Type 2 Diabetes mellitus Flashcards

1
Q

What is type 2 diabetes?

A

A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
Associated with obesity but not always

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is another term for type 2 diabetes?

A

Relative insulin deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does development of type 2 diabetes associate with age?

A

Can present in any decade of life
Increasing in all ages but rapidly in early-adulthood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Outline the epidemiology of type 2 diabetes

A

Prevalence varies across countries enormously
Increasing prevalence
Occurring and being diagnosed younger
Greatest in ethnic groups that move from rural to urban lifestyle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the stages of development of type 2 diabetes?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is type 2 diabetes diagnosed?

A

Random glucose >11.1 mmol/L + osmotic symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe beta-cell function at diagnosis of T2DM

A

Usually dropped quite low before diagnosis ~ 50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why doesn’t hyperglycaemia normally cause ketosis in T2DM?

A

Insulin is still being produced by beta cells and this is enough to prevent ketosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What may be observed in long-duration T2DM?

A

Beta-cell failure may progress to complete insulin deficiency
Usually on insulin at this point but important not to stop as at risk of ketoacidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What factors are involved in the pathophysiology of T2DM?

A

Genes, intrauterine environment and adult environment
Fatty acids are important in pathogenesis and complications
Insulin resistance and insulin secretion defects
Heterogenous - variable BMI, age and progression across individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What happens when an individual with T2DM is given an IV glucose challenge?

A

First phase insulin release is lost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does T2DM affect skeletal muscle and hepatic glucose production?

A

Less uptake of glucose into skeletal muscle
Hepatic glucose production is increased due to both a reduction in insulin action and increase in glucagon action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Aside from diet, what also contributes to high plasma glucose in T2DM?

A

Impaired glucose disposal (clearance) and increased hepatic glucose production (HGP) contribute to increased fasting plasma glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does insulin secretion differ in an individual with T2DM vs an individual without?

A

For a given degree of insulin sensitivity, people with T2DM secrete less insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the genetics of T2DM

A

Monogenic -> Single gene mutation ==> Diabetes (MODY)
Polygenic -> Polymorphisms increasing risk of diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Approximately how many hits were there in the GWAS for T2DM and how much did they affect risk?

A

Approximately 450 hits
Each individual SNP has only a mild effect on risk
However cumulative effect of all SNPs have a bigger effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the role of obesity in T2DM?

A

Major risk factor for T2DM
Fatty acids and adipocytokines important
Central vs visceral obesity
80% T2DM are obese
Weight reduction useful treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What other factors, aside from obesity, are associated with T2DM?

A

Perturbations in gut microbiota:
- Bacterial lipopolysaccharides fermentation to short chain FA
- Bacterial modulation of bile acids
- Inflammation
Intra-uterine growth retardation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does T2DM present?

A

Hyperglycaemia
Overweight
Dyslipidaemia
Fewer osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency

20
Q

What are the risk factors of T2DM?

A

Age
PCOS
Higher BMI
Family Hx
Ethnicity
Inactivity

21
Q

How is type 2 diabetes diagnosed?

A

First line test: HbA1c
1x HbA1c >/= 48 mmol/L with symptoms
Or
2x HbA1c >/= 48 mmol/L if asymptomatic

22
Q

What can lead to a type 2 diabetes diagnosis?

A

Osmotic symptoms
Infections
Screening test: incidental finding
At presentation of complication:
- Acute; hyperosmolar hyperglycaemic state
- Chronic; ischaemic heart disease, retinopathy

23
Q

What is hyperosmolar hyperglycaemic state?

A

Insufficient insulin for prevention of hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis
Absence of significant acidosis
Often identifiable precipitating event (infection, MI)

24
Q

What does hyperosmolar hyperglycaemic state commonly present with?

A

Presents commonly with renal failure

25
Q

What are the differences between DKA and hyperosmolar hypoglycaemic state?

A
26
Q

Compare management of type 1 vs type 2 diabetes

A

Type 1:
Exogenous insulin (basal-bolus regime)
Self-monitoring of glucose
Structured education
Technology

Type 2:
Diet
Oral medication
Structured education
May need insulin later
Remission / reversal

Both require prevention of diabetes-related complications and their risk factors

27
Q

What are the principles of a T2DM consultation?

A

Glycaemia: HbA1c, glucose monitoring if on insulin, medication review
Weight assessment
Blood pressure
Dyslipidaemia: cholesterol profile
Screening for complications: foot check, retinal screening

28
Q

What are some dietary recommendations for people with T2DM?

A

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

29
Q

What drug deals with excess hepatic glucose production?

A

Metformin

30
Q

What drug(s) deals with resistance to action of circulating insulin?

A

Metformin
Thiozolidinediones

31
Q

What drug(s) deal with inadequate insulin production required to combat insulin resistance?

A

Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists

Boost insulin secretion

32
Q

What drug(s) deal with excess glucose in circulation?

A

Alpha glucosidase inhibitor
SGLT-2 inhibitor

33
Q

What is the first line medication if dietary/lifestyle adjustment has made no difference?

A

Metformin

34
Q

What is the mechanism of action of Metformin?

A

Biguanide
Insulin sensitiser
Reduces insulin resistance by reducing hepatic glucose output and increasing peripheral glucose disposal

35
Q

What are the side effects and contraindications of Metformin?

A

GI side effects
Contraindicated in severe liver, severe cardiac or moderate renal failure

36
Q

What is the mechanism of action of sulphonylureas?

A

Sulphonylureas eg gliclazide, bind to the ATP-sensitive potassium channel and close it, independent of glucose / ATP

37
Q

What is Pioglitazone?

A

Peroxisome proliferator-activated receptor agonists PPAR-γ
Insulin sensitizer, mainly peripheral

38
Q

What is the mechanism of action of Pioglitazone?

A

Modifies adipocyte differentiation

39
Q

What are the effects of Pioglitazone?

A

Improvement in glycaemia and lipids
Evidence base on vascular outcomes
May cause peripheral weight gain
Side effects of older types hepatitis, heart failure

40
Q

What is GLP-1?

A

Gut hormone
Secreted in response to nutrients in gut
Transcription product of pro-glucagon gene, mostly from L-cell

41
Q

Why is GLP-1 used in the treatment of T2DM?

A

Stimulates insulin, suppresses glucagon
↑ satiety (feeling of ‘fullness’) - weight loss
However, short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPP4 inhibitor)

42
Q

What do DPPG-4 inhibitors (gliptins) do?

A

Increase half life of exogenous GLP-1
Increase [GLP-1]
Decrease [glucagon]
Decrease [glucose]
Neutral on weight

43
Q

What do SGLT-2 inhibitors do?

A

Inhibit Na-Glu transporter, increase glycosuria
E.g. dapagliflozin, canagliflozin

44
Q

What are the benefits of SGLT-2 inhibitors?

A

HbA1c lower
32% lower all cause mortality
35% lower risk heart failure
Improve CKD

45
Q

What treatments have the potential of T2DM remission?

A

Gastric bypass
DIRECT/DROPLET study - very low calorie diet for 3-6 months has potential to induce remission

46
Q

Does treatment stop beta-cell function decline?

A

No

47
Q

What are the other aspects of T2DM management?

A

Blood Pressure management
Lipid management