PROPORTIONAL PROINSULIN RESPONSES IN 1ST-DEGREE RELATIVES OF PATIENTSWITH TYPE-2 DIABETES-MELLITUS

Elevated fasting proinsulin immunoreactive material (PIM) has previous ly been found in patients with type 2 (non-insulin-dependent) diabetes mellitus. It is not known whether this is a genetic trait or whether it is related to the manifestation of type 2 diabetes. Neither is it c lear whether the raised fasting insulin immunoreactivity previously ob served in first-degree relatives of patients with type 2 diabetes is d ue to raised PIM. Furthermore, it has not been investigated whether fi rst-degree relatives have altered PIM responses to different secretago goues. To study this, PIM, insulin and C-peptide were measured in pati ents with type 2 diabetes, in their first-degree relatives and in heal thy control subjects in the fasting state and in relatives and control s during a hyperglycemic clamp. At the end of the hyperglycemic clamp, 0.5 mg of glucagon was given intravenously to stress the beta cells f urther. Fasting PIM concentrations were significantly higher in patien ts with type 2 diabetes (P < 0.05). These patients did not have signif icantly elevated fasting insulin levels when corrected for PIM. In the relatives, fasting insulin concentrations were elevated but PIM level s were normal suggesting that the increase in fasting insulin concentr ations reflected an increase in true insulin. The incremental PIM, ins ulin and C-peptide responses to glucose and glucagon in the relatives were not different from those in the controls. We conclude that elevat ed fasting PIM levels in patients with type 2 diabetes seem not to be a genetic trait. First-degree relatives of patients with type 2 diabet es are truly hyperinsulinemic in the fasting state, and they have prop ortional PIM, insulin and C-peptide responses to glucose and glucagon.