INTRODUCTION: Hyperproinsulinaemia has been reported in patients with type 2 diabetes. It is unclear whether this is due to an intrinsic defect in â-cell function or secondary to the increased demand on the â-cells. We investigated whether hyperproinsulinaemia is also present in patients with secondary diabetes, and whether proinsulin levels are associated with impaired â-cell area or function.PATIENTS AND METHODS: Thirty-three patients with and without diabetes secondary to pancreatic diseases were studied prior to pancreatic surgery. Intact and total proinsulin levels were compared with the pancreatic â-cell area and measures of insulin secretion and action.RESULTS: Fasting concentrations of total and intact proinsulin were similar in patients with normal, impaired (including two cases of impaired fasting glucose) and diabetic glucose tolerance (P=0.58 and P=0.98 respectively). There were no differences in the total proinsulin/insulin or intact proinsulin/insulin ratio between the groups (P=0.23 and P=0.71 respectively). There was a weak inverse association between the total proinsulin/insulin ratio and pancreatic â-cell area (r(2)=0.14, P=0.032), whereas the intact proinsulin/insulin ratio and the intact and total proinsulin levels were unrelated to â-cell area. However, a strong inverse relationship between homeostasis model assessment index of â-cell function and both the total and the intact proinsulin/insulin ratio was found (r(2)=0.55 and r(2)=0.48 respectively). The association of insulin resistance (IR) with intact proinsulin was much weaker than the correlation with fasting insulin.CONCLUSIONS: Hyperproinsulinaemia is associated with defects in insulin secretion rather than a reduction in â-cell area. The weak association between intact proinsulin and IR argues against the usefulness of this parameter in clinical practice.
Blood Glucose Diabetes Mellitus