Background: Elevated serum calcium has been associated with a variety of metabolic abnormalities and may be associated with a greater risk of diabetes. Objective: The purpose of this study was to test the hypothesis that serum calcium concentration is positively and independently associated with the incidence of diabetes and to evaluate the association of calcium-sensing receptor (CaSR) gene single nucleotide polymorphism (SNP) rs1801725 with incident diabetes. Design: Atherosclerosis Risk in Communities study participants free of diabetes at baseline (n = 12,800; mean age: 53.9 y; 22.6% black) were studied for incident diabetes. Serum calcium was measured at baseline and corrected for serum albumin. Diabetes was defined by use of glucose concentrations, self-report, or medication use. Cox proportional hazards regression was used. Results: During a mean 8.8 y of follow-up, 1516 cases of diabetes were reported. Participants in the highest compared with lowest calcium quintile were at greater risk of incident diabetes after adjustment for demographic and lifestyle factors [HR (95% CI): 1.34 (1.14, 1.57); P-trend across quintiles < 0.0001] and with further adjustment for waist circumference and body mass index [1.26 (1.07, 1.48); P-trend = 0.004]. Additional adjustment for biomarkers on the metabolic pathway (e.g., 25-hydroxyvitamin D, parathyroid hormone, phosphorus) had little impact. The calcium- diabetes association was statistically significant in blacks [1.48 (1.11, 1.98); P-trend = 0.002] but not whites [1.17 (0.96, 1.43); P-trend = 0.17] after adjustment for adiposity. In whites, CaSR gene SNP rs1801725 was associated with serum calcium but not with risk of diabetes. Conclusions: Consistent with 3 previous cohort studies, elevated serum calcium was found to be associated with a greater risk of type 2 diabetes. Further research is needed to understand the role, if any, that calcium plays in the pathogenesis of diabetes.
- Calcium-sensing receptor polymorphism
- Cohort study
- Diabetes mellitus
- Serum calcium