Abstract
Hyperinsulinemia of nondiabetic overweight and obese subjects is associated with weight-dependent
increased insulin secretion and decreased insulin clearance. The present analysis
examines whether similar effects can be observed in overweight and obese patients
with type 2 diabetes mellitus (DM2). Additionally basal and postprandial insulin secretion
and clearance were analyzed in relation to duration of disease. In a random sample
of 348 DM2 patients basal plasma insulin concentrations were significantly higher
in most BMI groups compared to matched nondiabetic (ND) controls. The weight-dependent
increase of basal insulin in DM2 was primarily the result of reduced clearance rather
than augmented secretion. Postprandial insulin concentrations were lower in DM2 patients
and did not show any BMI-related increase. The weight-dependent reduction of postprandial
insulin clearance was absent in DM2. At the time of diagnosis basal insulin concentration
was higher and secretion was comparable to ND subjects and this did not change with
duration of diabetes. The early postprandial insulin response was still comparable
between DM2 and ND subjects at the time of diagnosis but deteriorated with longer
duration of disease. The later postprandial response at diagnosis (AUC 90–180) was
characterized by significantly greater insulin secretion and concentration while later
on the 3-fold higher secretion was paralleled by comparable peripheral plasma concentrations
due to a significantly greater postprandial insulin clearance in DM2. In conclusion,
the present data indicate that apart from disturbances of insulin secretion substantial
changes of insulin clearance contribute to inadequate peripheral insulin concentrations
in obese DM2 patients.
Key words
insulin secretion - insulin resistance - body weight - obesity
