Met 1: T1D Pathophys

Question 1

What is the normal effect of insulin on the liver and muscle cells?

What happens in T1D?

Answer 1

• Normally, insulin
  
  • Prevents gluconeogenesis and glucose release in liver
  • Promotes uptake of insulin by cells
• In T1D,
  
  • Liver keeps making/releasing glucose
  • Cells can’t take glucose in and starve
  • Both of these contribute to high blood sugar

Question 2

T1D is __________ destruction of ___ cells, mediated by _________ immunity.

Answer 2

T1D is autoimmune destruction of beta cells, mediated by T-cell immunity.

Question 3

What are the cutoffs for fasting glucose?

Answer 3

Fasting glucose

• Normal: under 100
• Intermediate: 100-125
• DM: 126+

Question 4

What are the cutoffs for oral glucose tolerance test?

Answer 4

Oral glucose tolerance test (at 2 hrs)

• Normal: under 140
• Intermediate: 140-199
• DM: 200 +

Question 5

What are the cutoffs for HbA1c?

Answer 5

HbA1c

• Normal: 5.6 or less
• Intermediate: 5.7-6.4
• DM: 6.5+

Question 6

Are sugar abnormalities needed to diagnose T1D?

Answer 6

NO. T1D can be diagnosed based on presence of Beta-cell autoAbs

Question 7

Name 3 other conditions associated with T1D

Answer 7

1. Celiac
2. Hypothyroidism
3. Addison’s Disease

(all autoimmune conditions)

Question 8

Name 4 potential triggers for T1D

Answer 8

• Diet
• Weight
• Infection
• Hygiene Hypothesis (insufficient Ag exposure during childhood)

Question 9

What genes increase risk of T1D?

Compare the heritability of T1 and T2D

Answer 9

• HLA DR3/4 increase risk of T1D
  
  • (3,4 sugar no more)
• Overall T1D is much less heritable than T2D

Question 10

Describe normal insulin release from a beta cell

Answer 10

1. Glucose comes into cell via GLUT2
2. Glucose metabolism makes ATP
3. ATP causes K channels to close
4. Depolarization
5. Voltage gated Ca channels open
6. Vesicles full of insulin fuse with membrane

Question 11

Name 4 auto-Ab’s that can be found in T1D

Answer 11

• Zinc
• GAD
• IA-2
• Insulin

Geez, it would be incredible to have insulin!

Question 12

Describe T1D staging

Answer 12

Stage 1: AutoAb’s present, but no sugar abnormalities or sx

Stage 2: AutoAb’s and sugar abnormalities present, but no sx

Stage 3: AutoAb’s, sugar abnormalities, and sx all present

Question 13

Compare the typical BMI and age of onset for T1D and T2D

Answer 13

T1D: low BMI (lean), early childhood or adolescent onset

T2D: high BMI (overweight), post-puberty onset

Question 14

Is insulin always needed in T1D?

Answer 14

YES. Insulin tx is always needed in T1D

Question 15

Compare what comorbid conditions are associated with T1D and T2D

Answer 15

T1D: Autoimmune diseases (Hypothyroid, Celiac, Addision’s)

T2D: HTN, obesity, hyperlipidemia

Question 16

Which type of diabetes typically has DKA at onset?

Answer 16

T1D!

Question 17

What effect does intensive early treatment and immune-modulation have on T1D?

Answer 17

Both can delay the onset of symptomatic T1D (preserve beta cell function for a while).