Diabetes, Pathophysiology, Natural History, T2DM, Type 2

• Understanding this natural history of type 2 diabetes will help in understanding this chronic disease as a continuum, ranging from early insulin resistance to insulin secretion deficiency.
• Some patients with insulin resistance, who are able to maintain sufficient β-cell function to overcome the insulin resistance never progress to diabetes.
• Genetic predisposition to the development of type 2 diabetes.
• Clinical presentation is heterogeneous, with a wide range in age of onset, severity of associated hyperglycemia, and degree of obesity.
• The metabolic changes observed can occur years or even decades before a diagnosis of type 2 diabetes.

• Insulin resistance is an important defect in type 2 diabetes.
• Pancreatic β-cells are able to compensate by increasing insulin levels, leading to hyperinsulinemia.
• Keeps glucose levels normalized for a period of time.
• IGT develops with mild postprandial hyperglycemia.
• Glucose levels remain normal or near normal, when pancreatic beta cells are able to compensate for insulin resistance by increasing insulin production and secretion.
• β-cells are eventually damaged due to glucotoxicity and lipotoxicity.
• Insulin secretion declines resulting in increased hepatic glucose production, leading to further elevations in fasting blood glucoseconcentrations.
• Insulin resistance becomes more severe, a progression that may be due not only to full expression of genetic defects, but also to acquired factors such as obesity, decreased physical activity, and aging.

Expert Committee on the Diagnosis and Classification of Diabtetes. Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. January, 2008; 31: S62-S67

Kronenberg: Williams Textbook of Endocrinology, 11th ed. 2008 Saunders, An Imprint of Elsevier

Rakel: Integrative Medicine

IGT - Impaired Glucose Tolerance