Type 2 diabetes mellitus is a chronic metabolic disease in which blood glucose stays too high because the body’s tissues respond poorly to insulin and the pancreatic β cells eventually cannot secrete enough to compensate. It develops over years, is produced by both genetic and environmental factors, and during the last 40 years its total prevalence has increased about 6-fold. The idea that organises the topic is a balance: the disease appears when insulin resistance outruns the secretion the β cells can mount.
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The route follows the balance that organises the topic: first who is at risk and the normal physiology the disease departs from, then how that balance fails, and last the clinical notes.
- Risk factors for type 2 diabetes mellitus: who is more likely to develop the disease, in adults and in children and adolescents, and the environmental factors involved.
- Normal glucose homeostasis: how blood glucose is kept steady between meals and how a glucose load is disposed of after eating, including the difference between oral and intravenous glucose.
- Pathophysiology of type 2 diabetes mellitus: the sites of insulin resistance, how insulin secretion fails, and the natural history of the disease.
- Role of adipocytes in the pathogenesis of type 2 diabetes mellitus: how adipose tissue contributes, through adipokines, free fatty acids, the Randle cycle and fatty liver disease.
- Eight mechanisms of hyperglycemia in type 2 diabetes mellitus: the eight recognised mechanisms that act together to raise glucose.
- Genetic basis of type 2 diabetes mellitus: why type 2 diabetes is polygenic, and how its genetic susceptibility differs from that of type 1 diabetes.
With the mechanism understood, the remaining notes follow the disease from its recognition at the bedside to its consequences and management.
- Presentation of type 2 diabetes mellitus: how the disease usually appears, why it is often silent, and the emergencies that can be the first sign.
- Diagnosis of type 2 diabetes mellitus: the glucose and HbA1c (glycated haemoglobin) thresholds that define diabetes and prediabetes, how the diagnosis is confirmed, and who should be screened.
- Complications of type 2 diabetes mellitus: the microvascular and macrovascular damage the disease causes, and how it is prevented.
- Lifestyle prescription in type 2 diabetes mellitus: how diet and physical activity are prescribed, and how exercise intensity and duration select the fuels the muscle uses.