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YEAR 1: CSI > Case 5: Type II Diabetes Mellitus > Flashcards

Case 5: Type II Diabetes Mellitus Flashcards

1
Q

Describe the mechanism of insulin on muscle cells

A
  1. It is released by beta islet of langerhans cells in response to low blood glucose.
  2. Insulin binds to insulin receptors on muscle cells.
  3. This activates a signalling cascade through the formation of cAMP and results in the translocation of GLUT4 to the cell membrane.
  4. Glucose enters the cell and is converted into ATP.
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2
Q

What is the function of GLUT4?

A

They are glucose channels which are insulin dependent.

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3
Q

How is GLUT4 stored in the absence of insulin?

A

It is found in vesicles in the cytoplasm and only translocate to the membrane via insulin activation (or muscle stimulation).

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4
Q

How is glucose converted into pyruvate?

A

Via glycolysis

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5
Q

How is pyruvate converted into Acetyl CoA?

A

Via pyruvate oxidation

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6
Q

How is Acetyl CoA converted into ATP?

A

Via Kreb’s cycle and oxidative phosphorylation

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7
Q

What is the mechanism of insulin resistance in Type II Diabetes?

A

Insulin binds to insulin receptors on muscle, fat and liver cells but the signalling cascade (for translocation of GLUT4) is not initiated.

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8
Q

How does the body respond to insulin resistance initially?

A

The beta cells produce even more insulin to compensate for the insulin resistance.

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9
Q

What happens to the beta cells as insulin resistance continues?

A

Unregulated, high levels of plasma glucose can be toxic to beta cells (GLUT 2 transporters are not insulin dependent), resulting in beta cell dysfunction. This means that less insulin will be produced-> increased glucose -> more beta cell dysfunction. It is a vicious cycle.

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10
Q

Describe the properties of GLUT 1 transporters

A
  • Insulin independent
  • Has a baseline affinity for glucose
  • Found on the endothelium and erthyrocytes
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11
Q

Describe the properties of GLUT 2 transporters

A
  • Insulin independent
  • Low affinity for glucose (if concentration of glucose is low, it won’t transport glucose in)
  • Found in kidney, small intestines, pancreatic beta cells, liver
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12
Q

Describe the properties of GLUT 3 transporters

A
  • Insulin independent
  • High affinity for glucose (will transport glucose even if conc. is low)
  • Found in neurones and placenta.
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13
Q

Describe the properties of GLUT 4 transporters

A
  • Insulin dependent
  • High affinity for glucose
  • Found in skeletal muscle and adipocytes
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14
Q

What are the different methods of measuring blood glucose?

A
  • Fasting glucose test
  • Oral glucose intolerance test/ post-prandial glucose
  • Random Glucose
  • HbA1c
  • Urine dip glucose
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15
Q

Which one those tests is the least reliable and not used to diagnose diabetes?

A

Urine dip glucose: people without diabetes have sometimes had glucose in their blood

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16
Q

What is the fasting glucose test and what is the threshold for someone with diabetes?

A

Measuring glucose levels when the patient hasn’t eaten for 8 hours.
Diabetes threshold: ≥ 7 mmol/L

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17
Q

What is the random glucose test and what is the threshold for someone with diabetes?

A

Measuring glucose levels at a random time.

Diabetes threshold: ≥11.1 mmol/L

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18
Q

What is the post-prandial glucose test and what is the threshold for someone with diabetes?

A

Measuring glucose levels a few (2) hours after someone has a set meal.
Diabetes threshold: ≥11.1 mmol/L

19
Q

What are the levels of fasting glucose of someone with impaired fasting glucose?

A

6.1 (5.5 in some) - 6.9 mmol/L

20
Q

What usually causes impaired fasting glucose?

A

Hepatic insulin resistance: continuous glucose output from liver

21
Q

What are the levels of fasting glucose and post-prandial glucose of someone with impaired glucose tolerance?

A

Fasting glucose: 6.1- 7 mmol/L

Post-prandial glucose: 7.8-11.1 mmol/L

22
Q

What usually causes impaired glucose tolerance?

A

Poor cellular glucose uptake

23
Q

What test is usually used to test for gestational diabetes?

A

Post-prandial glucose test

24
Q

What is pre-diabetes?

A

It describes people who are at high risk of T2 Diabetes: blood glucose levels are high but not high enough to be considered Diabetes. Other terms for this are: impaired glucose tolerance and impaired fasting glucose.

25
Q

What is the HbA1c test?

What is the threshold for Pre-diabetes and Diabetes?

