Non-insulin Treatments and Monitoring of Diabetes Flashcards
First line treatment of T2DM.
Metformin
Action of metformin.
Reduces rate of gluconeogenesis and hepatic glucose output
Increases insulin sensitivity
Suppress appetite
Stabilise weight
Metformin effects on plasma glucose levels.
Lowers fasting plasma glucose by 2-4 mmol/l
Fall of 11-22 mmol/mol of HbA1c
Adverse effects of metformin.
Anorexia
Nausea
Abdo discomfort
Diarrhoea
Lactic acidosis
When is metformin contraindicated?
Renal impairment
Cardiac failure
Hepatic failure
Intravascular administration of iodinated contrast agent
What is the risk of giving metformin along with the contraindications?
Lactic acidosis
Mode of action of sulphonylureas.
Act on beta-cells to induce insulin secretion.
Binds to receptor to close ATP-sensitive potassium channels and blocks the potassium efflux.
This leads to depolarisation and influx of calcium -> Insulin release.
When is sulphonylurea used?
Alternative first-line if metformin is contraindicated or not well tolerated.
Add-on.
Sulphonylurea effects on plasma glucose and HbA1c.
Reduce fasting plasma glucose by 2-4 mmol/l
11-22 mmol/mol fall in HbA1c.
Sulphonylureas effect long term.
Will reduce as B-cell mass declines.
Adverse effects of sulphonylureas.
Due to the increase in insulin there is typically weight gain of 1-4 kg.
Hypoglycaemia (increases in risk with alcohol intake, older age and intercurrent infection)
What are meglitinides?
Short-acting agents that promote insulin secretion in response to meals.
Act like sulphonylureas but designed to restore early-phase post-prandial insulin release.
When are meglitinides used?
To treat people with post-prandial hyperglycaemia with normal fasting glucose levels.
ADR of meglitinides.
Hypoglycaemia
Weight gain
Most common (and in some countries the only available) Thiazolidinedione.
Pioglitazone
Mode of action of pioglitazone.
Reduce insulin resistance by interaction with PPAR-y.
Reduce hepatic glucose production.
Enhance peripheral glucose uptake
Potentiate the effect of endogenous or injected insulin.
Also promote TAG production.
When is pioglitazone used?
Monotherapy
Add-on
Benefits of pioglitazone as monotherapy?
Do not cause hypoglycaemia on its own.
Specifically beneficial in people with non-alcoholic fatty liver diease.
(May take up to 3 months to reach its maximal effect)
ADRs of pioglitazone.
Weight gain of 5-6 kg
Can cause fluid retention leading to heart failure.
Mild anaemia
Osteoporosis
Example of DPP-4 inhibitors.
Sitagliptin
Saxagliptin
Mode of action of DPP4i
Inhibit DPP4 leading to a prevention of rapid inactivation of GLP-1.
This leads to increased insulin secretion and reduces the glucagon secretion.
When are DPP4i used?
Most effective in early stages of T2DM.
Currently second-line use in combination with metformin or sulphonylurea.
Usually well tolerated.
Benefits of DPP4i.
Do not promote weight gain
Low risk of hypoglycaemia
Safely used in renal impairment
ADRs of DPP4i.
Nausea
Acute pancreatitis
Saxagliptin might increase risk of heart failure.
E.g. of SGLT2i.
Dapagliflozin
Mode of action of SGLT2i.
Lowers the renal threshold for glucose.
Increasing urinary glucose excretion leading to removal of both glucose and calories from the body.
SGLT2i effects on plasma glucose levels and weight.
Reduces blood glucose by 7-13 mmol/mol (???)
2-4 kg weight loss over 6-12 months
When are SGLT2i used?
Monotherapy
Typically in combination
Benefits of SGLT2i
Cardiovascular benefits
Low risk of hypo
Dependent on good renal function but is renoprotective.
Weight loss
ADRs of SGLT2i
Genital candidiasis
Dehydration
Diabetic ketoacidosis
Fournier’s gangrene
Lower limb amputation
Mode of action of alpha-glucosidase inhibitors.
Prevent alpha-glucosidase (last enzyme inolved in carb digestion) form breaking down disaccharides into monosaccharides.
Slows absorption of glucose after a meal.
ADRs of alpha-glucosidase inhibitors.
Flatulence
Abdo distention
Diarrhoea
E.g. of other rarely used oral therapies.
