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Y2 Clinical Pathology > Diabetes > Flashcards

Diabetes Flashcards

1
Q

What is diabetes characterised by?

A

it is a group of disorders characterised by:

hyperglycaemia - high blood glucose

caused by a lack of insulin of reduction in action of insulin

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2
Q

Label the components of the pancreas

A
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3
Q

What are the different pancreatic islet cells?

What do they secrete?

A
  1. alpha cells - secrete glucagon
  2. beta cells - secrete insulin
  3. delta cells - secrete somatostatin
  4. F cells - secrete pancreatic polypeptide
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4
Q

What can proinsulin be converted into?

What are the steps involved in these processes?

A

insulin:

  • prohormone convertase 3 coverts proinsulin to split (32-33) proinsulin
  • carboxypeptidase converts this into Des (31, 32) proinsulin
  • this is converted into insulin

C peptide:

  • prohormone convertase 2 converts proinsulin to split (65,66) proinsulin
  • carboxypeptidase converts this into Des (64, 65) proinsulin
  • this is converted into C peptide
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5
Q

What is the structure of insulin like?

A

it is a soluble protein

it has 2 chains - an alpha chain and a beta chain

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6
Q

Where is insulin synthesised?

A

insulin is synthesised in the beta cells of the pancreas

insulin mRNA is translated as a single chain precursor - preproinsulin

removal of the signal peptide during insertion into the endoplasmic reticulum generates proinsulin

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7
Q

What are the general actions of insulin?

A
  1. metabolic
  2. paracrine effects
  3. vascular, fibrinolysis, growth and cancer
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8
Q

What are the 4 factors involved in diabetes diagnosis?

A

fasting glucose >/= 7 mmol / litre

random plasma glucose >/= 11.1 mmol / litre

two hours reading post OGTT >/= 11.1 mmol / litre

HbA1c >/= 48 mmol/mol

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9
Q
A
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10
Q

What is normal fasting glucose?

How does this change in the oral glucose tolerance test (OGTT)?

A

normal fasting glucose is >/= 7 mmol / litre

patient ingests 75g of anhydrous glucose

after 2 hours their glucose reading >/= 11.1 mmol / litre

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11
Q

In the oral glucose tolerance test (OGTT) what would be an impaired fasting glucose and impaired glucose tolerance?

A

impaired fasting glucose:

  • 6.1 - 6.9 mmol / litre

impaired glucose tolerance:

  • glucose >/= 7.8
  • glucose < 11.1 mmol / litre
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12
Q

What is meant by “pre-diabetes”?

How is it diagnosed?

A

when blood glucose levels are too high, but not high enough to be called diabetes

people with prediabetes are at a higher risk of developing type 2 diabetes

it is diagnosed using the HbA1c criteria

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13
Q

How can the HbA1c criteria be used to distinguish between diabetes and prediabetes?

A

it reflects the average plasma glucose over the previous 8 - 12 weeks

>/= 48 mmol/mol in diabetes

>/= 41 and < 48 mmol/mol in prediabetes

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14
Q

How is diabetes classified?

A
  • type 1 diabetes
  • type 2 diabetes
  • gestational diabetes
  • specific types

genetics, endocrinopathies, disease of the exocrine pancreas

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15
Q

What causes type 1 diabetes?

A

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

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16
Q

What types of people tend to be affected by type 1 diabetes?

A

it can occur at any age but peaks around puberty

it has equal sex incidence but after 15 years of age, there is a two fold increased risk in males

incidence has increased by 3-4% in the last few years

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17
Q

What is involved in the pathophysiology of type 1 diabetes?

A

genetics of T1DM:

  • HLA class II
  • DR4 - DQ8
  • DR3 - DQ2
  • exposed / trigger to environmental factors
  • autoimmunity
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18
Q

What are the risk factors for type 1 diabetes mellitus?

A
  • family history (genetic susceptibility)
  • perinatal factors - low birth weight
  • viral infections
  • diet - cows milk
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19
Q

What are the 3 stages invovled in the development of type 1 diabetes?

A

stage 1:

  • trigger of beta cell immunity but no symptoms of diabetes

stage 2:

  • loss of beta cell secretory function and development of antibodies and slight glucose elevation
  • no symptoms

stage 3:

  • loss of beta cell capacity
  • symptoms present
20
Q

What autoantibodies are present as a result of humoral autoimmunity?

A
  • insulin autoantibodies
  • glutamic acid decarboxylase autoantibodies (GAD)
  • islet antigen-2 autoantibodies (IA-2)
  • ZnT8 transporter autoantibodies
21
Q

What is involved in the presentation of type 1 diabetes?

A
  • rapid onset - often a few weeks
  • weight loss + osmotic symptoms + low energy
  • abdominal pain
  • often slim
  • present as diabetes ketoacidosis
22
Q

What is involved in the management of type 1 diabetes mellitus?

A

always need insulin at the start of diagnosis

there is no role of an oral agent as the body is unable to produce any insulin

23
Q

What is the presentation of type 2 diabetes mellitus often like?

