Insulin deficiency rather than hyperinsulinaemia in newly diagnosed type 2 diabetes mellitus

Abstract

This paper reports beta cell function as assessed during OGTT using specific IRMAs for insulin, intact and 32/33 split proinsulin in subjects with newly diagnosed Type 2 diabetes matched to normal controls. The relationships between insulin and the proinsulins to risk factors for cardiovascular disease were also examined. Similar fasting insulin concentrations but lower 30-min post-glucose-load insulin concentrations were found in diabetic subjects (mean +/- SEM 143 +/- 12 pmol-1 vs 304 +/- 19 (p < 0.001). Subjects with diabetes had increased fasting intact (10.6 +/- 1.1 pmol-1 vs 3.3 +/- 0.2, p < 0.001) and 32/33 split proinsulin concentrations (8.1 +/- 0.9 pmol-1 vs 2.2 +/- 0.3, p < 0.0001). Beta cell dysfunction, as expressed by a reduction in the 30-min insulin to glucose ratio (9.4 +/- 1 vs 34.8 +/- 2.3, p < 0.0001) and an increase in the fasting percentage of total proinsulin-like to total insulin-like molecules (24.5 +/- 9% vs 11.6 +/- 5, p < 0.001), was present in subjects with diabetes. In diabetic subjects beta cell dysfunction and insulin deficiency increased relative to the degree of fasting hyperglycaemia. It seems clear that beta cell dysfunction and insulin deficiency are major features of Type 2 diabetes. Only the fasting concentration of 32/33 split proinsulin positively correlated with both the waist/hip ratio (r = 0.36, p < 0.001), diastolic blood pressure (r = 0.23, p < 0.01) in addition to plasma triglyceride concentration (r = 0.46, p < 0.001). It is questionable whether hyperinsulinaemia plays a pathogenic role in cardiovascular disease in subjects with glucose intolerance.