hypoglycaemia Flashcards
how would you manage acute hypoglycaemia in an alert and orientated patient ?
- Oral Carbohydrates:
- Rapid acting; juice / sweets
- Longer acting; sandwich
If Deteriorating: consider IM /SC 1mg Glucagon
how would you manage acute hypoglycaemia in a drowsy/confused patient ?
If swallow is intact;
- Buccal glucose
- Hypostop / glucogel
- > Consider IV access
Poor swallow OR unconscious;
- IV Access
- 50 ml, 50 % glucose mini-jet
- 100ml, 20% glucose
Deteriorating / refractory /insulin induced /difficult IV access: consider IM /SC 1mg Glucagon
patient has just had iv treatment for hypoglycaemia, they develop pain, redness, warmth and lump near the venous access site. whats happened?
extravasation of IV glucose: irritant, phlebitis
what 2 things should you remember about giving glucagon?
- mobilises glycogen stores so takes 15-20 mins to work
2. Danger of rebound hypoglycaemia, as will cause insulin release
What level of glucose defines hypoglycaemia?
numerous but generally less than 4
neonates is when it drops < 2.5 mmol/L (K meeran)
Neonate < 2 (according to NICU)
list some symptoms you may see in hypoglycaemia?
Adrenergic
- tremor
- sweating
- palpitations
- hunger
Neuro-glyco-paenic:
- somnolence
- confusion
- seizures, coma
- Incoordination
None
- hypoglycaemic unawareness (lack of adrenergic symptoms during hypoglycaemia)
- If a patient experiences recurrent hypoglycaemic episodes
what is the order of physiological change following the detection of hypoglycaemia?
○ Suppression of insulin
○ Release of glucagon
○ Release of adrenaline
○Release of acth, cortisol, gh
which hormones are involved in glucose counter-regulation?
The action of insulin is counterregulated by glucagon, adrenaline, noradrenaline, cortisol, and growth hormone.
These counterregulatory hormones constitute a principal defense against hypoglycemia, and levels are expected to rise as the glucose falls.
describe the events in glucose counter regulation
Low glucose -> A + B
A. Insulin suppressed + Glucagon increased:
- Reduce peripheral uptake of glucose - Increase glycogenolysis - Increase gluconeogenesis - Increase lipolysis
Subsequently -> inc Glucose + FFA:
FFA -> beta oxidation -> ATP (energy) + ketones
B. low neuronal glucose sensed in hypothalamus
- Sympathetic Activation - catecholamines
- ACTH, cortisol and GH production
how does the hormone profile change in exercise-induced reduction in blood glucose ?
glucagon willl not be released as part of counter regulation, only;
adrenaline, noradrenaline, cortisol, and growth hormone.
how can you measure blood glucose ?
what is the gold standard?
which source of blood?
caveats?
Lab Glucose: Grey top (flouride oxalate) Venous sample 2 mls blood Gold std to make the diagnosis Delay in results
Blood glucose meter -Point-of-care device -Instant result - Capillary blood But… - Poor precision at low glucose levels - Often poorly maintained
aetiology of hypoglycaemia in non-diabetic?
Fasting or reactive? Paediatric vs. adult Critically unwell Organ failure Hyperinsulinism Post gastric-bypass Drugs Extreme weight loss Factitious
aetiology of hypoglycaemia in a diabetic patient?
Diabetic Medications Inadequate CHO intake / missed meal Impaired awareness - due to to autonomic neuropathy Excessive alcohol Strenuous exercise
Co-existing autoimmune conditions - eg Addison’s- polyglandular autoimmune syndrome
Co-existing renal / liver failure alters drug clearance, and reduced doses needed.
which meds are associated with hypoglycaemia and why?
Oral Hypoglycaemic
Sulphonylureas e.g. glicazide
GLP-1 agents
Insulin
Rapid acting with meals: inadequate meal
Long-acting : hypo’s at night or in between meals
Other drugs
B-blockers, salicylates, alcohol ( inhibits lipolysis)
A very good HbA1c level in a diabetic, may be due to ?
reccurent hypos
impaired awareness of hypos may be due to __ ?
autonomic neuropathy
how does continuous glucose monitoring work?
This device is applied to the abdominal wall with a small cannula that sits in the interstitial space in the subcutaneous fat
• The sensor does NOT accurately read blood sugar when it drops below 2.2 mmol/L
How can we differentiate the cause of hypoglycaemia?
history, exam
take blood during hypos then;
biochemical tests; c-peptide, ketones, FFAs
what is c peptide?
utility?
cleavage product of PRO insulin
C-peptide levels are a good marker of beta-cell function
Also good to help differentiate the cause of hypoglycaemia
name some of the pharmacodynamics of insulin vs c-peptide?
