Endo - T2DM Flashcards
What is T2DM?
→ combination of insulin resistance + beta-cell failure result in hyperglycaemia
→ Associated with obesity but not always
→ resultant chronic hyperglycaemia may initially be managed by changes to diet / weight loss and may even be reversible
→ over time glucose lowering therapy including insulin, is needed
What contributes to the insulin resistance in T2DM?
→ genetic risk
→ obesity
Can DKA be a feature of T2DM?
yes
When can T2DM present in a person’s life?
→ commonly thought to be only a condition of late adulthood
→ literally in every decade tho
What is the trend in prevalence of T2DM? Why?
→ varies enormously
→ increasing prevalence
→ occurring + being diagnosed in younger groups
→ greatest ethnic groups moving from rural to urban lifestyle
What are the stages of development for T2DM?
→ normal state = normal glucose + insulin production + insulin resistance
→ intermediate state = impaired fasting glucose + impaired glucose tolerance + pre-diabetic or non-diabetic hyperglycaemia + increasing insulin production + insulin resistance
→ T2DM = low insulin production + insulin resistance
What are the fasting glucose levels for someone with impaired fasting glucose?
6 < x < 7 mmol/L
What are the glucose levels after an OGTT for impaired glucose tolerance?
7.7 < impaired glucose tolerance < 11 mmol/L
What are the HbA1c levels for pre-diabetic or non-diabetic hyperglycaemia
42 < pre-diabetic or non-diabetic hyperglycaemia < 48 mmol/L
What is relative insulin deficiency?
Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance → can’t have DKA under usual hyperglycaemic episodes
What is long-duration T2DM?
→ beta-cell failure may progress to complete insulin deficiency
→ usually on insulin but can’t come off at risk of DKA
What happens to the first phase insulin release in T2DM?
doesn’t exist
What happens to uptake of glucose in muscles in T2DM?
reduced insulin action = less uptake of glucose in skeletal muscles
What happens to hepatic glucose production in T2DM? Why?
reduced insulin action = increased hepatic glucose production + increased glucagon action
What is the relationship between insulin resistance and insulin secretion in T2DM?
→ as insulin resistance increases, insulin secretion also increases
→ directly proportional
What is MODY?
→ maturity onset diabetes of the young
→ monogenic inheritance of Diabetes, can’t avoid it
What is the polygenic risk of T2DM?
→ polymorphisms increasing the risk of diabetes
→ not born with it but could develop it later depending on other factors
What if the effect of individual SNPs on risk of T2DM?
very little effect
What if the effect of cumulative SNPs on risk of T2DM?
much bigger
What is the role of obesity in T2DM?
→ Major risk factor for T2DM → Fatty acids + adipocytokines important → Central vs visceral obesity → 80% T2DM are obese → Weight reduction useful treatment
What else is associated with risk of T2DM?
→ Perturbations in gut microbiota
→ Intra-uterine growth retardation
What are the symptoms of of T2DM?
→ Hyperglycaemia → Overweight → Dyslipidaemia → Fewer osmotic symptoms → With complications → Insulin resistance → Later insulin deficiency
What are the risk factors of T2DM to look for clinically in a patient?
→ Age → large BMI → ethnicity → PCOS → family history → inactivity
How is T2DM diagnosed?
→ First line test for diagnosis is HbA1c :
→ 1x HbA1c >=48mmol/L with symptoms
→ 2x HbA1c >=48 mmol/mol if asymptomatic
What is a hyperosmolar hyperglycaemic state?
→ Presents commonly with renal failure.
→ Insufficient insulin (NOT ABSENT) for prevention of hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis.
→ Absence of significant acidosis.
→ Often identifiable precipitating event (infection, MI).
→ osmotic diuresis = dehydration
How is T2DM managed?
→ Diet → Oral medication → Structured education → May need insulin later → Remission / reversal
What are the main principles of a T2DM consultation?
→ Glycaemia: HbA1c, glucose monitoring if on insulin, medication review
→ Weight assessment
→ Blood pressure
→ Dyslipidaemia: cholesterol profile
→ Screening for complications: foot check, retinal screening
What is the dietary advice over T2DM?
→ Total calories control
→ Reduce calories as fat
→ Reduce calories as refined carbohydrate
→ Increase calories as complex carbohydrate
→ Increase soluble fibre
→ Decrease sodium
What are the 4 facets of pathophysiology of T2DM?
How are the 4 facets of pathophysiology managed ideally?
How are the 4 facets of pathophysiology managed pharmacologically?
How does metaformin work?
→ Biguanide, insulin sensitiser
→ First line if dietary / lifestyle adjustment has made no difference
→ Reduces insulin resistance
→ Reduced hepatic glucose output
→ Increases peripheral glucose disposal
→ GI side effects
→ Contraindicated in severe liver, severe cardiac or moderate renal failure
How do sulphonylureas work?
→ Normal insulin release requires closing of the
ATP-sensitive potassium channel
→ Sulphonylureas e.g. gliclazide, bind to the ATP-sensitive potassium channel and close it, independent of glucose / ATP
How does pioglitazone work?
→ Peroxisome proliferator-actived receptor agonists PPAR-γ
→ Insulin sensitizer, mainly peripheral
→ Adipocyte differentiation modified, weight gain but peripheral not central
→ Improvement in glycaemia and lipids
→ Evidence base on vascular outcomes
→ Side effects of older types hepatitis, heart failure
What is a common side effect of glucose lowering therapies and drugs?
weight gain (except in metformin)
How can GLP-1 agonists be used to treat T2DM?
→ Liraglutide, Semaglutide → Injectable –daily, weekly → Decrease [glucagon] → Decrease [glucose] → Weight loss
How can DPP4-inhibitors be used to treat T2DM?
→ Increase half life of exogenous GLP-1 → Increase [GLP-1] → Decrease [glucagon] → Decrease [glucose] → Neutral on weight
How can SGLT-2 inhibitors be used to treat T2DM?
→ Inhibits Na-Glu transporter, increases glycosuria
→ Empagliflozin, dapagliflozin, canagliflozin
→ HbA1c lower
→ 32% lower all cause mortality
→ 35% lower risk heart failure
→ Improve CKD
How does beta-cell function change on drug therapies?
function of beta-cells still declines
What surgery can induce remission of T2DM?
gastric bypass surgery
How else can remission of T2DM be induced?
low calorie diet
What are the other aspects need to be considered in T2DM management?
blood pressure → hypertension is v common → clear benefits in reduction lipid management → clear benefit in lipid-lowering therapy
What is GLP-1? Why is it useful in T2DM?
→ Gut hormone
→ Secreted in response to nutrients in gut
→ Transcription product of pro-glucagon gene, mostly from L-cell
→ Stimulates insulin, suppresses glucagon
→ increases satiety (feeling of ‘fullness’)
→ Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPP4 inhibitor)
