Post Time: 2025-02-18
Error: No content files found.This is a mechanism of disease map for type 2 diabetes, covering the etiologies, pathophysiology, and manifestations of T2DM. ADDITIONAL TAGS: Chronic inflammation Signs / symptoms Labs / tests / imaging results Type 2 diabetes mellitus Etiologies Core concepts Social determinants of health / Risk factors Genetics / hereditary Microbial pathogenesis Osmolarity regulation Intercellular communication Glucose homeostasis Energy balance Manifestations Pathophysiology Genetic factors: -child with diabetic parent has 40% risk of T2DM -monozygotic twin concordance 75% Visceral adiposity (obesity) + Low grade chronic inflammation have a peek at this web-site + Oxidative and metabolic stress Risk factors: -Family history (1st degree relative) -Race/ethnicity -Physical inactivity -Hx cardiovascular disease -Polycystic ovary syndrome -Conditions associated with insulin resistance: (severe obesity, high-calorie diet) -Hypertension -Dyslipidemia -Hx gestational diabetes Initially, there is compensation (↑ insulin secretion). Over time, ↓ insulin secretion capacity Adipose catabolism (lipolysis → release of glycerol + fatty acids) Muscle catabolism (protein breakdown + release of amino acids) Amino acids and glycerol carbons are used for gluconeogenesis Polyphagia Weight loss ↑ hepatic glucose output, ↓ peripheral tissue glucose uptake Hyperglycemia ↑ glucose filtering at nephron Kidney unable to reabsorb filtered glucose Glycosuria Osmotic diuresis Polyuria Dehydration, volume depletion ↓ circulating volume → ↓ renal blood flow → ↓ glucose to nephron Polydipsia Hyperosmolarity in blood and tissues Stimulation of osmoreceptors in hypothalamus Blurred vision Dysfunction of blood-retinal barrier: retinal vessel microangiopathy → macular edema Central obesity → increased plasma levels of free fatty acids → impaired insulin-dependent glucose uptake into hepatocytes, myocytes, and adipocytes Dysfunction of pancreatic beta cells: accumulation of pro-amylin (islet amyloid polypeptide) in the pancreas → decreased navigate to this website endogenous insulin production Increased serine kinase activity in fat and skeletal muscle cells → phosphorylation of insulin receptor substrate (IRS)-1 → decreased affinity of IRS-1 for PI3K → decreased expression of GLUT4 channels → decreased cellular glucose uptake Peripheral insulin resistance ↑ demand for glucose lowering hormones → ↑ production of pro-insulin and pro-amylin click through the following document → enzymes can't keep up → accumulation of pro-amylin