diabetes

diabetes
Field	Endocrinology

diabetes. It is a group of metabolic disorders characterized by a sustained elevation in blood glucose levels, known as hyperglycemia. This condition arises from defects in insulin secretion, insulin action, or both, leading to the improper metabolism of carbohydrates, fats, and proteins. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, particularly the eyes, kidneys, nerves, heart, and blood vessels.

Definition and classification

The World Health Organization and the American Diabetes Association provide the principal diagnostic criteria and classification frameworks. The major categories include type 1 diabetes, type 2 diabetes, gestational diabetes, and other specific types. Type 1 diabetes results from an autoimmune-mediated destruction of the beta cells in the pancreatic islets, leading to absolute insulin deficiency. Type 2 diabetes, the most prevalent form, involves a combination of insulin resistance and an inadequate compensatory insulin secretory response. Gestational diabetes is glucose intolerance first recognized during pregnancy. Other types can be due to diseases of the exocrine pancreas, such as cystic fibrosis or pancreatitis, endocrinopathies like Cushing's syndrome, or induced by drugs such as glucocorticoids.

Signs and symptoms

Classic symptoms include polyuria, polydipsia, unexplained weight loss, and sometimes polyphagia. These are often acute in type 1 diabetes but may be subtle or absent in type 2 diabetes. Many individuals are asymptomatic initially, with hyperglycemia detected incidentally. Other presenting features can include blurred vision, fatigue, slow-healing wounds, and recurrent infections, such as candidiasis. Severe insulin deficiency can lead to acute, life-threatening complications like diabetic ketoacidosis, characterized by Kussmaul breathing and altered mental status, or the hyperosmolar hyperglycemic state.

Causes and risk factors

The etiology is complex and multifactorial, varying by type. For type 1 diabetes, a genetic predisposition involving the human leukocyte antigen region interacts with undefined environmental triggers, possibly including viral infections like coxsackievirus. Risk factors for type 2 diabetes include obesity, physical inactivity, and advancing age, with strong genetic influences evidenced by studies in populations like the Pima Indians. A family history of the condition, prior gestational diabetes, and conditions such as polycystic ovary syndrome also increase risk. Certain medications, including thiazide diuretics and atypical antipsychotics, are associated with its development.

Pathophysiology

The fundamental defect is an absolute or relative deficiency of effective insulin action. In type 1 diabetes, T cell-mediated autoimmune destruction of pancreatic islets abolishes insulin production. In type 2 diabetes, insulin resistance in tissues like skeletal muscle, liver, and adipose tissue impairs glucose uptake and promotes inappropriate gluconeogenesis. The beta cells initially compensate with hyperinsulinemia but eventually fail. Chronic hyperglycemia drives non-enzymatic glycation of proteins and lipids, activates the polyol pathway, and increases oxidative stress, contributing to microvascular and macrovascular complications affecting the retina, glomerulus, and peripheral nerves.

Diagnosis

Diagnosis is based on blood glucose criteria established by the American Diabetes Association. These include a fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dL), a glucose tolerance test value at or above 11.1 mmol/L (200 mg/dL) two hours after a 75g oral glucose load, a glycated hemoglobin (HbA1c) level of 6.5% (48 mmol/mol) or higher, or in a patient with classic symptoms, a random plasma glucose of ≥11.1 mmol/L (200 mg/dL). The glucose tolerance test is the standard for diagnosing gestational diabetes. Autoantibody tests, such as those for glutamic acid decarboxylase antibodies, can help distinguish type 1 diabetes.

Management and treatment

Management aims to normalize blood glucose and prevent complications. For type 1 diabetes, treatment is lifelong insulin replacement via multiple daily injections or insulin pump therapy, guided by self-monitoring of blood glucose or continuous glucose monitoring. Management of type 2 diabetes centers on lifestyle intervention—medical nutrition therapy and physical activity—often augmented by oral agents like metformin, sulfonylureas, or newer classes such as SGLT2 inhibitors and GLP-1 receptor agonists. All individuals benefit from comprehensive care addressing blood pressure control, lipid management with statins, and regular screening for complications like diabetic retinopathy and diabetic nephropathy.

Epidemiology and history

The International Diabetes Federation estimates hundreds of millions of people are affected worldwide, with prevalence rising rapidly, particularly for type 2 diabetes. The condition was known to ancient physicians; the term "diabetes" is attributed to Aretaeus of Cappadocia, while the sweet taste of urine was noted by Sushruta in India and later by Thomas Willis in Europe. The pivotal discovery of insulin by Frederick Banting and Charles Best at the University of Toronto in 1921 transformed a fatal disease into a manageable one. The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study provided definitive evidence for the benefits of intensive glycemic control.

Category:Endocrine diseases