16. Type 1 Diabetes Mellitus Flashcards
Epidemiology
Prevalence 0.5% Peak onset at adolescence 6/12 to 80 M=F White caucasian Seasonal variability More prevalent Northern latitudes
Genetic predisposition
0.5% background risk 1-2% if mother affected 3-6% if father has affected 6% if sibling has affected 36% if monozygotic twin affected
Association with HLA antigens:
HLA DR3-DQ2 and DR4-DQ8 predispose
90% of Scandinavians with type 1 diabetes positive for 1 or both
T1DM pathophysiology
Beta-cell events trigger autoimmune response
Antibodies to insulin or GAD generally appear first
Other beta-cell antibodies follow:
IA2, Zn2+ transporter 8
Selective immune beta-cell destruction
Process of type 1 diabetes evolution
genetic predisposition + environmental trigger = insulitis (autoimmune destruction), then prediabetes, then diabetes
what is insulitis?
autoimmune destruction of pancreatic islets
autoimmune triggers for type 1 diabetes
Viral infection e.g. Coxsackie, ER stress, cytokines
Associations with type 1 diabetes
Coeliac disease Hypothyroidism Grave’s disease Addison’s disease Hypogonadism Pernicious anaemia Vitiligo Autoimmune polyglandular syndromes
Symptoms of diabetes type 1
Lethargy Polyuria Polydipsia Blurred Vision Candida infections Weight Loss Ketosis/ Ketoacidosis Death
Age affects how you present. immune hit when you’re younger has a much greater effect, but much more slowly when you’re older.
ketone bodies
acetoacetate
beta-hydroxybutyrate
byproducts from alternative fuels (not glucose) when there is no insulin. makes blood acidic
Diagnosis of type 1 diabetes
Age of onset Rapidity of onset Phenotype PMH FH Weight loss Ketosis GAD/IA2/Zinc transporter 8 antibody positive
C-Peptide
What is C-peptide?
The cleaved off side-peptide of insulin
Produced in 1:1 molar ratio with insulin
Need adequate stimulus for secretion
insulin
Necessary for survival Peptide hormone needs to be given parenterally - Subcutaneously - Inhaled - Mucous membranes
Various types
- Primary structure (animal, human, analogue)
- Duration of action (addition of protamine, altered solubility, fatty acid chain)
- Strength: (100, 200, 300, 500 Units/ml)
injection sites for insulin
upper outer arms
lower abdomen
buttocks
upper outer thighs
typical insulin regimen
Basal bolus regimen
Rapid acting insulin pre-meal (bolus)
Long acting background insulin (basal)
Balanced regimen
Rapid acting insulin reflects CHO intake
Factors affecting blood glucose
Diet Injection site Temperature Exercise Illness Stress Alcohol Menstrual cycle
