Type 2 diabetes

Question 1

What is the definition of diabetes?

Answer 1

A state of chronic hyperglycaemia sufficient to cause long term damage to specific tissues notably the retina, kidneys, nerves and arteries

Question 2

What is the clinical definition of diabetes?

Answer 2

Fasting blood glucose > 7mmol/l

Question 3

What is impaired fasting glucose?

Answer 3

Space in between the defining markers for diabetes and normal when measuring fasting blood glucose

Question 4

What is impaired glucose tolerance?

Answer 4

Space in between the defining markers for diabetes and normal when measuring the 2 hour response in a glucose tolerance test

Question 5

What factors affect pathophysiology of T2DM?

Answer 5

Genetic
Intrauterine environment
Adult environment

Question 6

What is the aetiology of Maturity Onset Diabetes of the Young?

Answer 6

Several hereditary forms- autosomal dominant for ineffective pancreatic beta cell insulin production

Question 7

As a baby, what makes you more likely to develop T2DM?

Answer 7

Being small- intrauterine growth restriction (IUGR)

Question 8

What other problems apart from an increase in blood glucose does insulin resistance cause?

Answer 8

Dyslipidaemia which stimulates the mitogenic pathway causing smooth muscle hypertrophy and an increase in blood pressure which increases the risk of microvascular disease

Question 9

What happens to insulin production and resistance as we get older?

Answer 9

Production decreases and resistance increases

Question 10

Eventually, insulin production will intersect with insulin resistance and the insulin production won’t be enough to overcome the resistance, when does this happen in caucasians?

Answer 10

110 years

Question 11

What percentage of patients with T2DM are obese?

Answer 11

80%

Question 12

What are the 2 phases of insulin release in a normal person?

Answer 12

1st phase- stored insulin that is ready to be released in one go
2nd phase- over a period of time, more insulin is produced and released

Question 13

What happens to the insulin phases in people developing diabetes?

Answer 13

They will still have some insulin production but will lose their 1st phase response

Question 14

How can diabetes get round their lack of a 1st phase response?

Answer 14

Eating complex carbohydrates which release the glucose slowly and decrease the need for a 1st phase response

Question 15

What are triglycerides broken down into?

Answer 15

Glycerol and non-esterified fatty acids (NEFA)

Question 16

What is insulin’s effect on the breakdown of triglycerides?

Answer 16

It inhibits it because you don’t need to break down fat stores after a meal

Question 17

Where does the glycerol and NEFA go after formation?

Answer 17

To the liver

Question 18

What happens to the glycerol in the liver?

Answer 18

Converted to glucose (gluconeogenesis)

Question 19

How is glucose released from the liver?

Answer 19

Glycogenolysis

Question 20

What happens to the NEFA when they get to the liver?

Answer 20

They are chopped up into 2-carbon segments which can’t be used to make glucose but are used to make very low density lipoprotein triglycerides which are atherogenic

Question 21

What is insulin resistance modulated by?

Answer 21

Adipocytokines

Question 22

What system is thought to be associated with obesity, insulin resistance and T2DM?

Answer 22

Gut microbiota

Question 23

What is a common side effect of diabetes treatment and what is the only treatment that doesn’t cause this side effect?

Answer 23

Weight gain and metformin

Question 24

How does T2DM present?

Answer 24

Microvascular:
Retinopathy
Nephropathy
Neuropathy

Microvascular:
Ischaemic heart disease
Cerebrovascular
Renal artery stenosis
PVD

Metabolic:
Lactic acidosis
Hyperosmolar

Question 25

In terms of metabolic issues, how often do they present in T2DM compared to T1DM?

Answer 25

Much more common in T1DM with ketoacidosis

Question 26

What is the basis of management of T2DM?

Answer 26

Education Diet Pharmacological treatment Complication screening

Question 27

How should someone with T2DM control their diet?

