More Diabetes (Drugs And Monitoring Etc) Flashcards
What 4 main things does insulin withdrawal cause?
- Uncontrolled endogenous glucose production
- Tissue glucose deprivation
- Lipolysis
- Proteolysis
What is the average threshold for glucose to be found in the urine?
10 mmol/litre - glucose in urine
- lower threshold in pregnancy and elderly
What are the consequences of having high glucose levels in bodily secretions such as sweat?
- infection -
UTIs
skin infection
thrush
What are the consequences of the effect of high glucose on WBCs?
- recurrent infection
- leucocytosis, pyrexia - can be affected
See lecture on Pathophysiology of & signs/symptoms of diabetes for diagram
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What are the differential diagnosis for polyuria?
True polyuria:
• Heart failure • Diuretic therapy • polyuric renal failure
• hypercalcaemia • diabetes incipidus • water intoxication
Other:
• Urinary tract infection • Prostatism
Why might a patient with heart failure for example get up to urinate a lot in the night?
Backing up of fluid in lungs and legs - get up in the night to pass urine because legs elevated
What questions 3 central questions should you ask a patient with polyuria?
• How often? • How much? • Associated symptoms (flow problems, pain)
Name 4 main areas that are associated with infection in diabetes?
- Skin
- Mucosae
- Chest
- Urine
Name three symptoms/features of macrovascular complication in diabetes.
- Angina
- Claudication
- TIA
What are the 3 types of microvasular complication in diabetes?
- Retinopathy
- Nephropathy
- Neuropathy
What are the consequences of peripheral neuropathic microvascular complications in diabetes?
Numbness
pain
tingling feet and then hands
What are the clinical manifestations of autonomic neuropathy microvascular complications in diabetes?
Abnormal sweating Gastroparesis Diarrhoea Postural dizziness Erectile dysfunction Incontinence (very late complication)
What are the clinical manifestations of radiculopathy neuropathy microvascular complications in diabetes?
Pain, weakness (wasting)
What are the clinical manifestations of mononeuritis neuropathy microvascular complications in diabetes?
Diplopia
What are the clinical manifestations of compression neuropathy microvascular complications in diabetes?
Pain, tingling, weakness (carpal tunnel, ulnar n, lat popliteal n (around fibula head - foot drop))
What are nights sweats indicative of?
Night sweats - chronic infection, endocarditis, malignancys
Which substances should be measures to monitor diabetes control?
- Glucose control – Random glucose (venous / capillary) – Glycated haemoglobin ( HbA1c)\
- Ketones
- Lipids – TC and LDL / HDL / TG
- Renal function
- Urine protein
- Whole host of other substances which could be measured – CRP, Homocysteine, Leptin, Adiponectin
What is diabetic control?
- The extent to which metabolism differs from normal
- Other metabolites disordered in diabetes – e.g. ketones are a measure of insulin deficiency
- Many other substances are affected by diabetes?
What does a positive urine glucose test tell you?
Blood glucose has been above 10mmol/litre since last bladder voiding if you get glucose in urine
(Only useful for screening, not for monitoring?
What are the problems with urine glucose monitoring?
- Urine glucose is retrospective
- Renal threshold may differ between patients and even within people (eg. If they are ill or have renal dysfunction)
- Fluid intake affects urine concentration
- Cannot be used to diagnose diabetes
What are the possible problem whole blood monitoring of glucose levels?
• We can measure glucose in whole blood • Glucose concentration falls by about 0.5mmol over 3 hours due to glycolysis in RBC
• Inhibiting glycolysis (with fluoride oxalate)can reduce this
– There is still a 0.2-0.3 mmol/l drop in glucose over 2-3
• Plasma glucose is 10-15% higher than in whole blood (and cappilaries)
• Affected by hematocrit
What do measure is most commonly used to monitor glucose levels?
Plasma glucose?
Describe 2 measures of long-term blood glucose control
• Glycated haemoglobin (measure of mean glucose control over preceding 1-3 mo)
(50pc -control in last 30 days - rest - further back than that
If you have different types of haemoglobin eg.foetal - skews results )
• Serum fructosamine (mean glucose control over preceding 2 weeks)
What is meant by glycated haemoglobin?
Glucose attaches covalently but non-enzymatically to haemoglobin over lifetime of red cell
By how much are HBa1c and mean blood sugar usually different?
