Associations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes.

OBJECTIVE: To prospectively examine the associations of habitual calcium supplementation with cardiovascular disease (CVD) events and mortality in individuals with and without diabetes. RESEARCH DESIGN AND METHODS: The main analysis included 434,374 participants from the UK Biobank. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Interactions of calcium supplement use with diabetes status were tested on multiplicative and additive scales. RESULTS: Over a median follow-up of 8.1 and 11.2 years, 26,374 incident CVD events and 20,526 deaths were documented, respectively. After multivariable adjustment, habitual calcium supplementation was significantly associated with higher risks of CVD incidence (HR 1.34; 95% CI 1.14, 1.57), CVD mortality (HR 1.67; 95% CI 1.19, 2.33), and all-cause mortality (HR 1.44; 95% CI 1.20, 1.72) in participants with diabetes, whereas no significant association was observed in participants without diabetes (HR 0.97 [95% CI 0.92, 1.03] for CVD incidence; HR 1.05 [95% CI 0.90, 1.23] for CVD mortality; HR 1.02 [95% CI 0.96, 1.09] for all-cause mortality). Significant multiplicative and additive interactions were found between habitual calcium supplementation and diabetes status on risks of CVD events and mortality (all Pinteraction < 0.05). In contrast, no significant interactions were observed between dietary or serum calcium and diabetes status. CONCLUSIONS: Habitual use of calcium supplements was significantly associated with higher risk of CVD events and mortality in people with diabetes but not in people without diabetes. Further studies are needed to balance potentially adverse effects of calcium supplement against likely benefits, particularly among patients with diabetes.

Vitamin D status, genetic factors, and risks of cardiovascular disease among individuals with type 2 diabetes: a prospective study.

BACKGROUND: The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. OBJECTIVES: We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. METHODS: This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. RESULTS: The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D.

Serum selenium concentrations and risk of all-cause and heart disease mortality among individuals with type 2 diabetes.

BACKGROUND: The impact of selenium status on the long-term health of people with type 2 diabetes (T2D) remains unclear. OBJECTIVES: To prospectively examine the association of serum selenium concentrations with all-cause and heart disease mortality among individuals with T2D. METHODS: This analysis included 3199 adults with T2D from the third NHANES (NHANES III) and NHANES (2003-2004, 2011-2014). Mortality from heart disease and all causes was linked to National Death Index mortality data. Cox proportional hazard models were used to estimate HRs and 95% CIs. RESULTS: The median (IQR) concentration of serum selenium was 127.0 (115.0, 139.1) µg/L. During an average 12.6-y follow-up, 1693 deaths were documented, including 425 heart disease deaths. Compared with participants in the lowest quartile of selenium, the multivariate-adjusted HRs (95% CIs) for participants in the highest quartile were 0.69 (0.54, 0.89) for all-cause mortality (P-trend = 0.002) and 0.66 (0.45, 0.99) for heart disease mortality (P-trend = 0.03). In addition, a linear dose-response relation between serum selenium (range: 89-182 µg/L) and mortality was observed. For per-unit increment in natural log-transformed serum selenium, there was a 64% lower risk of all-cause mortality and a 66% lower risk of heart disease mortality (both P < 0.05). Similar results were observed when stratifying by age, sex, race, smoking status, BMI, physical activity, diabetes duration, and HbA1c concentrations. CONCLUSIONS: Our study suggested that higher selenium concentration was associated with lower all-cause and heart disease mortality among individuals with T2D. More studies are needed to confirm these findings.