Type 1 Diabetes

Question 1

Cause/Clinical Onset/Prevalence

Answer 1

AUTOIMMUNE DESTRUCTION OF PANCREATIC BETA ISLET CELLS
Clinical onset at 80% beta cells lost
Genetic and Environmental etiology
Prev: 1/300 gen pop, 1/20 if first degree rel, 1/1-3 in monozygotic twin
Higher in western Europe, US, Australia, Lower in Africa and Chine

Question 2

Genetics

Risk/Protective/Insulin gene

Answer 2

Risk is ADDITIVE!
Risk: HLA-DR3/4 (codes MHC class II)
Protective: HLA-DR2
Insulin gene: Class I VNTR (tandem repeats) in 5’ region –> less insulin expressed in thymus –> decreased ability to distinguish insulin as pathogen rather than self

Question 3

Environmental

Answer 3

Viruses, breastfeeding, timing of food introduction
Hygiene hypothesis, accelerator hypothesis (obesity speeds up onset)
Vit D may be protective

Question 4

Associated co-morbidities

Answer 4

Automimmune thyroid (15-20%)
Celiac (5-10%)
Addison’s (1-1.5%)

Question 5

DIAGNOSTIC: Fasting glucose/OGTT/random blood sugar

Answer 5

> 126 mg/dl on 2 occasions (FASTING so no food for >8hrs)
OGTT (2 hr oral glucose tolerance test): >200 mg/dl
Random blood sugar >200 AND sx of DM

Question 6

DIAGNOSTIC HbA1c/Ab/labs (4 things)

Answer 6

HbA1c >6.5% on 2 occasions
Islet cell Ab (ICA) to islet autoantigens (IA-2, GAD65, ZnT8) or insulin itself (mIAA)
If you have 2+ ICAs then will progress to DM
Most of the damage is T-cell mediated (although there are Ab, no good test for T-cell)
LOW C-PEPTIDE
Decreased First phase insulin response (FPIR = insulin released in 1st and 3rd minute following IV glucose)

Question 7

Treatment

Answer 7

humanized INSULIN (shots or continuous SC infusion)
STATINS (only >40 yrs if lipid profile normal)
CONTINUOUS GLUCOSE MONITORING SYSTEMS

Question 8

Primary Prevention

Answer 8

infant diet changes etc. to STOP BEFORE DEVELOPMENT OF autoAb

Question 9

Secondary Prevention

Answer 9

prevent the autoAb from developing clinical sx (ie. oral insulin)

Question 10

Tertiary Insulin

Answer 10

prevent progression of dz (ie with anti-CD3 Ab, Abatacept)

Question 11

DAISY study findings

Answer 11

Diabetes Autoimmune Study in the Young
AutoAb negative until ~8yrs
Clinical signs of M at 11-15 yrs
If have 2+ positive ICA then they’ll get diabetes (just matter of time)

Question 12

Presentation (age/sx/acute pres/family hx/)

Answer 12

Usually in childhood (peak incidence is 10-12 yrs old, though presenting more in