Hyperinsulinemia and Urinary Calcium Excretion in Calcium Stone Formers With Idiopathic Hypercalciuria

Abstract

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