Metabolism

Question 1

The low activity of insulin in type 1 diabetes results in what metabolic effects?

Answer 1

Catabolic actions of glucagon are unopposed

Breakdown of carbohydrate, protein and fat

Hyperglycaemia, ketoacidosis, hypertriglyceridaemia

Question 2

Differences in the effects starvation and type 1 diabetes?

Answer 2

Type 1 diabetes has absent insulin, in starvation there is still a small amount

In starvation blood glucose is maintained, but in diabetes there is hyperglycaemia

In Type 1 diabetes there is much more ketone formation

Question 3

Time course of type 2 diabetes?

Answer 3

Early: plasma glucose normal despite insulin resistance as B cells can compensate

B cells eventually cannot compensate leading to impaired glucose tolerance and inflammation

Insulin resistance and impaired secretion lead to a failure to suppress gluconeogenesis at all and there is fasting hyperglycaemia

Question 4

Difference in metabolic effects in Type 1 and 2 diabetes?

Answer 4

Type 2 generally has enough insulin to prevent ketosis, however can develop under stress

Question 5

What syndrome can cause insulin resistance?

Answer 5

Cushings syndrome

Question 6

Treatment options mechanism for diabetes treatment?

Answer 6

Sulphonylureas: enhanced insulin secretion

Alpha-glucosidase inhibitors: reduced post-prandial hyperglycaemia

Metformin: reduced hepatic glucose concentration

Metformin and thiazolidinediones: reduced insulin resistance

Insulin: reduced hyperglycaemia

Incretin, sensitise B cells in pancreas to glucose, reducing the threshold for insulin release

Question 7

Possible causes of hyperglycaemia?

Answer 7

Insulin deficiency/increased catabolic hormones

Increased hepatic gluconeogenesis and glycogenolysis (unapposed glucagon)

Renal gluconeogenesis

insulin resistance increased

Question 8

Mechanisms for microvascular dysfunction in diabetes?

Answer 8

Endothelial cell dysfunction

Insulin resistance causes hyperlipidaemia

NO and vasodilator actions are impaired

Inflammation by Oxidative stress, cytokines, NO and adiponectin

Question 9

Whats a hyperosmolar coma?

Answer 9

Extreme hyperglycaemia inducing coma, triggered by dehydration/infection/illness

Question 10

What in diabetes causes hypertriglyceridaemia?

Answer 10

LPL activity reduced = VLDLs and chylomicrons remaining in plasma

Question 11

Main cause for diabetic ketoacidosis?

Answer 11

Switch to catabolic processes stimulated by glucagon leads to increased lipolysis and generation of ketones.

Question 12

Symptoms and signs for ketoacidosis?

Answer 12

Increased thirst, polyuria

Dehydration, hypotension

Blurred vision

Nausea and vomiting

Can lead to coma

Question 13

Why are counter regulatory hormone concentrations increased in diabetic ketoacidosis?

Answer 13

Low insulin leads to an early rise in glucagon

This leads to hyperglycaemia and diabetic ketoacidosis and dehydration this leads to the release of catecholamines and cortisol

Induces a vicious cycle

Question 14

What exactly leads to the formation of ketones in diabetes?

Answer 14

Increased TG hydrolysis in adipose tissue leads to FA release, these circulate to the liver and are processed to produce Ketone bodies

Question 15

Why does illness in diabetes lead to worsening of ketoacidosis?

Answer 15

Illness can lead to increases in catabolic hormones

Increasing the action of LPL

Question 16

How are ketone bodies disposed?

Answer 16

Most tissues use them

Oxidised and excreted through kidney and lungs

Question 17

How does the body try to compensate for the ketoacidosis?

Answer 17

Increased rate of deep breathing, using respiratory compensation (Kussmaul’s respiration)

Question 18

Why do you get ketoacidosis in type 2 diabetics but not in type 1?

Answer 18

In type 2 there is still insulin present, so acetyl CoA is converted to fatty acids instead of ketones.