INSULIN RESISTANCE AND ITS ROLE IN THE PROGRESSION OF TYPE 2 DIABETES: EXPLORING MECHANISMS AND TREATMENT STRATEGIES

Abstract

Insulin resistance and slacking of the production of insulin characterizes Type 2 Diabetes Mellitus (T2DM) – a rapidly increasing worldwide health problem.  The causes of underpinning insulin resistance are investigated in this systematic review and meta-analysis, as well as the effectiveness of pharmacologic drugs, new therapies, lifestyle changes are among other treatment strategies.  A total of 45 appropriate research (systematic reviews, cohort studies and randomised controlled trials) were identified between 2000 and 2025.  Mechanistic findings attribute the underlying causes of insulin resistance to: failure of insulin receptor; lipotoxicity; failure of poor GLUT4 translocation; dysfunctional mitochondria and endoplasmic reticulum stress.  Among the strategies of treatment, lifestyle change with particular mention of food and exercise won the best response to glycemic control and sensitivity increase.  Pharmacologic treatment with GLP-1 receptor agonists, thiazolidinediones, and metformin were also effective, although associated with a varying extent of side effects.  Studies of early phase were particularly promising for new treatments, such as senomorphics, multitargeting phytochemicals, and astaxanthin.  Integration of classical therapies and new drugs that exploit the molecular basis underlying insulin resistance is in the focus of this review that underlines the necessity of a multiple and personal approach to the T2DM management.  Larger scale clinical studies with precision medicine methods should dominate future studies in efforts to optimize results to those with T2DM.