CSI 5: Diabetes

Question 1

What is prediabetes?

Answer 1

Blood sugars are higher than usual, but not high enough to be diagnosed with T2DM.

Are at a high risk of developing T2DM.

(Not a clinical term recognised by WHO → Starting to be used more by healthcare professionals and in the media to describe people who are at high risk of T2DM.

Question 2

4 other names for prediabetes

Answer 2

Borderline Diabetes

Impaired Glucose Regulation (IGR)

Non-diabetic hyperglycaemia

Impaired fasting glucose (IFG) together with Impaired Glucose Tolerance (IGT)

-

Question 3

List 5 modifiable factors that increase risk of diabetes

Answer 3

Smoking

History of high BP

Being overweight, especially with centripetal obesity

Sedentary lifestyle (physically inactive → Not doing enough physical activity; sedentary → sitting or lying down for long periods).

Alcohol

Question 4

List 5 non-modifiable factors that increase risk of diabetes

Answer 4

Older age; more at risk of white and over 40 OR over 25 and Afro-Caribbean, Black African or South Asian.

Having a parent, brother, sister or child with diabetes

Polycystic Ovary Syndrome (PCOS associated with insulin resistance)

Mental health conditions (e.g. schizophrenia, bipolar disorder, depression)

Antipsychotic medication (risk is quite low)

Question 5

Roughly what % of people who have diabetes have T2D?

Answer 5

90%

(Can come on slowly (Insidious onset), usually over the age of 40. Signs may not be obvious or there may be no signs at all, therefore it might be up to 10 years before diagnosis

Question 6

What is the NHS diabetes prevention programme?

Answer 6

Joint commitment from NHS England, Public Health England and Diabetes UK, to deliver at scale, evidence based behavioural interventions for individuals identified as being at high risk of developing T2MD.

Question 7

What are the long term aims of the NHS diabetes programme

Answer 7

Reduce T2DM
Reduce incidence of complications associated
Reduce health inequalities

Question 8

Which cells release insulin and which release glucagon?

Answer 8

Beta-cells → Insulin → Converts glucose into glycogen.

Alpha-cells → Glucagon → Converts glycogen into glucose.

Question 9

What are the core defects in T2DM?

Answer 9

Insulin resistance in muscle and liver
Impaired insulin secretion by the pancreatic Beta-cells

Question 10

List the 10 causes of hyperglycaemia (RULING HIVE)

Answer 10

Increased glucose reabsorption
Decreased glucose uptake
Increased lipolysis
Inflammation
NT dysfunction
Increased glucagon secretions
Increased hepatic glucose production
Decreased insulin secretion
Vascular insulin resistance
Decreased incretin effect

Question 11

Mechanism of increased glucose reabsorption

Answer 11

Increased renal glucose reabsorption by sodium/glucose co-transporter 2 (SGLT2) and the ^ed threshold for glucose spillage in the urine contribute to the maintenance of hyperglycaemia.

Question 12

Mechanism of decreased glucose uptake

Answer 12

Beta-cell failure → less insulin is secreted

Question 13

Mechanism of increased lipolysis

Answer 13

Insulin resistance in adipocytes results in accelerated lipolysis and ^ed plasma FFA levels, both of which aggravate the insulin resistance in muscle and the liver and contribute to Beta-cell failure.

Question 14

Mechanism of inflammation

Answer 14

Activates and ^ expression of several proteins that suppress insulin-signalling pathways making the body less responsive to insulin and increasing the risk for insulin resistance.

Question 15

Mechanism of NT dysfunction

Answer 15

Resistance to appetite-suppressive effect of a number of hormones + low brain dopamine + increased brain serotonin level contribute to weight gain, which exacerbates the underlying resistance.

Question 16

Mechanism of increased glucagon secretion

Answer 16

insulin inhibits glucagon secretion from alpha cells-over time after lots of insulin is being produced, alpha cells become insulin resistant→ glucagon secretion increases→blood glucose increases

Question 17

Mechanism of increased hepatic glucose production

Answer 17

increased glucagon levels and enhanced hepatic sensitivity to glucagon contribute to the excessive glucose production by the liver

Question 18

Mechanism of decreased insulin secretion

Answer 18

Beta-cell failure due to:

• GLP resistance
• Insulin resistant adipose, muscle and liver tissue.

Question 19

Mechanism of vascular insulin resistance

Answer 19

prolonged exposure to high levels of insulin causes increased vasculature resistance

Question 20

Mechanism of decreased incretin effect

Answer 20

the incretin ‘glucagon-like peptide 1’ (GLP1) stimulates β-cells to secrete insulin

Question 21

How is insulin involved in glucose metabolism?

Answer 21

Insulin from the blood binds to insulin receptor on skeletal muscle/adipose cell this induces blood glucose to be transported through the Glut-4 receptor via facilitated diffusion into the skeletal muscle/adipose cell glucose is converted to pyruvate via glycolysis pyruvate is converted to acetyl CoA via the link reaction/pyruvate oxidation acetyl CoA is converted to ATP (C) via the Krebs cycle and oxidative phosphorylation when inside the cell, 1 molecule of glucose can gene rate ~30ATP

Question 22

Where are GLUT-receptors not found?

Answer 22

Kidney and SI

Question 23

How do GLUT and SGLT receptors transport glucose into our body cells, respectively?

