01-07 DM Type 1

Question 1

LADA?

Answer 1

latent autoimmunity diabetes of adulthood

Question 2

peak incidence in DM1?

Answer 2

10-14 y/o

Question 3

Incidence of Type 1 DM:
—over time
—cross-countries?

Answer 3

—increasing over time
—greatly varied between different countries:
——Finland & Sardinia ~40 per 100,000 ♂s
——Hong Kong & Beijing < 3 per 100,000 ♀&♂

Question 4

Which HLA subtypes are assoc’d w/ DM1?

Answer 4

HLA DR3 & DR4

—DR2 protective

Question 5

What polymorphisms assoc’d w/ ↑ predisposition to DM1?

Answer 5

HLA DR3 & DR4 (DR2 protective)
—accounts for 50% of risk for family-based DM1

IDDM-2 insulin gene
—10% of risk for family-based DM1
—shorter VNTRs in promoter region

PTPN22
—codes lyphmphoid tyrosine phosphatase which is intracell part of antigen reception cascade

CTLA-4 (cytotoxic T-lymphocyte antigen 4)
—inhibits T-cell activation

**HLA Class II, CTLA-4 & PTPN22 also implicated in other autoimm (Hashimoto’s, Addison’s, sprue, etc.)

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Question 6

What evidence do we have that DM1 is, at least in part, brought on by an environmental precipitant?

Answer 6

— < 50% concordance in MZ twins
—migrating populations
—incidence ∆s seasonally

CONGENITAL RUBELLA
—definite enviro cause of DM (rare cases)

PUTATIVE CAUSES
—Coxackie B, encephalomyocarditis, CMV, EBV, mumps, rotavirus
—Diet: ?gluten, ?cow’s milk? (age at first beginning to eat that particular food likely matters)
—Nitrates
—β-cell toxins (e.g. pyrinuron, a rodenticide)
—Stress
—Hygiene hypothesis

Question 7

Which circulating Islet-Antibodies most predictive of T1DM?

Answer 7

Present in 90% of new cases!
—IAA (insulin autoantibodies) in youngest
—GAD 65 (Glutamic acid decarboxylase) and GAD 67 autoABs are most persistent
—IA-2 ABs (to tyrosine phosphatase) Indicate high risk, but are short-lived

**—the more different Ab’s you have, the higher your risk of developing T1DM

Question 8

1 Carb “choice” = how many grams carbohydrates?
—what should daily intake be?
—How much does 1 Carb raise your blood sugar?

Answer 8

—15g
—daily intake should be ~135-180/day (so < 60g/meal)
—1 carb raises BG by 50-75mg/dL

Question 9

How do you dose insulin w/ meals? (i.e. units/gms carbs)

Answer 9

—1u : 10g carbs

Question 10

How long of a window of time does an HbA1c give you?

Answer 10

2-3 months

Question 11

How do you measure long-view avg BG in pts w/ SCD or thalassemia?

Answer 11

Fructosamine

—gives avg over 2-4wks

Question 12

What is Type 1A vs. Type 1B DM?

Answer 12

Type 1A: autoimmune

Type 1B: non-autoimmune