79 - Autoimmune Diabetes

Question 1

Prevalence of type 1 DM

Answer 1

0.5% in Australia

Question 2

Main antigen in T1DM autoimmunity

Answer 2

Insulin

Question 3

Role of autoantibodies in T1DM

Answer 3

Probably not causative. Used to diagnose.

T cells probably cause disease.

Question 4

Stages in development of T1DM

1-5

Answer 4

1) Born with a predisposition, but not with full-blown DM
2) Precipitating event
3) Immune tolerance is broken, appearance of autoantibodies
4) Progressive loss of beta-cell mass
5) Overt diabetes appears, with C-peptide present

Question 5

Probability of developing diabetes over next fifteen years with appearance of autoantibodies

Answer 5

With three islet autoantibody types, 80% chance of developing DM over fifteen years

Question 6

Median age of seroconversion to islet autoantibodies

Answer 6

2.1 years

Question 7

Diagnosis of T1DM

Answer 7

• Clinical – symptoms, weight, ketoacidosis,
insulin requirement
• Autoantibodies
• Latent autoimmune diabetes in adults
– GAD antibodies
– 10% of type 2

Question 8

Latent autoimmune diabetes in adults

Answer 8

People who present as type II diabetes in adulthood who actually have type I (have autoantibodies, need insulin)

Question 9

C-peptide

Answer 9

Peptide that links alpha and beta chains of insulin.

Present in blood with T1DM

Question 10

Differences in insulin content between T1DM islets

Answer 10

Some have high insulin content, some are completely depleted.
Some have significant inflammatory infiltrate (often islets with less insulin)

Question 11

Cells present in T1DM islets

Answer 11

Only beta cells missing.

Glucagon can be detected (so alpha cells are intact)

Question 12

APS-1

Answer 12

Autoimmune polyglandular syndrome 1.

Mutations in AIRE leads to multiple autoimmune disorders (Addison’s, hypoparathyroidism, T1DM susceptibility)

Question 13

IPEX

Answer 13

Immune dysfunction, polyendocrinopathy, enteropathy, X-linked.

Mutation of FoxP3 gene, which controls Treg cells.
About 80% of children with IPEX develop DM

Can be treated with bone marrow transplantation.

Question 14

Part of pro-insulin that many T cells recognise in autoimmune DM

Answer 14

C-peptide

Question 15

Environmental triggers for autoimmunity

1-6

Answer 15

• UV
• Diet
• Drugs
• Tissue specific eg iodine
• “hygiene”
• Infection

Question 16

Trend of incidence of T1DM

Answer 16

Increasing since the second world war

Question 17

Problem with current insulin treatment

1-5

Answer 17

• Incapable of mimicking physiological
glucose control
• Therefore can’t prevent complications
– Hypoglycaemia
– Long-term complications
• Injected multiple times per day
• Burdensome
• Falls well short of a “cure

Question 18

What is islet transplantation currently used for?

Answer 18

Treating people with severe hypoglycaemia that is not controlled pharmacologically.
Very effective at reducing need for exogenous insulin, much more effective control of blood glucose

Question 19

Problems with islet transplantation

1-4

Answer 19

1) Availability of islet transplants
2) Viability, function of islets
3) Need immunosuppression
4) Cost