Diabetes 💘

Question 1

LADA

Answer 1

Late autoimmune disease in adults
Mixture of type one and two
Up to 25% of cases

Question 2

Gestational

Answer 2

Diabetes when pregnant

Hormone changes causes insulin resistance and resolves on birth of baby

Question 3

MODY

Answer 3

Maturity onset off diabetes in young
Very rare
Linked to mutation in one gene

Question 4

Type 1 diabetes

Answer 4

An auto immune condition while the immune system targets the insulin secreting beta cells in the islets of Langerhans in the pancreas for destruction

Question 5

Phase 1 of type 1 diabetes

Answer 5

Beta cells death, might be natural or infection induced.
Usually in pancreatic remodeling beta cells die via apoptosis and removed by macrophages.
In this case excess B cell apoptosis so macrophages can’t remove quickly enough

Question 6

Phase 2 t1

Answer 6

Priming of alter reactive b cells and T cells.

Dendritic cells pick up the antigen and take it to the pancreatic lymph nodes/islet of Langerhans, known as insulitis.

Question 7

Phase 3 t1

Answer 7

Back in the pancreas destruction of beta cells.
Period of regulation after initial influx of activated immune cells . Lots of regulation activities as well as cytokines cd 8+ T cells increase CTL potential and Kill b cells by apoptosis.
Innate natural killer cells and macrophages potentiate this destruction

Question 8

HLA

Answer 8

People who express HLA II molecule DQ8 and HLA I molecule A2 have a higher risk of developing t1 diabetes

Question 9

Genetics-signal strength

Answer 9

Signal strength between the tissue restricted antigen presented by MHC & TCR governs fate of new T cells.
If weak T cells live as it’s non-auto reactive if strong T cells die as it’s auto reactive.
This is called negative selection and it’s believed that diabetes is inadequate at this and causes weak bonds and auto reactive resulting in release

Question 10

Allelic variants

Answer 10

Altered based in genes encoding immunoregulatory proteins
Can occur in cytotoxic T cells associated antigen CTLA for involved in switching off T cells.
PTPN 22 is involved in regulation of signals for both the TCR and BCR

Question 11

Variable number of tandem repeats

Answer 11

This encodes insulin transcription in the thymus. Less than 50 VNTR leads to low insulin so weaker bonds and a higher risk of type one diabetes.

Question 12

Environmental factors of t1 diabetes

Answer 12

Type one diabetes is more prevalent in the northern hemisphere and can be linked to vitamin D levels as it makes immune response more affective but autoimmune less effective

Question 13

Incretin effect

Answer 13

Amounts of insulin produced in blood should be high when given oral glucose and lower amounts when given isoglycaemic intravenous glucose
in type two it’s low insulin produced for both

Question 14

Type 2 diabetes

Answer 14

Insulin resistance/Insentivity linked yo impaired trafficking of glut 4 to cell membrane which allows glucose to enter cell
High fat diet causes this because the fat kinases inhibit the glucose kinases
Also increase in ros reducing mitochondria activity

Question 15

Macrophage difference in type two

Answer 15

Normally m2 anti inflammatory macrophages on adipose with mediators IL4 IL13
In insulin resistance there’s m1 pro inflammatory macrophage and release of its cytokines and ssip oki Ed causing increased gluconeogenesis in liver and skeletal muscle as arteriosclerosis and hyaline arteriosclerosis occurs reducing blood flow and gas exchange in vessels

Question 16

Diabetic kidney disease

Answer 16

Raised glucose layers chemical composition of kidney leading to malfunction and leakage of protein into urine
Proteins can cross link causing fibrosis/scarring replacing normal tissue resulting in kidney failure

Question 17

Diabetic neuropathy

Answer 17

Family of nerve disorders
Can be symptomless tingling or loss if feeling
Large fibres affect ability to sense vibrations
Small fibres u can’t feel pain temp or body function
Proximal motor affects butt hops and thigh one sided
Entrapment is chronic compression of nerves -pain

Question 18

Diabetic foot syndrome

Answer 18

Due to nerve and artery damage if you get a cut u won’t feel it and it will get infected and cause ulcers
Increased risk of amputation

Question 19

Diabetic neuropathy

Answer 19

Leasing cause of blindness
Background retinopathy-tiny bulges in vessel but no damage
Pre proliferative- more severe damage to vessels leading to leakage of blood into eye
Proliferative-scar tissue formation and weaker new vessels causing extensive leakage of blood into eye

Question 20

Metformin

Answer 20

Biguanide which improves insulin resistance through a camp mediated mechanism
Reduced glucose production in liver glucose uptake in muscle and glucose absorption in gut

Question 21

Advantages of metformin

Answer 21

Hba1c reduction of 11mmol/mol
Weight neutral
Improves cardiovascular mortality

Question 22

Disadvantages of metformin

Answer 22

GI upset
Reduced vitamin b12 absorption
Should be avoided in people with kidney problems

Question 23

Sulfonylureas

Answer 23

Increases first and second phase insulin secretion in response to a rise in plasma glucose

Question 24

Advantages of sulfonylureas

Answer 24

Rapidly absorbed orally

Hba1c reduction of 11-15 mmol/mol

Question 25

Disadvantages of sulfonylureas

Answer 25

Hi disturbance Hypoglycaemia Weight gain Hypersensitivity reactions

Question 26

Thiazolidine

Answer 26

Modulates transcription of insulin sensitising genes in liver skeletal muscle and adipose tissue

Question 27

Tjiazolidine advantages and disadvantages

Answer 27

Reduce hb1ac by 11 No hypoglycaemia risk GI issues headache swelling weight gain liver dysfunction and increased of fractures and bladder cancer

Question 28

GLP drugs

Answer 28

Glucagon like peptide 1 derived from inestinal l cells GIP derived from k cells Incretin hormones which activate b cells and suppress a cells These drugs are agonists for these

Question 29

Advantages and disadvantages of GLP drugs

Answer 29

Reduce weight | Gi issues decreased appetite headache gastritis reflux disease and possible pancreatitis

Question 30

DPP 4 inhibitors

Answer 30

Aka gliptins | Make glp 1 stay in blood longer

Question 31

DPP 4 advantages and disadvantages

Answer 31

Weight neutral Oral preparation Mild gi symptoms Increase in respiratory infections possible pancreatitis and exfoliative dermatitis

Question 32

Types of Insulin

Answer 32

``` Shot acting Intermediate acting Premixed (mix of short and intermediate) Long acting Pens injection pump ```

Question 33

Side effects of insulin

Answer 33

Hypoglycaemia Allergic reactions/lipoatropy of subcutaneous fat Injection site problems

Question 34

Familial renal glucosuria

Answer 34

Rare disease causing glucose loss in urine at normal glucose levels (4-7) Two types a and b A has lower threshold so less glucose reavsorption SGLT2 receptors absorb glucose in kidneys and it’s defective in this disease

Question 35

Treatment for familial renal glucosuria

Answer 35

SGLT2 inhibitors tablets Promotes weight loss No hypoglycaemia risk But increased genitourinary infections