Type 2 Diabetes Mellitus Flashcards
What is type 2 diabetes mellitus?
“A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia”
- Body makes insulin but tissues don’t respond to it (reason not fully understood)
- INSULIN RESISTNACE
- obesity and genetic risk factors of T2DM
- Body makes excess insulin to try to move the glucose out of blood
- Eventually puts strain on beta cells (overworked)- beta cell damage
- Insulin starts to go down (depending on time of diagnosis, insulin levels will vary)
What is the fasting glucose level that shows impaired fasting glucose (pre-diabetes)?
patient doesn’t eat/ drink for 8 Hrs
6 mmol/L ≤ fasting glucose levels ≤ 7 mmol/L
(6-7 mmol/L is pre-diabetes)
(less than 6 is normal)
(more than 7 is diabetes)
What is the reading of an oral glucose tolerance test for impaired glucose tolerance (pre-diabetes)?
Give glucose & take blood samples at time intervals
7.7 mmol/L ≤ 2-hr glucose (OGTT) ≤ 11mmol/L
(7.7-11 is prediabetes)
(less than 7.7 is normal)
(more than 11 is diabetes)
What is the HbA1c level for pre diabetes or non-diabetic hyperglycaemia?
glycated hemoglobin (hemoglobin attached glucose)- glucose level for the part 3 months
42 mmol/L ≤ HbA1c ≤ 48mmol/L
(42-48 is prediabetes)
(less than 42 is normal)
(more than 48 is diabetes)
What is needed for the diagnosis of type 2 diabetes?
(1 positive test + symptoms or 2 positive tests)
Usually:
First line test for diagnosis is HbA1c.
1x HbA1c >=48mmol/L with symptoms
Or
2x HbA1c >=48 mmol/mol if aysymptomatic
What can occur from a long duration of T2DM?
In long-duration type 2 diabetes, beta-cell failure may progress to complete insulin deficiency
=Hyperglycaemia
important not to stop giving insulin as at risk of ketoacidosis
What effect does T2DM have on insulin release?
- Normally we encounter a “first phase insulin release” which is an immediate/ spike release
- This is lost in T2DM
How does the liver react to the reduced insulin levels seen after T2DM?
Hepatic glucose production is increased due to both a reduction in insulin action and increase in glucagon action
“excessive glucagon-mediated glucose output” (but reduced clearance of glucose- still not being removed from circulation”
What is the relationship b/t insulin secretion and insulin sensitivity?
As insulin secretion decreases, the insulin sensitivity increases
What is the random glucose (non-fasting glucose) level for diabetes?
(Can be done at any time)
levels greater than or equal to 11.1 mmol/L + symptoms
What consequences do other body tissues face from T2DM?
Skeletal muscle:
- Reduced glucose uptake
- Impaired glycogen synthesis
Adipocytes:
- Reduced glucose uptake
- Increased lipolysis
- Reduced lipogenesis
Liver:
- Increase in hepatic glucose production
- Increased lipogenesis
Is diabetes monogenic or polygenic?
Type I and II (most common types) are polygenic: not born with the diabetes but high risk and may develop later depending on other factors
MODY diabetes is monogenic: you are born with the single gene mutation and it is always going to develop into diabetes
What are other associations seen with T2DM?
- Obesity
- Perturbations/ abnormalities in gut microbiota (inflammation causes various signaling metabolic pathways)
- Intra-uterine growth retardation
What are the presentations of T2DM?
Hyperglycaemia
Overweight
Dyslipidaemia
Fewer osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency
What are the risk factors of T2DM?
- Age
- PCOS
- high BMI
- Family History
- Ethnicity
- Inactivity
What is hyperosmolar hyperglycaemic state?
EXTREME DEHYDRATION
Osmotic diuresis leads to severe fluid loss “Hypovolaemic shock” insulin for suppression of lipolysis and ketogenesis.
Symptoms:
- Polyuria
- Dehydration
- (if left untreated): lethargy, seizures, coma, death
treat with intravenous fluids immediately
(CAUTION: rectifying fluids too quickly can cause Central pontine myelinolysis (brain depletion) rapid rise in Na+ conc
What is the management for T2DM?
