load (from 0.28 ± 0.12 to 0.13 ± 0.07, P < .001). These results support the concept that glycemic control attained by calorie restriction allows recovery of disproportionate oversecretion of proinsulin in patients with NIDDM, presumably decreasing the demand for insulin secretion from β-cells.

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