EFFECT OF INSULIN ON RENAL SODIUM HANDLING IN HYPERINSULINEMIC TYPE-2 (NON-INSULIN-DEPENDENT) DIABETIC-PATIENTS WITH PERIPHERAL INSULIN RESISTANCE

The sodium retaining effect of insulin was studied in ten Type 2 (non-insulin-dependent) diabetic patients (mean age 56 (43-73) years, mean body mass index 29.5 (24.2-33.7) kg/m2) and eight age-matched control subjects (mean age 57 (43-68) years, mean body mass index 23.4 (20.8-26.6) kg/m2). The renal clearances of Tc-DTPA, lithium, sodium and potassium were measured over a basal period of 90 min. Then insulin was infused at a rate of 40 mU.min-1.m-2. After an equilibration period of 90 min, the clearance measurements were repeated during a new 90 min period. Blood glucose was clamped at the basal level (diabetic patients: 9.9 +/- 3.5, control subjects: 5.3 +/- 0.5 mmol/l) by a variable glucose infusion. Basal plasma insulin concentration was elevated in the diabetic patients (0.12 +/- 0.05 vs 0.05 +/- 0.02 pmol/ml,p < 0.01). Insulin infusion resulted in comparable absolute increments in plasma insulin concentrations in the diabetic group and in the control group (0.44 +/- 0.13 vs 0.36 +/- 0.07 pmol/ml.NS). The metabolic clearance rate of glucose during the last 30 min of insulin infusion was lower in the diabetic patients (155 +/- 62 vs 320 +/- 69 ml.min-1.m-2, p < 0.01), reflecting peripheral insulin resistance. The decline in sodium clearance during insulin infusion was similar in diabetic subjects (1.8 +/- 1.1 vs 0.7 +/- 0.4 ml.min-1.1.73 m-2, p < 0.01) and in control subjects (1.7 +/- 0.3 vs 0.8 +/- 0.3 ml.min-1.1.73 m-2, p < 0.01). The glomerular filtration rate and lithium clearance was unchanged, consequently calculated distal tubular fractional sodium reabsorption increased (diabetic patients: 92.9 +/- 4.1 vs 97.1 +/- 1.5, p < 0.01, control subjects: 93.1 +/- 1.1 vs 96.5 +/- 0.6%, p < 0.01). Estimated extracellular fluid volume was 10% higher in the diabetic subjects (16.3 +/- 2.1 vs 14.8 +/- 2.01.1.73 m-2, NS). In conclusion, the sodium retaining effect of insulin is preserved in Type 2 diabetic patients with peripheral insulin resistance. Insulin may contribute to sodium and fluid retention and thus to the increased frequency of hypertension in hyperinsulinaemic Type 2 diabetic patients.