Glucose metabolism disorders Flashcards
How does sorbitol play a role in pathology associated with hyperglycemia?
sorbitol accumulates in the cell as there are no transporters out of the cell, and it causes osmotic swelling -> cataracts
How does sorbitol accumulation in cells occur?
alders reductase pathway -> when BG is high, glucose enters the cell, goes through this pathway and the product is sorbitol
Why does increased reduction of glucose to sorbitol put the cell at risk for increased oxidative stress?
aldose reductase pathway requires NADPH
What diabetic complications does accumulation of sorbitol cause?
cataracts, peripheral neuropathy, vascular problems leading to neuropathy and retinopathy
What is HgBA1c a product of?
HgBA1c is a variant of hemoglobin that occurs due to glycation - excess glucose reacting with amino group of proteins - in this case reacting with N-terminal valine of hemoglobin beta chain
Why do we measure A1c?
Tells us about how high the BG has been over a period of about 4 months (lifespan of a red blood cell)
What is the difference between glycation and glycosylation? Which is more affected by hyperglycemia?
Glycation is unregulated, Non enzymatic, a product of time, temperature and glucose level.
Glycosylation is enzymatic and regulated by many factors other than glucose level.
Glycation is more affected by hyperglycemia
Why is A1c variable?
b/c lifespan of RBC is variable d/t differences in oxidative stress, etc
Why can increasing basal insulin dose worsen feelings of hunger/cause weight gain?
Drives the BG down during the day by preventing glycogenolysis and gluconeogenesis between meals, making the patient feel more hunger - need to replenish glucose
What is the job of basal insulin?
keeps BG down at night by suppressing glycogenolysis and gluconeogenesis overnight
Why does DKA usually only occur in patients with T1DM?
T2DM patients still have some restraint of glycogenolysis/glucoeneogenesis due to having some insulin
How does ketogenesis occur?
insulin drops -> glucose is not utilized and remains in the bloodstream -> lipolysis increases -> free fatty acids increase -> free fatty acids are converted into ketones
What happens when insulin is insufficient or absent?
proteolysis (muscle breakdown for conversion into glucose in the liver
lipolysis (fat breakdown into glycerol and FFAs to be converted into glucose and ketones in the liver)
Increased glucagon release -> increased processes that elevated blood glucose & ketogenesis
What is the pathology of T1DM?
autoimmune disease - causes death of pancreatic B-cells and then no circulating insulin to counteract glucagon and epinephrine or store glucose in cells
Why do diabetics have more fatty acids in their bloodstream?
insulin normally prevents the breakdown of adipose tissue
