U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes

Abstract

Background:Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare.Objective:We investigated the association between plasma manganese and newly diagnosed T2D as well as whether the association could be modified by manganese superoxide dismutase (MnSOD) polymorphisms.Methods:We conducted a case–control study of 3,228 participants in China: 1,614 T2D patients and 1,614 controls. Concentrations of plasma magnesium were measured, and all participants were genotyped for the MnSOD Val16Ala polymorphism (rs4880).Results:A U-shaped association was observed between plasma manganese and T2D, with increased odds ratios (ORs) in relation to either low or high plasma manganese levels. Compared with the middle tertile, the multivariate-adjusted ORs [95% confidence intervals (CIs)] of T2D associated with the lowest tertile and the highest tertile of plasma manganese were 1.89 (1.53, 2.33) and 1.56 (1.23, 1.97), respectively. In spline analysis, the U-shaped association was consistently indicated, with the lowest odds of T2D at the plasma manganese concentration of 4.95 μg/L. Minor allele frequencies (C allele) of the MnSOD Val16Ala polymorphism (rs4880) in the normal glucose tolerance (NGT) and the T2D groups were 13.57% and 14.50%, respectively. The MnSOD rs4880 polymorphism was not associated with T2D, and no interaction was found between plasma manganese and the MnSOD rs4880 polymorphism in relation to T2D.Conclusions:Our results suggested a U-shaped association between plasma manganese and T2D; both low and high levels of plasma manganese were associated with higher odds of newly diagnosed T2D. The U-shaped association was not modified by the MnSOD rs4880 polymorphism.Citation:Shan Z, Chen S, Sun T, Luo C, Guo Y, Yu X, Yang W, Hu FB, Liu L. 2016. U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124:1876–1881; http://dx.doi.org/10.1289/EHP176

Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes

“…Although previous studies have revealed that TMAO is linked to the development of diabetes in several animal models, no previous epidemiologic study, to our knowledge, has been designed specifically to examine the association between plasma TMAO and type 2 diabetes, with adjustment for other confounding factors. Plasma TMAO concentrations were found to be higher in patients with diabetes with or without cardiovascular comorbidities (5,20,24), but these studies did not investigate the associations between plasma TMAO and type 2 diabetes after adjustment for other confounding factors. Svingen and colleagues (18) found increased plasma TMAO in patients with type 2 diabetes, but no significant association was observed in their investigation.…”

“…In our study medians (IQRs) of plasma TMAO concentration of total samples were 1.55 mmol/L (0.93, 2.45 mmol/L), which were comparable with a study conducted in Austria [1.74 mmol/L (0.38, 3.48 mmol/L)] (23). Plasma TMAO concentrations were reported to be related to genetic predisposition, intake of dietary trimethylamine-containing compounds, intestinal microbiota constitute, FMO activity, health status, other predisposing factors on metabolism of TMAO, and different measurement methods (2,7,20), but the reasons for the wide variations in TMAO concentrations across populations remain to be elucidated. Although previous studies have revealed that TMAO is linked to the development of diabetes in several animal models, no previous epidemiologic study, to our knowledge, has been designed specifically to examine the association between plasma TMAO and type 2 diabetes, with adjustment for other confounding factors.…”

“…The cases were consecutively recruited from patients diagnosed as having new-onset type 2 diabetes at the outpatient clinics of the Department of Endocrinology at the Tongji Medical College Hospital during the period of January 2012-December 2014. Concomitantly, we recruited healthy individuals who were frequency matched by age (65 y) and sex to cases from an unselected population undergoing a routine health checkup in the same hospital, as described elsewhere (20,21). We excluded participants who had any of the following conditions: age ,30 y, BMI (in kg/m 2 ) $40, a history of diagnosed diabetes, a history of pharmacologic treatment of hyperlipidemia, any clinically systemic disease, any acute illness, or chronic inflammatory or any infective disease.…”

Dietary manganese and type 2 diabetes mellitus: two prospective cohort studies in China

“…Plasma Mn and Mn superoxide dismutase (MnSOD) have been recommended as potential biomarkers for Mn nutritional status in the human body [3], and both of them have been associated with type 2 diabetes. Low serum Mn has been associated with a high risk of type 2 diabetes [8]. However, higher levels of Mn in serum [9] and urine [10,11] have also been reported in individuals with diabetes, and similar wholeblood Mn levels between diabetic and non-diabetic individuals have been observed [12].…”

Changes of trace element status during aging: results of the EPIC-Potsdam cohort study

“…Alternatively, several TE can affect the process of aging [6] by contributing to numerous age-related mechanisms, via, for example, their role in the immune system or against oxidative stress. They have been, therefore, hypothesized to contribute to the pathogenesis of age-related chronic diseases [6][7][8][9][10][11].…”