April 18, 2016 - Vascular Complications of DM

Question 1

Hyperglycemia

Answer 1

A blood sugar greater than 9 mmol/L

Necessary for the development of microvascular complications

Not all people with hyperglycemia will develop complications, or may do so at different glycemic thresholds.

Question 2

Glycemic Injury

Answer 2

When high levels of glucose in the blood cause damage to cells.

Not all cells or tissues are vulnerable to glycemic injury. Only cells that are not capable of maintaining a normal intracellular glucose concentration will develop cellular damage leading to organ injury. These can include capillary endothelial cells (retina, glomerular mesangial cells), neurons, and Schwann cells.

Cells that can decrease glucose transport into cells in times of hyperglycemia are spared from injury.

Question 3

Mechanisms for Glycemic Injury

Answer 3

1. Accumulation of glycolytic intermediates that alter cell signalling and normal gene transcription
2. Glycation of normal proteins that leads to abnormal proteins with altered (or lost) function
3. Altered NAD/NADH balance leads to more oxidative stress and injury to the cell

The activation of multiple pathways lead to cellular injury. Examples are the polyol pathway, the hexosamine pathway, the protein kinase C pathway, and the AGE pathway

Question 4

Endothelium Function

Answer 4

Endothelium is a metabolically active interface between blood and tissue.

This modulates bloodflow, regulates nutrient delivery, modulates coagulation and thrombosis, and is involved in leukocyte activation and adhesion.

Question 5

Endothelium After Hyperglycemia

Answer 5

Normally the endothelium is in a healthy balance of derived factors.

After years of hyperglycemia, there is an imbalance in endothelial derived factors that lead to chronic vasoconstriction and arterial stiffening and prothombosis.

Question 6

Retinopathy

Answer 6

Leading cause of blindness in North America.

This occurs because of damage to the neurovascular unit. There is also vascular basement membrane thickening. There is also pericyte death because of the polyol pathway.

The loss of pericytes leads to loss of autoregulation of retinal bloodflow and the loss of the blood retinal-barrier.

Question 7

Diabetic Retinopathy

Answer 7

When damage occurs to the retina because of diabetes. This can eventually lead to blindness.

This is an ocular manifestation of diabetes, which affects up to 80% of all patients who have had diabetes for 20 years or more. The longer a person has diabetes, the higher his or her chances of developing diabetic retinopathy.

It is important to keep diabetes under control and blood pressure as well.

Question 8

Diabetic Neuropathies

Answer 8

Very insidious onset and is important to screen for.

This is the most commonly experienced diabetic complication. 25% of clinic patients have symptoms, and 50% have abnormal screening.

The major morbidity is the contribution to foot ulceration and the diabetic foot.

Question 9

Diabetic Amyotrophy

Answer 9

A nerve disorder that results as a complication of diabetes mellitus. It affects the thighs, hips, buttocks, and legs.

The sacral plaxus nerves can be damaged, which leads to huge weakness and atrophy of the muscles.

Question 10

Diabetic Autonomic Neuropathy

Answer 10

Damage to the autonomic nervous system can occur.

Can present in ways such as failure of your body to commence peristalsis. When a patient eats, they can get an insulin response, but the food isnt moving anywhere and being abosrbed so the patient can develop hypoglycemia.