Serum N1-methylnicotinamide is associated with obesity and diabetes in Chinese

Abstract

Context: Nicotinamide N-methyltransferase (NNMT) is a novel histone methylation modulator that regulates energy metabolism, and NNMT knockdown prevents diet-induced obesity in mice. However, whether NNMT plays a role in human obesity and type 2 diabetes (T2DM) remains to be elucidated. Objective: NNMT catalyzes methylation of nicotinamide to generate N1-methylnicotinamide (me- NAM). We aimed to investigate the associations of serum me-NAM with obesity and T2DM in Chinese. Design, Setting, and Participants: The study subjects (n = 1160) were recruited from Dali, a city of Yunnan Province, in southwest China. Anthropometric phenotypes, fasting glucose, and serum lipids were measured. Serum me-NAM was measured by liquid chromatography-mass spectrometry. Results: Serum me-NAM was positively correlated with body mass index and waist circumference and negatively with high-density lipoprotein (P ≤ .03). The correlations remained highly significant in the multivariate adjusted correlation analyses. In men (n = 691), positive correlations between me-NAM and fasting glucose, low-density lipoprotein, liver function, and serum creatinine levels were also observed in both simple and multivariate adjusted correlation analyses. In multiple logistic regression analyses, elevated serum me-NAM was associated with higher risks for overweight/obesity (odds ratios, 2.36 and 5.78; 95% confidence intervals, 1.10-5.08 and 1.78-18.76 for men and women, respectively; P ≤ .03) and diabetes (odds ratios, 1.56 and 1.86; 95% confidence intervals, 1.10-2.22 and 1.05-3.31 for men and women, respectively; P ≤ .03). Conclusions: This first large-scale population study shows that me-NAM, as an indicator of NNMT activity, is strongly associated with obesity and diabetes, supporting NNMT as a potential target for treating obesity and diabetes in humans.