Diabetes Flashcards
(22 cards)
Neonatal diabetes mellitus
Transient in __%
Onset
Lasts
50%
But 50-60% then develop DM later
1st week of life; median duration 12w
Transient neonatal diabetes
Features
Genetics
Ddx
SGA
Hyperglycaemia & glycosuria
Severe dehydration & metabolic acidosis. Minimal ketosis
Umbilical hernia, large tongue
Abnormalities of an imprinted locus on Ch6q24: over expression of paternal genes
Mutations in Katp channels
Ddx hypertonic dehydration
Permanent neonatal diabetes
Features
Syndrome of most severely effected
Genes
SGA
DEND: dev delay, epilepsy, neonatal distress
Homozygous for GCK (MODY2) or IPF-1 ( MODY4)
Genes which code for Katp
What is IPEX
Gene
Role of gene protein
Immunodysregulation
Polyendocrinopathy
Enteropathy
X linked
FOXP3 gene
Regulatory T Cells
Autoimmune diseases associated with diabetes
Chronic lymphocytic thyroiditis
- 1/5 IDDM have thyroid autoantibodies
- only a small proportion develop clinical hypothyroidism
When DM & Thyroid coexist: consider autoimmune adrenal disease (from 2nd decade)
Celiac in 7-15% develop in first 6 years of dx
Higher rate in females and <4y
MODY3 Gene Gene protein Inheritance pattern Rx Complications
HFN1a
Transcription factor
Most common: 50-60%
Glucosuria due to reduced renal threshold
Very sensitive to sulfonylureas
AD inheritance
Microvasular & macrovascular similar to T1DM
MODY2
Gene
Phenotype
Rx
Glucokinase (GCK)
Mild hyperglycaemia, non progressive
No Rx required
MODY1
HNF4a
Transcription factor
Can have neonatal hypoglycaemia
Sensitive to sulphonylureas
Mitochondrial diabetes Gene Identical to what mitochondrial condition Presents like Avoid what drug
Point mutation in transfer RNA leucine gene Identical defect to MELAS Presents insidiously Avoid metformin (theoretical risk of lactic acidosis)
Wolfram syndrome
Features in order of occurrence
Gene
First decade : IDDM
Second : Central DI and SN deafness
Third : Renal tract anomalies
Fourth : Neurological complications
WFS-1
Biguanide
Mechanism of action
Side effects
Avoid in
Example
Insulin sensitiser
GI, lactic acidosis
Hepatic, renal failure
Sulfonylureas
Mechanism
Example
Cause insulin release
Closing the potassium channel Katp on beta cells
Glipizide
Proportion of youth patients with T2DM with 2 or more features of metabolic syndrome
Percentage with hypertension
Metabolic syndrome features
92%
70%
Hypertension, hypertriglyceridemia, decreased HDL, increased waist circumference
Diabetic retinopathy
Risk after 15y duration in T1DM; T2DM
% develop proliferative retinopathy
Features of early / background retinopathy
Clinical effect
Features of proliferative retinopathy
98%
78%
Microsneurysms, dot and blot haemorrhages, hard & soft exudates, venous dilation and beading
Do not impair vision
Neovascularisation
Fibrous proliferation
Preretinal & vitreous harmorrhage
Laser Rx for proliferative disease
Diabetic nephropathy
% of T1DM after 20y
% of T2DM
Pathogenesis
20-30% T1
15-20% of T2 after 20y
Glycation of tissue protein: thickening of GBM
Microalbuminuria
Mg/24hr
30-300mg/24h
Symptoms of hypoglycaemia caused by
Surge in catecholamines
Insulin counters regulatory hormones
Loss of Hypoglycaemic awareness related to…
Growth hormone
Cortisol
Epinephrine
Glucagon
Long standing T1DM - lose ability to secrete glucagon in response to hypoglycaemia
Epinephrine deficiency as part of autonomic neuropathy
Calorie needs
0-12mo
1-10y
Young women
Young men
120kcal/kg
75-100 kcal/kg
35 kcal/kg
55-80 kcal/kg
Nonketotic hyperosmolar coma
Features
Severe hyperglycaemia Absence or very slight ketosis Nonketotic acidosis Severe dehydration Depressed LOC Neurological signs
DKA
Fluids & insulin
Normal saline with potassium maintenance + replacement over 48h
Insulin infusion 0.05-0.1 units/kg/hr
DKA
Biochemical definition
BSL >11mmol/L
pH < 7.3, bicarb <15 mmol/L (mild)
Ketonuria
Moderate: pH <7.2 and / or bicarb <10
Severe: pH <7.1 and / or bicarb <5
