Diabetes Lecture 2: Type 2 Diabetes

Question 1

How is type 2 diabetes normally caused

Answer 1

Reduced insulin secretion and insulin resistance

Question 2

What does insulin resistance mean

Answer 2

Normally biological effects are not observed at physiological insulin levels

Question 3

What is beta cell dysfunction and describe the phases it goes through

Answer 3

when type 2 diabetics secrete less insulin daily

Phase 1: less insulin initially

Phase 2: exaggerated insulin response- may cause hypoglycaemia 3-4 hours after meal

Question 4

What are the symptoms of type 2 diabetes

Answer 4

Increased thirst and hunger

Increased urination

Fatigue

Blurred vision

Infection

Question 5

What is HYPEROSMOLAR HYPERGLYCAEMIA STATE (HHS)

Answer 5

Medical emergency to do with

Hyperglycaemia
Dehydration and Uraemia

Question 6

How do you screen for type 2 diabetes

Answer 6

Random blood glucose levels

Fasted blood glucose levels

HbA1C levels

Question 7

What are the risk factors for type 2 diabetes

Answer 7

Family history: Parents or sibling has it

Health problems: stroke, hypertension, coronary heart disease, peripheral artery disease

Ethnicity: afro carribean or african, south asian

Age: 40+ years

Waist measurement

BMI: greater than 25

Past: gestational diabetes

has known glucose intolerance or impaired fasting hyperglycaemia

Question 8

What are the macrovascular complications that can occur in diabetic patients

Answer 8

Stroke

Heart attack

Angina

Question 9

What are the microvascular complications that can occur in diabetic patients

Answer 9

Diabetic retinopathy

Erectile dysfunction

Autonomic neuropathy

Question 10

What are the treatment goals of type 2 diabetes

Answer 10

Preserve life

Alleviate symptoms

Achieve good glycemic control- avoid long term complications

Avoid iatrogenic side effects- hypoglycaemia

Question 11

how do you manage type 2 diabetes: DEED

Answer 11

Dietary modification

Exercise

Education

Drug treatment

Question 12

What does the diabetic diet consist of in managing type 2 diabetes

Answer 12

Low fat- low saturated fat

Increase fibre and complex carbs

Weight loss- moderate caloric deficit diet

Question 13

What does exercise consist of in managing type 2 diabetes

Answer 13

Exercise 30 minutes per day

Increases glycemic control, reduces CVD risk

Reduces blood pressure and improves lipid profile

Improves insulin sensitivity

Question 14

What does education consist of in managing type 2 diabetes

Answer 14

Patient aware that good glycemic control will avoid diabetic complications

Diabetic patients have increased mortality and morbidity

Risk of CVD or diabetic retinopathy

Erectile dysfunction

Question 15

What does drug treatment consist of in managing type 2 diabetes

Answer 15

Insulin secretagogues
Stimulates insulin release from pancreas, restores early phase insulin release
Example: Meglitinides and SULPHONYLUREAS

Insulin sensitisers
Metformin

Question 16

Give examples of sulphonylureas

Answer 16

Short acting: Gliclazide or tolbutamide

Long acting: glibenclamide

Question 17

What is the mechanism of action of sulphonylureas and Meglitinides

Answer 17

Increase insulin release from pancreas by binding to sulphonylurea receptor

Closes the K+ ATP channel which causes a rise in intracellular calcium and insulin release

Reduces HbA1c levels by 1.5 to 2%

Question 18

What are the commonside effects of sulphonylureas

Answer 18

Weight gain

Hypoglycaemia

Question 19

Give an example of Meglitinides

Answer 19

Nateglinide- can only be used with metformin

Repaglinide- derivative of glibenclamide

Question 20

What is the mechanism of action of GLICLAZIDE

Answer 20

Promotes insulin secretion from pancreatic beta cells

Binds to the sulfonyl urea receptor (SUR1) which binds and blocks the ATP sensitive potassium channel

