Calcium and phosphate concentrations and future development of type 2 diabetes: The Insulin Resistance Atherosclerosis Study

Aims/hypothesis: Low phosphate and high calcium concentrations have been linked to altered glucose tolerance and reduced insulin sensitivity in non-diabetic individuals. The aim of this study was to examine the relationships of calcium and phosphate levels and the calcium-phosphate product with the development of type 2 diabetes. Methods: Participants were 863 African-Americans, Hispanics and non-Hispanic whites in the Insulin Resistance Atherosclerosis Study who were free of diabetes at baseline. The mean follow-up period was 5.2 years. The insulin sensitivity index (S_I) and acute insulin response (AIR) were directly measured using the frequently sampled IVGTT. Results: Calcium concentration (OR per 1 SD unit increase, 1.26 [95% CI 1.04, 1.53]) and calcium-phosphate product (OR 1.29 [95% CI 1.04, 1.59]) were associated with incident diabetes after adjustment for demographic variables, family history of diabetes, and 2 h glucose. The relationship between phosphate concentration and progression to diabetes was close to statistical significance (OR 1.21 [95% CI 0.98, 1.49]). Calcium concentration (OR 1.37 [95% CI 1.09, 1.72]) and calcium-phosphate product (OR 1.39 [95% CI 1.09, 1.77]) remained associated with incident diabetes after additional adjustment for BMI, plasma glucose, S_I, AIR, C-reactive protein, estimated GFR, diuretic drugs and total calcium intake. Conclusions/interpretation: Elevated serum calcium and calcium-phosphate product are associated with increased risk of developing type 2 diabetes independently of measured glucose, insulin secretion and insulin resistance. Future studies need to analyse the role of calcium-phosphate homeostasis in the pathophysiology of diabetes.