diabetes treatement

Question 1

what do high risk genes affect to cause t1dm

Answer 1

Cause HLA molecules to mutate

Question 2

what does HLA do?

Answer 2

HLA antigens are glycoproteins they sit on the surface of a cell and allow immune system to clear infection and foreign cells
class 1 - found on all nucleated cells
class 2 - only found on antigen presenting cells eg macrophages

Question 3

what is type 1 diabetes

Answer 3

autoimmune disease targets b-cells

Question 4

why are b cells targeted

Answer 4

• highly specialised cells which makes them vunerable
• low antioxidant defences
  -FasL / FasR controlled apoptosis kills remaining b cells
  -highly dependednt on the islet

Question 5

what are the units of insulin injections in the UK

Answer 5

all injections are 100iU/ml

Question 6

what are the 4 types of insulin regime

Answer 6

• once daily (mix of very long and short acting)
  -twice daily (mix of long and short acting)
  -insulin pump (short acting)
  -basal bolus ( once daily long acting and multiple short acting)

Question 7

what is the basal bolus routine and what are the disadvantages

Answer 7

nice recommended
- one long acting in the morning
- short acting insluin before meals

can be difficult to adhere to routine as you need to know excatly amount of carbs you eat and must frequently check BG levels.

Question 8

what is the initial standard of carbs into glucose

Answer 8

10g of carbs (1 carb portion) = 1unit of glucose this will thren be increased or decreased dependent on patient

Question 9

long acting insulin examples

Answer 9

glargine, detemir, lantus, levimir

Question 10

short acting insulin examples

Answer 10

lispro, aspart, novorapid, glulisine

Question 11

intermediate insulin

Answer 11

NPH, isophane

Question 12

Insulitus response

Answer 12

MHC11 molecule binda to antigen - presents itself to CD4 T helper cell - this activated the cell the activated CD4 cell produce cytokine (IL2 ) - recruit CD8 cells which clear the infection

in diabetes triggered by beta cells causuing inflammation (insulitus)

Question 13

Highest risk Genotype

Answer 13

DR3-DQ2/DR4-DQ8 (18.7 risk ratio)
important to note still need an environmental trigger

Question 14

what are some environmental triggers?

Answer 14

N-Nitro compounds
Viral triggers
vaccines
bacterial
psychological stress
difficult adaptation
pregnancy stress
Poor Diet
Energy intake
weight gain
puberty
vit D deficiency

Question 15

specific N-nitro compounds

Answer 15

-streptozocin (betacell killer )
-nitrosamines/ides (burnt/smoked food)
-alloxan (rat poison)
-vacor rat poison

Question 16

viral triggers

Answer 16

-mumps
-entero/cocksackie (most common)
-rota
-cytomeglo
- epstein-barr (herpes)

Question 17

cytolisis

Answer 17

direct killing of beta cells caused by mumps

Question 18

molecular mimicing

Answer 18

mimic autoantigens can stimulate diabetes process caused by rubella

Question 19

t cell activation

Answer 19

activating t cells can cause a cytokine storm caused by entero and rota

Question 20

interferon overproduced

Answer 20

increases amout of cytokines - more t cells - more b cells so reaction snowballs which causes over production of HLA (inflammation within islet) caused by cytomeglo and epstein barr

Question 21

link of t1d with enterovirus

Answer 21

cocsackie b virus cultured from pancreas of t1d patients caused diabetes when injected into mice
30% of newly diagnosed patients have IGM antibodies to cocksackie b 27% have entero RNA 51% of pre diabetic kids evidence of enteroviral infection

enterovirus triggers t cells to activate and subseqent b cell killing, virus incorparates into b cells making them look foreign.

Question 22

genes that are a marker for t1d

Answer 22

GAD-65 (gaba production) 70-80%
1A-2Ab (islet antigen) 60-70%
1AA(insulin) 50%
ZnT8Ab (zinc transport) 60-80%

Question 23

teplizumab

Answer 23

monoclonal antobody therapy
binds to cd3antigen present on t cell surface - deactivates pancreatic b cell autoreactive t cells

slows progression by around 2 years