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Clinical Pathology > Theme 5: Diabetes mellitus > Flashcards

Theme 5: Diabetes mellitus Flashcards

1
Q

Diabetes mellitus is a group of disorders characterised by what?

A
  • hyperglycaemia - high blood glucose

- caused by lack of insulin (reduced insulin secretion) or reduce action of insulin (usually due to insulin resistance)

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2
Q

What are the 4 types of pancreatic islet cells?

A
  1. Alpha cells - secrete glucagon
  2. Beta cells - insulin
  3. Delta cells - secrete somatostatin
  4. F cells - pancreatic polypeptide
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3
Q

How is insulin synthesied?

A
  • in beta cells in the pancreas
  • initially, you get production of pro insulin (consisting of C peptide and insulin)
  • you get cleavage and end up with equal amounts of insulin and C-peptide
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4
Q

What are the 3 main effects of insulin?

A
  1. Metabolic –> insulin reduces glucose production in the liver by inhibiting glycogenolysis and inhibits gluconeogenesis. Stimulates glycogen synthesis in liver
  2. Paracrine effects –> high insulin reduces glucagon secretion
  3. Vascular –> insulin has vasodilatory properties, hence why people with DM I and II develop atherosclerosis
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5
Q

What are the 4 ways of diagnosing diabetes?

A
  1. Fasting glucose
    - no calorie intake for 8 hours
  2. Random glucose
  3. Two hours reading post OGTT (oral glucose tolerance test)
  4. HbA1c
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6
Q

What level of fasting glucose confirms diabetes?

A

> 7mmol/litre

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7
Q

What level of random glucose confirms diabetes?

A

> 11.1 mmol/litre

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8
Q

What does impaired glucose tolerance mean?

A

After OFTT
IGT - glucose between 7.8 AND 11.1
Significant number of patients with this will develop DM in the next 5 years

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9
Q

What is the HbA1c criteria for ‘pre-diabetes?

A

HbA1c criteria:
-reflects average plasma glucose over the previous 8 to 12 weeks
>48 mmol/mol = diabetes
<41 and <48 mmol/mol = pre-diabetes
can be given advice on diet and lifestyle to delay onset of diabetes

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10
Q

What are the 4 types of diabetes

A
  1. type 1
  2. type 2
  3. gestational diabetes
  4. specific types
    - genetics
    - endocrinopathies
    - disease of the exocrine pancreas (‘secondary diabetes’)
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11
Q

What is type 1 diabetes?

A

autoimmune destruction of insulin producing beta cells in the islet of langerhans

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12
Q

Who gets type 1 diabetes?

A
  • occurs at any age but peaks around puberty

- equal sex incidence until 15 yrs then M»F

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13
Q

Explain the genetics of T1DM

A
  • certain variation of HLA Class II disposes to diabetes
  • DR4-DQ8
  • DR3-DQ2
  • numbers correspond to location of gene
  • once you have this genetic fingerprint you would develop autoimmunity where you would trigger destruction of pancreatic b cells
  • this is usually triggered by environmental factors e.g infection
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14
Q

What are the risk factors for T1DM?

A
  • family history (genetic susceptibility)
  • perinatal factors - low birth weight
  • viral infection
  • diet - cows milk
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15
Q

What is the clinical presentation of T1DM?

A
  • rapid onset (often few weeks)
  • weight loss
  • osmotic symptoms - polyuria, nocturia, thirst
  • low energy
  • abdominal pain
  • often slim
  • present as diabetes ketoacidosis (DKA)
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16
Q

What is the clinical presentation of T2DM?

A
  • often overweight
  • symptoms may present over few months
  • minimal weight loss
  • can present with complications such as vision loss or food ulcers or fungal infection
  • ca also present in state of hyperosmolar hyperglycaemia state (HHS) –> high blood glucose without acidosis
17
Q

How is T2DM managed?

A
  1. Lifestyle
    - exercise
    - change in diet + weight loss
  2. Oral therapy - metformin
  3. Insulin
18
Q

What is gestational diabetes?

A
  • diabetes diagnosed in pregnancy
  • new diabetes not present prior to pregnancy
  • hyperglycaemia first detected in pregnancy
19
Q

How is gestational diabetes diagnosed?

A
  • oral glucose tolerance test
  • BUT criteria for diagnosis different fro normal diabetes
  • fasting glucose above >5.6
  • plasma glucose > 7.8
  • do NOT use Hb1ac
20
Q

When in pregnancy do you test for gestational diabetes?

A

during booking scan (around 12 weeks)

if normal, repeat at 24 to 28 weeks

21
Q

What are the risk factors for gestational diabetes?

A
  • BMI>30
  • previous macrosomic baby (baby that weights more than 4.5kg)
  • previous gestational diabetes
  • FH of diabetes
  • ethic minority
22
Q

What are the short term sequelae of gestational diabetes?

A
  • macrosomia
  • pre-eclampsia
  • still birth
  • neonatal morbidity
23
Q

What are the long term sequeaelae of gestational diabetes?

A
  • obesity (child)

- developnent of T2DM (mother)

24
Q

How do we manage gestational diabetes?

A
  • diet (if mild)
  • majority require insulin (ONLY during pregnancy)
  • limited oral option e.g metformin
25
Q

What are the different types of genetic diabetes?

A
  • mature onset diabetes of the young (MODY) - autosomal dominant form of monogenic diabetes
  • maternal inherited diabetes and deafness
  • wolfram syndrome
26
Q

What are the causes of secondary diabetes? (disease of exocrine?

A

Essentially any condition that damages the pancreatic organ:

  • pancreatitis (gallstones, alcohol)
  • pancreatectomy (for tumour, trauma)
  • cystic fibrosis
  • haemochromotosis
27
Q

What are the causes of drug induced diabetes?

A
  • steroid
  • atypical anti-psychotics
  • immunotherapy
  • protease inhibitor
28
Q

What are the causes of endocrinopathie related diabetes?

A
  • cushings syndrome
  • acromegaly
  • somatostatin secreting tumours
  • glucagon secreting tumours
29
Q

What are counter regulatory hormones? Name 4 of them

A
  • hormones that usually oppose action of insulin
  • secreted as a result of stress response
  • released during hypoglycaemia
    1. glucagon
    2. epinephrine/norepinephrine
    3. glucocorticoid
    4. growth hormone
30
Q

What is glucagon?

A

polypeptide produced by alpha cells in the pancreas

rapidly degraded in the tissues (especially in the liver and kidney)

31
Q

What are some stiumuli for glucagon release?

A

glucose
somatostatin
ketones
insulin

32
Q

How does glucagon increase glucose levels?

A
  • glycogenolysis
  • gluconeogenesis
  • lipolysis
33
Q

Explain glucose homeostasis

A
  • hypothalamus senses hyperglycaemia which stimulates B cells to produce insulin that then lowers blood glucose
  • hypothalamus senses hypoglycaemia and stimulates a cells to produce glucagon which then raises blood glucose
  • at the same time, hypothalamus stimulates adrenal glands to secrete epinephrin and cortisol raising blood glucose further
  • hypothalamus also stimulates pituitary gland to secrete growth hormone which also raises blood glucose

Clinical Pathology (57 decks)

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