Hyperinsulinemia and urinary calcium excretion in calcium stone formers with idiopathic hypercalciuria.

Context: Calcium stone formers with idiopathic hypercalciuria (IH) are known to exhibit an exaggerated postprandial rise in urine calcium excretion compared with non-stone-forming individuals, and insulin has been proposed to mediate this difference.

Objective: Our objective was to investigate the impact of hyperinsulinemia on urine calcium excretion in IH compared with non-stone-forming controls.

Participants And Setting: Ten IH patients and 22 control non-stone-forming subjects (8 lean and 14 overweight and obese) participated at the University of Texas Southwestern Clinical and Translational Research Center.

Design: After stabilization on a fixed metabolic diet, subjects underwent a hyperinsulinemic-euglycemic clamp. Fasting 2-hour urine specimens were collected before and during the clamp.

Main Outcome Measures: Changes in fractional calcium excretion (F(E)Ca) during the clamp were compared between the 3 groups of subjects (IH, overweight/obese controls, and lean controls). Insulin sensitivity was measured by glucose disposal rate.

Results: IH had significantly higher 24-hour urine calcium excretion than controls, and exhibited similar age, body mass index, and insulin sensitivity as overweight/obese controls. The hyperinsulinemic-euglycemic clamp resulted in a significant increase in serum insulin with no significant changes in serum calcium and glucose. This was accompanied by a small increase in F(E)Ca, with no significant differences between the 3 groups. There was no correlation between insulin sensitivity and 24-hour urine calcium or the change in F(E)Ca during the hyperinsulinemic clamp.

Conclusions: The rise in urine calcium associated with euglycemic hyperinsulinemia was small and not statistically different between IH and non-stone-forming controls. Insulin is therefore unlikely to play a significant pathogenetic role in IH.