Answer 23

GLUT - Facilitated diffusion

SGLT - Active Transport (glucose transported into luminal epithelial cells in the kidney and small intestine)

Question 24

Primary distribution and function of GLUT1

Answer 24

Endothelium and erythrocytes
Basal transport (insulin independent)

Question 25

Primary distribution and function of GLUT2

Answer 25

Kidney, SI, liver, pancreatic beta cells Low affinity transport (insulin independent)

Question 26

Primary distribution and function of GLUT3

Answer 26

Neurones and placenta High affinity transport (insulin independent)

Question 27

Primary distribution and function of GLUT4

Answer 27

Skeletal muscle, adipose Insulin-regulated glucose transport

Question 28

What happens if your blood glucose is high, but you are insulin resistant?

Answer 28

Glucose not taken into skeletal muscle and adipose cells GLUT 1/2/3 cells take in lots of glucose

Question 29

What are the functional effects of insulin on the liver

Answer 29

Increases glucose uptake Increases glycogenesis Decreased gluconeogenesis and glycogenolysis Decreased lipolysis

Question 30

Functional effect of insulin on fat

Answer 30

Increased glucose uptake and lipogenesis Decreased lipolysis

Question 31

Functional effect of insulin on muscle

Answer 31

Increased glucose uptake Increased glycogenesis Increased P. Synthesis Decreased protein catabolism

Question 32

What are the core impairments of T2DM?

Answer 32

Insulin resistance: Liver, fat and muscle don't respond to insulin as well. This could cause a stage where lots of insulin is produced (hyperinsulinemia). Beta-cells eventually become worn down, so they don't produce as much insulin. There isn't enough insulin produced to overcome the resistance, so person becomes diabetic. Fat, liver, muscle tissue become insulin resistant and beta-cells are unable to produce enough insulin to compensate so increased BG AND FFAs

Question 33

What are the differences in pathogenesis between T1DM and T2DM?

Answer 33

T1DM → Very little/no insulin produced at all T2DM → Little insulin produced + insulin resistant cells.

Question 34

How is post-prandial glucose tested?

Answer 34

OGTT - get patient to fast for 8 hrs then give them a 75g oral glucose load, then measure their blood sugar 2 hour after. -

Question 35

What is the difference between impaired fasting glucose vs. impaired glucose tolerance?

Answer 35

Impaired fasting glucose: predominantly hepatic insulin resistance leads to continuous glucose output from the liver Impaired glucose tolerance: predominantly muscle insulin resistance plus impaired post-prandial insulin release results in poor cellular glucose uptake. Impaired fasting glucose and impaired glucose tolerance can occur together or separately, one could occur first

Question 36

What are the 3 symptoms of T2DM (can also be T1DM)?

Answer 36

Polydipsia- increase in thirst Polyurethane - frequent urination Polyphasic - rise in appetite

Question 37

How can you diagnose T2DM?

Answer 37

Symptoms + 1 red glucose range test OR No symptoms + multiple red glucose range tests -

Question 38

What is the renal threshold for glucose (RTG)?

Answer 38

The proximal tubule can only reabsorb a**limited amount of glucose** (~375 mg/min), known as the transport maximum. When the blood glucose level exceeds about 60–180 mg/dL, the **proximal tubule becomes overwhelmed** and begins to **excrete glucose** in the urine. This point is called the **renal threshold for glucose** (RTG).

Question 39

What is the HbA1c test?

Answer 39

HbA1c → Hb that has been glycosylated. - this process occurs **non-enzymatically** and can occur with the **monosaccharides glucose, fructose, and galactose** (although glucose least easily) - formation of HbA1C occurs **proportionately to plasma glucose levels** - therefore, HbA1C levels can be used to **diagnose and monitor diabetes**

Question 40

What are the advantages of the HbA1c test

Answer 40

Takes into account blood glucose for 2-3 months Easy to measure (fasting is not needed for A1C assessment and no acute perturbations (e.g., stress, diet, exercise) affect A1C) Cheap

Question 41

What are the disadvantages of the HbA1c test

Answer 41

Only an approximate measure. Not reliable in certain conditions e.g. Pregnancy (amount of Hb changes/rapid changes in glucose management) → Renal failure + Sickle cell

Question 42

What is used for first-line treatment of T2DM and how does it work?

Answer 42

Metformin Reduces the amount of sugar your liver releases into your blood. It makes your body respond better to insulin by stimulating GLUT-4 translocation It doesn't cause weight gain, unlike some other diabetes medicines Lower risk to hypoglycaemia Best to take with a meal to reduce the side effects

Question 43

What are the most common side effects of Metformin?

Answer 43

Sick, diarrhoea, stomach-ache and going off your food. -

Question 44

What is the behavioural insight approach?

Answer 44

Approach that uses knowledge of how and why people behave, to encourage positive behaviour change. Behavioural insights consider all aspect of behaviour (e.g. psychology, social anthropology and behavioural economics) and acknowledge the importance of the fast and intuitive automatic system driving behaviour. Behavioural insights are most helpful where individuals want to make positive behaviour changes but struggle to do so. - EAST Framework for behavioural change: [Untitled Database](https://www.notion.so/aa658c0f43e643ce9219366a96aeb0eb?pvs=21)