Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels

Abstract

Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention. Diabetic compared to non-diabetic db/L mice presented 10-fold higher TMAO, but lower L-carnitine plasma concentrations at 12 weeks of age. After 8 weeks of observation, diabetic db/db mice had significantly increased body weight, insulin resistance and TMAO concentration in comparison to non-diabetic control. In 191 patients undergoing percutaneous coronary intervention the median (interquartile range) plasma concentration of TMAO was 1.8 (1.2-2.6) µmol/L. Analysis of the samples showed a bivariate association of TMAO level with age, total cholesterol and L-carnitine. The multivariate linear regression analysis revealed that, in addition to L-carnitine as the strongest predictor of log transformed TMAO (p<0.001), the parameters of age, diabetes status and body mass index (BMI) were independently associated with increased log transformed TMAO levels (p<0.01).Our data provide evidence that age, diabetes and BMI are associated with higher TMAO levels independently of L-carnitine. These data support the hypothesis of TMAO as a cardiovascular risk marker and warrant further investigation of TMAO for diabetes research applications.

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.…”

Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites

“…This implies another metabolic pathway of indoxyl sulfate that is unique to this strain of mice. Another bacterial metabolite reported to have a negative effect on glucose metabolism (Dambrova et al, 2016) that is decreased by antibiotics in the plasma is TMAO, and this occurs with little effect on the cecal levels of the metabolite. On the other hand, propionate, which has been reported to have a favorable effect on insulin resistance (De Vadder et al, 2014), is also decreased in antibiotic-treated mice despite their improved insulin sensitivity.…”

Microbiome, trimethylamine N-oxide, and cardiometabolic disease

“…12 Several groups have observed that patients with diabetes tend to have higher TMAO and betaine levels when compared to healthy controls. 17–19 Nevertheless, betaine levels may not directly convert to TMAO, and in the absence of elevated TMAO levels have yet to demonstrate any detrimental adverse consequences. 8 …”