Lec13 Type 2 Diabetes Mellitus

Question 1

What is diabetes mellitus

Answer 1

A condition where blood glucose is above an internationally accepted level

Question 2

Describe the usually clinical diagnosis with respect to blood and HbA1c respectively

Answer 2

Glucose equal or greater than 11.1mmol/l and symptoms
Glucose equal or greater than 11.1mmol/l in two tests
HbA1c equal to or greater than 4mmol/mol

Question 3

In a 75g oral glucose tolerance test, describe the parameters of diagnosing DM:

Answer 3

Fasting plasma glucose =/ > 7mmol/l

2 hour plasma glucose =/> 11.1mmol/l

Question 4

In a 75g oral glucose tolerance test, describe the parameters of diagnosing IGT

Answer 4

2 hour glucose between 7-11mmol/l

Question 5

In a 75g oral glucose tolerance test, describe the parameters of diagnosing IFT

Answer 5

Fasting glucose between 6-6.9mmol/l

Question 6

What is Type 2 DM

Answer 6

A common condition characteristic of hyperglycaemia due to the inability of the pancreatic beta cell to produce enough insulin to regulate plasma glucose concentration and insulin resistance

Question 7

What is the exocrine function of the pancreas?

Answer 7

To make digestive enzymes

Question 8

What is the endocrine function of the pancreas?

Answer 8

To make insulin and glucagon in the Islets of Langerhans to maintain plasma glucose

Question 9

What causes damage to the islet cells in Type 2 dDM?

Answer 9

Amyloid deposition in the beta islet cells

Question 10

What causes the deposition of amyloid in the beta cells?

Answer 10

Islet amylin polypeptide polymers (amylin is co secreted with insulin) secreted from pancreatic islet beta cells converted to amyloid deposits in T2DM

Question 11

In T2DM, the islet is characterised by:

Answer 11

A deficit in beta cells
Increased beta cell apoptosis
Extracellular amyloid deposits derived from IAPP

Question 12

What does conversion of IAPP to amyliod and deposition of the amyloid involve?

Answer 12

Conversion of the IAPP-37 to beta fibrils involves changes in molecular conformation, cellular biochemistry and diabetes related factors

Question 13

What is the aetiology of T2DM?

Answer 13

Genetic - Polygenic
Epigenetic - foetal programming –> maternal hyperglycaemia leading to IUGR due to nutrient deficiency and reduced beta cell mass in the baby

Question 14

What are the other possible etiological factors in T2DM?

Answer 14

Sox5 gene - regulates beta cell phenotype and is reduced in T2DM causing beta cell regression
Old age
Other pancreatic pathology
Change in gut microbiota
Glucotoxicity and lipotoxicity

Question 15

Why do people become insulin resistant?

Answer 15

Over indulging
Obesity
Increased access to food - e.g. fast foods

Question 16

What is the cause of insulin resistance?

Answer 16

Visceral fat is metabolically active
& responds to adrenaline and noradrenaline - breaks down into FFAs which change the lipid profile

Epicardial adipose tissue
Ectopic fat

Question 17

What is ectopic fat and what is the problem with it?

Answer 17

An endocrine organ producing:

• FFAs causing insulin resistance and atherogenic lipids
• Cytokines causing insulin resistance and inflammation of atheroma
• procoagulant factors (PAI1)

Question 18

What is a vital statistic in diagnosis of DM?

Answer 18

Waist circumference - central obesity due to visceral fat causes insulin resistance
Visceral fat around the pancreas prevents normal insulin production

Question 19

What happens when diabetic patients go on diets?

Answer 19

The excess fat around the pancreas is reduced and beta cells work better when the pt goes on diets - seen on MRI scans

Question 20

How do you prevent complications?

Answer 20

Prevent the diabetes

• get BMI >23
• exercise
• healthy diet

Question 21

List 10 consequences of prolonged hyperglycaemia

Answer 21

Increased susceptibility to infection, retinopathy, (maculopathy/ cataracts) chronic renal failure, neuropathy, neuropathic ulcer, cheiroarthropathy (glycosylation of connective tissue), cataracts, coronary artery disease due to glycosylated HDL -> myocardial infarction, peripheral vascular disease

Question 22

A reduction of HbA1c by 1% leads to a:

Answer 22

37% reduction in chances of microvascular complications

Question 23

How do you treat T2DM?

Answer 23

Prevent the diabetes
Control/improve hyperglycaemia
Reduce the cardiovascular risk factors
Screen for complications and treat early

Question 24

Describe the treatment regime for DM2.

Answer 24

Lifestyle factors – better quality diet, increased exercise, smoking cessation
Pharmacotherapy – Reduce insulin resistance, increase insulin levels (increase production/provide replacement, treatment for any concomittant dyslipidaemia/hypertension/other CV risk factors

Question 25

What screening could you carry out for the patient?

Answer 25

Diabetic eye screening
Kidney function - measure protein in urine
control blood pressure with ACE inhibitors and ARBs
Diabetic foot screening - screen for neuropathy and vascular disease

Question 26

What are the goals of T2DM treatment?

Answer 26

Lifestyle modification
Screen for complications
Special clinics for complications - foot, eye, renal
HbA1c 6.5-7.5% = 38-58mmol/mol
BP 120-140/80
LDL <2.0mmol
Non HDL cholesterol <2.78

Question 27

Goals must be tailored to the individual, why?

Answer 27

Pregnant women - need tight control of plasma glucose

Older adults - reducing glucose conc induces falls –> hip fractures & over treating can cause cause heart attacks

Question 28

What types of surgery can be given to T2DM

Answer 28

Sleeve gastrectomy
Roux en Y bypass
Gastric band