Diabetes Flashcards
how is the anion gap calculated and what is its normal value
Anion gap = [Na + K] - [HCO3 + Cl]
normally between 8 & 12 mmol/L
what happens to the anion gap in DKA
elevated due to accumulation of ketoacids which are unmeasured anions
why is calculating the anion gap important in clinical practice
differentiated between high anion gap metabolic acidosis and normal
- if high, alerts clinicians to investigate for potential toxins, critical illness
what are causes of a normal anion gap or hyperchloraemic metabolic acidosis
- GI: diarrhoea, fistula
- RTA
- drugs e.g. acetazolamide
- Addison’s
what are causes of a raised anion gap metabolic acidosis
- lactate: shock, hypoxia
- ketones: DKA, alcohol
- urate: renal failure
- acid poisoning: salicylates, methanol
what is type 1 diabetes
autoimmune destructio of beta cells leading to absolute insulin deficiency
- without insulin, cells of body cannot absorb glucose from blood so levels keep rising causing hyperglycaemia
what are causes of T1DM
causes unclear - may be genetic
- Coxsackie B and enterovirus can trigger
what is the classic triad of symptoms of t1dm
- polyuria
- polydipsia
- weight loss
what is the ideal blood glucose concentration
4.4-6.1 mmol/L
where is insuli produced and what are its actions
beta cells in Islets of Langerhans
- anabolic
- causes cells to absorb glucose from the blood and use it as fuel
- causes muscle and liver cells to absorb glucose and store as glycogen (glycogenesis)
where is glucagon produced and what are its actions
alpha cells in islets of langerhans
- catabolic hormone
- glycogenolysis and gluconeogenesis (proteins and fats into glucose)
what is ketogenesis
production of ketones when there is insufficient glucose supply and glycogen stores are exhausted e.g. in prolonged fasting
- liver takes fatty acids and converts them to ketones
what are ketones
water-soluble fatty acids that can cross the BBB and be used as fuel
how can ketone levels be measured
in urine with urine dipstick
in blood with ketone meter
how are ketones buffered in healthy people
kidneys buffer ketones so the blood does not become acidotic
what are 3 common scenarios for DKA to occur
- inital presentation of T1DM
- existing T1DM whi is unwell w infection
- exisitng T1DM not adhering to insulin regime
what are 3 key features of DKA
- ketoacidosis
- dehydration
- K+ imbalance
how ketoacidosis arise in DKA
- without insulin, cells of body cannot recognise glucose even when levels in blood are sufficient so the liver produces ketones as an alternative fuel source
- over time, higher and higher glucose and ketones
- initally kidneys will produce bicarb to counteract ketones to maintain normal pH
- but over time, ketone acids use up the bicarb so the blood becomes acidic = ketoacidosis
why does dehydration occur in DKA
- hyperglycaemia overwhelms the kidneys and glucose leaks into the urine
- glucose in the urine draws water out by osmotic diuresis = polyuria and polydipsia
what causes K+ imbalance in DKA
- insulin normally drives K+ into cells so without insulin, K+ is not added to and stored in cells
- serum K+ can be high or normal as the kideys balance blood K+ w K+ excreted in the urine but total body K+ is low
when patients with DKA are started on insulin, what electrolyte abormality occurs
hypokalaemia –> fatal arrhythmias
what are the criteria for diagnosing DKA
- Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
- Ketosis (e.g., blood ketones above 3 mmol/L)
- Acidosis (e.g., pH below 7.3)
how is DKA managed
FIGPICK
- Fluids – IV fluid resuscitation with normal saline (e.g., 1 litre in the first hour, followed by 1 litre every 2 hours)
- Insulin – fixed rate insulin infusion (e.g., Actrapid at 0.1 units/kg/hour)
- Glucose – closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
- Potassium – add potassium to IV fluids and monitor closely (e.g., every hour initially)
- Infection – treat underlying triggers such as infection
- Chart fluid balance
- Ketones – monitor blood ketones, pH and bicarbonate
