Endocrine 1 - T2DM & Co-Morbidities

Question 1

What are 2 unique classifiers of T2DM?

Answer 1

1. Weight gain

2. Absence of auto-antibodies

Question 2

What are the 2 metabolic defects that characterise T2DM?

Answer 2

1. Peripheral insulin resistance –> which causes hyperglycaemia
2. Beta-cell dysfunction - hyperfunction as they try to compensate

Question 3

T1DM is caused by genetic mutations on genes involved in ___________.
T2DM is caused by genetic mutations on genes involved in ___________.

Answer 3

Immune tolerance and regulation (HLA, CDLA4)

Beta-cell function and insulin secretion

Question 4

Is there an increase in C-peptide in T2DM? T1DM?

Answer 4

Yes. Not in T1DM cos only produced if insulin is being produced.

Question 5

What is the number 1 factor that causes INSULIN RESISTANCE?

Answer 5

Obesity

Question 6

T2DM associated with ______ fat

IR associated with ______ fat

Answer 6

Visceral

Abdominal

Question 7

____ obesity = ____ sensitivity of peripheral tissue to insulin

Answer 7

Increased, decreased

Question 8

Obesity influences Insulin Resistance through 3 main mechanisms. What are they?

Answer 8

1. Non-esterified FAs (NEFAs) or Free FAs - compete with glucose for substrate oxidation
2. Adipokines - hormones released from adipocytes. Adiponectin (an adipokine that acts as an anti-hyperglycaemic) is reduced with obesity
3. Inflammation - release of pro-inflammatory cytokines (reducing these can restore insulin sensitivity)

Question 9

What is lipotoxicity?

What causes it?

Answer 9

A metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death.

Caused by: increased NEFAs with decreased glucose utilisation and decreased insulin sensitivity

Question 10

What are 4 components of T2DM management?

Answer 10

1. Diet
2. Exercise
3. Anti-diabetic medication
4. Weight loss surgery

Question 11

The effects of GLUCOTOXICITY are mediated by 3 pathways. What are they and how do they work?

Answer 11

1. Advanced Glycation End Products (ADEP): glucose + protein/lipid —> AMADORI products —> dicarbonyl bonds —> AGEP. The amadori products impairs enzymes, causes LDLs to not be recognised by their receptors etc. Affects the functioning of the cell. This process occurs naturally but is greatly accelerated by hypergycaemia. AGEPs promote atherogenesis, increase vessel stiffening.
2. Protein Kinase C (PKC): intracellular hyperglyceamia promotes formation of DAG which then alters PKC. PKC is a kinase and therefore affects other cells - impairs enzyme functions, cell proliferation + turnover etc., release of pro-inflammatory cytokines. Long term = diabetic microangiopathy.
3. Polyol Pathway: Glucose –> Sorbitol —> Fructose (and then back to glucose). Hyperglycaemia means lots of glucose is being converted into a lot of sorbitol. Result is: increased susceptibility to oxidative stress, diabetic abnormalities, nerve conduction abnormalities.

Question 12

What are 3 microvascular, 3 macrovascular and 2 other complications of diabetes?

Answer 12

Micro: neuropathy, nephropathy, vision disorders

Macro: heart disease, stroke, peripheral vascular disease

Other: infections, pregnancy problems

Question 13

Microalbuminuria is an initial indicator of ______ _____?

What 2 changes occur in the glomerulus in response to the above?

What are the 2 causes of the above?

Answer 13

diabetic nephropathy

1. Capillary basement membrane thickening
2. Sclerosis - ‘hyaline’
3. Metabolic disturbances - AGEP
4. Haemodynamic disturbances

Question 14

_____ _____ is the most common cause of death in diabetes.

Answer 14

Myocardial infarction