Week 3 type 2 diabetes

Question 1

What is diabetes?

Answer 1

A variable disorder of carbohydrate metabolism caused by a combination of hereditary and environmental factors

Question 2

What are the key characteristics of diabetes?

Answer 2

Poorly controlled blood glucose

Defective insulin production and/or utilisation

Defective lipid metabolism

Question 3

What is the difference between T1 and T11 diabetes?

Answer 3

1 usually occurs in earlier in life and pancreas doesn’t produce enough insulin

2 tends to happen later in life and is related to obesity / inflammation. Over time, poorly controlled glucose destroy beta cells in the pancreas so cant produce insulin anyways, this can lead to developing double diabetes.

Question 4

What does diabetes look like?

Answer 4

Fasting plasma glucose higher in a diabetic because liver producing too much glucose because insulin resistance has developed.

More exaggerated response after meals because of impaired glucose tolerance

Question 5

What is skeletal muscle responsible for after a meal?

Answer 5

clearing approx. 90% of circulatory glucose .

Question 6

What is the aim of diabetic therapies?

Answer 6

to bring glucose levels down into a healthy range

Question 7

What do microvascular diseased affect?

Answer 7

nerves / small vessels

Question 8

What do macrovascular diseases affect?

Answer 8

affects whole systems

Question 9

What is HbA1c?

Answer 9

Glycated haemoglobin - a clinical biomarker used to look at glucose control over a period of bout 3 months.

Question 10

How does high levels of HbA1C indicate high glucose levels?

Answer 10

Very high levels of glucose lead to the glycation of haemoglobin

Carbohydrates then attach to Hb producing HbA1C

HbA1C not affected by nutritional intake so doctor can monitor over about a 12 week period.

Question 11

What is an oral glucose tolerance test?

Answer 11

Used as part of diagnosis of diabetes

Drink sugary drink with 75mg glucose in, measurements then taken after two hours.

Question 12

What did a study by Tancredi et al (2015) find about T11 diabetes and excess mortality?

Answer 12

15% higher risk of death in T11 patients than control

Each 1% increase in A1C leads to a 12% increase in mortality

Question 13

What are some major complications of diabetes?

Answer 13

Diabetic retinopathy (leading cause of blindness)

Stroke (2-4x increased risk)

8/10pts with diabetes die of cardiovascular events

Diabetic neuropathy (affects 50% of T11 pts)

Diabetic nephropathy (leading cause of end-stage kidney disease).

Question 14

According to the triumvirate what three factors lead to hyperglycaemia?

Answer 14

Beta cell dysfunction (impaired insulin secretion)

Insulin resistance - skeletal muscle (Decreased glucose uptake)

Insulin resistance - liver (increased HGP)

Question 15

Obesity leads to chronic low grade inflammation, how does this lead to increased glucose levels?

Answer 15

Inflammatory proteins go through muscle tissues and block insulin signalling

This stops the muscle responding to insulin so cant take glucose out of the circulation.

Question 16

What is the liver responsible for and how can insulin resistance in the liver contribute to hyperglycaemia?

Answer 16

Responsible for releasing glucose when fasted but when we eat glucose levels rise and should shut off this process.

If the liver is insulin resistant it doesn’t pick up this signal so constantly producing too much glucose.

Question 17

What does lipotoxicity result from?

Answer 17

adipose tissues expand when obese which leads to having lots of free circulating fatty acids which leads to uncontrollable lipolisis.

Question 18

What can lioptoxicity lead to?

Answer 18

ectopic fat deposited in the pancreas which is toxic to beta cells so beta cells ultimately stop producing insulin and die.

Question 19

How can diabetes also be affected by genes?

Answer 19

Some individuals have genetic susceptibility, e.g. South Asian 4-5x more likely to develop diabetes than white Europeans.

Question 20

The ominous octet - how can increased glucagon secretion contribute to hyperglycaemia?

Answer 20

Causes liver to throw out too much glucose

Question 21

The ominous octet - how can neurotransmitter dysfunction contribute to hyperglycaemia?

Answer 21

Brain can become insulin resistant promoting increased food uptake leading to obesity

Question 22

The ominous octet - how can the kidneys contribute to hyperglycaemia?

Answer 22

As glucose levels increase initially the kidney compensates by changing the threshold that glucose is excreted in the urine - holds onto more glucose.

Question 23

The ominous octet - how can lipolosis contribute to hyperglycaemia?

Answer 23

Glycerol can go to the liver and undergo gluconeogenesis which produces glucose.

Question 24

What are incretin effects?

