CM: Diabetes

Question 1

What are the ADA criteria for diagnosing DM?

Answer 1

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

Question 2

What are the two categories for increased risk of diabetes (prediabetes)?

Answer 2

impaired fasting glucose - levels of 100-125

impaired glucose tolerance - 2 hr values in oral tolerance test of 140-199

Question 3

How do beta cells sense glucose levels?

Answer 3

GLUT2 actively transports glucose into beta cell - glucokinase phosphorylates and traps it in cell - glycolysis then produces ATP - inhibits ATP sensitive K channel –> depolarization

Question 4

How is insulin synthesized and secreted?

Answer 4

synthesized as preprohormone - cleaved by carboxypeptidase to yield alpha and beta chains joined by 2 disulfide bonds and C peptide

Question 5

What else do beta cells produce other than insulin and c peptide?

Answer 5

amylin - helps suppress glucagon, slows gastric emptying, promotes satiety
reduced or absent in DM

Question 6

How does insulin work?

Answer 6

binds receptor tyrosine kinase, autophosphorylates, binding sites for signalling molecules

Question 7

How does insulin promote glucose uptake?

Answer 7

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

Question 8

How does insulin inhibit glucose production and promote glucose storage?

Answer 8

inhibits hepatic gluconeogenesis (PEPCK)
inhibits glycogenolysis (glycogen phosphorylase)
promotes glycogen synthesis (glycogen synthase)

Question 9

What are insulin’s actions in the liver regarding fat metabolism?

Answer 9

promotes synthesis of FAs
inhibits FA oxidation
inhibits VLDL production

Question 10

What are insulin’s actions in adipose tissue regarding fat metabolism?

Answer 10

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

Question 11

What does insulin do to proteins?

Answer 11

promotes synthesis and storage - increases initiation and elongation factors and suppresses protein catabolism

Question 12

How do catecholamines act as counter-regulatory hormones?

Answer 12

increased secretion from adrenal medulla as glucose falls - stimulate beta2 adrenergic receptor mediated promotion of glycogenolysis and gluconeogenesis, promote symptoms of hypoglycemia

Question 13

What are 2 less important counter-regulatory hormones against hypoglycemia?

Answer 13

GH: stimulates glycogenolysis and gluconeogenesis, promotes FFA release for formation of ketones
cortisol: stimulates gluconeogenesis

Question 14

What is the natural history of type I DM?

Answer 14

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

Question 15

What is latent autoimmune diabetes of adulthood (LADA)?

Answer 15

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

Question 16

What controversial environmental associations have been made with type 1 DM?

Answer 16

coxsackie b, exposure to cow milk, shorter breast feeding, low vitamin D

Question 17

What is the criteria for LADA?

Answer 17

at least 30
1 of 4 antibodies present
not treated w insulin for first 6 mos after diagnosis

Question 18

What is type 1B diabetes (idiopathic)?

Answer 18

present w DKA but lack antibodies of type 1
obese
insulin required in acute insulin def state
insulin requirements decrease, some can transition to oral

Question 19

What is the natural history of type 2 DM?

Answer 19

long asymptomatic as compensatory hyperinsulinemia, macrovascular complications –> beta cells begin to fail, DIABETES, microvascular complications

Question 20

What is the ominous octet of type 2 DM?

Answer 20

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)

Question 21

What is maturity onset diabetes of the young (MODY)?

Answer 21

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

Question 22

What are the possible maternal complications of gestational DM?

Answer 22

preeclampsia
polyhydramnios
asymptomatic bacturia and UTI
future progression to type 2

Question 23

What are the possible fetal complications of gestational DM?

Answer 23

macrosomia (>4000g)
neonatal hypoglycemia
jaundice
hypcalcemia
polycythemia

Question 24

How is GDM diagnosed?

Answer 24

screen b/w 24-28 weeks gestation

75g oral glucose tt - fasting >92, 1 hr >180, or 2 hr >153