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
hypoglycaemia
Autonomic symptoms
- Palpitation, sweating, tremor
Neuroglycopaenic symptoms
- confusion
Mild and severe
Mild hypoglycaemia inevitable with good control
Loss of warning signs
transplantation
Pancreas - Almost always SPK or PAK Islet cell - Edmonton protocol - only for very bad T1DM - UK islet cell programme
3% mortality, and then need immunosuppression drugs which increase risk of skin and haem cancers, so major risks.
So less likely to have transplants and more likely to inject insulin
Glucose monitoring
Glucose monitoring
- Minimum 4 x daily
- Driving
- Unwell
- Hypoglycaemia
e. g. continuous glucose monitoring system (CGMS)
e. g. Freestyle Libre, available on NHS in certain circumstances
Ketone monitoring
Urine (acetoacetate)
Blood (beta-hydroxybutyrate)
Clinician monitoring of T1DM
HbA1c (glycated haemoglobin)
Reflects glucose over last 3 months
Weighted towards last 6 weeks
Affected by red cell lifespan
How patients can monitor T1DM
glucose monitoring
ketone monitoring
what is HbA1c
glycated haemoglobin - basically indicates sugary red blood cells
