Type I Diabetes Mellitus: Clinical Features, Pathophysiology, Treatment Flashcards
Most common cause of death in T1DM historically and in the present?
Historically, diabetic coma was very common
Now, the most common cause is cardiovascular
Why is T1DM incidence increasing?
T2DM is increasing due to diet and secondary lifestyle factors
T1DM is increasing due to genetic factors but there must also be environmental factors
Definition of T1DM?
State of absolute insulin deficiency
Probably caused by an environmental trigger in a genetically susceptible individual mediated, for the most part, by an autoimmune process of varying severity occurring within the pancreatic β-cells
How is T1DM diagnosed?
Fasting glucose ≥ 7.0 mmol/l
Random blood glucose ≥ 11.1 mmol/l
AND
Symptoms OR a repeat test
How is the type of diabetes diagnosed?
Often, T1DM is diagnosed on the Hx and presentation, e.g: DKA, alone
Although, GAD/IA2 antibodies and C-peptide can be checked if there is doubt
Difference between what occurs at islets in T1DM and T2DM?
T1DM - lymphocytes attack the islet and cause an insulitis
T2DM - there are assoc. pancreatic islet amyloid deposits
When does the risk of T1DM development increase, with regards to FH?
Risk increases if they have T1DM:
• Monozygotic and dizygotic twins
• HLA identical sibling and even in a sibling with one shared HLA gene
• Mother
• Father (3 times more likely to develop diabetes if father has diabetes than if mother does)
• Both parents
HLA assoc. with T1DM?
HLA genes represent half of familial risk of T1DM; the highest risk genotype is [DR3-DQ2 / DR4-DQ8]
Most people diagnosed with T1DM <30 years old have one/both of these genotypes
Environmental observations that relate to T1DM diagnosis?
Seasonality (more diagnoses in winter months)
Timing of birth (older the mother is, higher chance of gestational diabetes and thus higher risk of child with T1DM)
Potential environmental triggers of T1DM?
Viral infection
Maternal factors
Weight gain
Relationship between HLA genotype and development of T1DM?
Only 10% of those with susceptible HLA go on to develop T1DM; so, environmental factors are important
Different islet auto-antibodies?
ICA (Islet Cell Cytoplasmic Autoantibodies): • GAD 65 Ab • IA-2 Ab • IAA • ZnT8Ab
Respective antigens for each auto-antibody?
GAD 65 Ab - Glutamic acid Decarboxylase
IA-2 Ab - Islet antigen 2
IAA - insulin
ZnT8Ab - ZnT8 transporter
Sensitivity of GAD 65 Ab?
70-80% have presence at diagnosis
This increases with age and they tend to be +ve in females <10 years
Sensitivity of IA-2 Ab?
60-70%
This decreases with age and they tend to be +ve in males
Sensitivity of IAA?
50%
More sensitive in children; for both genders, the presence is similar
Sensitivity of ZnT8 Ab?
60-80%
More sensitive in older people; for both genders, the presence is similar
Presence of ICA antibodies pre-diagnosis?
Can be present for years before the onset of T1DM
Risk factors for T1DM in foetal life?
Maternal factors: • Infection • Age of mother • ABO mismatch • Birth order • Stress (may contribute)
Disease markers for T1DM in foetal life?
Genetic markers:
• HLA or non-HLA
Risk factors for T1DM pre-diabetes (months-years)?
Auto-immune trigger factors: • VIRAL INFECTION • Vit D deficiency • Dietary factors • Environmental toxins
Disease markers of T1DM in pre-diabetes?
Auto-immune process:
• Autoantibodies, e.g: GAD 65 and also IAA and IA2, ZnT8
• Candidate antigens
• Presence of insulitis
Risk factors for T1DM in clinical diabetes?
Accelerating factors: • Infection • Insulin resistance • PUBERTY • Diet • WEIGHT GAIN(patients with T1DM are normally lean but they go on to GAIN WEIGHT; so, they develop co-existing metabolic syndrome and insulin resistance) • Stress
