Endocrine - diabetes Flashcards
What are the types of insulin available?
Rapid-acting Short-acting Intermediate-acting Long-acting Continuous sub-cutaneous insulin infusion (insulin pump)
What are the regimes available for insulin therapy?
Twice daily
Three times daily
Four times daily
When do you take the twice daily regime?
Rapid acting mixed with intermediate acting Before breakfast (BB) and evening meal (BT)
What is the three times daily regime?
Rapid acting mixed with intermediate acting Before breakfast
Rapid acting Before dinner
intermediate acting at bedtime
What is the four times daily insulin regime?
Short acting Before breakfast, lunch and dinner
Intermediate BBed or long acting insulin at a fixed time once daily
What is the basal bolus therapy and who is it good for?
Long acting insulin in the background
Rapid acting insulin calculated before meals
Very good for shift workers who don’t know when they will eat
What are the cautions with insulin pumps?
No background insulin
Must check blood glucose themselves
What is the glucose needed to drive?
5 to drive (greater than 5mmoles)
What is the lowest blood glucose a diabetic should ever go to?
4s the floor
What are the main causes of hypoglycaemia?
Food (too little./wrong type)
Activity
Insulin (too much or taken poorly)
What are the symptoms of hypogylcaemia?
Sweating Palpitations Shaking Hunger Confusion Drowsiness Speech difficulty Incoordinatio Nausea
What are the symptoms of a DKA?
Polyuria Polydipsia Weakness Weight loss Nausea Abdominal pain Breathlessness
What are the signs of a DKA?
Dry mucus membranes Sunken eyes Tachycardia Hypotension Ketotic breath Altered mental state Hypothermia
What are the complications of DKA?
Hyper and hypokalaemia Hypoglycaemia >Rebound ketosis >Arrhythmias >Acute brain injury Cerebral oedema >Children more susceptible >70-80% diabetes related deaths in children <12 Aspiration pneumonia Arterial and venous thromboembolism ARDS
How do you treat a DKA?
Measure glucose / U and E’s / ketones / bicarbonate / arterial blood gas
Give iv saline (5 l in 24 hours)
Give iv insulin (drives glucose and potassium into cells)
Give iv potassium in saline
May need antibiotics
Consider heparin, NG tube
Mortality Rate 2%
Which drugs improve the action of insulin?
Biguanides
Thiazolidiones
What drugs improve the excretion of glucose?
SGLT2 inhibitors
Which drugs improve insulin release?
Sulphonylureas
Metglinides
Incretin mimics
DPPIV inhibitors
What is metformin?
A biguinide
>therefore improves insulin sensnitivity
Has half life of 6 hours
How does metformin improve the sensitivity of insulin?
Affects glucose production, decrease fatty acid synthesis
Improves receptor function
Inhibits gluconeogenic pathways
What are the advantages of metformin?
Improves cardiovascular outcomes and mortality in obese T2 DM Cheap Efficaceous Normally well tolerated Not associated with weight gain HbA1c by 12 – 17% reduction Also used in pregnancy now
What are the disadvantages of metformin?
Risk of lactic acidosis by inhibiting lactic acid uptake by liver especially in >Hypoxia >Renal failure (CI if creat<150) >Hepatic failure >Alcohol abuse GI side effects 20 – 30 % Risk vitamin B12 malabsorption
What is the mechanism of action of sulphonylureas?
Binds to sulfonylurea receptors (SUR-1) on functioning pancreatic beta-cells.
Binding closes the linked ATP-sensitive potassium channels
Decreased potassium influx depolarization of the beta-cell membrane.
Voltage-dependent calcium channels open and result in an influx of calcium
Translocation and exocytosis of secretory granules of insulin to the cell surface
What are the advantages of sulphoylnureas?
Used with metformin Rapid improvement in control Rapid improvement if symptomatic Rapid titration Cheap Generally well tolerated
What are the disadvantages of sulphonylureas?
Risk of hypoglycaemia Weight gain Caution in renal and hepatic disease CI in pregnancy and breastfeeding. SE include >Hypersensitivity and photosensitivity reactions >Blood disorders
What is the mechanism of action of thiazolidinediones?
selectively stimulates thenuclear receptorperoxisome proliferator-activated receptor gamma (PPAR-gamma) and to a lesser extentPPAR - alpha
modulates the transcription of theinsulin-sensitive genes involved in the control of glucose andlipid metabolismin themuscle,adipose tissue, and theliver.
reduces insulin resistancein the liver and peripheral tissues;
increases the expense of insulin-dependent glucose;
decreases withdrawal of glucose from the liver;
reduces quantity of glucose, insulin andglycated haemoglobinin the bloodstream.
What are the advantages of pioglitazone?
Good for people if insulin resistance significant HbA1c by 0.6-1.3% Cheap Cardiovascular safety established (Contrast with rosiglitazone)
What are the disadvantages of pioglitazone?
Increase risk of bladder cancer >Caution in those of increased risk bladder cancer (Age, industry etc) Fluid retention - CCF Weight gain Fractures in females >Small increased risk >TZDs affect bone turnover >Reduced BMD >Initial report were of increased distal fractures in women
What is the mechanism of action of gliptins (DDPV inhibitors)?
Inhibits DD4 enzyme which degrades incretins
Therefore increases active incretin levels
Results in increase in insulin release and decrease in glucagon
What are the advantages of gliptins?
Usually well tolerated Can be used as 2nd or 3rd line agent Can be used in renal impairment No risk of hypoglycaemia Weight neutral
What are the disadvantages of gliptins?
Trial data shows relatively small effects on glycaemic control
CI in pregnancy and breastfeeding.
Possible increased risk of pancreatitis and pancreatic cancer
SE: nausea
What is the mechanism of action of GLP-1 analogues?
Injectable analogues of GLP-1 resistant to enzymatic half life
Therefore greatly enhanced biological half life
Incretins stimulate the pancreas for longer
Results in more insulin release
What are the advantages of GLP-1 analogues?
Weight loss
No risk of hypoglycaemia
3rd line agent
Can be used with basal insulin
What are the disadvantages of GLP-1 analogues?
Injection Very expensive Possible increased risk of pancreatitis and pancreatic cancer CI in pregnancy and breastfeeding. SE: Nausea, vomiting
What is the Mechanism of action of SGLT2 inhibitors (gliflozins)?
Prevent glucose reabsorption at proximal tubule
Results in a lot more urinary excretion of glucose
What are the effects of SGLT2 inhibitors?
Gets rid of glucose/more glycosuria >Lowers HbA1C Gets rid of water/osmotic diuresis >(POSTURAL) hypotension, dehydration Gets rid of calories by wasting glucose >Weight loss with same intake Less uptake of sodium >Lowers systolic blood pressure Increases risk of urinary infection >Cystisis + candidiasis
What are the advantages of SGLT2 inhibitors?
Weight loss No risk of hypoglycaemia Good effects on glycemic control May have beneficial effect on cardiovascular morbidity & mortality 2nd or 3rd line agent Can add to insulin regimens in T2DM
What are the disadvantages of SGLT2 inhibitors?
Expensive SE: UTI, fungal infections, osmotic symptoms Risk of digital amputation Risk of DKA CI in pregnancy and breastfeeding. Cannot use in renal impairment
