Type 2 Diabetes

Question 1

T2DM

Answer 1

Due to progressive insulin secretory defect on the background of insulin resistance

Polygenic common complex disease

Question 2

Epidemiology

Answer 2

predominantly present in >40

Greatest prevalence in low and middle income countries

Question 3

Aetiology

Answer 3

Obesity
Chronic Pancreatitis
Peak age of onset: 50 years
Cushing’s syndrome

Question 4

Genetics

Answer 4

40% lifetime risk in offspring

Over 400 genetic variants

Twin studies: Monozygotic concordance rate of 90%

Highly heritable

Question 5

Pathophysiology

Answer 5

Combination of insulin resistance and inadequate production

• beta cell destruction
• Impaired secretion of insulin

Exceeding fat storage threshold

• lipid overspill
• lipotoxicity
• vulnerable beta-cells

The adiposity exceeding fat storage threshold leads to lipotoxicity causing vulnerable beta-cells

Question 6

Fat storage threshold

Answer 6

Insulin resistance occurs when fat can no longer be safely stored in subcutaneous adipose tissue causing spill over of FFA to. the viscera

People with ‘healthy’ obesity are able to safely store lots of fat; others have low fat storage threshold

Question 7

insulin resistance associations

Answer 7

hypertension
hyperlipidaemia
hyperglycaemia
Polycystic ovarian syndrome

Question 8

Signs

Answer 8

increased BMi
Retinopathy
Peripheral Neuropathy

Question 9

Symptoms

Answer 9

Often with complications of diabetes
- e.g. peripheral vascular disease, CVA, MI

Hyperosmolar Non-Ketotic Coma (HONK)

Recurrent infection

Pruritus

Question 10

Aims of Management

Answer 10

Treat Symptoms

Prevent microvascular complications

• glucose control
• aim for HbA1c <53mmol/L

Prevent CV complications

• cholesterol control
• BP control
• Antiplatelet therapy

Screen for complications early

• eye disease
• neuropathy
• kidney disease

Question 11

Management pathway

Answer 11

1. Diagnosis
2. Therapeutic Lifestyle change
3. Monotherapy
4. Combination therapy (NOT insulin)
5. Combination therapy with insulin

Question 12

Therapeutic management

Answer 12

Diet and exercise

Aim for realistic targets with weight maintanence/ modest weight loss
- 5 to 10kg in one year

General guidance on healthy eating
- Increase veg and decrease fats

Question 13

HbA1c Targets

Answer 13

Symptomatic control

Prevent complications
- HbA1c <53 mol/mol

Targets should be set with individuals in order to balance benefits with harm (in particular hypoglycaemia and weight gain)

For patients on triple oral therapy or insulin
- an HbA1c of 58 mol/L may be appropriate

Question 14

Glycaemic Control

Answer 14

Initially treat with diet

If unsatisfactory control, consider oral hypoglycaemic

Question 15

Complication Surveillance

Answer 15

Annual Review

• Fundoscopy
• Feet examination (neurological and vascular)

Check Insulin Sites

BP monitoring

Monitor renal function

Urine. protein dipstick

Thyroid function

Question 16

Metformin

Answer 16

1st line pharmacological treatment
Improve sensitivity to insulin

It is a biguanide

Question 17

Sulphonylureas

Answer 17

Stimulate pancreatic insulin release

E.g. Gliclazide

Side effects

• Risk of hypoglycaemia
• Weight gain

Question 18

Thiazolidinediones

Answer 18

Improve sensitivity to insulin

PPAR(gamma) agonists

E.g. pioglitazone

Side effects

• Weight gain
• Fluid retention
• Fracture risk