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Endocrine > Diabetes > Flashcards

Diabetes Flashcards

1
Q

What cells in the pancreas secrete insulin?

A

B cells in the Islets of Langerhans

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2
Q

Name two insulin dependant tissues

A

Skeletal muscle and adipose tissue

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3
Q

What is the pathophysiology of type 1 diabetes?

A

Cannot distinguish own cells from other cells -> autoimmune attack on pancreatic B cells

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4
Q

What is insulitis?

A

Disease of the pancreas caused by lymphocyte infiltration of the islets of Langerhans

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5
Q

List some potential environmental triggers for type 1 diabetes

A

? Chemicals
? Bacteria in gut altered in infancy
? Viral infection - ? Molecules on viral surface mimic molecules on outside of B cells

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6
Q

What is the aetiology of type 2 diabetes?

A

Not completely known. Likely a combination of..

1) reduced tissue sensitivity to insulin (insulin resistance) and
2) inability to secrete very high levels of insulin

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7
Q

What are some environmental causes of type 2 diabetes?

A

-Expanded upper body fat mass (due to increased food intake and lack of exercise)

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8
Q

What do excess fatty acids in blood do in a person with central adiposity?

A

Decrease insulin receptor sensitivity - so pancreas needs to secrete more insulin

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9
Q

What happens to insulin levels in person with central adiposity?

A

Less glucose removal from blood, so insulin levels have to increase more to combat peripheral insulin resistance.

Hyperinsulinaemia.

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10
Q

What genes are implicated in type 2 diabetes?

A

Genes for poor B cell ‘high end’ insulin secretion - so they cannot produce large quantities to make up for the increased resistance.

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11
Q

What genes are implicated in type 1 diabetes?

A

Genes related to HLA molecules (that help T cells recognise self from non-self)

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12
Q

What is the reversible component of type 2 diabetes?

A

Central adiposity resulting in free fatty acids -> peripheral insulin resistance

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13
Q

What is the main complication that results from poor glycaemic control?

A

Damage to vessels large/small vessel disease.

Accelerates atherosclerosis

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14
Q

What happens in arterioles in diabetes mellitus

A

Plasma proteins get trapped in subendothelial space - cant flux back in. Basal lamina thickens -» Decreased lumen size

Hyaline change. Leads to ischaemia

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15
Q

Where are some areas that might be particularly damages in arteriolar disease/hyaline change in diabetes?

A

Kidney, peripheral tissues (feet), eyes, and arterioles supplying nerves.

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16
Q

What complications can this arteriolar disease lead to?

A

Amputation
End stage renal disease
Blindness

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17
Q

What protein modification can occur in diabetes that leads to arteriolar disease?

A

Glycosylation

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18
Q

What does glycosylated collagen do to albumin?

A

Binds it - accumulation in subendothelial space

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19
Q

What can occur between neighbouring glycosylated proteins that increases accumulation?

A

Cross-linking

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20
Q

Why is it sometimes not appropriate to use HbA1c for diabetes diagnosis?

A

Blood cells typically last 8-12 weeks - may have a different status currently.

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21
Q

When is it inappropriate to use HbA1c in diagnosis?

A
  • All children and young people.
  • Pregnancy—current or recent (< 2 months).
  • Short duration of diabetes symptoms.
  • Patients at high risk of diabetes who are acutely ill
  • Patients taking meds that cause rapid glucose rise
  • Acite pancreatic damage/surgery
  • Renal Failure
  • HIV

etc

(When things can change too quickly)

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22
Q

What random venous plasma glucose level would allow for diagnosis of diabetes?

A

Random Glucose =/> 11.1 mmol/L

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23
Q

What fasting plasma glucose level would allow for diagnosis of diabetes?

A

Fasting Glucose =/> 7.0 mmol/L

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24
Q

What 2 hour OGTT plasma glucose level would allow for diagnosis of diabetes?

A

OGTT Glucose =/> 11.1 mmol/L

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25
Q

What HbA1c level would allow for diagnosis of type 2 diabetes?

A

=/> 48 mmol/L

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26
Q

In what situations should HbA1c not be used for diagnosing diabetes?

A
  • Children and young people
  • Suspected Type 1 diabetes
  • Symptoms <2 months
  • High risk patients who are acutely ill
  • Patients taking medication that may cause rapid glucose rise (e.g. steroids)
  • Acute pancreatic damage
  • Pregnancy

-Presence of genetic, haematological or illness-related factors that affect HbA1c and its measurement

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27
Q

Give some examples of diabetes point of care testing?

