Pathophysiology of Type 1 Diabetes

Question 1

Type 1 Diabetes

Answer 1

T cell mediated autoimmune disease against pancreatic beta cells

Probably involves some genetic predisposition and then a precipitating event

Antibodies can be identified years before symptoms even though t-cell mediated

Question 2

Autoantibodies seen in type 1 diabetes

Answer 2

Islet cell autoantibody (ICA) to: insulin, glutamic acid decarboxylase 65 (GAD65), tyrosine phosphatase like protein (IA-2), and a zinc transporter (ZnT8)

Multiple antibodies has a much higher risk of getting T1D than single antibody

Question 3

Typical progression of type I diabetes

Answer 3

As the autoimmune attack progresses, β cells are lost until the remaining β cell mass is no longer able to maintain normoglycemia and metabolic abnormalities develop.

The first metabolic abnormalities that develop are seen in states in which the most insulin is required

One of the first identifiable metabolic abnormalities is a decrease in the First Phase Insulin Response which can be tested through IV glucose tolerance test and oral glucose tolerance test.

Question 4

Glucose lab values for type 1 diabetes

Answer 4

Fasting glucose: normal (125)

Oral GTT: normal (199)

HbA1c ≥ 6.5%

Question 5

When do pts present with symptoms of type 1 diabetes? (What percent of beta-cells destroyed?)

Answer 5

80-90% of the β cell mass has been destroyed

Question 6

Symptoms of type 1 diabetes

Answer 6

Osmotic diuresis leading to polyuria, polydipsia, nocturia and new onset enuresis (bed wetting).

Weight loss or lack of expected weight gain may also occur.

Can result in the development of diabetic ketoacidosis (DKA), which can be life threatening.

Question 7

High-risk HLA genotypes

Answer 7

DRB10301, DQA10501, DQB10201 /DRB104, DQA10301, DQB10302 often referred to as DR3/4

Question 8

HLA genotypes protective for Type 1 Diabetes

Answer 8

DQA10102, DQB10602 haplotype

Question 9

Possible environmental factors that could be involved in the development of type I diabetes

Answer 9

Viruses, hygiene hypothesis (we are too clean and don’t get enough exposure so immune system gets messed up), diet, accelerator hypothesis (increasing incidence is due to increase in obesity)

No one explanation right now