Targeting Inflammatory Pathways in Type 2 Diabetes: A Focus on Adiponectin, Tumour Necrosis Factor-alpha and Interleukin-6 for Potential Therapeutic Interventions

Introduction: The escalating global prevalence of prediabetes and diabetes, particularly in India, underscores an urgent need for a thorough understanding of biochemical markers associated with insulin resistance (IR). This study aimed to comparatively evaluate insulin resistance level indexes (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI), Homeostasis Model Assessment of Beta-cell Function (HOMA-B), along with interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), adiponectin, C-peptide and insulin levels, across normal, prediabetic and diabetic subjects. Furthermore, a key objective was to investigate the correlation of IL-6, TNF-α and adiponectin with the established IR indexes. Materials and Methods: The study evaluated 309 participants, categorised into three groups according to their glycated haemoglobin and (fasting blood glucose) levels, following the American Diabetes Association 2023 guidelines: normal, prediabetic and diabetic, with each group consisting of 103 subjects. Biochemical markers were examined. This study employed the Pearson correlation coefficient to analyse the relationships between IR indices and TNF-α, IL-6 and other factors, such as adiponectin. Results: Diabetic individuals exhibit significantly lower levels of adiponectin. The levels of TNF-α and IL-6 progressively increase from normal to diabetic conditions. A negative and statistically significant correlation was observed between HOMA-IR and adiponectin in both normal and diabetic subjects ( R = −0.3752, P = 0.0001; R = −0.2281, P = 0.02), as well as between HOMA-IR and QUICKI in normal individuals ( R = −0.2851, P = 0.003). The study indicated a positive correlation between TNF-α and HOMA-IR in normal and pre-diabetic subjects ( R = 0.422, P = 0.000; R = −0.2523, P = 0.01). In addition, IL-6 was positively correlated with HOMA-IR in both normal and diabetic subjects ( R = 0.5679, P = 0.000; R = 0.2845, P = 0.0036). Conclusions: The levels of TNF-α, IL-6 and adiponectin showed varied correlations with IR indexes, suggesting their potential as biomarkers in IR and highlighting their differing impacts on the progression to diabetes from normoglycaemia.