Effects of a new diuretic piretanide on glucose tolerance,insulin secretion and 125I-insulin binding

Summary The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and ¹²⁵I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glyco-haemoglobin A₁ measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 µU/ml; p<0.05). Glucagon — stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 µU/ml, p<0.05) and after 8 weeks (1.67 vs. 2.90 µU/ml, p<0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of ¹²⁵I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.