AIM:To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS:Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N 1 -methylnicotinamide on glucose metabolism, plasma H2O2 levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS:Diabetic subjects had significantly higher plasma N 1 -methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N 1 -methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N 1 -methylnicotinamide. Moreover, cumulative exposure to N 1 -methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N 1 -methylnicotinamide in vitro . Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N 1 -methylnicotinamide clearance. CONCLUSION:These findings suggest that nicotinamide overload, which induced an increase in plasma N 1 -methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N 1 -methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N 1 -methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamideloading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease.

BackgroundTo date, effect of preoperatively continued aspirin administration in off-pump coronary artery bypass grafting (CABG) is less known. We aimed to assess the effect of preoperatively continued aspirin use on early and mid-term outcomes in patients receiving off-pump CABG.MethodsFrom October 2009 to September 2013 at the Fuwai Hospital, 709 preoperative aspirin users were matched with unique 709 nonaspirin users using propensity score matching to obtain risk-adjusted outcome comparisons between the two groups. Early outcomes were in-hospital death, stroke, intra- and post-operative blood loss, reoperation for bleeding and blood product transfusion. Major adverse cardiac events (death, myocardial infarction or repeat revascularization), angina recurrence and cardiogenic readmission were considered as mid-term endpoints.ResultsThere were no significant differences among the groups in baseline characteristics after propensity score matching. The median intraoperative blood loss (600 ml versus 450 ml, P = 0.56), median postoperative blood loss (800 ml versus 790 ml, P = 0.60), blood transfusion requirements (25.1% versus 24.4%, P = 0.76) and composite outcome of in-hospital death, stroke and reoperation for bleeding (2.8% versus 1.6%, P = 0.10) were similar in aspirin and nonaspirin use group. At about 4 years follow-up, no significant difference was observed among the aspirin and nonaspirin use group in major adverse cardiac events free survival estimates (95.7% versus 91.5%, P = 0.23) and freedom from cardiogenic readmission (88.5% versus 85.3%, P = 0.77) whereas the angina recurrence free survival rates was 83.7% and 73.9% in the aspirin and nonaspirin use group respectively (P = 0.02), with odd ratio for preoperative aspirin estimated at 0.71 (95% confidence interval, 0.49-1.04, P = 0.08).ConclusionsPreoperatively continued aspirin use was not associated with increased risk of intra- and post-operative blood loss, blood transfusion requirements and composite outcome of in-hospital death, stroke and reoperation for bleeding in off-pump CABG. Preoperative aspirin use tended to decrease the hazard of mid-term angina recurrence.