Hyperglycaemia Outweighs Obesity as the Primary Clinical Determinant of Gut Dysbiosis in Type 2 Diabetes Mellitus

Background: Gut dysbiosis is implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), but the relative contributions of hyperglycaemia, obesity, and medication use to dysbiosis remain poorly defined, particularly in African populations. Objective: To investigate the independent associations of hyperglycaemia, body mass index (BMI), and oral hypoglycaemic agent (OHA) use with gut dysbiosis in T2DM patients in Sokoto, Nigeria, and to determine which clinical factor is the primary determinant of microbial imbalance. Methods: This cross-sectional study enrolled 300 participants: 150 T2DM patients and 150 age-and sex-matched healthy controls. Gut Bacteroidetes and Firmicutes were quantified using qPCR, and dysbiosis was defined as bacterial load >75th percentile of controls. Associations between dysbiosis and clinical factors (BMI, glycaemic status, OHA use) were assessed using chi-square tests and logistic regression. Results: Among T2DM patients, 121 (80.7%) had gut dysbiosis. Hyperglycaemia showed the strongest association with dysbiosis (χ² = 107.47, p < 0.001); 92.2% of dysbiotic patients were hyperglycaemic, whereas no hyperglycaemic individual was in the control group. Hyperglycaemia was independently associated with increased odds of dysbiosis (adjusted odds ratio [AOR] = 2.30, 95% CI 1.33–3.98). BMI was also associated with dysbiosis (χ² = 12.30, p = 0.015), with normal-weight patients having the highest prevalence (55.1%) and highest adjusted odds (AOR = 3.24, 95% CI 2.74–4.02). OHA use was universal among T2DM patients and strongly linked to dysbiosis (AOR = 2.41, 95% CI 1.92–3.81), reflecting disease severity rather than an independent effect. Conclusion: Hyperglycaemia is the dominant clinical determinant of gut dysbiosis in T2DM, outweighing obesity. Normal-weight T2DM patients exhibit unexpectedly high rates of dysbiosis, identifying a high-risk subgroup. These findings highlight the importance of glycaemic control for maintaining gut microbial health and suggest that gut dysbiosis should be considered in all T2DM patients regardless of body weight.