Animal and human studies have reported conflicting results on the relationship between circulating trimethylamine N-oxide (TMAO) levels and risk of Type 2 diabetes (T2D). This study aimed to compare plasma TMAO levels in people with or without T2D and explore the association of TMAO and T2D. A prospective case-control study of 297 participants, 164 healthy controls and 133 patients with T2D, was conducted. TMAO levels were quantified by UPLC-MS/MS. Comorbidities, dietary patterns, physical activity, and blood biomarkers were assessed. Median (IQR) plasma TMAO levels were significantly higher in diabetes cases (4.95 (2.84–8.35) µmol/L) compared to healthy controls (3.07 (2.05–4.82) µmol/L) (p < 0.001). The association between TMAO and T2D was significant in the non-adjusted Model 1 (p < 0.001) and after adjusting for confounders of diabetes including age, BMI, and level of education in Model 2 (p = 0.04). When the association was further adjusted for physical activity and diet in Model 3, plasma TMAO levels at only the highest quartile (>6.40 µmol/L) were associated with the risk of diabetes (OR = 3.36, 95% CI [1.26, 9.04], p = 0.02). The results presented suggest an association between plasma TMAO levels and T2D. A significant correlation was found between red meat consumption and increased levels of TMAO in T2D patients. A longitudinal study is warranted to further evaluate the correlation between TMAO and T2D.

We previously demonstrated that the combination of phytosterols (PS) and curcumin administered as dietary supplements significantly lowers LDL-cholesterol (LDL-C) more than either treatment alone. The aim of this study was to investigate the effects of this combination in a novel food (bread) on plasma lipid profiles in hypercholesterolaemic individuals. In a double-blinded, placebo-controlled, 2 × 2 factorial trial, participants were randomised to receive bread fortified with placebo (PL), 2.3 g PS (PS), 228 mg curcumin (CC) or a combination of 2.3 g PS and 228 mg CC (PS-CC) daily for four weeks. Primary outcomes were fasting plasma lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)] and secondary outcomes were plasma LDL-particle (LDL-P) profile: LDL-P number and LDL-P size. Cardiovascular disease (CVD) risk (Framingham Risk Algorithm) was also explored. There was no significant difference between PL and CC or PS and PS-CC on blood lipids or CVD risk; therefore, groups were pooled for final analysis: the PL and CC group (PL-C, n = 36) and the PS and PS-CC group (PS-C, n = 39). PS-C significantly lowered TC (−0.52 mmol L⁻¹, p < 0.0001), LDL-C (−0.49 mmol L⁻¹, p < 0.0001) and CVD risk (−1.1 absolute %, p = 0.0005) compared to the PL-C group. Reductions from baseline in the PS-C group compared to that in the PL-C group were 7.6% and 10.6% for TC and LDL-C, respectively, and statistically significant (p < 0.0001). CVD-risk in the PS-C group reduced significantly (−12.7%) compared to that in the PL-C group (p = 0.0005). HDL-C and TG remained unchanged. The LDL-P number significantly decreased in the PS-C group by 124.33 nmol L⁻¹ compared to that in the PL-C group (p = 0.005) and both groups showed a significant decrease in LDL-P size (p < 0.01); however, the absolute nm change in LDL-P size did not differ between groups and the percent change in LDL-P size in the PS-C group was borderline significant (−0.89%, p = 0.05) compared to that in the PL-C group. Regular consumption of PS-enriched bread with or without curcumin lowers blood cholesterol; however, curcumin alone did not influence blood lipids. Bread may be a convenient means of delivering PS with greater compliance for reducing the blood cholesterol concentration.

Previous studies have linked elevated plasma trimethylamine N-oxide (TMAO) levels to poor renal function. The relationship between TMAO and chronic kidney disease (CKD) in type 2 diabetes (T2D) is still unclear. We investigated the association between plasma TMAO levels and CKD in patients with T2D. A cross-sectional study of 133 patients with T2D with or without CKD has been conducted. Blood biomarkers of kidney function, diabetes, and inflammation were assessed in the study participants. Plasma TMAO levels were quantified using UPLC-MS/MS. People with T2D and CKD exhibited significantly higher plasma TMAO levels [10.16 (5.86–17.45) µmol/L] than those without CKD [4.69 (2.62–7.76) µmol/L] (p = 0.002). Participants in the highest quartile of TMAO levels (>8.38 µmol/L) presented relatively elevated serum creatinine levels and a higher number of people with CKD than those in the lower quartiles. TMAO levels were significantly correlated with kidney function biomarkers, including estimated glomerular filtration rate and urinary albumin to creatinine ratio. The association between TMAO and CKD was evident (p < 0.0001) and remained significant after adjusting for risk factors of kidney disease, including age, gender, body mass index, duration of diabetes, and smoking. These findings suggest the association between plasma TMAO and CKD in patients with T2D.