DM and disorders of glucose homeostasis Flashcards
Discuss sources of glucose in the body
- Intestinal absorption from the diet
- Breakdown of glycogen storage (glycolosis)
- synthesis from precursors (gluconeogenesis) including lactate, pyruvate, amino acids and glycerol.
Only the liver and the kidney contain
glucose 6 phosphatase (G6p) the enzyme necessary for the release of glucose into the circulation
Discuss breifly glucose regulatory mechinisms
Insulin – major anabolic hormone - supresses glucose production and stimulates glucose use. Stimulates glucose uptake storage and use.
Counterregulatory hormones include - glucagon, GH, Adrenaline, norad, cortisol. Released in response to hypoglycaemia and stress, trauma infection exercise and starvation. Increase hepatic glucose production wihtin minutes alhtough transiently
Discuss diagnosis of Diabetes
CAn be in 1 of 4 ways ‘
1) randon glucose level above 11.1
2) fasting glucose above 7mmol/l
3) Previous standard was abnormal result of a 2 hour glucose tolerance test (BSL <11.1) -75 g glucose admin than 2 horus later BSL taken
4) HBA1c value above 6.5% is now considered diagnositc of diabetes.
Briefly discuss classes of oral hypoglycaemics
1) biguanides (metformin)
- Does not cause hypoglycaemia
- should not be used in renal failure due to risk of severe HAGMA, consider withholding if having contrast load in the ED
- suppresses hepatic gluconeogenesis
2) Sulgonylureas (gliclazide, glipizide)
- Increase insulin secretion by binding to specific beta cell receptors.
- cant use in sulfa allergy
- does cause hypoglycaemia
3) Dipeptidyl peptidase 4 inhibitors (sitagliptin, linagliptin)
- DDP 4 degrades endogenous glucagon like peptide by inhibiting this degredation the half life of GLP increases and increases insulin secretion.
4) Glucagon like peptide (exanatide)
- GLP analogues and agonist stimulate release of insulin from pancreatic cells.
5) SGLT2 inhibitor (dapagliflozin)
- Sodium cotransporter 2 inhibitors. SLGT transports glucose from the proximal renal tubule into the tubular epithelial cells, enahancing urinary excretion levels of glucose
- can cause euglycaemia ketoacidosis in fasting and is treated as DKA
Briefly discuss the pathophys of DKA
Insulin deficiency and glycagon excess combine to produce a hyperglycaemic, dehydrated acidotic patient with profound electrolyte imbalance.
Hyperglycaemia leads to increased osmotic diuresis leading to loss of water, saodium, potassium, magnesium calcium and phosphorous.
Total body potassium, magnesium and phosphorus are usually makred low. However as a result of acidosis and dehydration the intitial reported values for these electrolytes may be higher than actual body stores.
Insulin defiency results in activation of a hormane sensitive lipase that increased circulating free fatty acids levels. These are convered in the liver to acetoacetate and b-hydroxybutyrate.
Despite pathaological increase in the production of ketones the body acts as it dose in any starvation state to inhibit the peripheral use of ketones. THis leads to an accumuation and acidosis
What are the diagnostic criteria for DKA and HHS
DKA
- Acidosis with Ph >7.3 or hco3 <15
- Ketonaemia >3 or marked ketonuria
- hyperglycaemia >11
HHS
- BSL >33.3
- Ph >7.3 or hco3 >15
- osmalality >320
- minimal to no ketonaemia
Discuss Fluid replacement in DKA
If shocked give 10-20ml/kg of normal saline
If not shocked 1 Litre of 0.9% over 1 hour followed by a rate of 500mls for 4 hours then 250ml/hr for the next 8 hours.
Most IV fluid regimens recommend replacing the total volume deficit by 24 hours. However in a patient with significant co-morbidities it is prudent to aim to correct the deficit over 48 hours.
If serum glucose falls to <15mmol/L add 10% dextrose at 125ml/h alongside the 0.9% saline
Discuss insulin therapy in DKA and switching to intermittent insulin
Do not start if K <3.5
Initial infusions at a rate of 0.1units/kg/hour to a max of 6 units. Adjust the rate to reduce the serum glucose by around 3 mmom/l/H
Switching
- switching from an insulin infusion to intermittent insulin is unlikley to occur in the ED>
- 1st dose of subcut insulin should be given 1 hours prior to cessation of the infusion in assoiacted with a meal providing all the following are met
1) Serum glucose <11
2) ph >7.30
3) serum ketones <0.6
4) serum hco3 >15
5) patient is eating and drinking normally with a normal GCS
Discuss K management in DKA
Initial hyperkalaemia followed by hypokalaemia are the msot common life threatening electrolyte problems seen in DKA. Typically the total body deficit is 3-5mmol/kg
Hyperkalaemia intitially seen due to intracellular shift from acidosis and lack of insulin may cause dangerous arrythmias – this often quickly resolves with initiation of DKA therapy.
K should be added to fluids if >5.5mmol/L and the patient is passing urine
Replacing about 10-20mmol/hour is usually sufficeint with the rate adjusted to the serum K measurement
Discuss management of HHS
Similar to that of DKA although the patient are older, the water deficit is considerably greater, the sodium and potassium deficits greater and the overall mortality and morbidity are higher.
Fluid and electrolyte management can be treated simiarly to DKA – replace over 72 hours
Insulin infusions should be started after the intiatal fluid bolus and should be started at a rate of 0.05units/kg to a max of 3units as may be more sensitive to insulin
Reduce insulin rate when the serum glucose drops to 15-18 mmol/L to maintain serum glucose in the rage of 10-15 until the serum osmolarity is less than 315
Discuss the role of Hco3 in DKA
should never be given with pH >7.0 and its benifit under this is unclear
Potential complciations include
- worsening intracellular acidosis
- rapid fall in K
- reduced tissue o2 delivery
- delay in clearing ketones
- possible associated with cerebral oedema
Compare and contrast the deficits per body weight in DKA and HHS
DKA
- water 100ml/kg
- sodium 7 -10 mmol/kg
- potassium 3-5mmol/kg
HHS
water 100-220ml/kg
-Sodium 5-13mmol/kg
-K 4-6 mmol/kg
Describe Charcot neuropathic OA
Inflammation and destruction of the bones joints and soft tissues of the foot and ankle
Most commonly occurs with diabetic neuropathy
Contributing factors
-diabetes
-sensory motor neuropathy
-autonomic neuroapthy
-trauma
Most common defomrity is mid foot colllapse
Foot pain may vary depending on degree of neuropathy
Discuss proliferative and non proliferative diabetic retinopathy
Non proliferative
- microaneurysms (early sign)
- dialted veins
- soft haemorrhages
- flame haemorrahge
- hard exudates
- –yellow lipid depsits
- –form around leaking microaneurysms
- –may coalesce to form sheets
PROLIFERATIVE
- new vessel formation may cause
- –Retinal detachment
- –Viterous haemorrhage due to retinal ischaemia
- Greatest risk if proliferation occurs on the optic disc
- retinal oedema
- macular oedema
List causes of hypoglycaemia
1) inadequate food intake
2) Insulin
- change in dose
- dosage erros
3) increased exercise
4) Drugs
- paracetamol
- salicylates
- alcohol especially chdilren
5) hepatic disease
6) adrenal insufficiency
7) sepsis