A

Urine Testing (Glycosuria/Ketonuria)

Glucose meter-measurement of capillary blood glucose

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28
Q

What would elevated C peptide level be indicative of?

A

Insulinoma - insulin secreting tumour

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29
Q

What would high insulin levels in absence of elevated C-peptide concentrations indicate in a hypoglycaemic patient?

A

Factitious hypoglycaemia - patient has administered too much insulin

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30
Q

What can be measured biochemically in chronic diabetes?

A

Glucose (monitoring)
HbA1c
Urine Albumin/creatinine ratio (diabetic renal disease- microvascular screening)
Lipids (macrovascular screening)

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31
Q

What are some possible complications of worsening glycaemic state?

A

Retinopathy
Nephropathy
Neuropathy
Microalbuminaemia

32
Q

What are some macrovascular complications of diabetes?

A

Coronary vascular disease
Cerebrovascular disease
Peripheral vascular disease

33
Q

What are the effects of atherosclerosis in diabetes?

A

Ischaemic cerebrovascular disease - strokes

Ischaemic heart disease - angina, myocardial infarctions

Peripheral vascular disease - lower limb ischaemia. Ulceration, amputations.

34
Q

What eye disorders are increased in likelihood in diabetes?

A

Diabetic retinopathy
Glaucoma
Cataracts

35
Q

In autonomic neuropathy, what may be some of the systems affected?

A 
GI effects
Cardiovascular system (Tachycardia, BP fluctuations)
36
Q

What complication can sensory neuropathy on the lower limbs lead to?

A

Neuropathic ulcers

37
Q

In what morphology is unmodified insulin present in subcutaenous tissue when injected?

A

Present as hexamers - slowly dissociates into monomers

38
Q

What are some different types of insulin duration?

A 
Rapid acting, 
Short acting, 
Intermediate acting, 
Long acting, 
Continuous sub cut insulin infusion (CSII)
39
Q

What are some examples of rapid acting analogues of insulin?

A

Humalog,
Novorapid,
Apidra

40
Q

What sort of insulin therapy is useful for shift workers/flexible lifestyle etc?

A

Rapid (Short) acting insulin to cover CHO at meals 1 unit per 10g CHO

Basal long acting insulin as background

41
Q

In type 2 diabetes, with what types of patients may you consider relaxing target HbA1c levels?

A

People who are older/frail

  • Reduced life expectancy
  • High risk of consequences of hypoglycaemia (heavy machinery etc)
  • Intensive management not appropriate due to multiple comorbidities.
42
Q

In type 2 diabetes, when might you use sulfonylurea as a first line?

A

If patient is experiencing weight loss/osmotic symptoms

43
Q

What is the mechanism of action of metformin (biguanides)?

A

Improves insulin sensitivity.

44
Q

What are the advantages of metformin in type 2 diabetes?

A 
Improves cardiovascular outcomes and mortality in obese T2 DM
Cheap  
Efficaceous
Normally well tolerated
Not associated with weight gain
HbA1c by 12 – 17% reduction 
Also used in pregnancy now
45
Q

What are the disadvantages of metformin in diabetes type 2?

A

Risk of lactic acidosis by inhibiting lactic acid uptake by liver
GI side effects
Risk vitamin B12 malabsorption

46
Q

What is the mechanism of action of sufonylureas?

A

Binds to receptors in pancreatic beta cells -> Closes ATP sensitive potassium channels -> Cell depolarises (due to decreased K+ in)

Exocytosis of insulin

47
Q

List some sulfonylurea drugs

A

Glimepiride
Gliclazide
Glipizide

48
Q

What are the advantages of sulfonylureas in type 2 diabetes?

A 
Used with metformin
Rapid improvement in control 
Rapid improvement if symptomatic
Rapid titration
Cheap 
Generally well tolerated
49
Q

What are the disadvantages of sulfonylureas in type 2 diabetes?

A

Risk of hypoglycaemia
Weight gain
Caution in renal and hepatic disease
Contraindicated in pregnancy and breastfeeding.
SE include
-Hypersensitivity and photosensitivity reactions
-Blood disorders

50
Q

What is the mechanism of action of thiazolidinediones?

A

Selectively stimulates PPAR-alpha -> reduced insulin resistance in liver and peripheral tissues

51
Q

What are the advantages of thiazolidinediones (pioglitazone) in type 2 diabetes?

A

Good for people if insulin resistance significant
HbA1c by 0.6-1.3%
Cheap
Cardiovascular safety established

52
Q

What are the disadvantages of thiazolidinediones (pioglitazone) in type 2 diabetes?

