ASSOCIATION BETWEEN INSULIN SECRETORY PULSE FREQUENCY AND PERIPHERAL INSULIN ACTION IN NIDDM AND NORMAL SUBJECTS

Abnormalities of both insulin secretion and insulin action occur in NI DDM. It is not clear, however, which is the primary defect, Recently, it has been suggested that the frequency of insulin pulses is an impor tant factor regulating insulin action in normal humans, We examined th e relationship between pulsatile insulin secretion and insulin action in eight NIDDM subjects and eight healthy matched control subjects, In sulin action was assessed at prevailing fasting glucose levels before and after hyperinsulinemia (2-h insulin infusion at 2.0 mU . kg(-1) . min(-1)), Pulsatility of insulin was assessed by sampling every 2 min for 90 min after an overnight fast and identifying insulin pulses usin g the computer program Pulsar, Fasting plasma glucose and postabsorpti ve endogenous glucose production were both greater in diabetic subject s compared with control subjects (10.1 +/- 1.2 vs. 5.4 +/- 0.1 mmol/l, P < 0.01; 11.8 +/- 0.8 vs, 9.9 +/- 0.4 mu mol . kg(-1) . min(-1), P < 0.05), During the 2.0 mU insulin infusion, glucose clearance was lowe r in the diabetic subjects (3.6 +/- 0.7 vs, 6.9 +/- 0.5 ml . kg(-1) . min(-1), P < 0.05), whereas endogenous glucose production was suppress ed to a similar degree in both groups (4.5 +/- 0.8 vs. 3.6 +/- 0.7 mu mol . kg(-1) . min(-1), NS). The frequency of insulin pulses and gluco se clearance were negatively correlated in both diabetic subjects (r = -0.75, P < 0.05) and normal control subjects Cr = -0.82, P < 0.01), T his negative correlation was also present in both groups taken togethe r (r = -0.72, P < 0.001), There was no correlation between insulin pul se frequency and endogenous glucose production either in the fasting s tate or during hyperinsulinemia, We concluded that the frequency of in sulin pulses and peripheral insulin sensitivity are closely linked in NIDDM and normal subjects.