Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study

- Serum calcium levels have been associated with incident type 2 diabetes.
- Previous studies have relied on an indirect estimation of active calcium.
- Indirect calcium estimation can be biased in subjects at high cardiometabolic risk.
- In this study, incident diabetes was not associated with direct measurement of active calcium.
- Factors influencing indirect calcium estimation could bias the calcium/diabetes relationship.

Background and aimsPrevious prospective studies showing a positive association between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have relied on total calcium or an indirect estimate of active, ionized calcium (iCa). We aimed to assess this relationship using a direct measurement of iCa.Methods and resultsiCa and cardiometabolic risk factors were measured in a population-based sample of 2350 men without a known history of T2DM at baseline. Associations between iCa levels and incident cases of T2DM (self-reported, ascertained with a glucose tolerance test, or determined by record linkage to national registers) were estimated using Cox regression analyses adjusted for potential confounders. At baseline, mean (standard deviation) age was 53 (5) years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years, 140 new cases of T2DM were recorded. In a multivariable analysis adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, there was no association comparing second (hazard ratio 0.84; 95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98; 0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for C-reactive protein, physical activity level, and triglycerides did not change the estimates (p for trend 0.389).ConclusionIn this study, we did not find evidence of an association between direct measurement of active calcium and risk of T2DM. Further studies are needed to confirm our findings and define the relationship between factors influencing indirect calcium estimation and incident T2DM.