Answer 27

``` Control total calories/increase exercise Reduce refined carbohydrates Increase complex carbohydrates Reduce fat as proportion of calories Increase unsaturated fat as proportion of fat Increase soluble fibre ```

Question 28

How do you monitor T2DM?

Answer 28

Weight Glycaemia Blood pressure Dyslipidaemia

Question 29

What is orlistat and how does it work?

Answer 29

Pancreatic lipase inhibitor- it stops the breakdown of fat thus restricting fat absorption in the gut

Question 30

What is metformin and how does it work?

Answer 30

Biguanide- Treats insulin resistance in the liver

Question 31

How do sulphonylureas work?

Answer 31

Makes the existing pancreas secrete more insulin

Question 32

How do alpha glucosidase inhibitors work?

Answer 32

Delay glucose inhibition

Question 33

How do thiazolidinediones work?

Answer 33

They act on the adipocytes and addresses insulin resistance peripherally in fat and muscle

Question 34

How common is metformin as a treatment?

Answer 34

Used in more or less everyone with T2DM in particular overweight patients

Question 35

When would metformin not be used?

Answer 35

Severe liver failure Severe cardiac failure Mild renal failure

Question 36

How can beta cells gage the blood glucose levels and what does it lead to?

Answer 36

Glucokinase and insulin secretion

Question 37

How do sulphonylureas work?

Answer 37

They act on specific receptors and block the ATP sensitive potassium channel and cause the influx of calcium which leads to insulin secretion

Question 38

What is glibenclamide?

Answer 38

Sulphonylurea and insulin secretagogue

Question 39

What are the side effects of glibenclamide?

Answer 39

Hypoglycaemia | Weight gain

Question 40

What is acarbose?

Answer 40

Alpha gluconidase inhibitor

Question 41

How does acarbose work?

Answer 41

Prolongs the absorption of oligosaccharides which allows insulin secretion to cope following the loss of the first phase insulin response

Question 42

What are the side effects of acarbose?

Answer 42

Sugars reach the large intestine where they are fermented so flatus (gas) is an issue

Question 43

What are thiazolidinediones?

Answer 43

Peroxisome proliferator-activated receptor (PPAR-y) agonists

Question 44

What is an example of a thiazolidinedione?

Answer 44

Pioglitazone

Question 45

How do thiazolidinediones work?

Answer 45

They are an insulin sensitiser- mainly peripheral and cause weight gain- improvement in glycaemia and lipids

Question 46

What are the side effects of thiazolidinediones?

Answer 46

Hepatitis and heart failure

Question 47

What is the incretin effect?

Answer 47

Oral glucose load triggers a bigger release in insulin than IV glucose

Question 48

Why does the incretin effect occur?

Answer 48

Due to GLP-1 which is a gut hormone that is released on response to food in the gut and stimulate insulin and suppresses glucagon

Question 49

Where and how is GLP-1 produced?

Answer 49

It is produced by L-cells and is the transcription product of pro-glucagon gene

Question 50

What is a problem with GLP-1?

Answer 50

Short half life as it is rapidly degenerated by dipeptidyl peptidase-4 (DPP-IV)

Question 51

How do Gliptins work?

Answer 51

They make the GLP-1 that is present last longer because they are DPP-IV inhibitors

Question 52

What is gestational diabetes?

Answer 52

Temporary diabetes that is present in some pregnant women- helps identify women that are high risk for diabetes later in life

Question 53

In which type of diabetes is weight loss common in?

Answer 53

Type 1

Question 54

Which type of diabetes is ketone prone?

Answer 54

Type 1

Question 55

In which type of diabetes is serum insulin low or absent?

Answer 55

Type 1

Question 56

Which type of diabetes has HLA association?

Answer 56

Type 1- DR3 and DR4

Question 57

In which type of diabetes do islet B cells function?

Answer 57

Type 2

Question 58

In which type of diabetes are islet cell antibodies present?

Answer 58

Type 1