Endocrinology Flashcards
Type 1a vs. Type 1b diabetes
Type 1a - immune mediated (95%)
Type 1b - idiopathic (<5%)
Autoantibodies in T1DM
- Glutamic acid decarboxylase (GAD65)
- Insulin (IAA)
- Tyrosine phosphatases (IA-2, IA-2B)
- ZnT8
Not routinely used in diagnosis
Presence of autoantibodies predicts risk of developing clinical diabetes
Diagnosis of T1DM
Random BSL >11.1 with keoacidosis
Clinical clues towards T1DM in diagnosis
○ Rate of development of hyperglycaemia symptoms
○ Presence of ketosis
○ Personal/family history of AI disorders
○ Absence of family history of T2DM
○ Absence of other features of metabolic syndrome
○ Failure to respond to non-insulin treatments
Low/undetectable C-peptide
HLA associations in T1DM?
Accounts for 50% of genetic risk
HLA-DR2 confers protection
HLA-DR3 and HLA-DR4 confer risk
Strong linkage with HLA-DQA and HLA-DQB
Risk of T1DM with family history
Latent autoimmune diabetes of adulthood (LADA) - features
- Subtype of Type 1 diabetes
- Slow progressive destruction of beta cells
- May respond to oral agents initially
- More likely to have autoimmune history
- Less likely to have features of metabolic syndrome
- Age of onset usually ≥30
- Positive titre of at least 1 auto antibody
- Starting insulin early may preserve beta cell function
Idiopathic T1DM (Type 1b) - features
○ Permanent insulinopenia (low/undetectable plasma C-peptide)
○ Ketoacidosis prone
○ No evidence of B cell autoimmunity
○ Strongly inherited - not HLA associated
○ Most are Africa/Asian ancestry
Autoimmune conditions associated with T1DM
- AI thyroid disease*
- Addison’s disease
- Coeliac disease*
- Vitiligo
- AI hepatitis
- Myasthenia gravis
- AI gastritis* (increased risk of pernicious anaemia/B12 def)
- Regular screening encouraged
Autoimmune Polyendocrine Sndromes - type 2 - features
- Characterised by presence of Addison’s disease with AI thyroid disease and/or T1DM
- Female predominance
- Most common of the Autoimmune Polyendocrine Syndromes
Typical starting dose of insulin
0.5 units/kg/day
50% as basal insulin
Human insulin vs. insulin analogues
Analogues associated with:
- Less hypoglycaemia
- Less weight gain
- Lower HbA1C
CSII vs. MDI (multiple daily injections)
Modest advantages for HbA1C lowering
Lower severe hypoglycaemia risk
Insulin Carbohydrate Ratio (ICR)
How many grams of carbohydrate are covered/disposed of by 1 unit of insulin
Insulin Sensitivity Factor (ISF)
How much 1 unit of rapid acting insulin will generally lower BSL over 2-4 hours
- Expressed as mmol/L
SGLT2i in T1DM - outcomes of EASE trials?
- HbA1C reduction
- Body weight reduction
- Lower total daily insulin requirement (up to 13%)
- Lower SBP
- Increased risk of ketoacidosis with 10mg & 25mg
- No significant different in severe hypoglycaemic episodes
Surgical options for T1DM?
- Whole pancreas transplantation
> Performed with curative intent
> Usually performed with renal transplant - Islet cell transplantation
> Indications: severe recurrent hypos/hypo unawareness
Both require lifelong immunosuppression to prevent graft rejection
Risk factors for hypoglycaemic unawareness
- Increasing age
- Duration of disease
- Aggressive glycaemic control
- Frequent hypoglycaemic events
- Autonomic neuropathy
- Medications including beta blockers
Clarke Survey - assessment tool
- Score ≥4 = significantly impaired awareness of hypoglycaemia
Level 1 vs. 2 vs. 3 hypoglycaemia
Level 1: typical symptoms associated with measured BSL of <4
Level 2: BSL <3, level at which neuroglycopenic symptoms expected to begin
Level 3: severe, requiring another person’s assistance
What medications cause false positive aldosterone-renin ratios?
Beta blockers
Methyldopa, clonidine
NSAIDs
What medications cause false negative aldosterone-renin ratios?
ACEi/ARBs
All diuretics
Dihydropyridine CCBs
Results suggestive of Paget disease?
Isolated elevation of ALP
Normal calcium/phosphate/PTH
Xray - bone deformation/sclerotic/osteolytic lesions
1st line management of Paget disease?
Bisphosphonates
How to differentiate primary hyperparathyroidism vs. familial hypocalciuric hypercalcaemia?
Urinary calcium
Urinary Ca/Cr ratio
Both of these will be LOW in FHH
(<100mg/day and ratio <0.01)
In FHH: also have high serum Mg due to low urinary Mg
What causes familial hypocalciuric hypercalcaemia?
Inactivating mutation in calcium sensing receptor in PTH and kidneys
Polyglandular autoimmune syndrome type 2?
Primary adrenal insufficiency (Addison’s Disease)
T1DM
Autoimmune thyroid disease
