Hyperproinsulinemia of Type II Diabetes Is Not Present Before the Development of Hyperglycemia

Abstract

OBJECTIVE To examine proinsulin and insulin levels in first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Comparison of insulin and proinsulin responses to an oral glucose tolerance test in four groups of individuals: 1) 31 patients with newly diagnosed NIDDM treated with diet alone, 2) 34 first-degree relatives of NIDDM patients with impaired glucose tolerance (IGT), 3) 26 relatives with normal glucose tolerance (NGT), and 4) 30 subjects without a family history of diabetes. RESULTS Both fasting and post-glucose levels of proinsulin were elevated in patients with diabetes, but not in the relatives with IGT or NGT. Levels of true insulin were highest in the diabetic group, followed by the subjects with IGT, and were lowest among relatives with NGT. Proinsulin levels correlated with glucose levels, suggesting that hyperglycemia is the main stimulus for increased proinsulin secretion. CONCLUSIONS First-degree relatives of NIDDM patients, who have a high risk of developing diabetes, do not exhibit elevated levels of fasting or glucose-stimulated proinsulin as long as their fasting glucose levels remain normal.