Theme 5: Diabetes mellitus Flashcards
Diabetes mellitus is a group of disorders characterised by what?
- hyperglycaemia - high blood glucose
- caused by lack of insulin (reduced insulin secretion) or reduce action of insulin (usually due to insulin resistance)
What are the 4 types of pancreatic islet cells?
- Alpha cells - secrete glucagon
- Beta cells - insulin
- Delta cells - secrete somatostatin
- F cells - pancreatic polypeptide
How is insulin synthesied?
- 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
What are the 3 main effects of insulin?
- Metabolic –> insulin reduces glucose production in the liver by inhibiting glycogenolysis and inhibits gluconeogenesis. Stimulates glycogen synthesis in liver
- Paracrine effects –> high insulin reduces glucagon secretion
- Vascular –> insulin has vasodilatory properties, hence why people with DM I and II develop atherosclerosis
What are the 4 ways of diagnosing diabetes?
- Fasting glucose
- no calorie intake for 8 hours - Random glucose
- Two hours reading post OGTT (oral glucose tolerance test)
- HbA1c
What level of fasting glucose confirms diabetes?
> 7mmol/litre
What level of random glucose confirms diabetes?
> 11.1 mmol/litre
What does impaired glucose tolerance mean?
After OFTT
IGT - glucose between 7.8 AND 11.1
Significant number of patients with this will develop DM in the next 5 years
What is the HbA1c criteria for ‘pre-diabetes?
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
What are the 4 types of diabetes
- type 1
- type 2
- gestational diabetes
- specific types
- genetics
- endocrinopathies
- disease of the exocrine pancreas (‘secondary diabetes’)
What is type 1 diabetes?
autoimmune destruction of insulin producing beta cells in the islet of langerhans
Who gets type 1 diabetes?
- occurs at any age but peaks around puberty
- equal sex incidence until 15 yrs then M»F
Explain the genetics of T1DM
- 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
What are the risk factors for T1DM?
- family history (genetic susceptibility)
- perinatal factors - low birth weight
- viral infection
- diet - cows milk
What is the clinical presentation of T1DM?
- rapid onset (often few weeks)
- weight loss
- osmotic symptoms - polyuria, nocturia, thirst
- low energy
- abdominal pain
- often slim
- present as diabetes ketoacidosis (DKA)
What is the clinical presentation of T2DM?
- 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
How is T2DM managed?
- Lifestyle
- exercise
- change in diet + weight loss - Oral therapy - metformin
- Insulin
What is gestational diabetes?
- diabetes diagnosed in pregnancy
- new diabetes not present prior to pregnancy
- hyperglycaemia first detected in pregnancy
How is gestational diabetes diagnosed?
- 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
When in pregnancy do you test for gestational diabetes?
during booking scan (around 12 weeks)
if normal, repeat at 24 to 28 weeks
What are the risk factors for gestational diabetes?
- BMI>30
- previous macrosomic baby (baby that weights more than 4.5kg)
- previous gestational diabetes
- FH of diabetes
- ethic minority
What are the short term sequelae of gestational diabetes?
- macrosomia
- pre-eclampsia
- still birth
- neonatal morbidity
What are the long term sequeaelae of gestational diabetes?
- obesity (child)
- developnent of T2DM (mother)
How do we manage gestational diabetes?
- diet (if mild)
- majority require insulin (ONLY during pregnancy)
- limited oral option e.g metformin
What are the different types of genetic diabetes?
- mature onset diabetes of the young (MODY) - autosomal dominant form of monogenic diabetes
- maternal inherited diabetes and deafness
- wolfram syndrome
What are the causes of secondary diabetes? (disease of exocrine?
Essentially any condition that damages the pancreatic organ:
- pancreatitis (gallstones, alcohol)
- pancreatectomy (for tumour, trauma)
- cystic fibrosis
- haemochromotosis
What are the causes of drug induced diabetes?
- steroid
- atypical anti-psychotics
- immunotherapy
- protease inhibitor
What are the causes of endocrinopathie related diabetes?
- cushings syndrome
- acromegaly
- somatostatin secreting tumours
- glucagon secreting tumours
What are counter regulatory hormones? Name 4 of them
- 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
What is glucagon?
polypeptide produced by alpha cells in the pancreas
rapidly degraded in the tissues (especially in the liver and kidney)
What are some stiumuli for glucagon release?
glucose
somatostatin
ketones
insulin
How does glucagon increase glucose levels?
- glycogenolysis
- gluconeogenesis
- lipolysis
Explain glucose homeostasis
- 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
