endocrinology

Question 1

What is the regulation of CHO metabolism in non diabetic humans?

Answer 1

FASTING STATE
- all glucose comes from liver
- breakdown of glycogen and gluconeogenesis
- glucose delivered
- insulin lvls low
- muscle uses FFA for fuel

AFTER FEEDING
- rising glucose stimulates insulin secretion and supresses glucagon
- 40% ingested glucose goes to liver, 60% to muscle to replenish glycogen stores
- high lvls suppress lipolysis and lvls of FFA fall

Question 2

What is the microstructure of Islet of langerhans?

Answer 2

Beta cells- secrete insulin
Alpha cells- secrete glucagon
Paracrine cross talk between alpha and beta cells

Question 3

How does insulin action work?

Answer 3

Glucose entry, potassium depolarising cell membrane and calcium leading to insulin secretion

Insulin binding, intra cellular signalling cascades, GLUT4 mobilisation to plasma membrane, glucose entry

Question 4

What does insulin do?

Answer 4

Suppress hepatic glucose output (less glycogenolysis and gluconeogenesis)

Increase glucose uptake into insulin sensitive tissues

Suppresses lipolysis and breakdown of muscle

Question 5

What does glucagon do?

Answer 5

Increases hepatic glucose output (more glycogenolysis and gluconeogenesis)

Reduce peripheral glucose uptake

Stimulate peripheral release of gluconeogenic precursors (glycerol, AAs) via lipolysis and muscle breakdown

Question 6

What is diabetes mellitus?

Answer 6

Disorder of carb metabolism
Characterised by hyperglycaemia
Causes morbidity and mortality

Question 7

What are complications of diabetes

Answer 7

Retinopathy
Neuropathy
Nephropathy
Stroke
CVD

Question 8

What are types of diabetes?

Answer 8

Type 1
Type 2
Monogenic/MODY
Pancreatic
Endocrine
Malnutrition related

Question 9

What is the definition of diabetes?

Answer 9

Symptoms + random plasma glucose >11mmol/L

Fasting plasma glucose >7mmol/L

HbA1c >48mmol/mol

Question 10

What is the pathogenesis of Type 1 diabetes?

Answer 10

Insulin deficiency
Beta cells express HLA antigens
Activates chronic cell mediated immune process which destroys the beta cells

Leads to hyperglycaemia and raised plasma ketones (glycosuria, ketonuria)

Question 11

What does failure of tx hyperglycaemia cause?

Answer 11

Perceived stress leads to increased cortisol and adrenaline

Progressive catabolic state and increasing levels of ketones

Question 12

What is the aetiology of type 2 diabetes?

Answer 12

Impaired insulin secretion and insulin resistance due to genes and environment

Question 13

What does impaired insulin action lead to?

Answer 13

Less muscle and fat uptake after eating
Failure to suppress lipolysis and high FFAs
Abnormally high glucose output after meal

Hyperglycaemia (glycosuria)

Question 14

What are principles of tx?

Answer 14

Control symptoms
Prevent acute emergencies
Identify/prevent long term micro vascular complications
Glucose control

Question 15

How do we tx type 2 diabetes?

Answer 15

Weight loss and exercise
Meds- control BP, blood glucose and lipids

Question 16

What are sulphonylureas?

Answer 16

Eg gliclazide

Bind to beta cell receptors to stimulate insulin release

Doesn’t prevent gradual failure of insulin release
Can go hypoglycaemia

Rarely used

Question 17

What are thiazolidinediones?

Answer 17

Eg pioglitazone

Bind to nuclear receptor PPARgamma
Activates genes for glucose uptake and use and lipid metabolism
Improves insulin sensitivity

Increase weight, risk of HF and fractures

Question 18

What are GLP-1 analogues?

Answer 18

Eg. Liraglutide

GLP-1 is secreted from L cells in intestine

It stimulates insulin and suppresses glucagon, slows gastric emptying, reduces food intake, enhances B cell, improves insulin sensitivity etc

Analogue replaces this

Question 19

What are DPP-IV inhibitors?

Answer 19

Eg Vildagliptin

DPP-IV rapidly degrades native GLP-1
So this is inhibited

Question 20

What are SGLT2 inhibitors?

Answer 20

Eg. Dapagliflozin

Block reabsorption of glucose in kidney, increase glucose secretion to lower blood glucose

Side effects- genital thrush, increased risk of euglycaemic ketoacidosis

Question 21

What is the first line drug?

Answer 21

Metformin