Type 1 Diabetes

Question 1

At what HbA1c is someone suspected of having diabetes?

Give both % and mol/mol

Answer 1

6.5%

48mmol/mol

Question 2

When is HbA1c not used to diagnose someone of diabetes?

What alternative test is used and what is the cutoff value?

Answer 2

• People younger than 18
• pregnant or <2 months post-partum
• people on corticosteroids (as may cause hyperglycaemia
• people with pancreatic damage or CKD
• HIV+

Fasting blood glucose 7.0mmol/L or greater

Question 3

How many tests must be undertaken before diabetes can be diagnosed?

Answer 3

Single HbA1c or single fasting plasma blood glucose IF PATIENT IS SYMPTOMATIC

Multiple tests should be done if patient is NON-symptomatic

Question 4

What do pancreatic alpha cells produce?

What does this do?

Answer 4

Glucagon

Raises blood glucose levels

Question 5

What do pancreatic delta cells produce?

What does this do?

Answer 5

Somatostatin

Inhibits growth hormone

Question 6

What do pancreatic beta cells produce?

What does this do?

Answer 6

Insulin

Promotes cellular intake of glucose into muscle and adipose tissue

Question 7

How does insulin work with respect to glucose transport?

Answer 7

Encourages Glut4 transporters to translocate into muscle and adipose tissue cell membranes to take up glucose

Question 8

What is insulitis?

Answer 8

An infiltration or immune cells into the islet of langerhans seen in T1DM

Question 9

In what trimester of pregnancy does trans-placental transfer of antibodies occur?

Answer 9

3rd

Question 10

Are autoantibodies in T1DM pathogenic (disease causing)?

How do we know this/how can we prove this?

Answer 10

No, diabetic mothers pass their auto-antibodies to their offspring in trimester 3, but the baby is not then born with T1DM

Question 11

Which cells drive T1DM?

How do we know this?

Answer 11

Cytotoxic T cells

Bone marrow transplants from people with T1DM transfer the disease

Question 12

How does cyclosporin work?

Answer 12

It is a calcineurin inhibitor

Calcineurin is a protein phosphatase (removes phosphate groups) which activates T cells

Cyclosporin therefore is a pan-immunosuppressive agent which stops function of almost all T cells of the bodies immune system

Question 13

Why is cyclosporin not used to treat T1DM despite working?

Answer 13

It’s pan-immunosuppressant action results in an unacceptably high malignancy rate

Question 14

Explain the formation and structure of insulin.

Answer 14

Insulin is made from a precursor molecule called pro-insulin which is a coiled shape

It contains an A and B chain which are held together by disulphide bonds, with the extra section (called C peptide) being cleaved off to form the structure (by beta cell peptidases)

Question 15

How can to tell between injected insulin from naturally produced insulin?

Answer 15

Injected insulin is recombinant insulin only

Self-synthesised insulin releases C peptide (one per insulin molecule) therefore this can be measures as a surrogate for insulin that is self-synthesised. Also important as insulin is taken up quickly by cells upon release

Question 16

What is HLA?

Answer 16

Human leukocyte antigen = Gene complex on chromosome 6 = encodes for MHC’s

Question 17

When do islet cell autoantibodies develop in relation to T1DM disease?

Answer 17

Before the disease takes it effects, they are present in reform may be a marker of what is to come

They are NOT pathogenic as it is T cells that are the culprits, but are the smoke which show a fire is present

Question 18

What is the role of IL2 in T1DM?

Answer 18

It is the cytokines needed for the activation and maintenance of Treg cells, which are vital in keeping the autoimmune cells at fault in T1DM at bay

Giving recombinant IL2 may therefore help as a treatment, trials are underway