A

Glycated Hb: glucose covalently binds to Hb in RBCs.

  • It has a short half life of erythrocytes
  • Erythrocytes express GLUT 1
    1) prediabetes: 42-47 mmol/mol
    2) diabetes: ≥48 mmol/mol (6.5%)
26
Q

What are the advantages of the HbA1c test?

A
  • Gives average blood glucose over a period of 3 months (RBCs are turned over every 3 months), not just 30 mins before the test.
  • It can be taken at any time (no fasting is required).
  • Cheap
  • Useful to see patient’s response to treatment
27
Q

What are some of the disadvantages of the HbA1c test?

A
  • Careful interpretation of the test is required for people with blood disorders like Sickle cell anemia.
  • It is only an approximate measure
  • Not useful for people who have just developed it (within the last 3 months)
28
Q

What are the modifiable risk factors for Type II diabetes mellitus?

A
  • Diet
  • Physical activity
  • Weight
  • Smoking and alcohol
  • High blood pressure
  • Depression
29
Q

What are the non-modifiable risk factors for Type II diabetes mellitus?

A
  • Ethnicity (africans and asians are at higher risk)
  • Genetics + family history
  • Age
  • High BMI
  • PCOS
30
Q

What are some of the symptoms of Type II diabetes?

A

1) Polydipsia
2) Polyuria
3) Nocturia
4) Glycosuria

31
Q

What are some of the microvascular complications that can occur in Type II diabetes?

A

Neuropathy
Nephropathy
Retinopathy

32
Q

What are some of the macrovascular complications that can occur in Type II diabetes?

A

Heart attack
Stroke
Diabetic foot
Peripheral Vascular disease (poor circulation to the limbs)

33
Q

What is required to diagnose someone with Type II Diabetes Mellitus?

A
  • HbA1c levels are higher than 48mmol/mol on 2 separate occasions (2 positive tests)
  • 1 postive test + osmotic symptoms
34
Q

What are some ways to encourage behavioural changes in diabetics that are struggling to make positive changes but want to do so?
(EAST)

A

Make it…
Easy -> educate the patients; give them recipes rather then just telling them to eat healthier; be specific about your goals
Attractive -> offer incentives, tailor the goals to the individual
Social -> social support group
Timely -> text reminders, timely goals

35
Q

Describe the aims of the NHS Diabetes Prevention Programme -> (PHD)

A

Encourage ….

  • Physical activity: following CMO guidelines
  • Healthy weight
  • improving Diet (Mediterranean/ vegan/ vegetarian/ Nordic diets)
36
Q

What is the eligibility criteria for the Diabetes Prevention programme?

A
  • Over 18 yrs
  • Blood result for pre-diabetes diagnosis must have occurred within the last 12 months.
  • HbA1c levels: 42-47 mmol/mol
  • Fasting plasma glucose levels: 5.5-6.9 mmol/L
  • At least 1 symptom and 1 positive/red glucose test
    or No symptoms but all positive/red tests
37
Q

What is a drug treatment for Type II DM if the the lifestyle changes aren’t enough?

A
  • Metformin

- If glucose is too high or there are no functional beta cells, insulin needs to be given first.

38
Q

How does the Metformin work?

A

Not known but current theory is that it helps in the translocation of GLUT4 transporters to the cell membrane.
It requires some residual pancreatic action.

39
Q

Why is Metformin usually the first line drug for people with Type II diabetes Mellitus?

A
  • 1 of the only diabetic drugs that helps you to lose weight (others cause weight gain)
  • Doesn’t cause hypoglycaemia
  • Immediate effects
  • Improves insulin sensitivity
    All of these are because it doesn’t act on insulin but the actual glucose transporters.
40
Q

What is the main disadvantage of using Metformin?

A

It has some gastrointestinal side effects like diarrhoea and vomiting.

41
Q

What are some of the mechanisms of Type II Diabetes?

A
  • Impaired insulin secretion -> beta cell dysfunction -> lipotoxicity, glucotoxicity
  • Resistance to incretins
  • Increased gluconeogenesis (increased glucagon)
  • Excessive glucose reabsorption from kidneys
  • Inflammation
42
Q

What are some hypothesised causes of insulin resistance?

A
  • Genetic abnormalities
  • Lipid accumulation
  • Mitochondrial dysfunction
43
Q

Who is the diabetes screening programme currently available for?

A

Adults ≥45 yrs, obese or have a family history

44
Q

If you are insulin resistant, which GLUT transporters will still take up glucose?

A

GLUT 1,2,3

YEAR 1: CSI (9 decks)

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