monogenic diabetes, complications and emergencies Flashcards
what is monogenic diabetes?
diabetes caused by mutation in a single gene resulting in defects in insulin secretion or action
where would you see acanthosis nigricans
hyperinsulinaemic states - severe IR in type 2 or defects in insulin action
MODY is autosomal dominant/recessive
dominant
what are the two different types of MODY?
defects in transcription factor genes with mitochondrial metabolism
defects in glucokinase causing right shift
describe how glucokinase MODY would appear on OGTT and how this differs from that of T1DM
higher fasting blood glucose around 7mmol/L
due to right shift of glucokinase curve blood glucose is brought back under control but back to higher BG
T1DM - normal initial FBG but sharp and uncontrolled increase
true/false - glucokinase mutations conferring MODY has birth onset
true
true/false - transcription factor mutations conferring MODY have birth onset
false - adolescent/young adult onset
describe management plan for glucokinase MODY
no treatment beside dietary
hypothalamus uses glucokinase as set point so it cant really be treated
no association with increased risk of complications
managing HNF1A MODY?
suphonylureas 1st line
merformin not very good
you have a type 1 diabetic patient who is a 6m old infant. how do you treat it
reconsider diagnosis to KCNJ11/ABCC8 neonatal diabetes as T1DM doesnt usually present prior to 6m
suphonylureas are first line
true/false - in neonatal diabetes pancreatic autoantibodies are still +ve
false
why is SU effective in neonatal diabetes
act on Katp channel to cause K channel closure and insulin release
due to Katp channel opening consuming oral glucose enables incretin effect via GLP-1
reducing what reduces risk of microvascular complications?
HbA1c
what AA conditions are associated with MODY
thyroid disease coeliac addisons IgA deficiency pernicious anaemia autoimmune polyglandular syndromes AIRE mutations IPEX
what other condition has a strong association with diabetes and severe mutations, with insulin therapy needed
Cystic fibrosis
type 1 polyglandular endocrinopathy is associated with?
mucocutaneous candidiasis
primary hypoparathyroidism/alopecia/pernicious anaemia
type 2 polyglandular endocrinopathy has association to T1DM. what else is it associated with
addisons vitiligo primary hypogonadism primary hypothyroidism coeliac disease
who are islet cell transplants reserved for
severe hypoglycaemia
severe and progressive logn term complications despite max therapy
severe uncontrolled diabetes
what outcomes are desired from islet cell transplant
insulin independence
reduction in severe hypoglycaemia
improved glycaemic control
define diabetic ketoacidosis
absolute/relative insulin deficiency leading to disordered metabolic state with counter regulatory hormones
true/false - DKA is only in T1DM
false - it is most common in type 1 but can also occur in type 2 under enough stress
describe the pathophysiology of DKA
absolute/relative insulin deficiency activates stress hormones
leads to glyconenesis, proteolysis and decreased glucose use - hyperglycaemia
glycosuria, osmotic diuresis and renal function declines to cause dehydration
increased lipolysis, FFA and ketogenesis leading to increased lactate and acidosis
blood biochem in someone with DKA
ketonaemia >3mmol/L or significant ketonuria >2+ RBG - >11mmol/L or possibly normal bicarb <15 or venous pH <7.3 raised lactate low Na raised creat raised WCC in absent infection
highest causes of death in adults due to DKA
aspiration, ARDS, hypokalaemia
highest cause of death in children due to DKA
cerebral oedema due to fluid shift
causes of DKA
insulin deficiency, due to new diagnosis or poor management infection - pneumonia, UTI inflammatory - cellulitis, pancreatitis intoxication - alcohol, cocaine infarction - MI, stroke iatrogenic surgery, steroids
symptoms of DKA
thirst polyuria dehydration flushed ketones on breath vomiting kussmauls respiration underlying sepsis/gastroenteritis
what 4 losses are associated with DKA
potassium
phosphate
fluid
sodium
what 4 risks are there with DKA
aspiration
sepsis
potassium flux can lead to arrhythmia
thrombo embolism secondary to dehydration
management of DKA?
