Type 2 diabetes

Question 1

What is type 2 diabetes?

Answer 1

A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
Associated with obesity but not always
The resultant chronic hyperglycaemia may initially be managed by changes to diet / weight loss and may even be reversible
With time glucose lowering therapy including insulin, is needed

Question 2

At what age can you get type 2 diabetes?

Answer 2

Traditionally thought to be a condition of late adulthood
Now good evidence that it can present throughout every decade of life
Increasing in all age groups but rapidly in early-adulthood

Question 3

What are the fasting glucose levels at different stages of diabetes?

Answer 3

Normal - ≤ 6 mmol/L
Intermediate - impaired fasting glyaemia
Type 2 Diabetes - ≥7 mmol/L

Question 4

What are the 2 hour glucose results at different stages of type 2 diabetes?

Answer 4

Normal - <7.7 mmol/L
Intermediate - Impaired glucose tolerance
Type 2 Diabetes -≥ 11 mmol/L

Question 5

What are the HbA1c results at different stages of type 2 diabetes?

Answer 5

Normal - < 42 mmol/L
Intermediate - pre-diabetes or non diabetic hyperglycaemia
Type 2 Diabetes -≥ 48 mmol/L

Question 6

At what stage is insulin production the highest?

Answer 6

Intermediate stage of diabetes

Question 7

Why does hyperglycaemia in type 2 diabetes not normally cause ketosis?

Answer 7

Ketones are produced when there is no insulin, Insulin is produced by pancreatic beta-cells in T2D but not enough to overcome insulin resistance
There is therefore a relative deficiency of insulin

Question 8

Why do people with T2D end up needing insulin in the long term?

Answer 8

In long-duration type 2 diabetes, beta-cell failure may progress to complete insulin deficiency
, but important not to stop as at risk of ketoacidosis

Question 9

What causes insulin resistance in T2D?

Answer 9

perfect storm of internal adiposity, pro-inflammatory state and production of adipose cytokines. This cocktail makes the tissues resistant to the action of insulin.

Question 10

What is lost in T2D in terms of insulin response?

Answer 10

First phase insulin release is lost

Question 11

What are the problems with reduced insulin action?

Answer 11

In type 2 diabetes, reduced insulin action causes less uptake of glucose into skeletal muscle
Hepatic glucose production is also increased due to both a reduction in insulin action and increase in glucagon action. More glucose coming from the liver.

Question 12

Is type T2D monogenic or polygenic?

Answer 12

Polygenic

Question 13

What have GWAS shown in regards to T2D?

Answer 13

Individual SNP’s only have a mild effect on chance of developing T2D, but cumulative effects of all SNP’s have a bigger effect.

Question 14

What is the role of obesity in T2D?

Answer 14

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

Question 15

What are other associations with T2D?

Answer 15

Perturbations in gut microbiota

Obesity, insulin resistance T2DM
Bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids
Inflammation, signaling metabolic pathways
Most studies correlative

Intra-uterine growth retardation

Hales et al 1991
Weight at age 1 year <8.16kg, 22% had type 2 diabetes of IGT
Weight age 1 year >12.25 kg, 6% had type 2 diabetes or IGT

Question 16

What is the presentation of type 2 diabetes?

Answer 16

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

Question 17

What are the main risk factors for T2D?

Answer 17

Age		
PCOS
BMI       
Family Hx	
Ethnicity	
Inactivity

Question 18

What is the first line test for diagnosis?

Answer 18

HbA1c
1 x HbA1c> 48 mmol/L & symptoms
OR
2x HbA1c> 48 mmol/L & no symptoms

Question 19

What happens in a Hyperosmolar hyperglycaemic state?

Answer 19

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).

Question 20

What are acute and chronic T2D presentation?

Answer 20

Acute; hyperosmolar hyperglycaemic state,

Chronic; ischaemic heart disease, retinopathy

Question 21

What is the management for T2D?

Answer 21

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

Question 22

What are the principles for a T2D consultation?

Answer 22

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

Question 23

What are the dietary recommendations for T2D?

Answer 23

Total calories control
Reduce calories as fat 
Reduce calories as refined carbohydrate
Increase calories as complex carbohydrate
Increase soluble fibre
Decrease sodium

Question 24

Which drug reduces excess hepatic glucose production?

Answer 24

Metformin

weight loss

Question 25

Which drugs improve insulin sensitivity?

Answer 25

Metformin
Thiozolidinediones
weight loss

Question 26

Which drugs Boost insulin secretion?

Answer 26

Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists
weight loss

Question 27

Which drugs inhibit carbohydrate gut absorption & renal glucose resorption?

Answer 27

Alpha glucosidase inhibitor
SGLT-2 inhibitor
weight loss

Question 28

Describe the use of Metformin:

Answer 28

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

Question 29

Describe the mechanism of action of Sulphonylureas?

Answer 29

boost insulin production, When ATP-sensitive potassium channel closes you get insulin production. Sulphonylureas bind to this channel independent of glucose and close it.

Question 30

Describe the use of Pioglitazone:

Answer 30

Peroxisome proliferator-actived receptor agonists PPAR-γ
Pioglitazone
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

Question 31

What is the major side effect seen with some of the older T2D drugs?

Answer 31

Cause a slight increase in weight

Question 32

Describe the use of GLP-1:

Answer 32

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

Question 33

How are GLP-1 drugs prescribed in T2D?

Answer 33

Liraglutide, Semaglutide
Injectable –daily, weekly
Decrease [glucagon]
Decrease [glucose]
Weight loss

Question 34

How are DPP4-inhibitors used in T2D?

Answer 34

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

Question 35

How are SGLT-2 inhibitors used?

Answer 35

Inhibits Na-Glu transporter, increases glycosuria
Empagliflozin, dapagliflozin, canagliflozin
HbA1c lower
32% lower all cause mortality
35% lower risk heart failure
Improve CKD

Question 36

What has the potential to induce remission of T2D

Answer 36

weight loss

Gastric bypass surgery