Reframing insulin resistance and hypertension in type 2 diabetes: clinical and mechanistic-level insights from non-insulin-based biomarkers

Hypertension and insulin resistance (IR) are among the most powerful and closely interconnected drivers of cardiovascular disease in type 2 diabetes mellitus (T2DM).1 IR, defined as a diminished biological response to normal circulating insulin concentrations in insulin-responsive tissues such as skeletal muscle, liver, and adipose tissue, represents a central metabolic abnormality in T2DM.2 Despite extensive mechanistic insights accumulated over several decades, clinical assessment of IR remains largely dependent on fasting insulin measurements or surrogate indices such as the homeostatic model assessment of insulin resistance (HOMA-IR).3 These approaches are limited by biological variability, poor assay standardization, and restricted feasibility outside of research settings. In this context, the study by Yadegar et al. where they evaluated non-insulin-based markers of IR in relation to hypertension in T2DM provides timely and clinically meaningful insights.4 By demonstrating associations between simple metabolic indices, including the triglyceride–glucose (TyG) index and lipid ratios, and hypertension after age- and sex-matching, the authors present compelling translational evidence supporting the broader clinical adoption of these markers. Clinically, a TyG index is a practical surrogate marker of IR that can be calculated in routine clinical settings as the natural logarithm of fasting triglycerides multiplied by fasting plasma glucose and higher values (> 8.3) indicates increased risk of IR and CVD5 while TyG index < 8.3 indicates insulin sensitivity.6 This novel study is among the first to comprehensively evaluate and compare the association of six practical, non-insulin-based surrogate indices of IR namely TyG, TyG-Body mass index (BMI), TyG- Waist Circumference (WC), TyG- Waist-to-Height Ratio (WHtR), Metabolic Score for Insulin Resistance (METS-IR), and triglyceride–to–high-density lipoprotein cholesterol (TG/HDL-C) ratio with hypertension in a large, age- and sex-matched cohort of patients with T2DM. The key finding was a significant non-linear association between all indices and hypertension, with the TyG-BMI index demonstrating a modest-to-moderate discriminative ability (AUC 0.698) and the highest predictive odds. The study further revealed a TyG–BMI cutoff of 144.5 moderately discriminated hypertension, with 61% sensitivity and 71% specificity. Notably, these easily calculated indices, derived from routine anthropometric and lipid/glucose measures, provided significant incremental value over a basic clinical model in identifying hypertension risk. This highlights their utility as accessible stratification tools and underscores the central role of insulin resistance in hypertension pathogenesis among those with T2DM.