T2DM Flashcards
Define diabetes
State of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues
Fasting blood glucose >7mmol/L
Describe T2DM
NOT ketosis prone
NOT mild
Often invovles weight, lipids & BPs
What is the space between defining markers for diabetes and being normal called?
o Impaired Fasting Glucose
- when measuring fasting blood glucose
o Impaired Glucose Tolerance
- when measuring the 2hr response in a glucose tolerance test
Epidemiology of T2DM?
o Prevalent and mostly T2DM
o Affects adults (but children becoming affected)
o Varied across ethnic groups - greatest in those moving from rural to urban lifestyle
Pathophysiology of T2DM?
o MODY relatively uncommon BUT gives mtabolic insights
o Can be influenced by genetics, intrauterine & adult environment
- epigenetic changes in the intrauterine envrion. can affect functioning of developing gene
o Caused by insulin resistance & insulin secretion deficits
- FAs important in the complications of T2DM
Explain MODY?
Maturity onset diabetes of the young
o Several hereditary forms - autosomal dominant
o Mutations in TF Glucokinase gene
- produces ineffective beta cell insulin secretion
o Postivie FH but NO OBESITY
- specific treatment for each type of MODY
How do genes contribute to risk of insulin resistance?
ONENOTE!!
IUGR - intrauterine growth resistriction and greatly increase chances of developing T2DM
Insulin resistance ADIPOCYTOKINES –> DYSLIPIDAEMIA –> increased mitogenic pathway –> hypertrophy & increase in BP –> MACROvascular disease
Microvascular and Macrovascular?
Diabetes complications
o Dyslipidaemia –> MACROvascular
o Hyperglycaemia –> MICROvascular
What have twin studies shown about T2DM?
o Follows an almost AUTOSOMAL DOMINANT pattern
o T1DM on the other hand has LESS genetic input
Insulin resistance & insulin secretion link?
Insulin production decreases w. age
o become more RESISTANT w. age
At some point the IR and IS line bisect:
o at this point, we CANNOT make enough insulin for our resistance
Metabolism and presentation of T2DM?
o Heterogeneous - many forms/causes of T2DM
o Obesity
o Insulin resistant & secretion deficit
o Hyperglycaemia & dyslipidaemia –> acute & chronic complications
What happens in the body when you give some glucose?
They will have TWO phases of insulin secretion
- FIRST PHASE
o STORED insulin ready to be released - SECOND PHASE
o over a period of time, more insulin produced and secreted
What happens to people who are developing T2DM in relation to the glucose-insulin response?
Still have SOME insulin production BUT will LOSE their FIRST PHASE response to glucose
o make insulin eventually BUT takes a much longer time!
How can people get around the issue w. T2DM and the glucose-insulin response?
Eating COMPLEX CHOs
This is as it will release glucose more SLOWLY thus reducing the need for the FIRST PHASE Response
What causes increased blood glucose in TDM?
o DECREASED glucose disposal
o INCREASE HGO
Normal link between HGO and insulin and how is this impaired in T2DM?
Insulin LOWERS blood glucose via. REDUCING HGO
- When you have NOT eaten, HGO maintains blood glucose at 4mmol/L
- AFTER you’ve eaten, insulin STOPS HGO as do not need this output anymore!
- Insulin instead drives the glucose from the meal into muscle & adipose tissue
These affects are ABSENT in T2DM so:
o cannot inhibit HGO
o cannot move glucose into muscle/fat
Relationship between insulin sensitivity and insulin secretion
As you age, insulin sensitivity DECREASES
SO the secretions must INCREASE to compensate
BUT
those with diabetes cannot compensate enough
Effect of Insulin Resistance on body?
- TGs on adipocytes can be broken down to glycerol & NEFAs which is transported to the liver
o marker for OMENTAL ADIPOCYTES - hence why waist circumference predicitive of IHD - In liver gluconeogensis & glycogenolysis occurs
o hence increased HGO and decreased glucose uptake - FAs go to liver where they CANNOT be used to make glucose
o made into VLDL-TGs instead
o these contribute to the ATHEROGENIC risk!
Link between obesity and T2DM?
Appears to be a part of the mechanism of T2DM
o more than a precipitant
o FAs and Adipocytokines are important (modulate insulin resistance)
o Central/omental obesity common
- 80% of T2DM
o Weight reduction is useful treatment
Gut Microbiota link with T2DM?
Appears to be associated w.
o obesity, insulin resistance, T2DM, inflammation & adipocytokine pathways
- via. possible host signalling
Various lipopolysaccharides are fermented by gut bacteria to SHORT CHAIN FFAs
o these enter the host circulation
o modulate bile acids
Possible treatment in the future might involve microbiota transplants
What is a common SE of diabetes treatment?
WEIGHT GAIN!!
As it reduced blood glucose BUT increases appetite
Note - only METFORMIN reduces weight!
Only diabetic drug that reduces weight?
Metformin
How does T2DM progress?
o Intrauterine envrion. may influence insulin resistance in later life
o Late T2DM can make the pancreas produce IMMATURE insulin
- they don’t have FIRST PHASE insulin
- SO insulin does NOT work properly
Eventually there is an ABSOLUTE insulin deficiency
How can T2DM present?
o Osmotic symptoms
o Infections
- hyperglycaemic envrion. is favourable for certain bacteria
o Presentation of complications e.g. acute (hyperosmolar coma) OR chronic (IHD)
- Microvascular - retino/nephro/neuropathy
- Macrovascular - IHD, cerebrovascular, renal artery stenosis, PVD
- Metabolic (rarer than for T1DM)
- From treatment - e.g. hypo attack
