From the Guidelines
Type 2 diabetes is characterized by a combination of insulin resistance and impaired insulin secretion, resulting from a complex interplay of genetic, environmental, and lifestyle factors, including obesity, physical inactivity, and an unhealthy diet, as evident from the most recent study in 2025 1. The pathophysiology of type 2 diabetes involves multiple factors, including:
- Insulin resistance, where peripheral tissues such as muscle, liver, and fat cells become less responsive to insulin, requiring the pancreas to produce more insulin to maintain normal blood glucose levels
- Impaired insulin secretion, where pancreatic beta cells gradually lose their ability to secrete sufficient insulin to overcome insulin resistance
- Increased hepatic glucose output, where the liver increases glucose production (gluconeogenesis) when insulin signaling is impaired
- Glucotoxicity, lipotoxicity, amyloid deposition, oxidative stress, and inflammation, which all contribute to beta cell dysfunction and impaired insulin secretion.
As the disease progresses, the combination of insulin resistance, impaired insulin secretion, and increased hepatic glucose output creates the hallmark hyperglycemia of type 2 diabetes, which if left untreated can lead to microvascular and macrovascular complications throughout the body, as supported by studies in 2022 1 and 2021 1. Key factors that contribute to the development of type 2 diabetes include:
- Obesity and physical inactivity, which can lead to insulin resistance and impaired insulin secretion
- Genetic predisposition, which can affect insulin sensitivity and secretion
- Unhealthy diet, which can contribute to insulin resistance and impaired insulin secretion
- Increasing age, which can lead to decreased insulin sensitivity and secretion.
Overall, the pathophysiology of type 2 diabetes is complex and multifactorial, involving a combination of genetic, environmental, and lifestyle factors that contribute to insulin resistance, impaired insulin secretion, and increased hepatic glucose output, as summarized in the study from 2007 1.
From the Research
Pathophysiology of Type 2 Diabetes
The pathophysiology of type 2 diabetes is characterized by:
- Insulin resistance, which is an integral pathophysiological feature of type 2 diabetes mellitus 2
- Impaired insulin secretion, leading to hyperglycemia 3, 4
- Hyperinsulinemia, which is a consequence of insulin resistance 2, 5
- Abnormalities in glucose and lipid metabolism, resulting in hyperglycemia and dyslipidemia 3, 6
Key Mechanisms
The key mechanisms involved in the pathophysiology of type 2 diabetes include:
- Impaired insulin receptor signaling, leading to reduced glucose uptake in peripheral tissues 2
- Increased hepatic glucose output, contributing to hyperglycemia 3
- Reduced insulin secretion, resulting in inadequate glucose lowering 3, 4
- Inflammation and oxidative stress, which contribute to insulin resistance and beta-cell dysfunction 6
Risk Factors and Consequences
The risk factors for type 2 diabetes include:
- Obesity, which is strongly correlated with insulin resistance 3
- Family history, which increases the risk of developing type 2 diabetes 4
- Physical inactivity, which contributes to insulin resistance and impaired glucose metabolism 6 The consequences of type 2 diabetes include:
- Microvascular and macrovascular complications, such as nephropathy, retinopathy, and cardiovascular disease 4, 6
- Increased risk of morbidity and mortality, resulting from long-term hyperglycemia and associated complications 4, 6