Flashcards in CM: Diabetes Deck (24):
What are the ADA criteria for diagnosing DM?
fasting plasma glucose >126 mg/dl
random plasma glucose >200 mg/dl in a pt with classic symptoms
hemoglobin A1c >6.5%
plasma glucose 2 hrs after ingestion of oral load of >200 mg/dl
What are the two categories for increased risk of diabetes (prediabetes)?
impaired fasting glucose - levels of 100-125
impaired glucose tolerance - 2 hr values in oral tolerance test of 140-199
How do beta cells sense glucose levels?
GLUT2 actively transports glucose into beta cell - glucokinase phosphorylates and traps it in cell - glycolysis then produces ATP - inhibits ATP sensitive K channel --> depolarization
How is insulin synthesized and secreted?
synthesized as preprohormone - cleaved by carboxypeptidase to yield alpha and beta chains joined by 2 disulfide bonds and C peptide
What else do beta cells produce other than insulin and c peptide?
amylin - helps suppress glucagon, slows gastric emptying, promotes satiety
reduced or absent in DM
How does insulin work?
binds receptor tyrosine kinase, autophosphorylates, binding sites for signalling molecules
How does insulin promote glucose uptake?
stimulates translocation of GLUT1 and GLUT4 to membrane in muscle and fat
glucose uptake in liver is insulin independent - more goes here when insulin def
How does insulin inhibit glucose production and promote glucose storage?
inhibits hepatic gluconeogenesis (PEPCK)
inhibits glycogenolysis (glycogen phosphorylase)
promotes glycogen synthesis (glycogen synthase)
What are insulin's actions in the liver regarding fat metabolism?
promotes synthesis of FAs
inhibits FA oxidation
inhibits VLDL production
What are insulin's actions in adipose tissue regarding fat metabolism?
promotes breakdown of TGs into FFAs for uptake into fat cells
promotes re-esterification of FFAs into TGs inside fat cells
promotes synthesis of FAs
inhibits breakdown of TGs in and release of FAs from fat cells
What does insulin do to proteins?
promotes synthesis and storage - increases initiation and elongation factors and suppresses protein catabolism
How do catecholamines act as counter-regulatory hormones?
increased secretion from adrenal medulla as glucose falls - stimulate beta2 adrenergic receptor mediated promotion of glycogenolysis and gluconeogenesis, promote symptoms of hypoglycemia
What are 2 less important counter-regulatory hormones against hypoglycemia?
GH: stimulates glycogenolysis and gluconeogenesis, promotes FFA release for formation of ketones
cortisol: stimulates gluconeogenesis
What is the natural history of type I DM?
genetic predisposition & environmental trigger --> insulitis and beta cell injury (T cell mediated), humoral autoantibodies --> pre diabetes and loss of first phase insulin response --> glucose intolerance and clinical onset
What is latent autoimmune diabetes of adulthood (LADA)?
less severe type 1 in adults - progresses more slowly to full beta cell death in absence of insulin resistance
usually non-obese and quick progression to insulin
What controversial environmental associations have been made with type 1 DM?
coxsackie b, exposure to cow milk, shorter breast feeding, low vitamin D
What is the criteria for LADA?
at least 30
1 of 4 antibodies present
not treated w insulin for first 6 mos after diagnosis
What is type 1B diabetes (idiopathic)?
present w DKA but lack antibodies of type 1
insulin required in acute insulin def state
insulin requirements decrease, some can transition to oral
What is the natural history of type 2 DM?
long asymptomatic as compensatory hyperinsulinemia, macrovascular complications --> beta cells begin to fail, DIABETES, microvascular complications
What is the ominous octet of type 2 DM?
impaired insulin secretion by pancreas
excessive hepatic glucose output
decreased glucose uptake in muscle
insulin resistance in brain
increased glucagon secretion from alpha cells
increased lipolysis from fat cells
increased glucose reabsorption at kidney
decreased incretin effect from GI tract (normally released postprandial and stimulate insulin)
What is maturity onset diabetes of the young (MODY)?
onset before 25, not ketotic
AD defects in beta cell transcription factors
neither obese or insulin dependent like type 1
can be controlled w oral agents, like type 2
What are the possible maternal complications of gestational DM?
asymptomatic bacturia and UTI
future progression to type 2
What are the possible fetal complications of gestational DM?