Ursachen, Klinik und Folgen der Insulinresistenz bei Typ-2-Diabetes

Insulin resistance describes the reduced effect of insulin on its target organs and represents either a physiological phenomenon of dehydration and fever, or is a central feature of common metabolic diseases such as obesity and type 2 diabetes. Based on polygenic risk, insulin resistance is primarily due to hypercaloric nutrition and sedentary lifestyle. Conceptually, dysfunctional expanding adipose tissue leads to release of lipids and cytokines. This causes lipotoxicity, disrupted mitochondrial functionality, oxidative and endoplasmic reticulum stress and subclinical inflammation in other tissues. The complex intertissue communication via hormones and organokines defines the spectrum of the clinical features and the development of diabetes-related complications. Insulin resistance thereby determines the progression of steatotic liver disease (SLD), nephropathy, cardiovascular and cerebrovascular diseases via ectopic lipid storage, inflammation and fibrosis. Current research showed that insulin-resistant diabetes endotypes specifically associate with increased risk of certain diabetes-related comorbidities. The so-called metabolic syndrome is associated with the presence of insulin resistance, which can be easily measured using the homeostasis model assessment for insulin resistance (HOMA-IR) index. The prevention and treatment of insulin resistance is based on weight reduction by hypocaloric nutrition or pharmacotherapy in the case of obesity, which can even lead to diabetes remission. Insulin sensitizers improve insulin resistance directly, but are only used to limited extent in type 2 diabetes due to their side effects.