INTEGRATED ASSESSMENT OF ACE I/D POLYMORPHISM AND GUT MICROBIAL DIVERSITY IN RELATION TO METABOLIC, INFLAMMATORY, PHYSIOLOGICAL, AND RENAL HISTOPATHOLOGICAL FINDINGS IN TYPE 2 DIABETES MELLITUS: PUBLIC HEALTH IMPLICATIONS FOR RISK CHARACTERIZATION AN

Abstract

Background: Type 2 diabetes mellitus (T2DM) involves chronic hyperglycemia with metabolic, inflammatory, vascular, and organ-level abnormalities. Objective: To assess ACE I/D genotype and allele distributions and gut microbial diversity in adults with T2DM and non-diabetic controls and examine their associations with metabolic, inflammatory, physiological, and renal histopathological findings. Methods: A comparative cross-sectional study was included 200 adults (150 with T2DM and 50 controls). Demographic and clinical characteristics were assessed in a tertiary care hospital of Pakistan during the period from January 2026 to June 2026. ACE I/D polymorphism was determined by polymerase chain reaction, while stool specimens underwent 16S rRNA-based microbial profiling. Renal tissue specimens were assessed histopathologically. Group comparisons, correlations, and multivariable regression analyses were performed. Results: Compared with controls, participants with T2DM had higher BMI, glucose, HbA1c, triglycerides, total cholesterol, LDL-C, CRP, IL-6, systolic and diastolic blood pressure, and lower HDL-C. Overall ACE genotype distribution did not differ significantly (χ²=5.72, df=2, p=0.057), whereas the D-allele frequency was higher in T2DM (60.7% vs. 46.0%; p=0.010; OR=1.81, 95% CI 1.15–2.86). HbA1c, triglycerides, systolic blood pressure, and CRP differed across ACE genotypes. Faecalibacterium, Roseburia, and Akkermansia were reduced, whereas Enterobacteriaceae and Escherichia/Shigella were increased in T2DM. Microbial diversity and selected taxa correlated significantly with HbA1c and CRP. Renal inflammatory, vascular, degenerative, edematous, and fibrotic findings were more frequent in T2DM. Conclusion: ACE I/D variation, gut microbial alterations, metabolic and inflammatory characteristics, physiological parameters, and renal histopathological findings showed significant associations in T2DM, supporting integrated risk characterization and further investigation.