Diabetes
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Diabetes is a chronic disorder impacting carbohydrate, fat, and protein metabolism due to inadequate insulin response. Approximately 3% of the global population has diabetes, with around 13 million cases in the U.S., yet only about half are diagnosed. The condition can lead to serious health complications, including damage to the kidneys, eyes, and nerves. There are various types of diabetes, primarily Type 1 and Type 2, each with distinct characteristics, causes, and management strategies. Early diagnosis and intervention are crucial for better health outcomes.
Diabetes
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Presentation Transcript
Diabetes • Chronic disorder of carbohydrate, fat and protein metabolism due to defective or deficient insulin secretory response • Demographics: 3% of world population, 13 million in U.S. but only 50% are clinically diagnosed • 54,000 deaths/year in U.S., #7 leading cause of death • Lifetime risk: type 1 – 0.5%, type 2 – 5% • Numerous variations, all with hyperglycemia • Diagnosis: high fasting glucose or impaired glucose tolerance (without diabetes, oral glucose loads cause only slight rise in blood glucose due to brisk insulin response; with diabetes, blood glucose rises markedly for a sustained period) • Micro: Type 1 - inconsistent reduction in number and size of islets, uneven insulinitis (T lymphocytes) • Type 2 - subtle reduction in islet cell mass, amyloid replacement of islets due to amylin fibrils (also seen in • aging nondiabetics); associated with marked fatty replacement • Infants of diabetic mothers – islet cell hypertrophy/hyperplasia
Causes of Diabetes • Causes: destruction of islets due to • Pancreatitis • Tumours • Drugs (corticosteroids, thiazides, pentamidine) • Haemochromatosis (“bronze diabetes” due to hemosiderin deposition in pancreas) • Hereditary ceruloplasmin deficiency (copper deposition eg Wilson’s disease) • Surgery • Infections (congenital rubella, CMV, coxsackievirus) • Endocrinopathies (pituitary, adrenal, pregnancy) • Other: gestational diabetes or idiopathic
Long term complications • Damage to blood vessels in kidneys (nodular Kimmelstiel-Wilson glomerulopathy, pyelonephritis, papillary necrosis) • Eyes (exudative and proliferative retinopathy) • Nerves (symmetric polyneuropathy) • Peripheral vascular disease and coronary artery disease are major causes of morbidity / death
Type 1 Diabetes • Type 1A diabetes, Aka juvenile onset, IDDM; formerly called Type 1; 10% of all cases, is a chronic disorder that results from the immune-mediated destruction of the insulin-producing ß-cells of the pancreatic islets. • Onset at age < 20 years, normal weight, decreased blood insulin, anti-islet cell antibodies present, DKA common
Type 1 Diabetes • Autoimmunity: usually chronic (years); In its initial phase, which is clinically silent, T lymphocytes (CD8+ T cell infiltrate and other inflammatory cells) invade the islets and eventually destroy them. The disease then becomes clinically evident with the pathological consequences (hyperglycemia, ketosis and long-term complications) resulting from the inability to maintain glucose and lipid homeostasis. clinical disease when 90% of islet cells are destroyed • Islet cell autoantibodies seen in 70% of patients; antigens are glutamic acid decarboxylase (GAD), islet autoantigen 2, insulin associated antibody, gangliosides; GAD antibodies precede clinical symptoms • GAD antibody: in most newly diagnosed patients, 80% of first degree relatives; • GAD antibody causes stiff man syndrome, whose patients often have a history of Type I Diabetes
Stiff Man Syndrome • SMS is a rare, disabling neurological disorder characterised by progressive muscle rigidity and painful episodic spasms of the axial and proximal limb muscles.
Histology • Micro: Type 1 - inconsistent reduction in number and size of islets, uneven insulinitis (T-lymphocytes) • Infants of diabetic mothers – islet cell hypertrophy/hyperplasia
Type II Diabetes • Aka adult onset, NIDDM; formerly called type 2 • 80-90% of cases of diabetes • Usually > 30 years old, obese (80% of cases, abdominal obesity more important than subcutaneous obesity), • normal or increased blood insulin, no anti-islet antibodies, rare diabetic ketoacidosis • 90%+ concordance in twins, but no HLA association; apparently due to multiple genetic polymorphisms • Relative insulin deficiency is due to insulin resistance or derangement in beta cell secretion of insulin • Early: normal insulin secretion and plasma levels, but loss of pulsatile, oscillating pattern of secretion; also loss of rapid first phase of insulin secretion triggered by glucose; No insulinitis is present • Later: mild/moderate insulin deficiency, may be due to beta cell damage; beta cells may be “exhausted” due to chronic hyperglycemia and persistent beta cell stimulation • Insulin resistance in peripheral tissues also seen in obesity and pregnancy • Amylin: 37 amino acid peptide, normally produced by beta cells, packaged and cosecreted with insulin; in NIDDM patients, tends to accumulate outside beta cells and resembles amyloid • Note: Type II diabetes is associated with amyloid deposits in pituitary
Histology • Type 2 - subtle reduction in islet cell mass, amyloid replacement of islets due to amylin fibrils (also seen in aging nondiabetics); associated with marked fatty replacement
Gestational Diabetes • Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which progresses thereafter to levels seen in non-pregnant patients with type 2 diabetes. It is thought to secure glucose supply to the growing foetus. • Women with GDM have an insulin resistance they cannot compensate with increased production in the β-cells of the pancreas. • The mechanism is unknown
