Type 1 Diabetes Pathophysiology Flashcards
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
How common is type 1 diabetes in young people?
Accounts for 90% of diabetes in patients <25
What should intensive insulin therapy be delivered as part of?
A comprehensive support package
What should an intensified insulin regime in adults include?
Either regular human or rapid acting insulin analogues
What adult patients are basal insulin analogues recommended in?
Patients who are experiencing severe or nocturnal hypoglycaemia and who are using an intensified insulin regime
What should insulin therapy for children and adolescents involve?
May use either insulin analogues (rapid acting or basal), regular human insulin and NPH preparations (or an appropriate combination of all of the above)
What is the normal secretion of insulin after a meal?
Biphasic = rapid phase of pre-formed insulin lasts 5-10mins, slow phase lasts over 1-2hrs
Secreted into portal vein
What is the rate of insulin secretion in the fasted state in normal patients?
0.25-1.5 units/insulin/hr
What type of diabetes is most likely to cause neonatal diabetes?
Children diagnosed < 6 months old are more likely to have monogenic diabetes rather than type 1 diabetes
What is LADA?
Latent onset diabetes of adulthood = young adults aged 25-40, male predominance, usually non-obese
How is LADA diagnosed?
Presence of raised pancreatic autoantibodies in patients with “recently diagnosed” diabetes who don’t initially require insulin
What are some features that indicate a diagnosis of LADA in a patient?
Autoantibody positive, associated autoimmune conditions, non-insulin requiring at diagnosis, sub-optimal control on oral agents
What are some features of the diabetes that can occur in cystic fibrosis patients?
Occurs in >25% at 25 years, usually found in severe mutations, complications common, insulin therapy preferred
How should cystic fibrosis patients be screened for diabetes?
Screening with OGTT from age 10 recommended
What occurs in Wolfram syndrome (DIDMOAD)?
Diabetes insipidus, diabetes mellitus, optic atrophy, deafness, neurological abnormalities
What occurs in patients with Bardet-Biedl syndrome?
Often very obese, polydactyly, hypogonadal, visual impairment, hearing impairment, mental retardation, diabetes, often have consanguineous parents
What is the chance of a patient having type 1 diabetes when they have been diagnosed < 6 months old?
Less than 1%
What is the risk of a patient having type 1 diabetes if there is a history of type 1 diabetes in their parents?
Between 2-4%
How likely is a patient to have type 1 diabetes if they have detectable insulin production >= 3 years after diagnosis and are C-peptide positive with BG >8?
Between 1-5%
How likely is a patient to have type 1 diabetes if they have undetectable pancreatic antibodies at diagnosis?
Between 3-30%
What are some autoimmune conditions associated with diabetes?
Common = thyroid disease, Coeliac (5% in T1DM), pernicious anaemia, Addison's disease, IgA deficiency Rare = autoimmune polyglandular syndromes (both type 1 and 2 diabetes), AIRE mutations, IPEX syndrome
What are some polyglandular endocrinopathies associated with diabetes?
Addison’s disease, vitiligo, primary hypogonadism and hypothyroidism, Coeliac, mild immune deficiency, primary hypoparathyroidism, pernicious anaemia, alopecia
