Endocrinology Flashcards
(26 cards)
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
