Insulin secretion in uremia: effect of parathyroid hormone and vitamin D metabolites

Abstract

Insulin resistance is almost universal among uremic patients. There are, however, two different subgroups of uremic patients with regard to glucose tolerance. About half of uremic patients can augment their insulin secretion in response to glucose loads to overcome the insulin resistance and maintain glucose tolerance. In the other half of uremic patients, insulin secretion following glucose loads is not different from normal values so that glucose intolerance results. There is recent evidence that hyperparathyroidism or vitamin D deficiency may inhibit insulin secretion in uremia. Parathyroid hormone (PTH) concentrations correlated inversely with glucose tolerance in adolescents with chronic renal insufficiency. Insulin hypersecretion in response to glucose loads occurred only in uremic patients with normal PTH concentrations. Surgical correction of hyperparathyroidism in uremic patients on hemodialysis led to the resolution of glucose intolerance with an increase in insulin secretion and no change in insulin resistance. However, the role of vitamin D repletion was not separately assessed since these patients were supplemented with vitamin D post-operatively. Medical correction of hyperparathyroidism by high-dose phosphate binders and vitamin D led to similar changes in glucose metabolism in children with chronic renal insufficiency. Glucose intolerance resolved, insulin secretion increased, and insulin resistance persisted. In the latter study, plasma 1,25-dihydroxycholecalciferol (DHCC) increased significantly following phosphate restriction. Recently, a preliminary study showed that intravenous 1,25-DHCC acutely restored glucose tolerance and increased insulin secretion in uremic patients on hemodialysis without simultaneous changes in serum PTH, ionized calcium, phosphate, magnesium or potassium concentrations. Thus, 1,25-DHCC, independently of PTH and calcium, may be important in the control of insulin secretion in uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)