Answer 24

Hormones that are secreted after we eat to help the pancreas produce insulin?

Question 25

What do studies suggest about diabetes reversal?

Answer 25

Suggest T11 diabetes can be reversed within 4 years Predominantly through a low calorie diet, can now be prescribed on NHS (milkshake drinks) Although once its past 4 years, evidence suggests the beta cells of the pancreas are dead so then it cannot be reversed.

Question 26

What does observational evidence suggest about PA and T11 diabetes?

Answer 26

Dose response - as weekly PA energy expenditure increases, risk of T11D decreases. Cohort studies show a 20-30% reduction in risk for people who are regularly active.

Question 27

What does lifestyle intervention evidence suggest about PA and T11D? Study by Knowler et al (2002) - USA

Answer 27

Intervention group - goals were at least 7% weight loss and at least 150 min/wk PA Compared to control, people in intervention had 58% decrease in risk of getting T11D. This was superior to improvement induced by metformin medication.

Question 28

What does exercise intervention evidence suggest about PA and T11D? Sigal et al (2007)

Answer 28

251 adults with T11D 6month training programme - 3x per week Aerobic group - half a % decrease in HbA1C Resistance group - still a reduction but not as much as in aerobic group Combined group - biggest % reduction (almost out of high risk criteria)

Question 29

Describe the process that happens when we eat (healthy person)

Answer 29

Insulin levels increase in blood Bind to insulin receptors on muscle and stimulate phosphorylation events This leads to the activation of proteins which cause GLUT4 to move from intracellular vesicles in the muscle to muscle membrane to allow facilitated diffusion down a concentration gradient into the muscle. Diabetics are insulin resistant - this process does not happen / is less effective.

Question 30

How can exercise stimulate the mechanisms by which glucose diffuses down a concentration gradient into the muscle, completely separate to insulin?

Answer 30

Increase in AMP which gets phosphorylated to ATP When ratio of AMPK goes up (which is an energy crisis within the cell) this stimulates phosphorylation of AS160 which leads to GLUT4 translocation When a muscle contracts there is an influx of calcium within the cell, that can also stimulate this Stretch and mechanical response can also stimulate

Question 31

What do guidelines for exercise and T11D say?

Answer 31

Not to have more than two days off between bouts of exercise because regardless of diabetic/non-diabetic, insulin sensitivity can be improved for two days after a single bout of exercise.

Question 32

In an untrained individual during bout of exercise there is an increase in muscle glucose uptake, what is this due to?

Answer 32

Increased microvascular recruitment and blood flow Increased Glut4 translocation Increased glycolysis Increased oxidative phosphorylation

Question 33

What increases in an untrained individual post exercise, compared to at rest?

Answer 33

Microvascular recruitment in insulin resistance GLUT4 translocation by insulin Glycogen synthesis

Question 34

What did Little et al (2011) state about mitochondrial capacity and T11D?

Answer 34

Low volume high intensity interval training reduces hyperglycaemia and increased muscle mitochondrial capacity in T11D patients

Question 35

Outline some of the mechanisms by which exercise impacts T11D - chronic

Answer 35

Myokines Fat partitioning Hepatokines Incretin response

Question 36

Outline some of the mechanisms by which exercise impacts T11D - acute

Answer 36

Ectopic fat Body composition Low grade inflammation (adipokines) B-cell function Adipose tissue browning Muscle capillarisation

Question 37

role of glucagon?

Answer 37

break down glycogen in liver to provide fuel

Question 38

what is the aim of diabetic therapies?

Answer 38

to reduce plasma glucose levels to normal range

Question 39

what is lipolysis?

Answer 39

(the breakdown of triglyceride and adipose tissue into glycerol and FFA)

Question 40

what can now be prescribed by NHS?

Answer 40

low calorie diet (800kcal)

Question 41

what is the reduced risk of T2DM if we are regularly active?

Answer 41

20-30%

Question 42

how does exercise enhance insulin sensitivity during exercise?

Answer 42

delivery of glucose and substrate improved because exercise creates dilation around muscle, aiding delivery of glucose, so less glucose in blood increase in glut4 translocation to cell membrane to allow glucose in when exercising, increase in glycolysis and phosphorylation stimulating glucose uptake

Question 43

HITT training, what improvements can be seen?

Answer 43

improvement in glucose control after 6 weeks 25% reduction of glucose after just 2 weeks, 3 fold increase in levels of glut4 improved mitochondrial function

Question 44

What is diabetes usually characterised by?

Answer 44

an inadequate secretion or utilisation of insulin, excessive urine production, thirst, hunger, weight loss.