The Central Role of Lipid Metabolism Disorders in Diabetes Mellitus: Mechanisms, Clinical Manifestations, and Emerging Therapeutic Strategies

Abstract: Diabetes mellitus, as a metabolic disease, is characterized by dual metabolic disorders of glucose and lipids. Effective prevention and control of the progression of diabetes is the key to its treatment. Dyslipidemia in Diabetes is not merely a simple increase in lipid levels; it also involves the disordered coordination of multiple lipoprotein systems and molecular pathways, serving as both a driver and accelerator for diabetes. Lipid metabolism disorders directly magnify the harm of hyperglycemia, especially for the cardiovascular and cerebrovascular systems, and are one of the core pathological links of diabetes. Mechanisms involve multiple interactions such as insulin resistance and enhanced lipolysis, increased lipid synthesis and modification induced by hyperglycemia, oxidative stress and inflammatory responses, and hormonal and signaling pathway imbalances. Lipid metabolism disorders not only accelerate large vessel lesions such as atherosclerosis, but also promote microvascular damage (such as nephropathy and retinopathy) through lipotoxicity. This article systematically reviews the mechanisms, clinical features, and management strategies of dyslipidemia in diabetes, with a particular focus on lipid metabolism pathways (e.g, cholesterol synthesis) and the therapeutic potential of novel drugs targeting the gut microbiota or inflammation. The primary objective is to provide a detailed analysis of the metabolic mechanisms in diabetes, using lipid metabolism as a framework, and to offer new perspectives for the treatment and prognosis of the disease. At the top, ’Insulin resistance/deficiency’ is shown leading to two pathways. On the left, ’Lipid export overload’ from the liver is indicated, with increased free fatty acids, triglycerides and very low-density lipoproteins. On the right, ’Reduced lipid handling capacity’ affects adipose tissue and muscle. In adipose tissue, storage decreases and steatolysis increases. In muscle, oxidation-reduction capacity decreases. Below, it states ’The lipoproteins rich in triglycerides in the circulation are above the normal level.’ This leads to ’Lipid exudation and ectopic deposition’ in the liver, skeletal muscle and pancreas. At the bottom, this results in ’Lipotoxicity’, ’Chronic inflammation’ and ’IR intensifies’.Flowchart of insulin resistance effects on lipid metabolisam and related health issues. Keywords: diabetes mellitus, dyslipidemia, insulin resistance, oxidative stress, lipotoxicity, cholesterol synthesis