Type 1 Diabetes Pathophysiology Flashcards
(45 cards)
What is type 1 diabetes?
Absolute insulin deficiency
What causes type 1 diabetes?
An environmental trigger in a genetically susceptible individual mediated by autoimmune processes occurring in pancreatic beta cells
How is type 1 diabetes diagnosed?
Fasting glucose >= 7mmol/L, random glucose >= 11mmol/L and symptoms
Often diagnosed in history and presentation alone
GAD/IA2 antibodies and C-peptide may help
Is there a hereditary aspect to type 1 diabetes?
Yes = if both parents have type 1 diabetes then the risk of the child developing diabetes is 30%
What is HLA association with type 1 diabetes?
Represent 50% of familial risk
Highest risk genotypes confer 19 fold increase in risk
What are the two highest risk genotypes for HLA associated diabetes?
DR3-DQ2 and DR4-DQ8 = 95% of type 1 diabetics under 30 have one of both genotypes
How many factors have been identified that cause non-HLA type 1 diabetes?
47 factors
What can be some environmental triggers of type 1 diabetes?
Viral infection, maternal factors, weight gain
What are some environmental observations associated with type 1 diabetes?
Seasonality, timing of birth, only 10% with susceptible HLA develop diabetes
What are some antibodies associated with type 1 diabetes?
GAD65 antibodies
IA2 antibodies
IAA antibodies
ZnT8 antibodies
What are some features of GAD65 antibodies?
GABA production, 70-80% at diagnosis, increases with age, females <10
What are some features of IA-2 antibodies?
Unknown function, 60-70% at diagnosis, decreases with age, male
What are some features of IAA antibodies?
Regulates glucose, 50% at diagnosis, better in children
What are some features of ZnT8 antibodies?
Zn function in beta cells, 60-80% at diagnosis, better in older patients
What is the pathogenesis of type 1 diabetes?
Immune dysregulation
Variable insulitis and beta cell sensitivity to injury
Pre-diabetes then overt diabetes
What are some environmental triggers and regulators of type 1 diabetes pathogenesis?
IAA, GAD, loss of first phase insulin, glucose intolerance, C-peptide (positive/negative)
What are is the classical triad of symptoms of type 1 diabetes?
Polyuria (enuresis in children), polydipsia and weight loss
What are some general symptoms that may occur in type 1 diabetes?
Fatigue and somnolence, blurred vision, in established ketoacidosis, candidal infections (pruritus vulvae, balanitis)
What questions should you consider in a newly diagnosed diabetic?
Has diabetes been confirmed? If so, what type is it? (antibody testing)
Is hospitalisation required? (DKA, vomiting, severe ketonuria)
Are they are school/college/uni? If not, are they employed?
Do they drive?
What occurs in the initial management of new patients?
Blood glucose and ketone monitoring
Carbohydrate estimation, regular DSN and dietician contact
Regular check of prevailing glycaemic control
What is the target HbA1c range for diabetics?
48-58m/m
What insulin regime are new type 1 diabetics usually put on?
Usually basal (once daily) - bolus (with meals) regime
What is checked in an annual diabetic review?
Weight, blood pressure, bloods (HbA1c, renal function, lipids), retinal screening, foot risk assessment
What should diabetics keep a record of?
Severe hypoglycaemic episodes, admissions for DKA