Dietary manganese and type 2 diabetes mellitus: two prospective cohort studies in China
The association between dietary Mn and type 2 diabetes is unclear. We aimed to elucidate whether dietary Mn is associated with type 2 diabetes, to investigate whether this association is independent of dietary total antioxidant capacity (TAC) and to explore the underlying mechanisms in their association.
Two prospective cohorts of 3350 and 7133 Chinese adults (20–74 years old) were enrolled including, respectively, 244 and 578 individuals newly diagnosed with type 2 diabetes, with mean values of 4.2 and 5.3 years of follow-up. Cox’s proportional-hazards regression and linear regression were performed to investigate the association between dietary Mn and type 2 diabetes (diagnosed by OGTT) or HbAlc and to analyse the joint association between dietary Mn and TAC. Restricted cubic spline (RCS) regression was applied to the non-linear association between dietary Mn and incidence of type 2 diabetes. Mediation analysis was applied to explore potential mediators in their association in a subgroup of 500 participants.
Dietary Mn intakes were 4.58 ± 1.04 and 4.61 ± 1.08 (mean ± SD) mg/day in the two cohorts. Dietary Mn was inversely associated with type 2 diabetes incidence and HbAlc concentration in both cohorts (ptrend < 0.01 and <0.01 for type 2 diabetes, and ptrend < 0.01 and =0.02 for HbAlc, respectively, in each cohort) independent of TAC, adjusted for age, sex, BMI, tobacco use, alcohol consumption, physical activity, diabetes inheritance, total energy, carbohydrate, total fatty acids, fibre, calcium, Mg, hypertension, hyperlipidaemia, and impaired glucose tolerance or FBG (all at baseline). Their inverse association was stronger in the presence of diets with high, compared with low, TAC. In RCS, intakes of >6.01 and 6.10–6.97 mg/day were associated with a significantly lower type 2 diabetes incidence in the two respective cohorts. Mediation analysis showed that high plasma Mn and low oxidative stress (increased Mn superoxide dismutase and decreased 8-hydroxydeoxyguanosine) contributed to the association between dietary Mn and both type 2 diabetes and HbAlc.
Dietary Mn was inversely associated with type 2 diabetes independently of TAC. In addition, this association was stronger in a high- rather than low-TAC diet. Plasma Mn and oxidative stress were mediators in the association between dietary Mn and type 2 diabetes. Future studies on absolute Mn intake should be conducted to study the potential non-linearity and optimal levels of dietary Mn and type 2 diabetes.
KeywordsAntioxidant capacity Diet Manganese Type 2 diabetes
Diastolic blood pressure
Fasting blood glucose
Food frequency questionnaire
Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases
Harbin People’s Health Study
Mn superoxide dismutase
Postprandial blood glucose
Restricted cubic spline
Systolic blood pressure
Structural equation modelling
Total antioxidant capacity
We thank Y. Li (Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, China) for help with study design.
CS and LN contributed to the conception and design of the study. XW, SD, WD, LL, JQ and YN contributed to acquisition of data. SD, XW and TH contributed to data analysis. YN, LN and CS contributed to funding acquisition. SD, XW and TH wrote the original draft. All authors reviewed and edited the draft, and approved the final manuscript. CS and LN are responsible for the integrity of the work as a whole.
This study was funded by research grants from the National Natural Science Foundation of China (no. 81372997, no. 81472981 and no. 81202188) and the Wu Liande Grant of Harbin Medical University (WLD-QN1406).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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