Type 1 diabetes mellitus (mechanism of disease)

This is a mechanism of disease map for type 1 diabetes, covering the etiology, pathophysiology, and clinical manifestations.

ADDITIONAL TAGS:
Autoimmunity
Signs / symptoms
Labs / tests / imaging results
Type 1 diabetes mellitus
Etiologies
Core concepts
Genetics / hereditary
Microbial pathogenesis
Osmolarity regulation
Intercellular communication
Glucose homeostasis
Energy balance
Manifestations
Pathophysiology
Genetic predisposition:
HLA-DR3 and HLA-DR4
Viral infection
Autoimmune destruction of pancreatic beta cells:
anti-glutamic acid decarboxylase Ab (anti-GAD)
and/or anti-islet cell cytoplasmic Ab (anti-ICA)
Other autoimmune conditions: Hashimoto thyroiditis; type A gastritis; Celiac disease; primary adrenal insufficiency
↓ insulin secretion → compensatory ↑ glucagon secretion
Adipose catabolism (lipolysis → release of glycerol + fatty acids)
Muscle catabolism (protein breakdown + release of amino acids)
↑ hepatic fatty acid oxidation
↑ ketone body production
Ketosis: ↑ urine and serum ketones
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