what criteria must be met before insulin and fluid infusions can be stopped in treatment of DKA
- Ketosis and acidosis should have resolved
- They should be eating and drinking
- They should have started their regular subcutaneous insulin
what are 4 complications that can arise during treatment of DKA
- Hypoglycaemia (low blood sugar)
- Hypokalaemia (low potassium)
- Cerebral oedema, particularly in children
- Pulmonary oedema secondary to fluid overload or acute respiratory distress syndrome
what are examples of autoantibodies in T1DM
Anti-islet cell antibodies
Anti-GAD antibodies
Anti-insulin antibodies
what subtance can be used as a measure of insulin production
serum C-peptide
- low w low insulin and high w high insulin
what is an important side of effecting of injecting insulin
lipodystrophy where the s/c fat hardens
- areas of lipodystrophy do not absorb insulin properly so important to change injection sites
how do insulin pumps work
small devices that continuously infuse insulin at different rates to control blood sugar levels
- alternative to basal-bolus regime
- pump pushes insulin through a cannula inserted under the skin which is replaced every 2 – 3 days
- the insertion sites are rotated to prevent lipodystrophy and absorption issues
what are advantages of using an insulin pump
- better blood sugar control
- more flexibility w eating
- less injection
what are disadvantages of insulin pumps
- Difficulties learning to use the pump
- Having it attached at all times
- Blockages in the infusion set
- A small risk of infection
what are 2 types of insulin pumps
- tethered pump
- patch pump
how do tethered insulin pumps work
- devices with replaceable infusion sets and insulin
- usually attached to the patient’s belt or around the waist with a tube connecting the pump to the insertion site
- controls for the infusion are on the pump itself
how do patch insulin pumps work
- sit directly on the skin without any visible tubes
- when they run out of insulin, the entire patch pump is disposed of, and a new pump is attached
- a separate remote usually controls patch pumps
what are 3 management options of T1DM
- basal-bolus regime
- insulin pumps
- pancreas transplant
how does pancreas transplant work and what are its risks
- implant donor pancreas to produce insulin
- original pancreas left in place to continue producing digestive enzymes
- ‼️ life-long immunosuppresion to prevent rejection
in what patients is a pancreas transplant appropriate
- those with severe hypoglycaemic episodes
- those also having kidney transplants
give 4 ways in which DM is monitored
- HbA1c
- CBG
- flash glucose monitor e.g. freestyle libre
- continuous glucose monitors (CGM)
how often is HbA1c measured
reflects average glucose level over previous 2-3 months (rbc have lifespan of 4 months)
- measured every 3-6 months to track average blood sugar levels
what do flash glucose monitors measure
glucose level of the interstitial fluid in the s/c tissue
- 5 min lag behind blood glucose
what can cause hypoglycaemia
- too much insulin
- not consuming enough carbs
- not processing carbs correctly e.g. malabsorption, vomiting, diarrhoea
what are typical symptoms of hypoglycaemia
- hunger
- tremor
- sweating
- irritability
- dizziness
- severe: reduced consciousness, coma, death
how is hypoglycaemia treated in adults who are conscious, orientated and able to swallow
initally with 15-20g rapid-acting glucose e.g. high sugar content drink
- once glucose levels improves, consume slower-acting carbs e.g. biscuits/toast to stop levels dropping agains
how can severe hypoglycaemia be treated
- IV dextrose
- IM glucagon
how do chronic high blood glucose levels cause damage
- damage endothelial cells of blood vessels
- causes leaky, malfunctioning vessels that are unable to regenerate
- can also cause immune system dysfunction and create optimal environment for infectious organisms to thrive
what are macrovascular complications of DM
- CAD
- peripheral ischaemia causing poor skin healing and diabetic foot ulcers
- stroke