admit to HDU 3L fluid by 4hr insulin K when it drops phos/bicarb? NG tube? monitor K LMWH CXR and culture for sepsis
what blood ketone level is normal
<0.6 mmol/L
what blood ketone level is at risk of DKA
0.6-3 mmol/L
what blood ketone level is defined as ketosis
> 3mmol/L
true/false - HHS is more common in type 1 diabetes
false - type 2
pathophysiology of HHS
relative insulin deficiency causes stress hormone activation
causes increased proteolysis, glycogenolysis, decreased glucose utilisation
hyperglycaemia, fluid loss, decreased renal function, dehydration, osmotic fluid loss and glycosuria
ketosis avoided as there is enough insulin to prevent the ketogenic pathway
biochemical diagnosis of HHS?
hypovolaemia hyperglycaemia often >30mmol/L mild/no ketonaemia <3mmol/L bicarb <15 or venous pH<7.3 osmolality >320mosmol/kg renal impairment normal/raised Na
how is osmolality calculated and what is the normal value
2xNa +urea+glucose
275-295
demographically whos more at risk of HHS
older pt or afro-caribbean
high refined CHO pre presentation
sepsis, diuretics
cardiovascular disease
causes of HHS
infection - pneumonia, UTI iatrogenic surgery/steroids/diuretic inflammatory cholecystitis/pancreatitis infarction intoxication
management of HHS
fluids 0.9 sodium unless if osmolality is not decreasing, then give 0.45 not usually insulin monitor U&E screen for vascular events LMWH
describe the pathophysiology of alcohol induced ketoacidosis
alcohol inhibits gluconeogenesis to cause decreased insulin and increased glucagon - increased catecholamines and cortisol to lead to volume depletion
less calories in alcohol so leads to reduced glycogen stores
decreased insulin and increased glucagon leads to increased ketogenesis and FFA to liver so acidosis
biochemical diagnosis of alcohol ketoacidosis?
glucose normal/low bicarb<15mmol/L ketonaemia >3mmol/L or significant ketonuria dehydration careful hx
management of alcohol ketoacidosis
fluids especially dextrose anti emitics insulin on occasion IV pabrinex address alcohol dependency
assessing someone admitted to hospital with diabetes?
blood glucose and ketone monitoring what type DHx renal function evidence of peripheral/autonomic neuropathy
reasons for type 1 diabetes admission
cannot tolerate fluids persistent vomiting persistent hyperglycaemia increasing ketones abdominal pain/breathless
blood glucose target as an inpatient for T1DM
6-10mmol/L
accept 4-12mmol/L
what should you pre-assess on a diabetic patient pre surgery
anaesthetic risk cardiac function autonomic dysfunction foot risk glycaemic control place on surgical risk - place them high on list
what is lacate
end product glucose through anaerobic metabolism
clearance requires hepatic uptake to convert to pyruvate/glucose before metabolism
what is the normal lactate range
0.6-1.2mmol/L
causes of type A lactic acidosis
infact tissue
cardiogenic/hypovolaemic shock
sepsis
haemorrhage
causes of type B lactic acidosis
liver disease
metformin
rare metabolic conditions
presentation of lactic acidosis
hyperventilation mental confusion coma low bicarb rasied anion gap variable glucose absent ketones raised phosphate
management of lactic acidosis
treat underlying cause
fluids
Abx
describe normal glucose metabolism and suggest what may go wrong
glucose oxidised via glycolysis and undergoes TCA and electron transfer to yield ATP
mitochondrial metabolism is not as fast as glycolysis so this can lead to glucose being broken down by alternative pathways
what pathways may glucose be broken down under and what are the consequences
polyol pathway pentose phosphate pathway hexosamine pathway diacyl glycerol pathway convert to glycarion end products increased ROS, inflammation, osmotic damage, fibrosis
how often should a standard diabetic pt be screened for eve disease
annually
what signs may be seen on fundoscopy indicating mild non-proliferative retinopathy
cotton wool spots
hard exudates
dot haemorrhage
microaneurism/blot haemorrhage
what signs may be seen on fundoscopy indicating moderate non-proliferative retinopathy
multiple blot haemorrhage in one eye field
what signs may be seen on fundoscopy indicating severe-non proliferative retinopathy
IRMA and microvascular haemorrhages
what signs may be seen on fundoscopy indicating proliferative retinopathy
retinal detachment/angiogenesis
what signs may be seen on fundoscopy indicating maculopathy
hard exudates or haemorrhage within 1 disc diameter of macula/fovea
management of diabetic retinopathy
pan retinal photocoagulation to reduce O2 requirement of retina and ischaemia
vitrectomy if vitreal haemorrhage
what is macular oedema, how is it assessed and managed?
