Immunology of diabetes

Question 1

How do you diagnose antibodies to the pancreatic islets?

Answer 1

Healthy pancreas section
Type I serum
Fluorochrome labelled for anti-human antibody

Question 2

What are the major islet autoantigens?

Answer 2

GAD
IA2
Insulin
ZnT8

Question 3

What is the NOD mouse model of T1D?

Answer 3

For studying the pancreas in T1D
Destruction of the beta cells
Non-obese diabetic mouse

Question 4

What is insulitis?

Answer 4

Disease of the pancreas caused by the infiltration of lymphocytes

Question 5

What is T cell antigen transfer?

Answer 5

The T cells from a type I diabetes patients would induce type I diabetes in a healthy patient
Modelled in NOD mouse

Question 6

What happened when cyclosporin immunosuppression in newly diagnosed T1D?

Answer 6

Cyclosporin is an immunosuppressor

Increased C peptide levels

Question 7

What evidence is there for type 1 diabetes being immune mediated?

Answer 7

Histology of insulitis
Disease can be transferred through transfer of T cells
Immunosuppression preserves beta cell function
Genes identified are related to the immune system
Antibodies predate and predict disease

Question 8

What happens to beta cell function

Answer 8

After diagnosis of type 1 diabetes, C-peptide levels fall

Lessening of beta cell function with time

Question 9

How is c-peptide linked to retinopathy?

Answer 9

Higher c-peptide levels reduce chance of retinopathy

Question 10

How can we prevent type 1 diabetes in at risk relatives?

Answer 10

Anti CD3
Oral insulin
CTLA4 Ig
Omega 3

Question 11

How can we treat type 1 diabetes in newly diagnosed patients?

Answer 11

Intensive glucose control
anti IL1beta
GAD
CTLA4 Ig
Anti CD20
Daclizumab
Mycophenolate mofetil

Question 12

What is Rituximab?

Answer 12

Anti CD20 monoclonal antibody

Preserved beta cell function

Question 13

What are non-genetic contributions to type 1 diabetes?

Answer 13

Migrants acquire same risk for type 1 diabetes as their new area
Obesity and insulin resistance
The hygiene hypothesis
Vitamin D deficiency

Question 14

What was the effect of parasitic infection on mice?

Answer 14

Prevented murine diabetes

Question 15

Can exercise preserve beta cell function in type I diabetes?

Answer 15

In a NOD mouse model of type I
Treated with streptzotocin to destroy islets of Langerhans
Beta cell mass increases and is better maintained
Fewer cases of insulitis

Question 16

What is the EXTOD study?

Answer 16

Conducted by the NIHR
30 on exercise, 28 on control
Insulin sensitivity significantly decreased
Beta cell preserved with exercise