Diabetes 💘 Flashcards
LADA
Late autoimmune disease in adults
Mixture of type one and two
Up to 25% of cases
Gestational
Diabetes when pregnant
Hormone changes causes insulin resistance and resolves on birth of baby
MODY
Maturity onset off diabetes in young
Very rare
Linked to mutation in one gene
Type 1 diabetes
An auto immune condition while the immune system targets the insulin secreting beta cells in the islets of Langerhans in the pancreas for destruction
Phase 1 of type 1 diabetes
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
Phase 2 t1
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.
Phase 3 t1
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
HLA
People who express HLA II molecule DQ8 and HLA I molecule A2 have a higher risk of developing t1 diabetes
Genetics-signal strength
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
Allelic variants
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
Variable number of tandem repeats
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.
Environmental factors of t1 diabetes
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
Incretin effect
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
Type 2 diabetes
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
Macrophage difference in type two
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
Diabetic kidney disease
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
Diabetic neuropathy
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
Diabetic foot syndrome
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
Diabetic neuropathy
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
Metformin
Biguanide which improves insulin resistance through a camp mediated mechanism
Reduced glucose production in liver glucose uptake in muscle and glucose absorption in gut
Advantages of metformin
Hba1c reduction of 11mmol/mol
Weight neutral
Improves cardiovascular mortality
Disadvantages of metformin
GI upset
Reduced vitamin b12 absorption
Should be avoided in people with kidney problems
Sulfonylureas
Increases first and second phase insulin secretion in response to a rise in plasma glucose
Advantages of sulfonylureas
Rapidly absorbed orally
Hba1c reduction of 11-15 mmol/mol
Disadvantages of sulfonylureas
Hi disturbance
Hypoglycaemia
Weight gain
Hypersensitivity reactions
Thiazolidine
Modulates transcription of insulin sensitising genes in liver skeletal muscle and adipose tissue
Tjiazolidine advantages and disadvantages
Reduce hb1ac by 11
No hypoglycaemia risk
GI issues headache swelling weight gain liver dysfunction and increased of fractures and bladder cancer
GLP drugs
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
Advantages and disadvantages of GLP drugs
Reduce weight
Gi issues decreased appetite headache gastritis reflux disease and possible pancreatitis
DPP 4 inhibitors
Aka gliptins
Make glp 1 stay in blood longer
DPP 4 advantages and disadvantages
Weight neutral
Oral preparation
Mild gi symptoms
Increase in respiratory infections possible pancreatitis and exfoliative dermatitis
Types of Insulin
Shot acting Intermediate acting Premixed (mix of short and intermediate) Long acting Pens injection pump
Side effects of insulin
Hypoglycaemia
Allergic reactions/lipoatropy of subcutaneous fat
Injection site problems
Familial renal glucosuria
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
Treatment for familial renal glucosuria
SGLT2 inhibitors tablets
Promotes weight loss
No hypoglycaemia risk
But increased genitourinary infections
