Endocrinology Session 2 CLINICAL

Question 1

What is diabetes?

Answer 1

When blood glucose is too high (hyperglycaemia) and over the years, leads to damage of small and large blood vessels causing premature death from cardiovascular diseases.

Question 2

What caused an epidemic in diabetes?

Answer 2

Environment (obesity, reduced activity)

- Not necessarily genetics

Question 3

What is the pathophysiology of diabetes?*

Answer 3

• Food is broken down into glucose
• Rising blood glucose signals the pancreas to start releasing insulin
• Insulin binds to a place on the cell wall/insulin receptor
• Unlocks the cell so that glucose can enter the cell
• Most glucose used immediately

Question 4

What are pancreatic islet cells?*

Answer 4

• Endocrine cells in pancreas

- Responsible for glucagon and insulin production (blood glucose control)

Question 5

What are the 2 reasons for rises in blood glucose?

Answer 5

• Inability to produce insulin (beta cell failure)

- Insulin production is adequate but insulin resistance prevents insulin working effectively (linked to obesity)

Question 6

What is the normal range for blood glucose?

Answer 6

3.9-7.1 mmol/L

Question 7

What causes type 1 diabetes?

Answer 7

AUTOIMMUNE BETA CELL DESTRUCTION

• Autoantibodies made against beta cells
• Cells destroyed
• Absolute insulin deficiency (not enough insulin)

Question 8

What causes T1 diabetes?

Answer 8

• Genetic predisposition (HLA-DQB1)

- Environmental trigger and genetic susceptibility combined

Question 9

What causes type 2 diabetes?

Answer 9

• Pancreas may not produce enough insulin

- Cells may not be able to use insulin to unlock the cells and allow glucose to enter (resistance)

Question 10

What is the presentation of diabetes mellitus (above 10 mmol/L)?

Answer 10

• Polyuria
• Polydipsia
• Blurring vision
• Urogenital infections
• Dehydration
• Lethargy and weakness
• Weight loss

Question 11

How is diabetes diagnosed?

Answer 11

• Fasting glucose test
• Oral glucose tolerance test
• HbA1c (glycosylated haemoglobin test)

Question 12

What is needed to diagnose diabetes?

Answer 12

• Symptomatic: 1 abnormal test

- Asymptomatic: 2 abnormal tests

Question 13

What is the potential aetiology of type 1 diabetes?

Answer 13

• Twin studies (higher risk if sibling has it)

- Hygiene hypothesis - immature immune system produces antibodies against own cells accidentally

Question 14

When is T1 diabetes most commonly diagnosed?

Answer 14

90% under 30 years of age, but can occur at any time. 1

Question 15

What is the presentation of type 1 diabetes?

Answer 15

PATIENT:

• Usually young
• Ketone presence

SYMPTOMS:

• Rapid onset weight loss, polyuria and polydipsia
• Ketoacidosis when late presentation

Question 16

How is type 1 diabetes treated?

Answer 16

• Exogenous insulin the only treatment
• Started immediately
• Given by subcutaneous injection several times a day

Question 17

Why are ketones important in diabetes?

Answer 17

• Insulin suppresses the production of ketones, unless in starvation
• Activated in absence of insulin
• Presence indicates immediate need for insulin therapy

Question 18

What are ketones?

Answer 18

Breakdown products of free fatty acid metabolism

acetone, acetoacetic acid and 3-beta-hydroxybutarate

Question 19

What is ketoacidosis?

Answer 19

A life threatening condition requiring immediate treatment and hospitalisation. Characterised by hyperglycaemia and ketonaemia, which leads to acidosis.

Question 20

What causes ketoacidosis?

Answer 20

Enhanced lipolysis

Question 21

How is ketoacidosis diagnosed?

Answer 21

• Ketonaemia >3.0 mmol/L or significant ketonuria (2+ on standard urine sticks)1

Question 22

What are some statistics about type 2 diabetes?

Answer 22

• 90% of sufferers are overweight or obese
• Many are asymptomatic and diagnosis made
• Managed by diet and tablets
• Most 40+ but increasing prevalence in children

Question 23

What causes the development of insulin resistance?

Answer 23

• Central obesity (85%)
• Fat deposition in muscle and liver
• High circulating free fatty acids
• Physical inactivity
• Genetic influences

Question 24

What happens after gastric bypass surgery?

Answer 24

• Glucose metabolism normalises
• No longer in diabetic range 1-2 weeks post-surgery
• Normalises even before any weight loss
• Fall in liver fat content
• Return to NORMAL insulin sensitivity

Question 25

What are the symptoms of type 2 diabetes?

Answer 25

- Polyuria/polydipsia/weight loss - No urinary ketones - A lot are asymptomatic and found by routine screens - Very variable due to slower rises in blood glucose - Most patients over 40 - 90% obese

Question 26

How should type 2 diabetes be managed?

Answer 26

- Weight loss (lifestyle) - Non-insulin therapy - Reducing other vascular risk factors (high BP, lipids, exercise, smoking) - Surveillance for chronic complications

Question 27

What drugs are used to treat diabetes?

Answer 27

- Biguanides (METFORMIN) - Sulphonyureas - SGLT2s - GLP1 analogues

Question 28

What are acute complications of hyperglycaemia?

Answer 28

- Massive metabolic decompensation - Diabetic ketoacidosis (T1) - Damage to micro and macrovasculature over time - Hyperosmolar non-ketoic syndrome (T2)

Question 29

What are acute complications of hypoglycaemia?

Answer 29

- Coma (brain deprived of glucose) | - Often iatrogenic by hypoglycaemic therapy

Question 30

What are chronic complications of diabetes related to macrovasculature?

Answer 30

- Cerebrovascular, cardiovascular and peripheral vascular disease - Stroke, heart attack, intermittent claudication, gangrene

Question 31

What are chronic complications of diabetes relating to microvasculature?*

Answer 31

- Retinopathy (blindness due to damage to retinal blood vessels) - Nephropathy (renal replacement therapy needed; thickened glomerular basement membrane reduces effectiveness of filtration) - Neuropathy (foot ulceration, peripheral neuropathy) - Constipation/diarrhoea

Question 32

What is metabolic syndrome?

Answer 32

Cluster of the most dangerous risk factors associated with cardiovascular disease (diabetes, raised fasting plasma glucose, abdominal obesity, high BP and cholesterol)

Question 33

What are the criteria for metabolic syndrome?

Answer 33

- Waist measurement > 94 cm men and > 80 cm women + 2 of: - Reduced HDL <1.0 men and <1.2 mmol/L women - Raised BP (>135/85) - Raised fasting blood glucose >5.6mmol/L or treated diabetes

Question 34

What causes metabolic syndrome?

Answer 34

- Insulin resistance - Central obesity - Genetics - Physical inactivity - Ageing