Serum Calcitonin and Parathyroid Hormone in Experimental Diabetes: Effects of Insulin Treatment*

Abstract

Rats with streptozotocin-induced diabetes mellitus are hypocalcemic after an overnight fast. The hypocalcemia appears to be a result of abnormal vitamin D metabolism (serum 1,25-dihydroxyvitamin D3 concentrations 1/8 those of controls) and persists despite secondary hyperparathyroidism. Excessive plasma calcitonin concentrations may be involved in pathogenesis of the hypocalcemia and depressed 1,25-dihydroxyvitamin D3 levels. Serum immunoreactive calcitonin (iCT), parathyroid hormone (iPTH) and Ca were measured in control, streptozotocin-diabetic and insulin-treated diabetic male rats fasted overnight. Two separate experiments were done. Serum iPTH was increased in untreated diabetics by 46 and 61% over controls (P < 0.05), and insulin treatment returned iPTH to control levels. Among all groups serum iPTH correlated negatively with serum Ca (r [correlation coefficient] = -0.49 to -0.73; P < 0.01-0.001). In both experiments, serum iCT was detectable in 60% of nondiabetic controls (range, < 25-105 pgeq/ml, median 30 pgeq/ml), but was undetectable in 87% of diabetic rats (range, < 25 to 36 pgeq/ml, median < 25 pgeq/ml), P < 0.005. Among all groups, serum iCT correlated positively with serum calcium (r = 0.56-0.82, P < 0.05-0.001). A group of fed control rats showed increased iCT and decreased iPTH compared to fasted animals. Ca deficiency, probably from intestinal Ca malabsorption, may be the primary cause for hypocalcemia in untreated diabetics. Decreases of 1,25-dihydroxycholecalciferol may also impair the effect of parathyroid hormone on bone resorption. The hypocalcemia results in secondary hyperparathyroidism and depression of calcitonin secretion. Calcitonin has no primary role in the disturbed Ca metabolism of diabetes, but is responding appropriately to changes in serum Ca concentrations.