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These studies suggest type 2 diabetes is caused by a combination of genetic and environmental factors, defective insulin secretion, insulin resistance, and lifestyle factors such as physical inactivity and poor nutrition.
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Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder influenced by both genetic and environmental factors. Genetic predisposition plays a significant role in an individual's susceptibility to T2DM, with numerous genetic variants identified as contributing to the disease. Environmental factors, such as obesity, unhealthy diet, and physical inactivity, are also critical contributors to the development of T2DM. The interplay between these genetic and environmental factors leads to the multifactorial nature of the disease .
The core defects in T2DM are insulin resistance and impaired insulin secretion. Insulin resistance occurs when insulin-sensitive tissues, such as muscle, liver, and adipose tissue, fail to respond appropriately to insulin, leading to elevated blood glucose levels . This resistance is often exacerbated by central obesity, which is a common etiological factor. Concurrently, pancreatic β-cells fail to secrete sufficient insulin to compensate for the increased demand, further contributing to hyperglycemia .
Several molecular mechanisms and pathways are implicated in the pathogenesis of T2DM. Defects in insulin synthesis, release, and sensing are critical factors. These defects disrupt glucose homeostasis and lead to metabolic imbalances. Additionally, chronic energy imbalance, often due to excessive nutrient intake and insufficient energy expenditure, can lead to insulin resistance through inflammatory pathways and other metabolic disturbances.
Obesity, particularly the accumulation of excess fat in the liver and pancreas, is a significant factor in the development of T2DM. Excess fat in the liver impairs insulin responsiveness, leading to increased glucose production, while fat-induced metabolic stress in the pancreas hampers β-cell function. Weight loss has been shown to improve insulin sensitivity and β-cell function, highlighting the reversible nature of fat-induced metabolic disturbances in the early stages of T2DM.
Lifestyle factors, including diet and physical activity, play a crucial role in the development and management of T2DM. Sedentary lifestyles and poor dietary habits contribute to obesity and insulin resistance, increasing the risk of T2DM. Nutritional factors, such as high intake of refined carbohydrates and saturated fats, can exacerbate insulin resistance and metabolic dysfunction.
T2DM is associated with numerous complications, both microvascular and macrovascular. Microvascular complications include retinopathy, nephropathy, and neuropathy, while macrovascular complications encompass cardiovascular diseases . These complications arise due to chronic hyperglycemia and the metabolic abnormalities associated with insulin resistance.
Type 2 diabetes mellitus is a multifactorial disease driven by a combination of genetic predisposition, environmental factors, and lifestyle choices. Insulin resistance and impaired insulin secretion are the primary defects, with obesity and fat accumulation playing significant roles. Understanding these underlying causes is essential for developing effective prevention and management strategies for T2DM.
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