Association of serum 25-hydroxyvitamin D with metabolic syndrome and type 2 diabetes: a one sample Mendelian randomization study.
Level 3 - non-randomized controlled study
One-sample Mendelian randomization study using genetic instrumental variables
PubMed 34187381 · doi:10.1186/s12877-021-02307-6
What was done
Researchers analyzed 2,393 middle-aged and elderly adults selected from the Nantong Chronic Diseases Study (2017–2018) in rural eastern China. They measured serum 25-hydroxyvitamin D (25[OH]D) concentrations and genotyped four single-nucleotide polymorphisms (SNPs): two synthesis variants (DHCR7-rs12785878, CYP2R1-rs10741657) and two metabolism variants (GC-rs2282679, CYP24A1-rs6013897). Genetic risk scores served as instrumental variables in a one-sample Mendelian randomization (MR) analysis (Wald ratio method, validated with F statistics) to evaluate causal associations with metabolic syndrome (MS) and type 2 diabetes (T2D).
What was found
In observational analyses compared to vitamin D sufficiency: - Vitamin D insufficiency: OR for MS = 1.30 (95% CI 1.06–1.61); OR for T2D = 1.32 (95% CI 1.08–1.64). - Vitamin D deficiency: OR for MS = 1.50 (95% CI 1.24–1.79); OR for T2D = 1.47 (95% CI 1.12–1.80). - Severe deficiency: OR for MS = 1.52 (95% CI 1.29–1.85); OR for T2D = 1.54 (95% CI 1.27–1.85). In Mendelian randomization analysis using the two synthesis SNPs (DHCR7 and CYP2R1), a 25-nmol/L decrease in genetically instrumented 25(OH)D was associated with: - T2D: OR 1.10 (95% CI 1.02–1.45). - Abnormal diastolic blood pressure (DBP): OR 1.14 (95% CI 1.03–1.43).
Why it matters
This study provides genetic instrumental variable evidence supporting a modest causal role for lower circulating vitamin D in the development of type 2 diabetes and elevated diastolic blood pressure in older Chinese adults.
Limits
The sample size of 2,393 is relatively small for a one-sample Mendelian randomization study, limiting precision and power. The cohort is restricted to middle-aged and elderly participants from rural eastern China, which limits generalizability. Only four SNPs were evaluated, and potential residual confounding or horizontal pleiotropy cannot be excluded.
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