A
  • often overweight
  • symptoms present over few months
  • minimal weight loss (unless left for long period)
  • can present with complications such as vision loss, foot ulcers or fungal infection
  • can present in state of hyperosmolar hyperglycaemia state (HHS) or HONK
24
Q

What is indicated by the lines on this graph?

A
25
Q

What are the 3 stages in the management of type 2 diabetes mellitus?

A

Lifestyle changes:

  • exercise
  • change in diet and weight loss

oral therapy:

  • metformin is first line therapy
  • DDP4 inhibitor, SGLT-2 inhibitor, GLP-1 agonist, sulphonylureas
  • up to three agents

insulin:

  • once a day insulin to start
  • multiple injections of insulin
26
Q

What is gestational diabetes?

A

this is diabetes in pregnancy

it must be diabetes that was not present prior to pregnancy

hyperglycaemia is first detected in pregnancy

27
Q

What are the criteria for gestational diabetes?

A

fasting glucose > 5.6 mmol / litre

OR

2 hours plasma glucose level of 7.8 mmol / litre

this is different from the normal diabetes diagnosis

28
Q

How is gestational diabetes diagnosed?

A

HbA1c is NOT used

the oral glucose tolerance test is used

if they have had previous gestational diabetes, you can ask to use self-monitoring using capillary blood glucose

29
Q

When should gestational diabetes be tested in pregnancy?

A

it is done during a booking scan at around 12 weeks

if this is normal, repeat at 24-28 weeks

30
Q

What are the risk factors for gestational diabetes?

A
  • BMI > 30
  • previous macrosomic baby
  • previous gestational diabetes
  • family history of diabetes
  • ethnic minority
31
Q

What are the short-term and long-term complications of gestational diabetes?

A

short-term:

  • macrosomia
  • pre-eclampsia
  • stillbirth
  • neonatal morbidity

long-term:

  • obesity of the child
  • development of type 2 diabetes mellitus in the mother
32
Q

What are the stages involved in the management of gestational diabetes?

A
  1. diet (if mild)
  2. limited oral options - metformin or glibenclamide
  3. the majority require insulin ONLY during pregnancy
33
Q

What is involved in the screening of gestational diabetes post-pregnancy?

A

the mother has an increased risk of diabetes

fasting glucose OR HbA1c should be repeated 13 weeks after delivery

then there is an annual diabetes screening check

34
Q

What are 3 examples of genetic diabetes?

A
  • mature onset diabetes of the young (MODY)
  • mitochondrial diabetes
  • maternal inherited diabetes and deafness
35
Q

What are examples of secondary diabetes?

(disease of exocrine?

A

this is essentially any condition that damages pancreatic organ

  1. pancreatitis (gallstones, alcohol)
  2. pancreatectomy (for cancer, trauma)
  3. cystic fibrosis
  4. haemochromotosis
36
Q

What drugs are can lead to drug induced diabetes?

A
  1. steroids - normally high doses and prolonged
  2. atypical anti-psychotics
  3. immunotherapy - e.g. nivolumab used in melanoma treatment
  4. protease inhibitor - used in HIV treatment
37
Q

What are examples of diabetes caused by endocrinopathies?

A
  1. cushings syndrome
  2. acromegaly
  3. somatostatin secreting tumours (somatostatinoma)
  4. glucagon secreting tumours (glucagonoma)
38
Q

What is a counter-regulatory hormone?

Why are they secreted?

A

hormones that usually oppose the action of insulin

they are secreted as a result of stress response

39
Q

What are the 4 counter-regulatory hormones?

A
  1. glucagon
  2. epinephrine / norepinephrine
  3. glucocorticoid
  4. growth hormone
40
Q

What are the stimuli for insulin release?

A
  • glucose
  • fatty acids and ketones
  • vagal nerve stimulation
  • gut hormones
  • drugs (diabetes medication)
  • prostaglandins
41
Q

What are the stimuli for inhibition of insulin release?

A
  • sympathetic stimulation
  • alpha adrenergic agents (adrenaline)
  • beta blockers
  • dopamine
  • serotonin
  • somatostatin
42
Q

What is glucagon?

A

a polypeptide made from 29 amino acids

it was rapidly degraded in the tissues, especially in the liver and kidney

43
Q

What are the stimuli for glucagon release?

A
  • amino acids
  • beta adrenergic stimulation
  • fasting and hypoglycaemia
  • exercise
  • gastrin, CCK, cortisol
44
Q

What are the stimuli for inhibition of glucagon release?

A
  • glucose
  • somatostatin
  • free fatty acids
  • ketones
  • insulin
45
Q

What are the actions of glucagon?

A
  • increase secretion of insulin and growth hormone
  • reduces intestinal motility and gastric acid secretion
  • increases glucose levels through glycogenolysis, gluconeogenesis and lipolysis
46
Q

What hormones are involved in glucose homeostasis?

A

insulin lowers blood glucose levels

glucagon, epinephrine, cortisol and growth hormone raise blood glucose levels

47
Q

What are the differences in the roles of insulin and glucagon?

A

insulin stimulates glycogen formation from glucose and lowers blood sugar

glucagon stimulates glycogen breakdown and raises blood sugar

Y2 Clinical Pathology (76 decks)

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