Diabetes Flashcards
What is diabetes characterised by?
it is a group of disorders characterised by:
hyperglycaemia - high blood glucose
caused by a lack of insulin of reduction in action of insulin
Label the components of the pancreas
What are the different pancreatic islet cells?
What do they secrete?
- alpha cells - secrete glucagon
- beta cells - secrete insulin
- delta cells - secrete somatostatin
- F cells - secrete pancreatic polypeptide
What can proinsulin be converted into?
What are the steps involved in these processes?
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
What is the structure of insulin like?
it is a soluble protein
it has 2 chains - an alpha chain and a beta chain
Where is insulin synthesised?
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
What are the general actions of insulin?
- metabolic
- paracrine effects
- vascular, fibrinolysis, growth and cancer
What are the 4 factors involved in diabetes diagnosis?
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
What is normal fasting glucose?
How does this change in the oral glucose tolerance test (OGTT)?
normal fasting glucose is >/= 7 mmol / litre
patient ingests 75g of anhydrous glucose
after 2 hours their glucose reading >/= 11.1 mmol / litre
In the oral glucose tolerance test (OGTT) what would be an impaired fasting glucose and impaired glucose tolerance?
impaired fasting glucose:
- 6.1 - 6.9 mmol / litre
impaired glucose tolerance:
- glucose >/= 7.8
- glucose < 11.1 mmol / litre
What is meant by “pre-diabetes”?
How is it diagnosed?
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
How can the HbA1c criteria be used to distinguish between diabetes and prediabetes?
it reflects the average plasma glucose over the previous 8 - 12 weeks
>/= 48 mmol/mol in diabetes
>/= 41 and < 48 mmol/mol in prediabetes
How is diabetes classified?
- type 1 diabetes
- type 2 diabetes
- gestational diabetes
- specific types
genetics, endocrinopathies, disease of the exocrine pancreas
What causes type 1 diabetes?
autoimmune destruction of insulin producing beta cells in the islet of langerhans
What types of people tend to be affected by type 1 diabetes?
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
What is involved in the pathophysiology of type 1 diabetes?
genetics of T1DM:
- HLA class II
- DR4 - DQ8
- DR3 - DQ2
- exposed / trigger to environmental factors
- autoimmunity
What are the risk factors for type 1 diabetes mellitus?
- family history (genetic susceptibility)
- perinatal factors - low birth weight
- viral infections
- diet - cows milk
What are the 3 stages invovled in the development of type 1 diabetes?
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
What autoantibodies are present as a result of humoral autoimmunity?
- insulin autoantibodies
- glutamic acid decarboxylase autoantibodies (GAD)
- islet antigen-2 autoantibodies (IA-2)
- ZnT8 transporter autoantibodies
What is involved in the presentation of type 1 diabetes?
- rapid onset - often a few weeks
- weight loss + osmotic symptoms + low energy
- abdominal pain
- often slim
- present as diabetes ketoacidosis
What is involved in the management of type 1 diabetes mellitus?
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
What is the presentation of type 2 diabetes mellitus often like?
- 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
What is indicated by the lines on this graph?
What are the 3 stages in the management of type 2 diabetes mellitus?
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
What is gestational diabetes?
this is diabetes in pregnancy
it must be diabetes that was not present prior to pregnancy
hyperglycaemia is first detected in pregnancy
What are the criteria for gestational diabetes?
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
How is gestational diabetes diagnosed?
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
When should gestational diabetes be tested in pregnancy?
it is done during a booking scan at around 12 weeks
if this is normal, repeat at 24-28 weeks
What are the risk factors for gestational diabetes?
- BMI > 30
- previous macrosomic baby
- previous gestational diabetes
- family history of diabetes
- ethnic minority
What are the short-term and long-term complications of gestational diabetes?
short-term:
- macrosomia
- pre-eclampsia
- stillbirth
- neonatal morbidity
long-term:
- obesity of the child
- development of type 2 diabetes mellitus in the mother
What are the stages involved in the management of gestational diabetes?
- diet (if mild)
- limited oral options - metformin or glibenclamide
- the majority require insulin ONLY during pregnancy
What is involved in the screening of gestational diabetes post-pregnancy?
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
What are 3 examples of genetic diabetes?
- mature onset diabetes of the young (MODY)
- mitochondrial diabetes
- maternal inherited diabetes and deafness
What are examples of secondary diabetes?
(disease of exocrine?
this is essentially any condition that damages pancreatic organ
- pancreatitis (gallstones, alcohol)
- pancreatectomy (for cancer, trauma)
- cystic fibrosis
- haemochromotosis
What drugs are can lead to drug induced diabetes?
- steroids - normally high doses and prolonged
- atypical anti-psychotics
- immunotherapy - e.g. nivolumab used in melanoma treatment
- protease inhibitor - used in HIV treatment
What are examples of diabetes caused by endocrinopathies?
- cushings syndrome
- acromegaly
- somatostatin secreting tumours (somatostatinoma)
- glucagon secreting tumours (glucagonoma)
What is a counter-regulatory hormone?
Why are they secreted?
hormones that usually oppose the action of insulin
they are secreted as a result of stress response
What are the 4 counter-regulatory hormones?
- glucagon
- epinephrine / norepinephrine
- glucocorticoid
- growth hormone
What are the stimuli for insulin release?
- glucose
- fatty acids and ketones
- vagal nerve stimulation
- gut hormones
- drugs (diabetes medication)
- prostaglandins
What are the stimuli for inhibition of insulin release?
- sympathetic stimulation
- alpha adrenergic agents (adrenaline)
- beta blockers
- dopamine
- serotonin
- somatostatin
What is glucagon?
a polypeptide made from 29 amino acids
it was rapidly degraded in the tissues, especially in the liver and kidney
What are the stimuli for glucagon release?
- amino acids
- beta adrenergic stimulation
- fasting and hypoglycaemia
- exercise
- gastrin, CCK, cortisol
What are the stimuli for inhibition of glucagon release?
- glucose
- somatostatin
- free fatty acids
- ketones
- insulin
What are the actions of glucagon?
- increase secretion of insulin and growth hormone
- reduces intestinal motility and gastric acid secretion
- increases glucose levels through glycogenolysis, gluconeogenesis and lipolysis
What hormones are involved in glucose homeostasis?
insulin lowers blood glucose levels
glucagon, epinephrine, cortisol and growth hormone raise blood glucose levels
What are the differences in the roles of insulin and glucagon?
insulin stimulates glycogen formation from glucose and lowers blood sugar
glucagon stimulates glycogen breakdown and raises blood sugar
