TYPE 2 DIABETES MELLITUS Flashcards
What is type 2 diabetes?
Condition where combination of insulin resistance and beta-cell failure result in hyperglycaemia. Not always associated with obesity
Which type of diabetes causes relative insulin deficiency and absolute insulin deficiency?
Type 1 - absolute insulin deficiency
Type 2 - relative insulin deficiency because insulin still produced but not enough to overcome insulin resistance
In what age groups does T2DM develop in?
T2DM traditionally thought to be condition of late adulthood but now increasing in all age groups especially in early-adulthood
T2DM is most prevalent in which population?
Ethnic groups which move from rural to urban lifestyle
What are the targets of glucose levels for those at risk of developing T2DM?
Fasting glucose: < 6mmol/L
2-hr glucose (OGTT): < 7.7 mmol/L
HbA1c: < 42 mmol/mol
What are the targets of glucose levels for those with T2DM?
Fasting glucose: < 7mmol/L
HbA1c: < 48mmol/mol
Describe the relationship between insulin resistance and production as you go through the 3 stages of T2DM
Normal: Insulin resistance begins increasing with insulin production mirroring in order to make up for this
Intermediate: Insulin resistance keeps increasing. Insulin production increases until a certain point where it then decreases due to beta cells being worn out
Type 2 diabetes: Insulin resistance stays at its max level and insulin production continues to fall
What are the tests for diagnosis of T2DM?
First line test for diagnosis:
1 x HbA1c >= 48 mmol/L with symptoms
2 x HbA1c >= 48 mmol/L with no symptoms
Random glucose level of > 11.1 with symptoms of diabetes
What is the range of an impaired fasting glycaemia?
6-7 mmol/L
What is the range of an impaired glucose tolerance?
7.8 - 11.1 mmol/L in a 2 hour glucose test (OGTT)
Why does the hyperglycaemia of T2DM not cause ketosis under normal circumstances?
Insulin is still being produced in T2DM (relative deficiency of insulin) which means ketone body synthesis from fatty acids and acyl-coA inhibited
When could ketoacidosis occur in patients with T2DM?
Infections or if insulin not taken for those with long duration T2DM
Why do you have to be careful in long duration T2DM?
Beta-failure may progress to complete insulin deficiency so need to make sure patient doesn’t stop taking insulin as risk of ketoacidosis
After a glucose load to the body what is lost in T2DM?
First phase insulin release is lost causing a blunted amount of plasma insulin compared to the normal peak for those with normal glucose tolerance
Why does hepatic glucose output increase in T2DM?
Reduction of insulin action
Increase in glucagon action
What is the relationship between insulin resistance and insulin sensitivity in those with T2DM?
For a given degree of insulin sensitivity secrete less insulin
How does insulin resistance of the organs and tissues occur in T2DM?
Adipocytes release vast amounts of adipokines e.g. glucocorticoids, TNF alpha, IL-6, leptin… which drive a toxic pro-inflammatory state
What type of diabetes is monogenic?
MODY (mature onset of diabetes in young)
What types of diabetes are polygenic?
Type 1 + 2
Other factors also in play
What percentage of those with T2DM are obese?
80%
What are some associations of T2DM other than obesity?
Disturbances to gut microbiota
Intra-uterine growth retardation
What are the clinical presentations of T2DM?
Hyperglycaemia Overweight Dislipidaemia Fewer osmotic symptoms Insulin resistance Later insulin deficiency
List the risk factors of T2DM
Age Increased BMI PCOS Genetics Inactivity Ethnicity
What is hyperosmolar hyperglycaemic state?
A diabetic emergency where patients often present with acute renal failure
No significant ketoacidosis because insulin enough to suppress lipolysis and ketogenesis but not enough to prevent hyperglycaemia
Usually an identifiable precipitating event (infection, MI)
Describe the management of T2DM
- Diet
- Oral medication
- Structured education
- May need insulin later
Blood pressure management e.g. ACE inhibitors
- hypertension common
Lipid management
- cholesterol and triglycerides raised
- HDL cholesterol reduced
What is checked during a T2DM consultation?
HbA1c, glucose monitoring if on insulin and medication review for glycaemia
Weight assessment
Blood pressure
Cholesterol profile for dyslipidaemia
Screening for complications e.g. foot check, retinal screening
What drug is used to reduce HGO?
Metformin
Which drugs improve insulin sensitivity?
Metformin, thiozolidinediones
Which drugs boost insulin secretion?
Sulphonyleureas
DPP4 inhibitors
GLP-1 agonists
Which drugs inhibit carbohydrate gut absorption and inhibit renal glucose output?
Alpha glucosidase inhibitor
SGLT-2 inhibitor
Why is weight loss recommended for those who have T2DM?
It helps with every pathophysiology of T2DM
When should metformin not be used?
Severe liver, cardiac or moderate renal failure
Which drug should be used as first line if dietary/lifestyle change has made no difference?
Metformin
What is the mechanism of action of sulphonylureas?
Normal insulin release needs ATP sensitive potassium channels to close so that potassium can open the calcium channel
Sulphonylureas bind to the potassium channel and close it, independent of ATP and thus glucose
What class of drug does Pioglitazone belong to?
Thiozolidinediones
What is the mechanism of Pioglitazone?
PPAR-gamma agonist causing mainly peripheral insulin sensitisation
What is GLP-1?
Glucagon like peptide-1
Gut hormone which is secreted in response to nutrients in gut causing insulin increase and glucagon decrease.
It is a transcription product of pro-glucagon gene mostly from L cell
Gives feeling of satiety
Short half life due to rapid degradation from enzyme DPP4
What is the incretin effect?
There is a greater response in insulin secretion when an oral glucose load is administered rather than IV
What are some GLP-1 agonists and there effects on weight?
Liraglutide, semaglutide
Weight loss
What are some DPP4 inhibitors and what do they do?
What are their effects on weight?
Gliptins
Increase half life of exogenous GLP-1
Neutral on weight
How do SGLT-2 inhibitors work and what additional effects do they have?
Inhibits Na-Glu transporter increasing glycosuria
Lowers HbA1c
Improves chronic kidney disease
Decreases risk of myocardial infarction
What is the effect of drug treatment on beta cell function?
May slow down beta-cell function loss but cannot stop it
How can remission of T2DM occur?
Gastric bypass surgery has potential
Very low calorie diet for 3-6 months
