Chemical pathology of diabetes W2

Question 1

What are the most wildly reported long-term diabetes complications?

Answer 1

• Heart disease
• Diabetic retinopathy
• Neuropathy
• Nephropathy

All of the above associated with accumulation of blood vessel and nerve damage over many years as a consequence of elevated blood glucose levels

Question 2

Extremely high glucose levels can lead to

Answer 2

Keto acidosis

Question 3

What is the common theme amongst the biochemical consequences of elevated glucose?

Answer 3

Oxidative stress
- generation of high levels of toxic oxidising molecules
- damage proteins and biological processes
- causes CV and nerve tissue damage in long-term

Question 4

What are the main toxic oxidants

Answer 4

Hydrogen peroxide
Superoxide
Hydroxy radicals

These are also called reactive oxygen species (ROS)

Question 5

What does glutathione do?

Answer 5

Is a cofactor (GSH) which maintains an intracellular reducing environment and helps neutralise reactive oxygen species

Question 6

What does increased NADH/FADH2 do

Answer 6

Increases proton gradient across in a mitochondria membrane

This inhibits the electron transfer from complex three endothelial cells

Question 7

Protein kinase pathway

Answer 7

Excess DHAP is converted to DAG which activates PKC

PKC activity then affects function of various proteins associated with blood flow abnormalities, capillary and vascular occlusion, pro-inflammatory gene expression, increased NADPH oxidise activity

Question 8

Methylglyoxal

Answer 8

A toxic by products of glycolysis

A very reactive carbonyl

Formed by the chemical degradation of DHAP and GAP

Irreversible elimination of the phosphate leaving group

Question 9

Insulin functions

Answer 9

1. Stimulate glucose into cells.
2. Stimulate conversion of excess glucose into glycogen.
3. Promote triacylglycerol(TAG) biosynthesis.
4. Inhibit hydrolysis of TAG.

Question 10

Keto acidosis: what happens?

Answer 10

When the body produces too many ketones

Low insulin = body thinks that it is starving = body uses fat for fuel = fats breakdown to produce ketones = ketone buildup = blood becomes acidic

Question 11

How long does the red blood cell last for?

Answer 11

Live for 120 days

Question 12

How is glycated haemoglobin formed?

Answer 12

Haemoglobin is contained in a red blood cell

Glucose enters the bloodstream and the red blood cell

It will naturally bind to the haemoglobin and the binding creates glycated haemoglobin (HbA1c)