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Diabetes Mellitus Pathophysiology Behind Lab Findings

Diabetes Mellitus: Pathophysiology behind laboratory findings Author: Nathan Archibald Reviewers: Gurreet Bhandal, Julia Gospodinov, Luiza Radu Samuel Fineblit* * MD at time of publication ↓ Transit of glucose transporter GLUT4 to cell surface (mainly adipose & muscle cells) ↓ Glucose uptake into cells Autoimmune destruction of pancreatic beta cells (type 1 diabetes mellitus) Insulin resistance (type 2 diabetes mellitus) Other causes of diabetes mellitus (genetic, drug- induced, pregnancy, etc.) ↑ Lipolysis (fat breakdown) in adipose tissue ↑ Free fatty acids & glycerol in bloodstream ↑ Oxidation of fatty acids in liver to form acetyl CoA ↑ Conversion of acetyl CoA to ketone bodies (ketogenesis) to be used as fuel for the brain Relative or absolute insulin deficiency ↓ Activation of adipose (fat tissue) & muscle cell transmembrane insulin receptors ↓ Activation of intracellular insulin signaling pathways (PI3K & MAP kinase) Cells cannot use glucose as a source of energy; thus body reacts as if it is starving ↑ Protein breakdown in muscle tissue ↑ Amino acids & lactate in bloodstream ↑ Substrates (glycerol, amino acids & lactate) available to produce glucose in the liver ↑ Glycogenolysis (breakdown of stored glucose - glycogen) & gluconeogenesis (production of glucose) in liver Glucose in bloodstream glycates (coats) hemoglobin in red blood cells; thus ↑ blood glucose leads to ↑ glycated hemoglobin ↑ Hemoglobin A1C ↑ Fasting blood glucose level ↑ Random blood glucose level ↑ Blood glucose following oral glucose tolerance test Diabetic ketoacidosis (DKA) in absolute insulin deficiency *See DKA slide Filtered ketone bodies exceed the reabsorption capacity of renal tubules Ketonuria (↑ ketones in urine) ↑ Glucose in bloodstream Build-up of glycation end products causes damage to glomerular tissue Transient glomerular hyperfiltration followed by long-term ↓ in glomerular filtration rate Albuminuria (↑ albumin in urine) Diabetic nephropathy *See slide Filtered glucose exceeds reabsorption capacity of renal tubules in the kidney Glucosuria (↑ glucose in urine) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 8, 2024 on www.thecalgaryguide.com