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

What does fasting glucose show?

Answer 2

≤ 6 mmol/L

Impaired fasting glycaemia

≥7 mmol/L

Question 3

What does 2-hr glucose (OGTT)

Answer 3

< 7.7 mmol/L

Impaired glucose tolerance

≥11 mmol/L

Question 4

What does HbA1c show

Answer 4

< 42 mmol/mol

Pre-diabetes or non-diabetic hyperglycaemia

≥ 48 mmol/mol

Question 5

What does random glucose show?

Answer 5

> 11.1 with symptoms is diabetic

Question 6

How is the beta cell function diagnosis of T2DM different from T1

Answer 6

The start of treatment is at a higher level of beta cell function

Question 7

Why type of insulin deficiency is present in type 2 diabetes and why is this important

Answer 7

Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance
There is therefore a relative deficiency of insulin
This is important to understand as it explains why the hyperglycaemia encountered does not cause ketosis under ‘usual’ circumstances

Question 8

What are factors that affect insulin secretion and action

Answer 8

Body weight
Physical activity
Smoking
Heavy alcohol consumption
Genetic predisposition
Gene-environment interaction
Epigenetics

Question 9

What does insulin resistance and beta cell dysfunction lead to

Answer 9

Increase in hepatic glucose production (also due to increase in glucagon action)

Decrease in glucose uptake in adipose tissue and skeletal muscle

Question 10

What happens to the first phase inulin release in type 2 diabetes?

Answer 10

There is no sharp first phase insulin release

Question 11

Describe the relationship between insulin resistance and insulin secretion

Answer 11

The more sensitive, the less is needed to be secreted

People developing type 2 diabetes have ‘fallen off the curve’
And for a given degree of insulin sensitivity secrete less insulin

Question 12

Where are the consequences of insulin resistance seen

Answer 12

Liver
Adipocytes
Muscle

Question 13

What happens in terms of inflammatory adipokines?

Answer 13

There is an excess

Question 14

What is monogenic

Answer 14

Single gene mutation ==> Diabetes (MODY)
‘Born with it, always going to develop diabetes’

Question 15

What is polygenic

Answer 15

Polymorphisms increasing risk of diabetes
‘Not born with it but high risk and may develop later depending on other factors

Question 16

What is the role of obesity in type 2 diabetes

Answer 16

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

Question 17

What else plays a role in type 2 diabetes

Answer 17

Perturbations in gut microbiota
Intra-uterine growth retardation

Question 18

What are the presentations of T2DM

Answer 18

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

Question 19

What are the risk factors for T2DM

Answer 19

Age
PCOS
Inc BMI
Family Hx
Ethnicity
Inactivity

Question 20

How to diagnose type 2 diabetes

Answer 20

First line test for diagnosis is HbA1c. – more practical

1x HbA1c >=48mmol/L with symptoms

Or

2x HbA1c >=48 mmol/mol if aysymptomatic

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

Question 21

What is hyperosmolar hyperglycaemic state

Answer 21

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).

Dehydration -

Question 22

What is the management difference between type 1 and type 2 diabetes

Answer 22

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

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

Question 23

What diabetes-related complications and their risk factors are we trying to prevent

Answer 23

Retinopathy
Neuropathy
Nephropathy
Cardiovascular

Question 24

What are the principles of a diabetes consultation

Answer 24

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

Question 25

What to do when there is excess hepatic glucose production

Answer 25

Reduce hepatic glucose production

Meformin

Question 26

What to do when there is resistance to action of circulating insulin

Answer 26

Improve insulin sensitivity

Metformin
Thiozolidinediones

Question 27

What to do when there is an inadequate insulin production for extent of insulin resistance

Answer 27

Boost insulin secretion

Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists

Question 28

What to do when there is excess glucose in circulation

Answer 28

Inhibit carbohydrate gut absorption
Inhibit renal glucose resorption

Alpha glucosidase inhibitor
SGLT-2 inhibitor

Question 29

Metformin

Answer 29

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 30

Sulphonylureas

Answer 30

Normal insulin release requires closer of the
ATP-sensitive potassium channel

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

Question 31

Pioglitazone

Answer 31

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 32

Glucagon like (GLP-1) peptide-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

Incretin effect?

Answer 33

Orally ingested glucose elicits a much greater insulin response than that obtained when glucose is infused intravenously to give identical blood glucose levels

Question 34

GLP-1 agonist

Answer 34

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

Question 35

Gliptins (DPPG-4 inhibitor)

Answer 35

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

Question 36

SGLT-2 inhibitors

Answer 36

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

Question 37

Remission of T2DM?

Answer 37

Gastric bypass surgery has the potential to induce remission of type 2 diabetes

Very low-calorie diet (800 kcal/day) for 3-6 months has the potential to induce remission, which appears to be sustained at 2 years

Question 38

What are the other aspects of management for T2DM?

Answer 38

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