Pathophysiology of Type 2 Diabetes

Question 1

What factors contribute to the development of insulin resistance?

Answer 1

Genetic predisposition and obesity lifestyle factors

Question 2

What does insulin resistance cause?

Answer 2

Compensatory beta cell hyperplasia, leading to beta cell failure

Question 3

What does early beta cell failure cause?

Answer 3

Impaired glucose tolerance = progresses to diabetes as beta cell failure progresses

Question 4

What are the factors linked to hyperglycaemia?

Answer 4

Increased incretin effect, decreased insulin secretion
increased lipolysis, increased glucose reabsorption, neurotransmitter dysfunction, decreased glucose uptake, increased hepatic glucose production, increased glucagon secretion

Question 5

What contributes to the susceptibility of an individual to type 2 diabetes?

Answer 5

Genetic component, foetal development, postnatal nutrition

Question 6

What adaptions occur in the cells during type 2 diabetes?

Answer 6

Beta cell mass expansion, insulin secretion

Question 7

Failure of what processes are linked to type 2 diabetes?

Answer 7

Glucolipotoxicity, oxidative stress, ER stress, de-differentiation

Question 8

How do weight and insulin resistance change as the disease progresses?

Answer 8

They both increase

Question 9

What affect does obesity have on disease progression?

Answer 9

It accelerates the disease presentation

Question 10

What is type 2 diabetes a disease of in most people?

Answer 10

Disease of beta cells

Question 11

How does beta cell dysfunction cause microvascular disease?

Answer 11

Beta cell dysfunction causes hyperglycaemia = chronic hyperglycaemia leads to microvascular disease

Question 12

How can progression of microvascular disease be reduced?

Answer 12

By intensive glucose control

Question 13

How is CVD risk best treated?

Answer 13

Through use of statins and anti-hypertensives

Question 14

What is the first step of treating someone with type 2 diabetes?

Answer 14

Lifestyle advice = information, reduce weight by 5-10%, give exercise target
Medications = metformin, may need statin/ACE inhibitor

Question 15

What does metformin do?

Answer 15

Decreases hepatic gluconeogenesis = increases peripheral glucose uptake

Question 16

What are the adverse effects of metformin?

Answer 16

GI effects, lactic acidosis

Question 17

What are the diabetic outcome of metformin?

Answer 17

Reduce HbA1c by 0.8-2.0%
Get weight to neutral
No hypoglycaemia

Question 18

What are factors that lead to failure to meet glycaemic targets?

Answer 18

Younger patient, female, obese, not at BP/lipid targets, more complex glucose lowering therapy, poor adherence to drugs and lifestyle changes

Question 19

What is the first step of drug prescription for type 2 diabetes?

Answer 19

Metformin

Sulphonylurea if intolerant to metformin

Question 20

What is the second step of drug prescription for type 2 diabetes?

Answer 20

Add sulphonylurea
Use TZD if hypoglycaemia a concern
Use DPPIV if weight gain a concern

Question 21

What is the third step of drug prescribing for type 2 diabetes?

Answer 21

Add TZD
Use DPPIV if weight gain a concern
Use insulin if osmotic symptoms or rising HbA1c
Use GLP-1 if BMI > 30mg/kg

Question 22

How should glycaemic targets be created?

Answer 22

Must be individualised, as should glucose lowering therapies

Question 23

What is the optimal first line drug for treating type 2 diabetes?

Answer 23

Metformin (unless contra-indicated)

Question 24

What is the foundation of any type 2 diabetes treatment programme?

Answer 24

Diet, exercise and education

Question 25

What should be the major focus of therapy for type 2 diabetics?

Answer 25

Comprehensive CV risk reduction

Question 26

How does sulphonylurea act?

Answer 26

Blocks beta cell KATP channels = increases first and second phase insulin secretion Efficacy reduced at higher doses

Question 27

What are the diabetic outcomes for sulphonylurea?

Answer 27

Reduce HbA1c by 1.0-2.0% Increase weight gain by 2kg Increase hypoglycaemia

Question 28

What are the adverse effects of sulphonylurea?

Answer 28

Abnormal LFTs, increased CHD

Question 29

What are some features of GLP-1 and DPPIV?

Answer 29

``` GLP-1 = injected, affects hypoglycaemia when used in combination DPPIV = oral, weight stays the same or decreases ```

Question 30

How does glitazone work?

Answer 30

PPAR gamma inhibitor = increases peripheral glucose uptake

Question 31

What are the diabetic outcome for glitazone?

Answer 31

Decrease HbA1c by 0.6-1.5% | Increase weight gain by 3.5 kg

Question 32

What are the adverse effects of glitazone?

Answer 32

Fracture risk increase, hepatotoxicity, fluid retention

Question 33

What is the general treatment plan for type 2 diabetics?

Answer 33

Therapeutic lifestyle change = results in remission in 10-15% Monotherapy Combination therapy (not insulin) Combination therapy with insulin