Decrease in potassium efflux leads to depolarisation of Beta cells, opens up voltage dependent calcium channels

Activation of CALMODULIN- releases insulin secretory granules

Question 21

What is an insulin sensitiser

Answer 21

Enhances the effect of endogenous circulating insulin, reduces insulin resistance and decrease hepatic glucose production

Question 22

What are the two examples of insulin sensitiser

Answer 22

BIGUANIDES

THIAZOLIDINEDIONES (glitazones)

Question 23

Explain the role of the Biguanide METFORMIN

Answer 23

Increases glucose uptake in skeletal muscle and adipocytes, suppress hepatic glucose generation (gluconeogenesis)

Reduces glucose absorption from the small intestine (high drug concentration)

Suppress appetite, achieves weight loss and has cardio protective effect

Reduces HbA1c levels by 1 to 2%

Question 24

What are the side effects of metformin

Answer 24

GI side effects, anorexia, nausea, pain in abdomen, diarrhoea

minimised with gradual increase to dose or modified release

Question 25

What is the mechanism of action of metformin

Answer 25

Inhibit pyruvate mechanism which increases lactic acid production Reduces glucose production in liver and decrease glucose absorption Involves activating AMP activated protein kinase in liver and skeletal muscle

Question 26

Give an example of Thiazolidinediones and risks associated with it

Answer 26

Pioglitazone Risk in heart failure and bladder cancer patients

Question 27

What is the mechanism of action of thiazolidinediones

Answer 27

Bind to PPAR-gamrha (peroxisome proliferator activated receptor gamma) Regulates: gene transcription, enhances glucose and fatty acid uptake, utilises adipocytes, reduce secretion of cytokines that inhibit insulin action Reduce glucose output of liver

Question 28

What is an inhibitor of gastrointestinal glucose absorption

Answer 28

Acarbose

Question 29

What is an mechanism of action of acarbose

Answer 29

Alpha-glucosidase inhibitor that reduces glucose uptake in small intestine Slows digestion and absorption of glucose after a meal

Question 30

Explain how therapies based on glucagon like peptide 1 (GLP-1) work

Answer 30

Glucagon release from alpha cell is regulated by pancreas secreting insulin When stimulated, it has roles of slowing gastric emptying, slowing digestion and nutrient absorption, moderating blood glucose levels

Question 31

Give examples of Dipeptidylpeptidase 4 inhibitors

Answer 31

Saxagliptin Sitagliptin

Question 32

Explain the mechanism of action of Dipeptidylpeptidase 4 inhibitors

Answer 32

Inhibits DPP-4 which decreases GLP-1 degradation which leads to increased insulin secretion and decrease glucagon secretion

Question 33

Give examples of GLP-1 mimetic analogues

Answer 33

EXENATIDE and liraglutide (delivered by subcutaneous injection)

Question 34

What is the mechanism of action for GLP-1 mimetic analogues

Answer 34

DPP4 resistant analogues that bind to and active GLP-1 receptor Leads to increased insulin secretion, decrease of glucagon secretion, slow gastric emptying and promotes weight loss

Question 35

How do selective sodium glucose co-transporter 2 (SGLT-2) inhibitors work and give examples of them

Answer 35

Dapaglifozin Independent insulin mediated glucose control pathways, SGLT-2 block the reabsorption of glucose in the kidneys and promote urinary excretion

Question 36

When is insulin used in type 2 diabetes

Answer 36

When impossible to control good glycemic control with oral hypoglycaemic drugs Often given alongside metformin etc

Question 37

What is gestational diabetes

Answer 37

Diabetes that occurs during the first time in pregnancy

Question 38

How do you monitor for gestational diabetes

Answer 38

Routine tests for glycosuria

Question 39

How do you treat gestational diabetes

Answer 39

Lifestyle modification Exercise First line: insulin therapy or some oral hypoglycaemic drugs