T2DM

Question 1

What tests are performed to diagnose diabetes and what are the defining values?

Answer 1

Fasting Blood Glucose:
Normal < 6
Impaired Fasting Glucose = 6-7
Diabetes > 7

Glucose Tolerance Test (2 hr measurement)
Normal < 7.8
Impaired Glucose Tolerance = 7.8-11.1
Diabetes > 11.1

Question 2

State three factors that influence the pathophysiology of T2DM.

Answer 2

Genetics
Intrauterine environment (low birth weight associated with higher risk via inter-uterine epigenetic changes)
Adult environment

Question 3

What is MODY?

Answer 3

Mature onset diabetes of the young (8 types)
It is autosomal dominant
Ineffective pancreatic beta cell insulin production Caused by mutations of transcription factor genes (glucokinase gene)
Positive family history with NO obesity

Question 4

What can modulate insulin resistance through adult life beforesomeone develops diabetes?

Answer 4

Adipocytokines

Question 5

How does insulin resistance lead to hypertension?

Answer 5

Insulin resistance -> compensatory hyperinsulinaemia.

Though the insulin doesn’t affect the glycaemic control pathway, it stimulates the mitogenic pathway causing smooth muscle hypertrophy –> high blood pressure

Question 6

What eventually happens to the beta cells in T2DM?

Answer 6

Insulin resistance damages the beta cells, eventually results in beta cell failure

Question 7

Describe how beta cell reserve and insulin resistance change with age.

Answer 7

Beta cell reserve decreases with age and insulin resistance increases

Question 8

Describe the presentation of a typical patient with T2DM.

Answer 8

Obese (80%)
Insulin resistance and insulin secretion deficit Hyperglycaemia and dyslipidaemia
Acute and chronic complications

Question 9

DKA tends to be in patients with T1DM, however, some subsets of T2DM also get ketoacidosis. What are these subsets?

Answer 9

Black and Asian patients with T2DM May be due to pancreatic insufficiency at a time of stress

Question 10

What dietary changes can someone with T2DM make to reduce the effect of the missing first phase insulin release?

Answer 10

Complex carbohydrates – release glucose more slowly

Question 11

Describe glucose clearance and hepatic glucose output in T2DM.

Answer 11

Glucose clearance is decreased

Hepatic glucose output is increased

Question 12

Which adipocytes are particularly marked for breakdown of triglycerides?

Answer 12

Omental adipocytes (this is why omental fat correlates with risk of heart disease)

Question 13

What happens to fatty acids when they go into the liver?

Answer 13

They cannot be used to make glucose so they are converted to very low-density lipoproteins (VLDLs), which are highly atherogenic

Question 14

Describe how gut microbiota is implicated in T2DM.

Answer 14

They may be important in host signalling – they ferment various lipopolysaccharides to produce short chain fatty acids, which enter the circulation and modulate bile acids (so they can also affect host metabolism) They are also important in inflammation and adipocytokine pathways

Question 15

What is a very common side effect of diabetes treatment?

Answer 15

Weight gain (Metformin is exempt for this and almost universally indicated for use in diabetic patients)

Question 16

What are the potential complications of T2DM?

Answer 16

Stroke 
Myocardial Infarction 
Neuropathy 
Retinopathy 
Nephropathy 
Hypoglycaemia

Question 17

What dietary measures are recommended for someone with T2DM?

Answer 17

Decreased fat (particularly saturated fats) 
Decreased refined carbohydrates 
Increased complex carbohydrates 
Increased soluble fibre 
Control total calories/increase exercise

Question 18

What is orlistat and why is it sometimes used in T2DM?

Answer 18

Pancreatic Lipase Inhibitor It reduces the break down of fats in the intestines thus reducing the absorption of fats.

Question 19

State 5 classes of drugs that are used to treat T2DM and state how they work.

Answer 19

Metformin – insulin sensitiser (biguanides)
Sulphonylureas – makes the existing pancreas produce more insulin
Alpha-glucosidase inhibitors – prolongs the absorption of glucose from the intestine
Thiazolidinediones – addresses peripheral insulin resistance (muscle and fat)
GLP-1 agonists and DPIV inhibitors – increase insulin secretion

Question 20

When should you NOT use metformin?

Answer 20

Severe liver failure
Severe cardiac failure
Mild renal failure

Question 21

How do sulphonylurears work and when are they prescribed?

Answer 21

They bind to receptors and block the ATP-sensitive K+ channel This leads to Ca2+ influx, which causes insulin release

E.g. Glibenclamide Given to lean patients with T2DM (Also given to MODY patients)

Question 22

Name one alpha-glucosidase inhibitor. Explain how it works and state some side effects.

Answer 22

Acarbose
It prolongs the absorption of oligosaccharides and allows the body to cope with the loss of first phase insulin
Side effect: it means that some sugars get to the colon and are fermented –> flatus

Question 23

Name on thiazolidinedione. What are its effects?

Answer 23

Pioglitazone
These are peroxisome proliferator-activated receptor (PPAR-) agonists These are insulin sensitises mainly in peripheral tissues (leads to peripheral weight gain)

Question 24

What does GLP-1 do?

Answer 24

Responsible for the incretin effect

Stimulates insulin and suppresses glucagon

Question 25

What breaks down GLP-1? What drugs prevent this?

Answer 25

Dipeptidyl peptidase-4 (DP-IV)

Gliptins inhibit DP-IV to prolong GLP-1 action

Question 26

What effect do long-acting GLP-1 agonists and gliptins have on weight gain?

Answer 26

GLP-1 agonists = weight loss

Gliptins = neutral

Question 27

What other pharmaceutical interventions must be considered with T2DM patients?

Answer 27

Many T2DM patients also have dyslipidaemia and hypertension, which need to be dealt with as well

Question 28

What can occur during pregnancy to identify women who are at high risk of getting diabetes in the future?

Answer 28

Gestational diabetes