- HTN
what are microvascular compliccations of DM
- peripheral neuropathy
- retinopathy
- kidney disease esp glomerulosclerosis
what are other causes of neuropathy
- diabetes
- alcohol
- B12 deficiency
- B6 excess
- chemo
what are infection-related complications of DM
- Urinary tract infections
- Pneumonia
- Skin and soft tissue infections, particularly in the feet
- Fungal infections, particularly oral and vaginal candidiasis
give 3 examples of ketone bodies
- 3-beta-hydroxybutyrate
- acetoacetic acid
- acetone
what are metabolic treatment targets of DKA
- Reduction in blood ketones by 0.5mmol/l/hour
- Increase venous bicarbonate by 3.0mmol/l/hour
- Maintain potassium between 4 and 5.5mmol/l
- If not achieved the FRIII should be increased
- Introduce 10% dextrose when the blood glucose falls below 14mmol/l – alongside N saline and continue until patient is eating
*
when treating ketoacidosis, when can FRIII be switched to s/c insulin
when ketones <0.6mmol/L and ready to eat
what is HHS and what are the specific features that differentiate it from DKA
hyperosmolar hyperglycaemic syndrome
- hypovolaemia
- marked hyperglycaemia >30mmol/L without significant hyperketonaemia <3mmol/L
- acidosis ph>7.3, bicarb >15mmol/L
how do you calculate osmolality
2Na + glucose + urea
what are the treatment goals of HHS
- normalise osmolality
- replace fluid and electrolyte lossed
- normalise blood glucose
key principles of fluids and insulin FRIII
- Crystalloids
- Aim to replace 50% of estimated loss within first 12 hours
- FRIII 0.05 units/Kg/hour
- Monitor potassium and renal function
- Glucose fall 4 to 6mmol/hour
- Remember treat co-morbidities
- Anticoagulation
what are risk factors of hypoglycaemia
- medical issues: long duration of T1DM, renal failure on dialysis, AKI, impaired renal function, terminal illness
- lifestyle issues: inc exercise, irregular lifestyle, inc age, alcohol, early pregnancy, breast feeding
- reduced carb intake
what are potential causes of inpatient hypoglycaemia
medical issues
- recovery from acute illness/stress
- mobilisation after illness
- major limb amputation
- incorrect type of insulin/oral hypoglycaemic therapy
- change of insulin injection site
reduced carb intake
- missed/delayed meals
- change of timing of meals
- lack of access to between meal snacks
- reduced appetite
- vomiting
how is hypoglycaemia treated in adults who are conscious and able to swallow but confused, disoriented
- 1.5-2 tubes of glucogel or dextrogel squeexed between teeth and gums
- 1mg IM glucagon
describe the pathophysiology of T2DM
- repeated exposure to glucose and insulin make the cells in the body resistant to the effects of insulin
- over time pancreas becomes fatigued and damaged so insulin output is reduced
- high carb diet + insulin resistance + reduced pancreatic functio –> chronic hyperglycaemia –> micro/macrovascular complications + infections
what are non-modifiable risk factors of T2DM
- older age
- ethnicity
- FHX
what are modifiable risk factors of T2DM
- obesity
- sedentary lifestyle
- high carb diet
what are possible presenting features of diabetes
- Tiredness
- Polyuria and polydipsia (frequent urination and excessive thirst)
- Unintentional weight loss
- Opportunistic infections (e.g., oral thrush)
- Slow wound healing
- Glucose in urine (on a dipstick)
what clincial sign is associated with insulin resistance
Acanthosis nigricans - characterised by the thickening and darkening of the skin (giving a “velvety” appearance), often at the neck, axilla and groin
what is pre-diabetes
- indication that the patient is heading towards diabetes
- do not fit the full diagnostic criteria but should be educated about the risk of diabetes and lifestyle changes
HbA1c: 42-47 mmol/mol
what HbA1c level indicates T2DM
48 mmol/mol or above
sample is typically repeated after 1 month to confirm the diagnosis
what are the NICE guideline recommendations on managing T2DM
- A structured education program
- Low-glycaemic-index, high-fibre diet
- Exercise
- Weight loss (if overweight)