HBa1c is usually lower by 1.5
4 facts about Hba1c
- Linear relationship with mean blood glucose over life of RBC
- Affected by conditions affecting red cell turnover turnover
- Inaccurate in patients with Hb variants and Hb S or C carriers
- 50% of the value determined by glucose control in the past month
What are the potential interferences with HbA1c measurement depending on method?
• Hb variants can interfere, e.g. -HbF (elevated in diabetes) can elevate -HbS, HbC can lower
• Altered red cell survival: -Haemolytic anaemia lowers
• Chemically modified Hb -Carbamylation in uraemia can elevate
-Acetylation with large doses aspirin can elevate
• Reduced glycation process -Vitamin C can lower
Is HBa1c more closely related to a single blood glucose in type 1 or type 2 diabetes?
Type 2 - less variation in glucose
How can Fructosamine be used as another measure of long-term control in addition to HBa1c?
- Serum proteins also glycated (like Hb)
- Fructosamine is essentially glycated albumin
- Measure of long-term control over lifetime of serum albumin – about 2 weeks (useful when control changing quickly e.g. diabetic pregnancy)
- Usually measured with colorimetric assay
- Less used than HbA1c
- Reference range ~200-285 micromol/l
Name 3 ketone bodies
- Acetone
- 3-Hydroxybutyric acid (Beta-hydroxybutyric acid)
- Acetoacetic acid
What is the series of events in ketone body formation in diabetes?
Insulin lack → Adipose tissue triglyceride
→ fatty acids + glycerol →acetyl CoA → TCA cycle (if insulin)
But if no insulin acetyl CoA → acetoacetic acid
Then acetoacetic acid → 3 hydroxybutyrate or acetone
acetone
What do you know about ketone testing using strips?
- Strips and tablets based on Rothera’s test: nitroprusside/glycine turns purple with acetoacetic acid/acetone
- 3-hydroxybutyric acid not detected
- Most ketone strips/tablets insensitive measure of ketosis
What Do you know about blood ketone testing using monitors?
- Measures 3-hydroxybutyrate electrochemically
- Based on strips with immobilized 3-hydroxybutyrate dehydrogenase
- Not yet widely used
What does high creatinine indicate?
Poor renal function
What are the features of dislipidaemia common in type 2 diabetes?
• Fasting lipid profile as part of annual review
- Triglyceride - VLDL triglyceride - ↓HDL cholesterol
When should LDL levels be measures?
Fasting because it will be lowered postprandially.
What do you know about monitoring albumin in diabetes?
• Proteinuria -hallmark of diabetic kidney disease
• Dipstick proteinuria: albumin conc. in spot urine sample -depends on patient hydration and therefore inaccurate
• 24 hour urine albumin excretion best
(300perdl - threshold of measurement
Muscular, low body fat, unwell, high temperature - can be why - false readings)
What is microalbuminuria and why is it useful?
- Microalbuminuria: very small excretion of protein in urine, not detectable by standard dipstick but immunoassay
- Earliest sign of diabeteic nephropthay
- Predicts later development of diabetic nephropathy
- Albumin: creatinine ratio (ACR) in spot clinic urine sample simple now commonly used, corrects for errors in time of collection
What are the normal threshold values for microalbuminuria, normal ACR and protienuria?
- Normal ACR < 2.5 (3.5 male) mg/mmol
- Microalbuminuria 2.5-30 mg/mmol
- Proteinuria > 30 mg/mmol
What is continuous glucose monitoring and how does it work?
- Subcutaneously implanted enzyme electrode
- Glucose oxidase immobilized at electrode
- Glucose proportional to current response
- Measures glucose in the tissue • Lags behind blood glucose ( 5-15 mins
- Provides “real time” glucose readings – Glucose concentration – Direction / rate of change
- Alarms to warn of high or low blood sugars
- “closed loop systems” in development
What are 6 extra considerations when managing a DKA patient?
- NG tube/ bicarbonate/ arterial lines
- Where to look after patient?
- What is the trigger?
- Infection/ antibiotics?
- Prophylactic heparin?- High osmolarity - DVT and PE risk increased
- Always check feet
What are 6 possible complications in DKA management?
