What are the core defects of Diabetes Mellitus type 2 (DM2)?

From the Guidelines

The core defects of Type 2 Diabetes Mellitus (DM2) include insulin resistance, impaired insulin secretion, and increased hepatic glucose production, as stated in the most recent and highest quality study 1. These defects are characterized by the body's inability to properly respond to insulin, leading to high blood glucose levels. Insulin resistance occurs when muscle, fat, and liver cells don't respond properly to insulin, requiring the pancreas to produce more insulin to overcome this resistance. Over time, the pancreatic beta cells become unable to produce sufficient insulin to maintain normal blood glucose levels, leading to impaired insulin secretion. Some key points about the core defects of DM2 include:

• Insulin resistance: muscle, fat, and liver cells don't respond properly to insulin, requiring the pancreas to produce more insulin to overcome this resistance 1.
• Impaired insulin secretion: the pancreatic beta cells become unable to produce sufficient insulin to maintain normal blood glucose levels 1.
• Increased hepatic glucose production: the liver inappropriately increases glucose production through gluconeogenesis, especially during fasting states, further contributing to hyperglycemia 1. These combined defects create a vicious cycle where hyperglycemia itself can worsen insulin resistance and further impair beta cell function, a phenomenon known as glucotoxicity. Genetic predisposition, obesity, physical inactivity, and aging all contribute to the development and progression of these core defects in DM2, as supported by the evidence from 1.

From the Research

Core Defects of DM2

The core defects of Type 2 Diabetes Mellitus (DM2) include:

• Insulin resistance: a condition in which the body's cells do not respond effectively to insulin, leading to impaired glucose uptake in the muscles and increased glucose production in the liver 2, 3, 4
• Impaired insulin secretion: a condition in which the pancreas does not produce enough insulin to meet the body's needs, leading to hyperglycemia 2, 3, 4

Pathophysiological Abnormalities

In addition to insulin resistance and impaired insulin secretion, at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism in DM2, including:

• Environmental factors such as obesity, an unhealthy diet, and physical inactivity 2, 3, 4
• Genetic factors that contribute to the development of insulin resistance and impaired insulin secretion 2, 3, 4
• Mitochondrial dysfunction, impaired regulation of the enteroinsular axis, and endoplasmic reticulum stress 4
• Adipose tissue dysfunction, which secretes adipocytokines with diverse central and peripheral metabolic effects 4

Clinical Features

The clinical features of insulin resistance and beta-cell dysfunction in DM2 include:

• Reduced insulin-stimulated glucose uptake, reduced insulin-suppression of endogenous glucose production, and reduced antilipolysis 3
• Decreased insulin-induced vasodilation, dyslipidemia, and platelet hyperaggregability 3
• Hyperglycemia, both post-absorptively and postprandially 3