Increased Serum Calcium Levels and Risk of Type 2 Diabetes in Individuals at High Cardiovascular Risk Diabetes Care 2014;37:3084–3091 | DOI: 10.2337/dc14-0898 OBJECTIVE Insulin resistance and secretion depend on calcium homeostasis. Cross-sectional studies have associated elevated serum calcium levels with markers of impaired glucose metabolism. However, only one prospective cohort study has demon- strated an increased risk of diabetes in individuals with increased serum calcium concentrations. The aim of the current study was to prospectively investigate the association between albumin-adjusted serum calcium concentrations and type 2 diabetes in subjects at high cardiovascular risk. RESEARCH DESIGN AND METHODS Prospective assessment of participants from two Spanish PREDIMED study cen- ters where serum calcium levels were measured at baseline and yearly during follow-up. Multivariate-adjusted Cox regression models were fitted to assess associations between baseline and changes during follow-up in serum calcium levels and relative risk of diabetes incidence. RESULTS After a median follow-up of 4.78 years, 77 new cases of type 2 diabetes occurred. An increase in serum calcium levels during follow-up was related to an increased risk of diabetes. In comparison with individuals in the lowest tertile (20.78 6 0.29 mg/dL), the hazard ratio (HR) and 95% CI for diabetes incidence in individuals in the higher tertile of change (0.52 6 0.13 mg/dL) during follow-up was 3.48 (95% CI 1.48–8.17; P for trend = 0.01). When albumin-adjusted serum calcium was ana- lyzed as a continuous variable, per 1 mg/dL increase, the HR of diabetes incidence was 2.87 (95% CI 1.18–6.96; P value = 0.02). These associations remained signif- icant after individuals taking calcium supplements or having calcium levels out of normal range had been excluded. CONCLUSIONS An increase in serum calcium concentrations is associated with an increased risk of type 2 diabetes in individuals at high cardiovascular risk. Type 2 diabetes is an important health problem worldwide. In the last three decades, the number of individuals with type 2 diabetes has doubled (1). Di- abetes is associated with such complications as blindness, renal failure, and lower-limb amputation (2) and increases the risk of premature cardiovascular disease (3). 1 Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d’Investigaci ´ o Sanit ` aria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain 2 CIBERobn Physiopathology of Obesity and Nu- trition, Institute of Health Carlos III, Madrid, Spain 3 Department of Internal Medicine, August Pi i Sunyer Institute of Biomedical Research, Hospital Clinic, University of Barcelona, Barcelona, Spain 4 Cardiovascular Risk and Nutrition (Regicor Study Group), Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park, Barcelona, Spain 5 Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain Corresponding author: Jordi Salas-Salvad´ o, jordi.salas@urv.cat. Received 9 April 2014 and accepted 29 July 2014. Clinical trial reg. no. ISRCTN35739639, www.isrctn .org. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. Nerea Becerra-Tom´ as, 1,2 Ram´ on Estruch, 2,3 M` onica Bull ´ o, 1,2 Rosa Casas, 2,3 Andr´ es D´ ıaz-L ´ opez, 1,2 Josep Basora, 1,2 Montserrat Fit ´ o, 2,4 Lluis Serra-Majem, 2,5 and Jordi Salas-Salvad ´ o 1,2 3084 Diabetes Care Volume 37, November 2014 CARDIOVASCULAR AND METABOLIC RISK