diabetes Flashcards
presentation of acute diabetes
- polyuria
- weight loss
- polyphagia (always hungry)
- polydipsia (always thirsty)
- sweet breath + rapid breathing
presentation of chronic diabetes
- fatigue
- reduced wound healing
- poor vision
- reduced peripheral sensation (numbness in feet)
how are insulin and glucagon secretions coordinated
- glucose triggers insulin secretion by B-cells
- insulin inhibits glucagon secretion from a-cells by paracrine action
how is glucose sensed by B-cells of islets of langerhans
- glucose enters B-cells via GLUT2 transporter -> undergo glycolysis to produce ATP
- ATP used by ATP-dependent K+ channel in B-cell membrane to pump K+ intracellularly
- K+ cause depolarization -> voltage dependent Ca2+ channel open -> Ca2+ influx -> trigger insulin release from vesicles
production of functional insulin
PREPROINSULIN -> PROINSULIN by cleaving signal peptide + form disulfide bonds -> MATURE INSULIN by cleaving C-peptide
downstream effects of insulin on receptors
binds to RTK -> recruit IRS (insulin receptor substrates) and phosphorylate them -> phosphorylated IRS activate downstream signaling cascades
- Steroid receptor binding protein (SREBP) → lipid synth
- Mitogen activated protein kinase (MAPK) pathway → cell growth
- Phosphoinositide-3-kinase (PI3K) pathway
‣ ↑GLUT4 transporters, ↑K+ uptake
‣ ↑ protein synth via mammalian target of rapamycin (mTOR) pathway
‣ ↑ glycogen synth via dephosphorylation of glycogen synthase (↑protein phosphatase-1/↓glycogen synthase 3-β kinase)
types of diabetes
Type 1 (10%):
- zero insulin production, normal tissue response
Type 2 (90%):
- decreased insulin production, defective tissue response
pathogenesis of Type 1 diabetes
- destruction of beta cell (eg viral infection), usually by T-lymphocyte activation & immune mediated destruction
- pts develop AUTOANTIBODIES that can be detected & used for diagnosis (eg GAD, ICA)
acute type 1 diabetes presentation - pathophysiology
due to little insulin pdn:
- gluconeogenesis not inhibited + GLUT4 downregulated -> BGL high -> osmotic diuresis -> POLYURIA
- B-oxidation not inhibited -> excess ketone bodies -> metabolic acidosis -> RAPID BREATHING + SWEET BREATH (acetone in breath)
- protein breakdown + lipolysis not inhibited -> WEIGHT LOSS
- increase urea buildup from protein breakdown -> MENTAL (confusion) + DECREASE APPETITE
management of acute diabetes type 1
- fluid/ electrolyte replacement -> esp crucial to HEART function (needs K+, Na+ for depolarisation/ repolarisation)
- insulin replacement
treatment of chronic diabetes type 1
- continuous infusion of insulin via infusion pump OR
- intermittent dosing of insulin through subcutaneous injection
*key is to achieve glycemic + metabolic control
long term monitoring of blood glucose
- use HbA1c levels -> high BGL -> cause non-enzymatic glycation of hemoglobin (form Schiff base -> amadori product) -> INCREASE HbA1c levels
biggest risk factor of Type 2 diabetes
- CENTRAL OBESITY (visceral fat deposition) -> linked to metabolic syndrome
how does visceral fat lead to insulin resistance
- visceral fat accumulation is due to hypertrophy of adipocytes -> hypertrophy cause inflammatory response (M2 switch to M1 macrophages) -> secrete pro-inflammatory cytokines & release FFA (free fatty acids) -> INFLAMMATION
effect of cytokines & FFA:
- cytokines: block TNFa & NFkB pathway + PKC DESPITE IRS activation by insulin -> effects of insulin decreased
- FFA: increase fatty acid metabolism DESPITE IRS activation by insulin -> effect of insulin decreased
type 2 diabetes presentation pathophysiology
due to partial insulin effects:
- gluconeogenesis not inhibited + GLUT4 downregulated -> BGL high -> osmotic diuresis -> POLYURIA + THIRST -> DEHYDRATION
- protein breakdown + lipolysis not inhibited -> WEIGHT LOSS
- increase urea buildup from protein breakdown -> MENTAL (confusion) + DECREASE APPETITE
