Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism

Abstract

A high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus. Cross-sectional study of glucose metabolism in PHPT patients without other risk factors for diabetes mellitus, compared to age and body mass index (BMI) matched healthy subjects. Nineteen non-obese, non-diabetic, normotensive patients with PHPT and 11 age and BMI matched healthy subjects. The continuous infusion of glucose test was used to assess glucose tolerance. Plasma glucose and insulin were measured during a 1-hour continuous infusion of glucose (5 mg/kg ideal body weight/min); insulin sensitivity and beta-cell function were derived from the glucose and insulin data by mathematical modelling. Fasting serum concentrations of parathyroid hormone, ionized calcium and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in all subjects. PHPT patients attained higher plasma glucose levels at the end of the glucose infusion (median 9.0 (interquartile range 8.1-9.8) mmol/l) than did controls (7.9 (7.1-8.9) mmol/l, P < 0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin sensitivity was lower in PHPT (60.3% (49.8-85.4)) than in controls (113.7% (89.3-149.2), P < 0.001); beta-cell function was not different in PHPT subjects. PHPT subjects with impaired glucose tolerance had reduced beta-cell function compared to PHPT subjects with normal glucose tolerance (89.9% (70.5-106.4) vs 120% (98.8-156.6) respectively, P < 0.05). No significant correlations were found between insulin sensitivity and PTH (rs = -0.21), 1,25(OH)2D (rs = -0.14), ionized calcium (rs = -0.11) and inorganic phosphate (rs = 0.34). Beta-cell function did not correlate with PTH (rs = 0.15), 1,25(OH)2D (rs = 0.04), ionized calcium (rs = 0.23) or inorganic phosphate (rs = -0.35). Insulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta-cell function are more likely to develop glucose intolerance.