Vitamin B12 and risk of diabetes: new insight from cross-sectional and longitudinal analyses of the China Stroke Primary Prevention Trial (CSPPT)

Abstract

Introduction: Previous studies in mostly Western populations have yielded conflicting findings on the association of vitamin B₁₂ with diabetes risk, in part due to differences in study design and population characteristics. This study sought to examine the vitamin B₁₂-diabetes association in Chinese adults with hypertension by both cross-sectional and longitudinal analyses.

Research design and methods: This report included a total of 16 699 participants from the China Stroke Primary Prevention Trial, with pertinent baseline and follow-up data. Diabetes mellitus was defined as either physician-diagnosed diabetes, use of glucose-lowering drugs, or fasting blood glucose (FBG) ≥7.0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or FBG ≥7.0 mmol/L at the exit visit.

Results: At baseline, there were 1872 (11.2%) patients with diabetes; less than 1.5% had clinical vitamin B₁₂ deficiency (<148.0 pmol/L). Over a median follow-up period of 4.5 years, there were 1589 (10.7%) cases of new-onset diabetes. Cross-sectional analyses showed a positive association between baseline vitamin B₁₂ levels and FBG levels (β=0.18, 95% CI 0.15 to 0.21) and diabetes (OR=1.16, 95% CI 1.10 to 1.21). However, longitudinal analyses showed no association between baseline vitamin B₁₂ and new-onset diabetes or changes in FBG levels. Among a subset of the sample (n=4366) with both baseline and exit vitamin B₁₂ measurements, we found a positive association between an increase in vitamin B₁₂ and an increase in FBG.

Conclusions: In this large Chinese population of patients with hypertension mostly sufficient with vitamin B₁₂, parallel cross-sectional and longitudinal analyses provided new insight into the conflicting findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B₁₂ and its longitudinal trajectory in order to better elucidate the role of vitamin B₁₂ in the development of diabetes. Such findings would have important clinical and public health implications.

Keywords: diabetes mellitus, type 2; hypertension; longitudinal studies; vitamin B12.

Figure 1

Multivariable-adjusted smoothing curves of change in vitamin B₁₂ and change in FBG in a subsample that included a total of 4366 subjects with both baseline and exit FBG and vitamin B₁₂ measurements. Adjusted for age, sex, MTHFR gene C677T polymorphisms, SBP and DBP at baseline, mean SBP and DBP during the treatment period, body mass index, study center, baseline serum concentrations of folate, homocysteine, FBG, vitamin B₁₂, total cholesterol, triglycerides, and high-density lipoprotein cholesterol, treatment group, smoking status, and alcohol consumption status. DBP, diastolic blood pressure; FBG, fasting blood glucose; MTHFR, methylenetetrahydrofolate reductase; SBP, systolic blood pressure.