Quick release bromocriptine
Colesevelam
Give an example of a non-insulin injectable therapy for T2DM.
GLP-1 receptor agonists.
There are two types of GLP-1 receptors agonists.
Which?
Drugs derived from the protein exendin. This one is resistant to DPP-4 cleavage.
The second group are analogues of human GLP-1.
How often are GLP-1 receptor agonists given?
Once-weekly.
Mode of action of GLP-1 receptor agonists.
Enhance the incretin effect by activating GLP-1 recpetor.
They are more potent than DPP4is.
They act on pancreas to increase insulin secretion and decrease glucagon secretion.
They also act on the hypothalamus to reduce appetite and promote weight loss.
Short acting GLP-1s also slow gastric emptying.
Benefits of GLP-1 receptor agonists.
Protect heart against ischaemic damage.
Lowers BP
Lowers free fatty acids.
When are GLP-1 receptor agonists used?
Second or third-line therapy.
Should not be combined with DPP4i - no additional benefit.
ADRs of GLP-1 receptor agonists.
Nausea
Vomiting
Bloating
Diarrhoea
Low risk of hypo.
Pancreatitis
Individuals with established atherosclerotic cardiovascular disease.
What might you give?
GLP-1 receptor agonist
SGLT2i
Diabetes with heart failure and chronic kidney disease.
SGLT2 inhibitor
If there is a pressing need to minimise weight gain or pormote loss.
What should be given?
GLP-1 receptor agonists or SGLT2i
What surgeries can be done in diabetes?
Islet transplantation (T1DM)
Whole pancrease transplantation (T1DM)
Explain islet transplantation.
Harvesting pancreatic islets from cadavers (two or three needed)
Injected into the portal vein and seed themselves into the liver.
When might islet transplanation be done?
In T1DM with hypoglycaemic unawareness, severe hypoglycaemic episodes and marked glucose variability.
Treatment goal of islet transplantation.
Prevent severe hypoglycaemia.
50-70% of people receiving islet cell transplants also achieve insulin independence after 5 years.
When might whole-pancrease transplantation be done?
T1DM in end-stage kidney disease.
This means that the pancreas transplantation is done when another transplant is done as well.
Disadvantages of whole-pancrease transplantation.
Long-term immunosuppression.
Ways of measuring the metabolic control of diabetes.
Short-term measures such as:
Self-monitoring of capillary blood glucose
Continuous glucose monitoring
Long-term measures such as:
Glycated haemoglobin HbA1c
Frucosamine
When is self-monitoring of capillary blood glucose recommended?
For everyone treated with insulin.
Also some people with diet or tablet treated T2DM.
Explain continuous glucose monitoring
Measures interstitial glucose every few minutes allowing the user to see trends in glucose throughout the day.
It is particularly good at night when testing is not usually done.
Freestyle Libre is a sort of continuous glucose monitoring.
Two types of continuous glucose monitoring.
Real time
Retrospective
Main disadvantage of CGM.
The lag of 15-20 minutes between changes in blood glucose and interstitial glucose.
This means that if there is an indication of hypoglycaemia the individual should test their capillary glucose as well.
When is CGM recommended?
T1DM who have problematic hypoglycaemia.
Recurrent severe hyperglycaemia.
Impared awareness of hypoglycaemia
Extreme fear of hypoglycaemia.
Explain glycated haemoglobin HbA1c.
Measure of an individual’s average blood glucose concentration over the previous 6-8 weeks.
This is because glucose will glycate the haemoglobin.
The rate at which it occurs is related to the glucose concentration in the blood.
Limitations to HbA1c
Molecular variants of haemoglobin such as fetal Hb
Variation in red blood cell lifespan such as in haemolytic anemia, acute or chronic blood loss.
Pregnancy
Longer lifespan like in iron deficiency.
Renal failure
HIV infection.
If there are known problems of anaemia or haemoglobinpathy, what can be used as a long-term measurement instead of HbA1c?
Glycation of albumin measured as fructosamine.
Only used rarely.
T2DM diabetes treatment algorithm.
Explain the diabetes health check.
Every 3-6 months you do an HbA1c (3monthly when newly diagnosed and then 6monthly when stable)
Annually
Feet
Eyes
BP, lipid profile, heart and kidney disease (Urine albumin:creatinine ratio + eGFR)
Weight check
Update on medication
