Increased Serum Calcium Levels and Risk of Type 2 Diabetes in Individuals at High Cardiovascular Risk

Diabetes Care
Q1
Oct 2014
Citations:94
Influential Citations:5
Observational Studies (Human)
80
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Methods
Prospective analysis within the PREDIMED randomized, multicenter parallel-group trial conducted in Spain; older adults at high cardiovascular risk (men 55-80; women 60-80), non-diabetic at baseline; data from Reus-Tarragona and Barcelona centers; serum calcium measured at baseline and yearly; incident type 2 diabetes diagnosed by ADA criteria; Cox proportional hazards models with time-dependent covariates and multiple confounder adjustments; sample size for this analysis: 707 participants; median follow-up 4.78 years.
Results
Increase in albumin-adjusted serum calcium during follow-up was associated with higher risk of developing type 2 diabetes among elderly Mediterranean adults at high cardiovascular risk. Highest tertile of change (+0.52 ± 0.13 mg/dL) had HR 3.48 (95% CI 1.48-8.17) in model 2; after adjusting for fasting plasma glucose (model 3) HR 2.87 (95% CI 1.18-6.96). When calcium is analyzed as a continuous variable, HR per 1 mg/dL increase was 3.52 (95% CI 1.84-6.75) in the fully adjusted model including fasting glucose. The associations persisted after excluding calcium and/or vitamin D supplement users and after excluding out-of-range calcium values. Baseline albumin-adjusted calcium showed no significant association after adjustment for fasting glucose. Conclusion: A rise in albumin-adjusted serum calcium during follow-up is linked to increased diabetes risk in this population; results remained robust across sensitivity analyses; causality not established and further research is needed.
Limitations
Observational analysis within an RCT; not causal; ionized calcium not measured (total calcium used with albumin adjustment); lack of data on parathyroid hormone and vitamin D for all participants; potential residual confounding; older white Mediterranean population at high cardiovascular risk limits generalizability; some participants excluded (prevalent diabetes or missing calcium data) introducing potential selection bias; no insulin measurements to directly assess insulin resistance/secretion.

Abstract

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 demonstrated a...