- Antidiabetic drugs
- Monitoring and managing complications
what are the treatment targets for diabetics
- 48 mmol/mol for new type 2 diabetics
- 53 mmol/mol for patients requiring more than one antidiabetic medication
how often is HbA1c measured
every 3 to 6 months until under control and stable
what is 1st line medical management of T2DM
metformin
- once settled, add SGLT-2 inhibitor e.g. dapagliflozin if pt has exisitng CVD or HF
in what patients does NICE recommend adding an SGLT-2 inhibitor to treatment regime
QRISK > 10%
what is 2nd line treatment for T2DM
add a sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor
what is 3rd line treatment for T2DM
- Triple therapy with metformin and two of the second-line drugs
- Insulin therapy (initiated by the specialist diabetic nurses)
what option is appropriate if triple therapy fails and pt BMI >35
switch one of the drugs to a GLP-1 mimetic (e.g., liraglutide)
what can pt experiencing GI side effects from metformin trial as an alternative
modified release metformin
what is HHS
rare but potentially fatal complication of type 2 diabetes
- characterised by hyperosmolality > 320 mosmol/kg (water loss leads to very concentrated blood), hyperglycaemia and the absence of ketones
absence of ketones distinguishes it from ketoacidosis
what is the pathiphysiology of HHS
hyperglycaemia = ↑ serum osmolality → osmotic diuresis → severe volume depletion
what are precipitating factors of HHS
- intercurrent illness
- dementia
- sedative drugs
how can DKA and HHS be differentiated
- DKA complication of T1DM, HHS normally in elderly pt w T2DM
- ketones present in DKA
- DKA presents within hours but HHS can come on over many days
what are potential signs and symptoms of HHS
- clinical signs of dehydration: skin turgor, dry mucous membranes
- polyuria, polydipsia
- lethargy, N&V
- altered consciousness, focal neuro deficits
what is a haematological sign of HHS
hyperviscosity –> MI, stroke, peripheral arterial thrombosis
what is the management of HHS
- IV 0.9% NaCl at 0.5-1L/hr
- monitor K+ levels and add to fluids accordingly
- VTE prophylaxis due to hypervisocity
should insulin be given as part of treating HHS
insulin should NOT be given unless blood glucose stops falling whilst giving IV fluids
how is hypoglycaemia treated in adults who are unconscious and unable to swallow/ NBM
- check ABC
- stop IV insulin
- IV glucose over 15 mins as 75ml 20% glcuose or 150ml 10% glcuose
- 1mg IM glucagon
- recheck glucose after 10mins, if <4.0 mmol/L, repeat
what is stress hyperglycaemia
transient hyperglcyaemia which normalises after discharge
what is the pathophysiology of hyperglycaemia in acute illness
- increased gluconeogenesis
- accelerated glycogenolysis
- impaired glucose utilisation by peripheral tissues
give 4 consequences of hyperglycaemia in a hospital setting
- inc in-hospital morbidity and mortality
- inc length of stay
- poorer post discharge outcomes
- excess health care costs
what are the diagnostic criteria of HHS
- Plasma glucose >30.0mmol/L
- pH >7.3
- Serum bicarbonate >15.0mmol/L
- Plasma ketones <3.0mmol/L
- Serum osmolality >320mOmol/kg
what are you looking for in general assessment of diabetic foot
- visibly unwell
- drowsy
- abnormal breathing
- abnormal pulse
- fever
urgent hospital admission
what are 3 signs of active foot disease
ulceration
gangrene
cellulitis
what are you examining for in foot disease
- foot temperature >2 degrees difference between same point on both feet
- presence of pulses (monophasic, biphasic, etc)
what does it indicate if the foot is cold, pale or dusky
ischaemia
urgent hospital admission
what does it indicate if foot is warm, red, swollen
acute infection and/or charcot foot
urgent hospital admission
what are appropriate investigations into diabetic foot following hospital admission
- weight bearing x-ray
- soft tissue from wound and swab
- bloods: FBC, CRP, U&Es, HbA1c, blood culutures
what conditions can cause a falsely low HbA1c level
- sickle cell anaemia
- hereditary spherocytosis
- G6PDH deficiency
