Diabetes Mellitus, Type 2

Type 2 diabetes mellitus is a chronic metabolic disease characterised by hyperglycaemia arising from a combination of insulin resistance in target tissues and progressive failure of pancreatic beta cells to compensate. It is the most common form of diabetes, is strongly associated with obesity and ageing, and develops gradually, often remaining asymptomatic for years before diagnosis.

Definition

Type 2 diabetes mellitus is a form of diabetes in which hyperglycaemia results from insulin resistance combined with an inadequate, relative deficiency of insulin secretion, in the absence of the autoimmune beta-cell destruction that defines type 1 diabetes.

Scope

The entry covers type 2 diabetes as a pathological and laboratory-defined entity: the dual defect of insulin resistance and relative insulin deficiency, the metabolic and genetic factors that drive it, its biochemical diagnosis, and its distinction from type 1 diabetes. It does not provide glucose-lowering regimens or individualised management advice.

Key concepts

• Insulin resistance
• Relative insulin deficiency
• Beta-cell dysfunction and decline
• Obesity and adiposity
• Glucotoxicity and lipotoxicity
• HbA1c and impaired glucose regulation
• Microvascular and macrovascular complications

Mechanisms

Type 2 diabetes results from two interacting defects: reduced responsiveness of liver, muscle, and adipose tissue to insulin (insulin resistance) and a beta-cell secretory response that is insufficient to overcome it (relative insulin deficiency). Early in the disease the pancreas compensates by secreting more insulin, maintaining near-normal glucose; over time beta-cell function declines, often worsened by chronic hyperglycaemia (glucotoxicity) and excess lipid (lipotoxicity), so that secretion can no longer match demand and hyperglycaemia becomes manifest. The condition develops on a background of genetic susceptibility interacting with adiposity, physical inactivity, and ageing, and sustained hyperglycaemia drives the microvascular and macrovascular complications that account for much of its morbidity.

Clinical relevance

Type 2 diabetes is a leading chronic disease and a major contributor to cardiovascular, renal, retinal, and neuropathic complications, and its diagnosis and monitoring rest heavily on laboratory measurements such as fasting glucose, oral glucose tolerance testing, and HbA1c. This entry describes how the disease is defined and classified for reference and does not constitute treatment guidance for any individual.

Epidemiology

Type 2 diabetes accounts for the large majority of all diabetes cases worldwide and its prevalence has risen sharply with increasing obesity, urbanisation, and population ageing. It is typically diagnosed in adulthood but is increasingly seen in younger people, and a substantial fraction of cases remain undiagnosed.

Evidence & guidelines

The pathophysiology is summarised in major disease reviews, and consensus frameworks for the management of hyperglycaemia have been issued jointly by the American Diabetes Association and the European Association for the Study of Diabetes; these are cited for orientation rather than as prescriptive instructions.

History

Type 2 diabetes was distinguished from the insulin-dependent form in the mid-twentieth century, and the recognition of insulin resistance as a central defect, alongside progressive beta-cell failure, shaped the modern two-component model of the disease. The introduction of HbA1c as a measure of chronic glycaemia and the demonstration that glycaemic control affects complications further established its laboratory-centred framework.

Seminal works

• defronzo-2015
• chatterjee-2017

Frequently asked questions

Why is insulin deficiency in type 2 diabetes called relative rather than absolute?

Because the pancreas still produces insulin, often in normal or raised amounts early on, but the quantity is insufficient relative to the heightened demand created by insulin resistance; this contrasts with the absolute deficiency of type 1 diabetes.

How is type 2 diabetes diagnosed in the laboratory?

It is diagnosed by demonstrating hyperglycaemia using criteria such as fasting plasma glucose, the oral glucose tolerance test, or HbA1c, in the absence of the autoimmune markers that characterise type 1 diabetes.