Lecture 35 - Coordinating Metabolism: Diabetes (Type II)

Question 1

What is the main diagnostic criteria for type 2 diabetes?

Answer 1

HbA1C >50mmol/mol

Question 2

What are common symptoms of type 2 diabetes?

Answer 2

Glycosuria, osmotic diuresis and dehydration

Question 3

What is more common in type 1 diabetes?

Answer 3

Ketoacidosis

Question 4

What is a possible complication associated with type 2 diabetes?

Answer 4

Vascular diseases

Question 5

What causes glycated haemoglobin? (HbA1c)

Answer 5

When glucose builds up in your blood, it binds to the haemoglobin in RBCs.

Question 6

Why is HbA1C used as a measure of diabetes?

Answer 6

It measures how much glucose is bound and as RBCs have a half-life of ~3 months it shows blood glucose concentration over a long period of time

Question 7

How does diabetes increase risk of vascular disease?

Answer 7

Structural proteins in arteries can be made less compliant from glycosylation and the formation of advanced glycation end-products

Question 8

What would you see in a glucose tolerance test for a diabetic?

Answer 8

Elevated fasting glucose >7mmol/L and impaired lowering after ingestion

Question 9

What would you see in a glucose tolerance test for a pre-diabetic?

Answer 9

Slightly elevated fasting level of glucose 5.6-7mmol/L and impaired lowering after ingestion

Question 10

What would you see in a glucose tolerance test for someone without diabetes?

Answer 10

Fasting level ~3.5, peaks after ingested and returns to fasting levels within 2 hours

Question 11

What happens to lead to type 2 diabetes?

Answer 11

Over time hyperinsulinaemia diminishes the ability of beta-cells to respond to further increases in blood glucose and the individual becomes glucose-tolerant (prediabetic) and eventually diabetic

Question 12

What does insulin resistance do in fat storage?

Answer 12

Reduces the hydrolysis of TAGs in chylomicrons and VLDL by LPL. This leads to their accumulation and increase in blood TAGs

Question 13

What does insulin resistance do in the whole body?

Answer 13

Processes normally stimulated/inhibited by insulin aren’t. Decreases glucose uptake and gluconeogenesis, elevated FFAs and sometimes beta-cells responses diminish and insulin levels drop

Question 14

What processes are normally stimulated by insulin?

Answer 14

Glucose uptake, glycolysis, glycogenesis, lipogenesis

Question 15

What processes are normally inhibited by insulin?

Answer 15

Gluconeogenesis, lipolysis, fatty acid oxidation and ketogenesis

Question 16

What can diabetics develop?

Answer 16

Fatty livers which can lead to cirrhosis

Question 17

What happens in the cell with insulin resistance?

Answer 17

Reduced levels of phosphorylation and mis-phosphorylation occur in insulin signalling proteins which reduces GLUT4 translocation likely promoted by FFAs, inflammatory cytokines and oxidative stress

Question 18

What are treatments for type 2 diabetes?

Answer 18

Lifestyle changes e.g. dietary and exercise and some drugs e.g. metformin sulfonylureas, GLP-1 agonist, SGLT2 inhibitors and insulin

Question 19

How do metformin and exercise act to treat type 2 diabetes?

Answer 19

Both metformin and exercise increase AMP levels, which activates AMPK, which reduces gluconeogenesis. This reduces blood glucose levels.

Question 20

How is insulin secretion increased in beta cells?

Answer 20

GLP-1 peptide hormone synthesised in the liver acts through its receptor to stimulate insulin secretion

Question 21

How do sulfonylureas increase insulin secretion?

Answer 21

Block the K+ channel

Question 22

What is empaglifozin?

Answer 22

A SGLT2 inhibitor

Question 23

How do SGLT2 inhibitors work?

Answer 23

They block glucose reabsorption in the kidney by blocking the receptor. Therefore glucose is urinated to lower blood levels