Insulin:
Half-life, 4-6 minutes
Hepatic clearance
Exogenous insulin may interfere
C-peptide:
Half-life, ~ 30 minutes
Renal Clearance
Hypoglycaemia due to excess injected insulin would result in what c-peptide level?
LOW c-peptide
because it comes from pro-insulin not insulin/ ready formed insulin
patient presents with hypoglycaemia. what do the following results mean;
a. Low insulin, low C-peptide
b. High insulin, high C-peptide
c. High insulin, low C-peptide
which is the appropriate response to a hypo?
a. Hypoinsulinaemic hypoglycaemia
- appropriate response to a hypo
- not t1dm/dka as they would have hyperglycaemia
b. Hyperinsulinaemic hypoglycaemia - excess endogenous insulin production is causing the hypo
c. Exogenous insulin - injection
What is 3-hydroxybutyrate?
a ketone body
aka beta-hydroxybutyrate
What does the absence of ketones signify
(glucose 1.9, ketones negative)?
Fatty acid oxidation defect
list some explainable and then pathological causes of neonatal hypoglycaemia
Explainable Maternal gestational diabetes Premature, co-morbidities, IUGR, SGA Inadequate glycogen and fat stores Should improve with feeding
Pathological
Inborn metabolic defects eg:
- Fatty acid oxidation defect
what is going on in the following picture and name some possible causes?
Neonatal hypoglycaemia with suppressed insulin + C-peptide.
FFA raised, but low ketones
suppressed insulin + C-peptide and rasied FFA is the appropriate response to hypoglycaemia BUT
there must be an error of metabolism of FFAs BECAUSE ketones must be raised as well
causes; Inherited metabolic disorders: FAOD : no ketones produced GSD type 1 ( gluconeogenetic disorder) Medium chain acyl coA dehydrogenase def. Carnitine disorders
fatty acid oxidation defect
Glycogen Storage Disease
name 3 ketone bodies?
Betahydroxybutyrate/ acetoacetate / acetone
list some causes of the following presentation in a neonate:
persistent hypoglycaemia <2.5 (despite correction)
FFA normal/low
ketone normal/low
hyperinsulinism
(think logically: suppression of insulin normally leads to inc fatty acid production. so normal/low ffa must mean insulin is not suppressed)
hypopituitarism
list some causes of the following presentation in a neonate:
persistent hypoglycaemia <2.5 (despite correction)
FFA raised
Ketone raised
Hepatomegaly:
haemochromatosis
gsd 1,3,6
fructose 1,6 phosphatase defi
No hepatomegaly: GSD type 0 hereditary fructose intolerance septicaemia GH, corticosteroid deficiency and more
list some causes of innapropriately high insulin levels?
Islet cell tumours – insulinoma
Drugs; insulin, sulphonylurea
Islet cell hyperplasia:
Infant of a diabetic mother
Beckwith Weidemann syndrome
Nesidioblastosis
how would you screen for Sulphonylurea abuse?
Sulphonylurea drug screen – urine or serum
what is the physiology of normal insulin secretion?
Glucose crosses the membrane and enters glycolysis via glucokinase
Glycolysis will produce ATP
The rise in ATP leads to closure of the ATP-sensitive K+ channel
The closure of this channel leads to membrane depolarisation, calcium influx and insulin exocytosis
NOTE: there are a lot of genetic mutations that affect this channe
A Negative screen of what is required for diagnosing insulinoma?
why?
sulphonylurea
Sulphonylureas bind to the ATP-sensitive K+ channel and makes it close, independently of ATP
So, you get insulin release even when there is no ATP around - this is why sulphonylureas can cause hypoglycaemia
charactersie and give the epidemiology of insulinomas.
hwo are they treated?
Usually small solitary adenoma
10% malignant
8% associated with MEN1
Treatment: resection
whats is the diagnosis and reason behind:
Hypoglycaemia persists – glucose infusion
Insulin and C-peptide undetectable
Free fatty acids – undetectable
Ketones negative
Non-islet cell tumour hypoglycaemia
the secretion of big IGF-2
Big IGF-2 binds to IGF-1 receptors and insulin receptors
This behaves like insulin so your own endogenous insulin production is switched off and FFA production is suppressed
list some genetic causes of hypoglycaemia with high insulin and c peptide
Glucokinase activating mutation
Congenital hyperinsulinism: KCNJ11 /ABCC8 GLUD-1 HNF4A HADH
list causes for reactive/post-prandial hypoglycaemia?
Hypoglycaemia following food intake Can occur post-gastric bypass Hereditary fructose intolerance Early diabetes In insulin sensitive individuals after exercise or large meal