A 
Increase risk of bladder cancer
Fluid retention - CCF
Weight gain
Fractures in females
Small increased risk
53
Q

What does carbohydrate counting help to determine in type 1 diabetes?

A

The dose of quick acting insulin to administer (also includes correction dose if blood glucose is high)

54
Q

What does alcohol do to glycogenolysis?

A

Inhibits it (inhibits gluconeogenesis!)

55
Q

What should be the adjustment of insulin with exercise?

A

Insulin should be reduced before/after exercise (reduces hypo risk)

56
Q

What must be considered with driving and diabetes?

A

Risks of hypos, poor vision, neuropathy
Can drive with diabetes
Inform DVLA if on insulin

Check blood glucose within 2 hours of starting driving

57
Q

What limits to employment are there with insulin treated diabetes?

A

Armed foces/polic absolute exclusions

Up to employer / individual
offshore oil limited but increasing
Blue light rapid response drivers
Driving restrictions

58
Q

What must be considered with holidays and diabetes?

A
  • Monitor glucose
  • Drink plenty of fluids
  • Avoid risks of gastroenteritis
  • Always carry insulin on you!
  • Adjust insulin to cross time zones
59
Q

What is the national target for HbA1C for type 1 diabetes?

A

48 mmol/L

60
Q

What does stress do to glucose levels?

A

Stress ^increases blood [glucose]

61
Q

What factors affect the ability of people with long term conditions to engage with healthy behaviours?

A 
Emotional well-being (or lack)
Motivation
Importance
Health Beliefs
Experiences
62
Q

What does increased BMI do to type 2 diabetes development risk?

A

Increased BMI increased type 2 diabetes risk

63
Q

What is the relationship between diabetes and coronary heart disease mortality?

A

Diabetes increases risk of coronary heart disease mortality.

64
Q

What can reduce risk of type 2 diabetes development?

A

-Physical activity
-Smoking cessation
-Weight loss
Etc

65
Q

What does exercise do to glucose transport into muscle?

A

Glucose transport into muscle increases with exercise

Also increases insulin sensitivity

66
Q

What is the mode of action of DPP-IV inhibitors?

A

Increase insulin release

Gliptins delay breakdown of incretins -> increase active incretin levels

67
Q

What are the advantages of DPP-IV Inhibitors?

A 
Usually well tolerated
Can be used as 2nd or 3rd line agent
Can be used in renal impairment
No risk of hypoglycaemia
Weight neutral
68
Q

What are the disadvantages of DPP-IV Inhibitors?

A

Trial data shows relatively small effects on glycemic control
CI in pregnancy and breastfeeding.
Possible increased risk of pancreatitis and pancreatic cancer
SE:
nausea

69
Q

What is the mode of action of GLP-1 Analogues/Incretin mimetics?

A

Increase insulin release

Resistant to enzymatic degradation - prolonged half-life -> Greater Insulin release

70
Q

What are the advantages of GLP-1 Analogues/Incretin mimetics?

A

Weight loss
No risk of hypoglycaemia
3rd line agent
Can be used with basal insulin

71
Q

What are the disadvantages of GLP-1 Analogues/Incretin mimetics?

A 
Very expensive
Possible increased risk of pancreatitis and pancreatic cancer
CI in pregnancy and breastfeeding.
SE:
Nausea, vomiting
72
Q

What is the mechanism of action of SGLT2 inhibitors/Gliflozins?

A

Increase excretion of glucose

73
Q

What are the advantages of SGLT2 inhibitors/Gliflozins?

A 
Weight loss
No risk of hypoglycaemia
Good effects on glycemic control
May have beneficial effect on cardiovascular morbidity &amp; mortality
2nd or 3rd line agent
Can add to insulin regimens in T2DM
74
Q

What are the disadvantages of SGLT2 inhibitors/Gliflozins?

A 
Expensive
SE:
UTI, fungal infections, osmotic symptoms
Risk of digital amputation
Risk of DKA
CI in pregnancy and breastfeeding.
Cannot use in renal impairment
75
Q

What are the disadvantages of insulin therapy in type 2 diabetes?

A

Weight gain

Risk of hypoglycaemia

76
Q

List the 5 step framework in choosing a glucose lowering drug?

A
  1. Set a target HbA1c
  2. “Take 5” Are there other risk factors that should be treated first?
  3. Are the current treatments optimised?
  4. What are the glucose lowering options?.
  5. Agree a review date and the target HbA1c with the patient

Endocrine (4 decks)

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