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Flashcards in Metabolic Changes in DM Deck (17)
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1

describe T1DM

  • insulin dependent diabetes mellitus/juvenile onset 
  • autoimmune destruction of B-cells in the islets of the pancreas, causing a reduciton in insulin secretion
  • presents during adolescence
  • patients need to be on life-long insulin

2

describe T2DM

  • non-insulin dependent 
  • obesity is an important risk factor for dev. of T2D and insulin resistance
  • target tissues for insulin (liver, muscle, adipose) do not respond to circulating insulin (insulin resistance) and there is a decrease in insulin secretion with time (B-cell dysfunction)
  • usually respond to oral hypoglycemia agents 

3

describe the mechanisms of hyperglycemia in T1 and T2 diabetes

4

why does gluconeogenesis occur in diabetics?

  • the insulin/glucagon ratio is low (no insulin)
  • key gluconeogenic enzymes are activated (induced)
    • pyruvate carboxylase
    • PEPCK
    • F1,6 BPase
    • G6Pase
    • amino acids from muscle proteolysis are used as well
  • Glycolysis is inhibited in the liver
  • glycogenesis is inactive in liver and muscle

5

explain the basis of glycosuria and polyuria

  • in hyperglycemia, a large amount of glucose is filtered that exceeds the reabsorptive capacity of the tubule
  • glucose is osmotically active (holds water) that results in polyuria/osmotic diuresis

6

describe the flowchart of problems caused by decreased secretion of insulin/insulin resistance

7

describe why ketosis occurs in T1D

  • insulin deficiency results in uncontrolled adipose tissue lipolysis
    • HSL is overactive due to low insulin/glucagon ratio makes HSL in the active, phosphorylated form
  • this leads to an increase in free FA delivery to the liver
  • increased rates of B-oxidation (active CPT-1 and increased free FAs) results in the formation of acetyl CoA that is used for ketone body synthesis
  • ketogenesis in liver >>>> peripheral utilization of ketone bodies

8

explain the cause of metabolic acidosis

  • excessive ketone bodies are excreted in the urine (ketonuria) 
  • increased formation of 3-HB and acetoacetate; ketone bodies are weak acids and bicarb levels fall since they are used for buffering the excessive protons produced (metabolic acidosis)
  • increased anion gap 
  • compensation by the resp system = increased rate and depth of ventilation (hyperventilation) = Kussmaul breathing

9

describe effects of hyperglycemia

  • elevated blood glucose levels leads to glycosuria which results in increased water loss --> dehydration -> stimulation of the thirst center
  • coma is usually due to hyperglycemia (osmotic effect: water moves out of ICF resulting in neuronal dehydration) and is worsened by metabolic acidosis

10

describe changes in potassium levels in a diabetic

  • insulin deficiency and acidosis result in a shift of potassium from the ICF to the ECF
    • this results in loss of K in urine 
    • whole body K is reduced even though serum K is high
  • when insulin is injected during treatment, K moves back into the ICF
    • since K reserves are low, patient is in danger of hypokalemia; may have to give K along with insulin

11

describe the hyperosmolar, hyperglycemia state in T2D

  • most common in T2D, usually caused by infxn/acute illness which causes worsening of insulin resistance
  • hyperglycemia: plasmua glucose levels are markedly elevated
  • hyperosmolarity: osmolarity of blood is increased due to the high blood glucose levels (>320 mOsm/L)
  • polyuria caused by excessive loss of water in urine
  • low blood volume caused by polyuria
  • ketone body prod. NOT significant 
    • patients have some insulin secretion which inhibits ketogenesis

12

explain the cause of a coma in hyperglycemia patients

  • intracellular dehydration in the neurons, as ICF water moves into ECF 
    • high plasma osmolarity since glucose is osmotically active, which causes changes in hydration of neurons, which leads to neurological deficits and unconsciousness (coma)

13

what are chronic complications of diabetes?

  • patients have a higher plasma glucose levels -> higher HbA1c levels
  • microvascular: eyes, retina, neurons, kidney
  • macrovascular: atherosclerosis

14

explain how sorbitol causes microvascular complications

  • in the lens, nerve and kidney, sorbitol is formed by aldose reductase
    • sorbitol is osmotically active and results in cell swelling due to water retention

15

describe the effect of advanced glycation end products (AGE)

  • non-enzymatic addition of glucose to intracellular and extracellular proteins (process similar to formation of HbA1c)
  • glycation of proteins results in cross-linking of glycated proteins and altered function
    • this leads to glomerular dysfunction, endothelial damages and changes in extracellular matrix
  • AGE modified proteins are also more prone to oxidative damage

16

describe how AGE affects neurons, nephrons, endothelium

  • AGEs alter metabolism and function of neuronal proteins
    • AGEs bind to their receptors and cause release of proinflammatory molecules
  • alteration of the glomerular basement membrane proteins of nephron -- loss of albumin in urine (microalbuminuria)
  • changes in endothelium -- peripheral vascular disease

17

explain how dyslipidemia leads to macrovascular complications

  • patients with T1 and T2D have hypertriglyceridemia (increased circulating triglycerides) = there is increased chylomicrons and VLDL in circulation
    • due to decreased action of endothelial LPL (induced by insulin)