13. Type 2 Diabetes Mellitus

Question 1

What is diabetes mellitus?

Answer 1

A condition where the blood glucose is above an internationally accepted level

Question 2

Blood test diagnosis

Answer 2

Blood
• Glucose = or > 11.1 mmol/l + symptoms
• Glucose = or > 11.1 mmol/l x 2
• HbA1c = or > 48mmol/mol (6.5%)

Question 3

75g glucose tolerance test

Answer 3

Diabetes mellitus
	• Fasting plasma glucose =/> 7 mmol/l
	• 2 hour plasma glucose =/> 11.1 mmol/l
Impaired glucose tolerance
	• 2 hour glucose between 7-11 mmol/l
Impaired fasting glucose
	• Fasting glucose between 6-6.9 mmol/l

Question 4

What is type 2 diabetes?

Answer 4

A common condition where there is insulin resistance
AND
Beta cells which cannot produce enough insulin to keep blood glucose normal

Question 5

What damages the islet cells in type 2 diabetes?

Answer 5

Amyloid polymers made up of amylin which is co-secreted with insulin

Question 6

How are islet cells in type 2 diabetes characterised?

Answer 6

In type 2 diabetes (T2DM), the islet is characterized by
A deficit in β-cells
Increased β-cell apoptosis,
Extracellular amyloid deposits derived from IAPP

Question 7

Type 2 diabetes aetiology

Answer 7

Genetic
	• Polygenic
Foetal programming (epigenetic)
	• Maternal hyperglycaemia
	• Intrauterine growth retardation
Reduced beta cell mass
Beta cell regression (Sox 5 gene)
Old age
Other pancreatic pathology
Change in the gut microbiota
Glucotoxicity & lipotoxicity - later effects

Question 8

Epicardial fat

Answer 8

A strong risk factor for vascular disease

Question 9

Why is ectopic fat a problem?

Answer 9

Fat is an endocrine organ producing free fatty acids, cytokines, and procoagulant factors (PAI1)

Question 10

Effect of free fatty acids in obesity

Answer 10

insulin resistance

atherogenic lipids

Question 11

Effect of cytokines in obesity

Answer 11

insulin resistance

inflammation

Question 12

What is a characteristic specific to type 2 diabetes mellitus

Answer 12

Excess fat in the diabetic pancreas is specific to Type 2 diabetes mellitus and is important in preventing normal insulin production

Question 13

Type 2 diabetes prevalence in UK

Answer 13

4.6 million persons + 12.3 million at risk

In 2017

Question 14

Obesity epidemiology

Answer 14

ADULT OBESITY IN ENGLAND
RISEN from 15% in 1993 to 26% in 2016.
The age group most likely to be overweight or obese is age 55-64, but only by a small margin.
Prevalence of overweight and obesity above 70% among from 45 upwards.

Question 15

According to the Nurses health study, 96% of type 2 diabetes is attributed to what?

Answer 15

BMI >23
Lack of exercise
Unhealthy diet

Question 16

What cause serious side effects/morbidity in type 2 diabetes?

Answer 16

• Hyperglycaemia
  
  • Dysregulation of lipid metabolism
  • High levels of proinflammatory cytokines
  • High levels of free radicals
  • Increased susceptibility to infection

Question 17

What does diabetes type 2 do to the eye?

Answer 17

Maculopathy/retinopathy
as a result of blood glucose too high for too long

Cataracts due to increased generation of polyols from glucose - reducing HBA1c by 1% reduces cataract risk by 19%

Question 18

What else can type 2 diabetes mellitus cause?

Answer 18

Renal disease in type 2 diabetes
- need haemodialysis for chronic renal failure, as a result of blood glucose being too high for too long

Neuropathic ulcer - blood glucose too high for too long

Glycosylation of connective tissue e.g. cheroarthropathy

Question 19

How does type 2 diabetes affect bone?

Answer 19

• Mechanically weaker

* Increased fractures x2 in spite of normal bone density

Question 20

Type 2 diabetes effect and coronary artery disease

Answer 20

Coronary artery disease is a major problem in type 2 diabetes

Can result in STEMIs

Consequences of the dyslipaemia & proinflammatory state

increased chylomicrons, VLDL, and their catabolic remnants (all potentially pro-inflammatory) and low HDL (potentially anti-inflammatory)

Athterosclerotic lesion:
dyslipoproteinemia, inflammation, thrombosis

peripheral vascular disease

Question 21

Type 2 diabetes - what to do?

Answer 21

Prevent the diabetes
Improve the hyperglycaemia
Reduce the cardiovascular risk factors
Screen for complication and treat early

Question 22

Treating type 2 diabetes

Answer 22

Stage 1: lifestyle
• Diet
• Exercise

Prevention/Treatment:
Lifestyle manouvres
	• Diet / Exercise / smoking
Treatment of 
	• Dyslipaemia
		○ Statins 
	• Hypertension
Use of Aspirin

Question 23

Screening to enable early treatment

Answer 23

Eyes
	• Retinal Photography
	• Laser treatment when required
Kidneys
	• Measure urine albumin ( EMU)
	• Control Blood Pressure
	• ACE inhibitors & ARBs
Feet
	• Screen for neuropathy & Vascular disease

Question 24

Diabetes type 2 treatment goals

Answer 24

Lifestyle Modification
Screen for complications
Special clinics for complications
	• Foot, Renal, Eye
HbA1c  6.5 – 7.5 % (48 – 58 mmol/mol)
BP   120 -140 /80
LDL  < 2.0  mmol/l
Non HDL cholesterol  < 2.78

Goals must be tailored to individual e.g. pregnancy or elderly

Question 25

Treating type 2 diabetes

Answer 25

Pharmacological Interventions
	• Reduce Insulin Resistance
	• Increase Insulin production /secretion
	• Provide Insulin replacement
Metabolic / Obesity Surgery
Sleeve Gastrectomy
Roux en Y Bypass 
Gastric Band