Type 1 DM

Question 1

Pathophysiology

Answer 1

• autoimmune destruction of beta cells so no insulin to maintain glucose and FA metabolism
• sensitive to insulin but low levels
• T cells cause damage but antibodies are just a marker of destruction (not major cause of destruction)
• Lymphocytic infiltrate on histo

Question 2

Which 2 antibodies are used clinically?

Answer 2

• ICA (islet cell antibodies) - used clinically; dec w/ DM duration (used in peds)
• GAD (glutamic acid decarboxylase) - used clinically; in adults too

Question 3

Risk Factors / Susceptibility (5)

Answer 3

• Childhood - peaks 5-7 yo; puberty; can also present in young adults
• Caucasians > blacks
• Seasonal / geographic - Finland high
• Only 30-50% MZ concordance
• HLA-DR3, DR4, DQ alpha and DQ beta

Question 4

Natural Hx

Answer 4

• Genetic predisposition + precipitating event –> insulin secretion declines until it becomes insufficient to maintain normal glucose homeostasis –> hyperglycemia symptoms (patient presents)
• Initial presentation = glycosuria, dehydration, thirst, nocturia, CATABOLIC (wt loss, polyphagia - hungry, weak, lethargic)
• Often diagnosis occurs after an acute stress or illness which transiently increases insulin requirement THEN when the stress is relieved the residual islet tissue may be sufficient to maintain normal glucose homeostasis for a period of a few months (HONEYMOON PERIOD)
• After this period, permanent insulin deficiency usually ensues

Question 5

Diabetic Ketoacidosis Process

Answer 5

• Insulin inc endothelial lipoprotein lipase (extracellular) and inhibits hormone sensitive lipase (intracellular) to inc TG storage (AKA TGs not broken down in cells)
• SO… if no insulin / inc glucagon –> inc glucose in blood AND TG/AA breakdown (provide gluconeogenesis substrates)
• Excess FAs to liver –> ketone body production
• Why? b/c glucose (glycolysis) or FAs (beta oxidation) –> acetyl CoA –> Krebs cycle or ketogenesis; w/o insulin the OAA is shunted to gluconeogenesis NOT Krebs cycle so get acetyl CoA –> ketogenesis

Question 6

DKA Labs

Answer 6

Hyperglycemia (although may be normal blood glucose)

low bicarb/low pH (acidosis)

Osm < 320 (as opp. to HHS)

Question 7

Ketones

Answer 7

• Beta-hydroxybutyrate, acetoacetate (both excreted in urine so test in urine)
• Acetone by-product excreted by expiration (smell on breath)
• Ketones are acids, meaning that for each mmol of ketone formed, one mmol or hydrogen ion (H+) is produced (high anion gap acidosis >12)
• Anion Gap = Na - (Cl + bicarb)

Question 8

Common Causes of DKA

Answer 8

5 I’s

• Infection
• Infarction - MI, stroke
• Insulin Omission -new onset - no treatment yet; or stop insulin purposefully
• Indiscretion - drugs/alcohol
• Infants - pregnancy

Question 9

DKA Tx

Answer 9

• Volume replacement (need more in HHS generally)
• Anticipate that giving insulin will drive K+ into cell (K+ replacement?)
• Insulin - lower blood glucose and stop ketogenesis (cont insulin even when serum glucose normalizes b/c takes longer to stop ketogenesis)
• Monitor electrolytes and ketones in urine (about every 4 hrs)