- Hypoglycaemia
- Hypokalaemia
- Arrhythmias
- Cerebral oedema
- Adult respiratory distress syndrome
- Thromboembolism
What are the features of HHS – Hyperosmolar Hyperglycaemic state?
usually people with type 2 diabetes mellitus Hyperglycaemia -Dehydration - Hyperosmolarity - Absent/ minimal ketosis - +/- without coma
What is ketosis absent/minimal in HHS?
Minimal ketone body generation
- why? Relative insulin deficiency ask opposed to absolute
- enough to prevent that generation of free fatty acids which gives ketones
- dehydration and hyperosmolarity limit lipolysis?
What is the pathophysiology of HHS?
relative insulin deficiency and increase in glucagon
- Increased gluconeogenesis & glycogenolysis
- Increased hepatic glucose output
• lipolysis and ketogenesis less
• circulating NEFA lower than in DK
• dehydration and hyperosmolarity limit lipolysis?
What at the 4 criteria for diagnosis of DKA?
- Serum glucose > 33mmol/l
- Hyperosmolarity >320 mOsm/l
- Absence of acidosis - (Might have meta if acidosis from pre-renal failure- dried out, old, diabetic nephropathy etc)
- Small or no ketonuria
In what types of diabetes do you get DKA and HHS?
DKA: type 1 (and type 2)
HHS: type 2
What ages are patients with DKA and patients with HHS likely to be?
DKA: Any age esp. young
HHS: elderly
How fast is the onset of DKA and Of HHS?
What are the mortalities of these conditions?
DKA: rapid onset (less than 24hrs), mortality - less than 5%
HHS: onset can take weeks, mortality - up to 50%
What are the pH levels like in DKA and in HHS?
What are the bicarbonate levels like in these 2 conditions?
DKA: pH - less than 7.3, bicarbonate - low
HHS: pH - normal, bicarbonate - normal
What are urine ketone levels like in DKA and in HHS?
DKA: high
HHS: normal/1+
What are glucose levels like in DKA and in HHS?
DKA: Glucose >15mmol/L
HHS: Glucose >30mmol/L
What are the precipitating factors of HHS?
- Infection 40-60%
- New onset DM 33%
- Acute illness 10-15%
- Non compliance 5-15%
What would be a typical history for an HHS patient?
- Often ill several weeks beforehand
- Age >60
- Polyuria, polydipsia, thirst
- Drinking sugary drinks to quench thirst
- Altered mental state
- Abdominal symptoms - not to same extent as surgical abdomen in DKA
What are 4 signs of HHS?
- Osmotic - dehydration
- Nausea and vomiting
- Neurological- may mimic stroke resolution, resolution is expected
- Impaired mental status - severe cases -10% with coma
What are the 5 principles in the management of HHS?
- Fluids
- Insulin
- Correct electrolytes
- Precipitants
- Anticoagulation
How are fluids used in HHS treatment?
• More cautious fluid replacement More gentle -1l of saline in one hour 1L - 2 hourly for next 2 hours Then 1L every 4 • Urine catheter essential • Low threshold for CVP
What is the use of insulin in HHS therapy?
IV insulin as per DKA regimen but half infusion rate
More insulin sensitive
Rapid decrease in glucose causes a rapid fluid shift/ coma
Other than fluids and insulin what is used in the management of HHS?
- Potassium replacement
- Full dose anticoagulation with LMW heparin
- Proton pump inhibitor?
- Broad spectrum antibiotic?
What are 5 complications associated with HHS management?
- High rate of arterial and venous thrombosis
- Cerebral oedema
- ARDS
- Hypoglycaemia and hypokalaemia
- Death
What are the considerations after a hyperglycaemic emergency has been dealt with?
- What caused it? • Can it be prevented in future? • Does the day to day diabetes mnx need changing? • Need to see DSN / Dr
- Phone contact on discharge • Expedite outpatient follow up
What are three principles for prevention of hyperglycaemic crisis?
- Better education
- Effective communication during acute illness
- Sick day rules
What are the diabetic sick day rules?
• NEVER STOP insulin, even if vomiting • CHECK CBG frequently, 3-4 hrly • CHECK urine for ketones • EXTRA short acting insulin if CBG>20 g • Small sugary drinks frequently if hypo, keep drinking even if not eating • GET MEDICAL HELP if -vomiting/diarrhoea -CBG >20 >3hrs -ketones persist -troublesome hypos
