Inim3006 - Type I Diabetes

Front 1

What are the characteristics of type I?

Back 1

High blood glucose, insulin deficiency and absolute loss of insulin secretion as a result of autoimmune destruction of beta-cells in islets of pancreas.

Front 2

What is common presentation of type I?

Back 2

Polydipsia, polyuria, precipitous weight loss, fatigue. Acute diabetic ketoacidosis.

Front 3

Main complications of diabetes?

Back 3

Microvascular disease: retinopathy, neuropathy and nephropathy.

Front 4

What is the pathogenesis of background retinopathy?

Back 4

Increased glucose in blood = increased blood velocity.
Local damage causes release of GF and angiogenesis.
BV that develop in ischaemic areas are delicate.
Bleeding as a result causes localised damage and loss of vision.
Scarring can cause detachment and blindness.

Front 5

How to treat diabetic retinopathy?

Back 5

Bevacizumab (Avastin) - VEGF-A inhibitor.

Front 6

What are the effects of a neuropathic ulcer?

Back 6

Abnormal foot shape and wound formation as a resul of arch remodelling and uneven redistribution of pressure.

Front 7

HLA class I involvement in type I?

Back 7

AH 8.1 characterised by, amongst other, HLA-A1, B8 and A1*05.

Front 8

HLA class II involvement in type I?

Back 8

HLA-DQ301, -DR401 <-- together known as a 3/4 genotype (very rare in non-diabetics)

However DQB1 is main risk

Front 9

Name one major beta cell antigen in type I diabetes. (1)

Back 9

Islet cell antigen (ICA); a complex of auto antigens. Abs to ICA that is present in 90%.

Front 10

Name one major beta cell antigen in type I diabetes. (2)

Back 10

Abs to insulin and proinsulin; 23% and 34% prevalent in type 1 patients, respectively

Front 11

Name one major beta cell antigen in type I diabetes. (3)

Back 11

GAD (constituent of ICA); GAD Abs present in 73%

Front 12

Name one major beta cell antigen in type I diabetes. (4)

Back 12

Protein tyrosine phosphatase (IA-2); Transmembrane protein from insulin secretory granule. IA-2 Abs are present in 75%.

Front 13

Evidence for immune aetiology to type I diabetes.

Back 13

Pacncreatic beta cells contain immune cell infiltrates.
Immunosuppressive drugs reduce disease incidence.
HLA genes associate with disease risk or protection.

Front 14

Take a moment and write/talk about 1st degree relatives.

Back 14

- Within two years of age, >10% of first degree relative infants present with at least one islet antibody, suggesting auto immune process is initiated early.
- This islet immunity, however, doesnt necessarily imply loss of beta cell function. In fact, there may abnormalities in glucose tolerance testing that may only be detectable years after presence of antibodies
- This suggests the preclinical period for type 1 is longer than classically though and interventions could take place to save residual beta cell mass and perhaps delay or even prevent type 1.
- Following diagnosis you get a 'honeymoon' phenomenon where the patient temporarily becomes insulin independent.
- Beta cells that survive at time of diagnosis continue to be attacked by immune system and gradually disappear of a 5 year period.

Front 15

What is APS?

Back 15

Autoimmune polyglandular syndrome.

Front 16

What is APS?

Back 16

Autoimmune polyglandular syndrome.

Front 17

In APS, what is the prevalence of a) thyroid disease, b) coeliac disease, c) AI gastritis and d) Addison's?

Back 17

a) 25%
b) 7%
c) 20%
d) 2%

Front 18

What is APS?

Back 18

Autoimmune polyglandular syndrome.

Front 19

In APS, what is the prevalence of a) thyroid disease, b) coeliac disease, c) AI gastritis and d) Addison's?

Back 19

a) 25%
b) 7%
c) 20%
d) 2%

Front 20

What are the characteristics of APS1?

Back 20

At least two of: Addison's, hypoparathyroidism and recurrent mucocutaneous candidiasis.

Front 21

What is APS?

Back 21

Autoimmune polyglandular syndrome.

Front 22

In APS, what is the prevalence of a) thyroid disease, b) coeliac disease, c) AI gastritis and d) Addison's?

Back 22

a) 25%
b) 7%
c) 20%
d) 2%

Front 23

What are the characteristics of APS1?

Back 23

At least two of: Addison's, hypoparathyroidism and recurrent mucocutaneous candidiasis.

Front 24

What is Schmidt's disease?

Back 24

APS 2, Addison's with type 1 and/or thyroiditis.

Front 25

What is LADA?

Back 25

Latent autoimmune diabetes of adults

Front 26

What is LADA?

Back 26

Latent autoimmune diabetes of adults

Front 27

What are the characteristics of LADA?

Back 27

Autoimmune destruction of the Islets resulting in decreased residual beta cell function.
Does not respond well to diet or oral hypoglycaemics, progresses rapidly to insulin dependency.

Front 28

What is LADA?

Back 28

Latent autoimmune diabetes of adults

Front 29

What are the characteristics of LADA?

Back 29

Autoimmune destruction of the Islets resulting in decreased residual beta cell function.
Does not respond well to diet or oral hypoglycaemics, progresses rapidly to insulin dependency.

Front 30

Outline one new strategy for prevention of T1D. (1)

Back 30

Avoidance of putative environmental triggers e.g. gluten, cow's milk, certin viruses.

Front 31

What is LADA?

Back 31

Latent autoimmune diabetes of adults

Front 32

What are the characteristics of LADA?

Back 32

Autoimmune destruction of the Islets resulting in decreased residual beta cell function.
Does not respond well to diet or oral hypoglycaemics, progresses rapidly to insulin dependency.

Front 33

Outline one new strategy for prevention of T1D. (1)

Back 33

Avoidance of putative environmental triggers e.g. gluten, cow's milk, certin viruses.

Front 34

Outline one new strategy for prevention of T1D. (2)

Back 34

Vitamin D deficiency has been implicated in T1D, ensure provision of adequate daily vitamin D intake for those at risk.

Front 35

What is LADA?

Back 35

Latent autoimmune diabetes of adults

Front 36

What are the characteristics of LADA?

Back 36

Autoimmune destruction of the Islets resulting in decreased residual beta cell function.
Does not respond well to diet or oral hypoglycaemics, progresses rapidly to insulin dependency.

Front 37

Outline one new strategy for prevention of T1D. (1)

Back 37

Avoidance of putative environmental triggers e.g. gluten, cow's milk, certin viruses.

Front 38

Outline one new strategy for prevention of T1D. (2)

Back 38

Vitamin D deficiency has been implicated in T1D, ensure provision of adequate daily vitamin D intake for those at risk.

Front 39

Outline one new strategy for prevention of T1D. (3)

Back 39

Blocking of CD3 has been shown to have an immunouppressive effect: anti-CD3 mAb - hOKT3y1 - HSP, GAD or insulin.