Phenotypes of type 2 diabetes in the Uzbek population

Type 2 diabetes mellitus (DM2) affects more than 500 million people worldwide and is one of the leading causes of cardiovascular mortality, chronic kidney disease, and liver cirrhosis. A key limitation of existing treatment approaches is the use of unified therapy algorithms for biologically heterogeneous patient populations. In 2018, Ahlqvist et al. proposed a revolutionary concept for subclassifying type 2 diabetes based on data-driven cluster analysis of six variables (GADA, age of manifestation, BMI, HbA1c, HOMA2-B, and HOMA2-IR by C-peptide). Of the five identified clusters, three - severe insulin resistance (SIRD), moderate obesity-associated (MOD), and moderate age-associated (MARD) - belong to GADA-negative forms of diabetes mellitus type 2 and carry various risks of complications. SIRD is associated with the highest risk of diabetic kidney disease and non-alcoholic fatty liver disease, while MARD has been described as the most "benign" phenotype. The reproducibility of this classification has been confirmed in cohorts from Germany, India, Mexico, and China. However, all existing studies have been conducted on European, South Asian, or East Asian populations. Data for the Central Asian region, where type 2 diabetes demonstrates one of the highest rates of morbidity growth, are absent. Additionally, none of the existing studies have analyzed gender differences in the association of type 2 diabetes phenotypes with STIs markers, used the eGDR (estimated Glucose Disposal Rate) index to assess peripheral insulin resistance and as a predictor of liver fibrosis risk by phenotype, or investigated the HOMA2-B/IR ratio as an integral indicator of beta-cell adaptation to insulin resistance.