Metabolic and clinical markers of T2D in obese Indians: an age-sex matched case-control study

Type 2 diabetes (T2D) is a significant metabolic disorder with disproportionately high burden in obese South Asian populations, yet not all obese individuals develop the disease. This study identified the metabolic, inflammatory, and pharmacological markers associated with prevalent T2D in obese Indians using age- and sex-matched case-control analysis.

A matched-pair analysis was performed on 514 age- and sex-matched pairs with and without T2D. Patients had obesity [body mass index (BMI) 25-45 kg/m², aged 20-75 years] and participated in a one-year lifestyle intervention program in India. Anthropometric, biochemical markers and medical history were analyzed. Homeostatic model assessment for insulin resistance (HOMA2IR) and beta-cell function (HOMA2%B) was calculated. Significant markers were incorporated into a logistic regression model and temporally validated in an independent time-cohort (n=966). Performance was evaluated through discrimination [receiver operating characteristics area under the curve (ROC-AUC)], calibration, and decision curve analysis. A nomogram was constructed based on the logistic regression model.

Median age and BMI were 46 (IQR 12) years and 29.7 (IQR 5.5) kg/m². Key markers associated with prevalent T2D were poor beta-cell function (HOMA2%B ≤50; OR = 40.9, 95% CI: 24.5-68.2), insulin resistance (HOMA2IR ≥2; OR = 4.5, 95% CI: 3.0-6.7), low HDL-C (OR = 2.1, 95% CI: 1.5-3.0), elevated hsCRP ≥3 mg/L (OR = 1.9, 95% CI: 1.4-2.7), Obesity Class I (BMI 25.0-29.9 kg/m²; OR = 2.1, 95% CI: 1.5-2.9), and antihypertensive medication use (OR = 1.7, 95% CI: 1.2-2.4). Model discrimination was good (AUC 0.860 development, 0.865 validation, both p<0.001). The Hosmer-Lemeshow test showed good model fit (p=0.562). Isotonic-calibrated Models 1 and 2 had Brier scores 0.14 and 0.162, indicating acceptable calibration. Decision curve analysis confirmed net clinical benefit across threshold probabilities 0.10-0.85.

This study identified and temporally validated key metabolic and clinical markers associated with prevalent T2D, demonstrating good discrimination (AUC 0.860) in obese Indian individuals. External validation and prospective evaluation are needed before clinical application.