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OS 33-03 SERUM N1-METHYLNICOTINAMIDE IS ASSOCIATED WITH OBESITY AND DIABETES IN CHINESE.

OBJECTIVE: 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 mellitus (T2DM) remains to be elucidated. NNMT catalyzes methylation of nicotinamide to generate N-methylnicotinamide (me-NAM). We aimed to investigate the associations of serum me-NAM with obesity and T2DM in Chinese.

DESIGN AND METHOD: The study subjects (n = 1160) were recruited from Dali, a city of Yunan 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 = 0.03). 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 < 0.03) 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 < 0.03).

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.

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