- Diet
- Oral medication
- Structured education
- May need insulin later
- Remission / reversal
What are some possible risks from prevention-diabetes treatments?
(too much blood glucose)
- Retinopathy
- Neuropathy
- Nephropathy
- Cardiovascular
What investigations are made during 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 are the dietary recommendations for T2DM
Healthy eating or diet
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 drug treatments for T2DM? What do each drug tackle?
- Metformin (Reduces hepatic glucose production + Improves insulin sensitivity + Increases peripheral glucose disposal)
- Thiozolidinediones
- Pioglitazone (2/3 Improves insulin sensitivity)
- Sulphonylureas
- DPP4-inhibitors
- GLP-1 Agonists (4-6 boost insulin secretion)
- Alpha glucosidase inhibitor
- SGLT-2 inhibitor (7/8 Inhibit carbohydrate gut absorption + Inhibit renal glucose reabsorption)
Weight loss help to achieve all of these solutions
What are some cons of taking metformin?
- GI side effects
- Contraindicated in severe liver, severe cardiac or moderate renal failure
How does Sulphonyleuras work?
“Boosts insulin secretion”
Normal insulin release requires closure of the
ATP-sensitive potassium channel
- Sulphonylureas binds to the ATP-sensitive potasssium channels and closes them (independent of glucose/ ATP)
How does Pioglitazone work?
“Improves insulin sensitivity”
- 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 the role of Glucagon like peptide-1 (GLP-1)
- Gut hormone
- Secreted in response to nutrients in gut
- Transcription product of pro-glucagon gene, mostly from L-cell
- Stimulates insulin, suppresses glucagon
- ↑ satiety (feeling of ‘fullness’)
- Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPP4 inhibitor)
- Used in treatment of diabetes mellitus
What is meant by the gastrointestinal “incretin” effect?
A phenomenon by which insulin secretion is increased substantially when glucose is given by the oral or enteral route when compared to an intravenous glucose infusion
- Is attributable to the secretion of the “incretin” hormones, GLP-1 and GIP, from the gut
How do GLP-1 Agonists work?
“Boost insulin secretion”
- Injectable –daily, weekly
- Decrease [glucagon]
- Decrease [glucose]
- Weight loss
e.g: Liraglutide, Semaglutide
How do DPP4-inhibitors work?
- Increase half life of exogenous GLP-1
- Increase [GLP-1]
- Decrease [glucagon]
- Decrease [glucose]
- Neutral on weight
e.g: Gliptins
How do SGLT-2 inhibitors work?
“Inhibit carbohydrate gut absorption + Inhibit renal glucose reabsorption”
- Inhibits Na-Glu transporter, increases glycosuria
- HbA1c lower
- 32% lower all cause mortality
- 35% lower risk heart failure
- Improve CKD (chronic kidney disease)
E.g: Empagliflozin, dapagliflozin, canagliflozin
What effect does treatment have on beta cell function?
Despite treatment, beta-cell function continues to decline
What effect can Gastric bypass surgery have on T2DM?
Gastric bypass surgery has the potential to induce remission of type 2 diabetes
(remission= blood sugar levels (also known as blood glucose levels) are below the diabetes range NOT A CURE
What effect can a low-calorie diet have on T2DM?
low-calorie diet (800 kcal/day) for 3-6 months has the potential to induce remission, which appears to be sustained at 2 years
(remission= blood sugar levels (also known as blood glucose levels) are below the diabetes range NOT A CURE
Other than attempting to restore blood glucose levels, what are toher aspects of T2DM management?
Blood Pressure management
Hypertension very common in T2DM
Clear benefits for reduction esp with use of ACE-inhibitors
Lipid management
Total cholesterol raised
Triglycerides raised
HDL cholesterol reduced
Clear benefit to lipid-lowering therapy
What is the language matters movement?
Language matters movement: use language that empowers rather than disengages people with type 1 diabetes
