Abstract
OBJECTIVES: To examine the association of dietary Manganese (Mn) intake with type 2 diabetes (T2D) incidence, total cardiovascular disease (CVD), and CVD mortality by analyzing data from the UK Biobank and conducting a meta-analysis of available prospective cohorts. DESIGN: Prospective analysis of a primary cohort with a dose-response meta-analysis of prospective cohorts. SETTING: The UK Biobank cohort and the meta-analysis of prospective cohorts. PARTICIPANTS: UK Biobank participants aged 40-69 years at baseline were enrolled between 2006 and 2010 and followed until December 2022. We included 165,194 participants in T2D analytic cohort and 164,111 individuals in CVD analytic cohort. Our systematic review and meta-analysis of six studies comprised over 270,000 participants. EXPOSURE: Dietary manganese (Mn) intake. MEASUREMENTS: The outcome measurements were T2D incidence, total CVD, and CVD mortality. Dietary intake was assessed using 24-h dietary instrument. Cox proportional hazards models were used to assess associations of Mn intake with T2D and CVD risk. Effect estimates were presented in hazard ratios (HR) with 95% confidence intervals (CI). In meta-analysis, a pooled risk for a 1 mg/day increase in Mn intake was estimated using restricted maximum likelihood (REML). RESULTS: High Mn intake (Q5) was not significantly associated with lower risk of T2D as compared to Q1 (adjusted HR 0·91; 95% CI 0·82, 1.01, P(trend) = 0·07). The dose-response meta-analysis revealed a 4% reduction in T2D risk with each mg/day increase in Mn intake (pooled RR 0·96; 95% CI 0·94, 0·99), with potential non-linearity (P(nonlinear)< 0.01). Q5 Mn intake was not significantly associated with reduced risk of CVD (adjusted HR 0·99; 95% CI 0·92, 1.05; P(trend) = 0·61) or CVD mortality (adjusted HR 0·85; 95% CI 0·64, 1.13; P(trend) = 0·66). CONCLUSIONS: Our meta-analysis suggested that increasing Mn intake may lower T2D risk, potentially exhibiting a dose-response non-linear pattern, although not corroborated by UK Biobank analysis.