CP9-3 Diabetes Flashcards
What is the epidemiology of diabetes type 1?
Approx 400,000 people in UK
Most common in Europe globally
What is the epidemiology of diabetes type 2?
More than 4.5 million people in UK
Rising globally
How many premature deaths per week are attributed to diabetes?
700
What percentage of NHS budget is spent on diabetes?
10%
What is diabetes mellitus?
A group of disorders characterised by hyperglycaemia
What organ is involved in diabetes?
Pancreas
What endocrine cells are found in the pancreas?
Islets of Langerhans
Pancreatic exocrine acini
What are the types of pancreatic islet cells? What do they produce?
Alpha cells = glucagon
Beta cells = insulin
Delta cells = somatostatin
F cells = pancreatic polypeptide
How is insulin produced?
From proinsulin using prohormone convertase 3 and carboxypeptidase
What affects insulin action?
Metabolic changes
Paracrine effects
Vascular growth
Cancer
When is diabetes diagnosed?
When fasting glucose =/> 7 mmol/L
Random glucose =/> 11.1 mmol/L
HbA1c =/> 48 mmol/L
Two hour reading post OGTT =/> 11.1 mmol/L
What is an OGTT?
Oral glucose tolerance test done if fasting glucose =/> 7 mmol/L. Patient given 75g of anhydrous glucose to ingest and test repeated 2 hours later
What results of OGTT suggests although patient isn’t diabetic, they have not got healthy function?
What is pre-diabetes?
How is diabetes classified?
What is type 1 diabetes?
Autoimmune destruction of insulin producing beta cells in the islet of Langerhans which often presents at puberty.
What genes are associated with type 1 diabetes?
HLA class II coding genes like DR4-DQ8 and DR3-DQ2
What are risk factors for type 1 diabetes?
Family history of autoimmune disease
Low birth weight
Viral infections
Diet high in cows milk
What are the stages of type 1 diabetes and what happens at each stage?
Stage 1 = trigger of beta cell immunity but asymptomatic
Stage 2 = loss of beta cell secretory function, development of antibodies and slight glucose elevation
Stage 3 = loss of beta cell capacity causing symptoms to present
What insulin autoantibodies are present in type 1 diabetes?
Glutamic acid decarboxylase autoantibodies (GAD)
Islet antigen-2 autoantibodies (IA-2)
ZnT8 transporter autoantibodies
How do patients with type 1 diabetes present?
Rapid onset:
Weight loss with osmotic symptoms and low energy
Abdominal pain
Often slim
DKA
How is type 1 diabetes managed?
With insulin
How do patients with type 2 diabetes present?
Gradual onset (usually):
Overweight with minimal weight loss
Vision loss
Foot ulcers
Fungal infections
Hyperosmolar hyperglycaemic state (HHS)
How is type 2 diabetes managed?
Lifestyle - exercise, change in diet and weight loss
Non-insulin therapy - up to 3 agents with metformin (first line) + DDP4 inhibitor, SGLT-2 inhibitor, GLP-I agonist or sulphonylureas
Insulin once a day/multiple dependening
What is gestational diabetes?
Diabetes in pregnancy/hyperglycaemia first detected in pregnancy which was not present before
How is gestational diabetes diagnosed?
With fasting glucose >5.6 mmol/Lor 2 hour plasma glucose level of 7.8 mmol/L
What is not recommended in diagnosing gestational diabetes?
HBA1c
Who is tested for gestational diabetes?
BMI > 30
Previous macrosmoic baby
Previous gestational diabetes
Family history of diabetes
Ethnic minorities e.g. south Asian
What are consequences of gestational diabetes?
Macrosomia
Pre-eclampsia
Stillbirth
Neonatal morbidity
Childhood obesity of baby
Mother developing type 2 diabetes
How is gestational diabetes managed?
Diet of mild
Limited oral options including metformin or glibenclamide
Insulin (only during pregnancy as goes away once given birth)
How is gestational diabetes managed post-birth?
Repeat fasting glucose of Hba1c as increased risk of type 2 diabetes and annual diabetes screening
What are types of genetic diabetes?
Mature onset diabetes of the young (MODY)
Maternal inherited diabetes and deafness
Wolfram syndrome (DIDMOAD)
What is secondary diabetes?
Diabetes secondary to pancreas damage
What are causes of secondary diabetes?
Pancreatitis (due to gallstones or alcohol)
Pancreatectomy (for cancer or trauma)
CF
Haemochromotosis
What drugs can induce diabetes?
Steroids
Atypical anti-psychotics
Immunotherapy e.g. nivulomab
Protease inhibitors (used in HIV treatment)
What endicrinopathies can cause diabetes?
Cushing’s syndrome
Acromegaly
Somatostatin secreting tumours (somatostatinoma)
Glucagon secreting tumours (glucagonoma)
What are counter regulatory hormones?
Hormones that oppose the action of insulin which are secreted in response to stress
What are counter regulatory hormones?
Hormones that oppose the action of insulin which are secreted in response to stress
What are examples of counter regulatory hormones?
Glucagon
Epinephrine/norepinephrine
Glucocorticoid
GH
What are examples of stimuli for insulin release?
Glucose
Fatty acids and ketones
Vagal nerve stimulation
Gut hormones
Drugs that medicate diabetes
Prostaglandins
What stimuli inhibits insulin release?
Sympathetic stimulation
Alpha adrenergic agents e.g. adrenaline
Beta blockers
Dopamine
Serotonin
Somatostatin
Where is glucagon rapidly degraded?
In tissues especially liver and kidneys
How many amino acids make up glucagon?
29
What stimulated glucagon release?
Amino acids
Beta adrenergic stimulation
Fasting
Hypoglycaemia
Exercise
Cortisol
What stimulates inhibition of glucagon release?
Glucose
Somatostatin
Free fatty acids
Ketones
Insulin
What is the action of glucagon?
Reduces intestinal motility and gastric acid secretion
Increases glucose levels via glycogenolysis, gluconeogensis and/or lipolysis
How does insulin work as a metabolic regulator?
Decreases lipolysis and glucose production but increases glucose utilisations
How does gucagon work as a metabolic regulator?
Increases glucose production
How does epinephrine work as a metabolic regulator?
Increases glucose production and lipolysis and decreases glucose utilisation
How does cortisol work as a metabolic regulator?
Increases glucose production and lipolysis and decreases glucose utilisation
How does GH work as a metabolic regulator?
Increases glucose production and lipolysis and decrees ease glucose utilisation
How does free fatty acids work as a metabolic regulator?
Increases glucose production and decreases glucose utilisation
A 23 year old man presents to the hospital with 10kg weight loss over two weeks. He feels thirsty and recently developed penile thrush. What is the most likely aetiology of his diabetes?
- T1D
- T2D
- MODY
- Cushings syndrome
- T1D
A 58 year old lady attends her GP for a routine appointment. She has blood tests taken which show a HbA1c of 45 mmol/mol. What is the diagnosis:
- T1D
- T2D
- Gestational diabetes
- Impaired glucose tolerance
- Impaired glucose tolerance
Does everybody on insulin with diabetes have type 1?
No - more common in type 1 but can also be used in type 2
