Increased Plasma Endogenous Ethanol Correlates with and Discriminates Against Microvascular Complications in Type-2 Diabetic Traditionally Alcohol-Abstinent Saudi Patients: A Biomarker Cross-Sectional Analysis

Background/Objectives: Endogenously produced ethanol (EndoEth) from a dysbiotic microbiome is an under-recognized pathogenic factor in metabolic diseases, including type-2 diabetes (T2DM). EndoEth is any systemically detectable alcohol in abstinent individuals. We aimed to assess EndoEth changes, its correlation with patients’ characteristics, metabolic indices, the disease outcomes, and its biomarker and independent risk factor characteristics as compared to healthy controls. Methods: EndoEth was cross-sectionally assayed using a specific enzymatic colorimetric method in 125 abstinent T2DM patients and 55 matching healthy controls. Its associations with glycemic control [fasting blood glucose (FBG), HbA1c, and triglyceride–glucose insulin resistance (TyG-IR) index], lipid profile [total, LDL-(LDL-C), and HDL-cholesterol (HDL-C), and triglycerides (TGs)], and the disease duration, treatment and microvascular complication profile (ophthalmopathy, neuropathy and nephropathy) were assessed. Its biomarker ability was assessed using the area under the ROC curve (AUC). Results: Significantly higher levels of EndoEth were detected in T2DM patients. EndoEth had significant associations with disease duration, complications particularly ophthalmopathy, insulin treatment, fasting blood glucose, TyG-IR index, and plasma triglycerides. Complications were also significantly associated with age, male gender, disease duration, FBG and total cholesterol. ROC curve analysis showed acceptable moderate ability of plasma EndoEth to discriminate against T2DM complications (AUC mean ± standard error = 0.766 ± 0.047, p = 0.001, and at a cut-off ≥ 0.016 µmol/mL, sensitivity = 75.7% and specificity = 61.0%). Conclusions: EndoEth is higher in abstinent T2DM patients than in healthy controls, and is correlated with disease duration, insulin resistance and treatment and complications, particularly for ophthalmopathy. It had a moderate biomarker performance (AUC = 0.766) in discriminating against diabetic complications.