leaky angiogenesis causing fluid buildup in macula, cannot be effectively cleared
optical coherence tomography
intravitreal anti-VGEF
grid laser to macula
what is diabetic nephopahty
progressie kidney disease caused by damage to capillaries in kidneys glomeruli
proteinuria and scarring of glomeruli
consequences of diabetic nephropathy
reduction in GFR by 1ml/month if untreated
development of HTN
accelerated vascular disease
what is the normal ACR for males and females
<3.5 for females and <2.5 for males
describe the biochemical diagnosis of microalbuminuria
> 2.5/3.5-<30 OR <50 if PCR
repeat twice and diagnosis established if 2/3 are +v e
describe the biochemical diagnosis of proteinuria (overt nephropathy)
ACR >30 or PCR >50
how do you calculate daily creatinine loss from PCR
multiply it by 10
what may cause a false positive in microalbuminuria
menstruation vaginal discharge UTI pregnancy non-diabetic renal illness
if microalbuminuria is established what else should be checked for
retinopathy
not another cause for proteinuria
check for PVD, aim for 130/70 HTN, discourage smoking and have HbA1c <53 mmol/L
management of microalbuminuria?
ACEI/ARB 1st line
SGLT2i
how often should diabetics be screened for nephropathy
urine alb and serum creat at diagnosis and at least annually
what is diabetic amyotrophy
proximal neuropathy pain/weakness in hips, thighs, buttocks prox muscle wasting and weight loss more common elderly T2DM self limiting
what is peripheral neuropathy
lost feeling in hands/feet with glove/stocking distribution
numb/insensitive, pain/cramp, lost balance, hypersensitive
consequences of diabetic peripheral neuropathy
charcot foot
foot ulcer
painless trauma
management of diabetic peripheral neuropathy
gabapentin/amitriptyline
capsaicin cream
what is diabetic focal neuropathy
weakness in one or a group of nerves
cranial nerve palsy, foot drop, carpal tunnel, bells palsy
diabetic autonomic neuropathy symptoms of gut include
gastroparesis
nausea, vomiting, boating, lost appetite
smaller meals more frequent, liquid meals
ondansetron, metclopramide, gastric pacing
low dose tricyclics
diabetic autonomic neuropathy symptoms of oesophagus nerve damage include
dysphagia
diabetic autonomic neuropathy symptoms of heart and vessels include
postural hypotension - syncope/lightheaded
high heart rate
how is diabetic neuropathy causing excess sweating managed
botox
topical glycopyrrolate
risk factors diabetic neuropathy
type 1 increased length diabetes poor glycaemic control high lipids genes mechanical injury alcohol smoking
symptoms of peripheral vascular disease in a diabetic patient
cool peripheries
lost peripheral pulses
lost leg hair
dry skin
low risk diabetic foot?
sensation unimpaired and foot pulses present
annual review
moderate/high risk diabetic foot?
cannot self care for feet or absent sensation with impaired pulses
previous ulcer or amputation
annual review by podiatrist
active diabetic foot?
ulcer, infection, critical ischaemia, gangrene, unexplained red, hot, swollen foot
urgent referral
what is charcot arthropathy
destructive inflammatory process where there is fracture and bony deformity of the foot
presentation of charcot arthropathy
hot, swollen foot in someone with neuropathy
MRI to differentiate from infection
management and complication of charcot arthropathy
non-weight bearing
total contact cast/aircast boot
foot ulceration due to mishaping
