Diabetes Flashcards
List some of the first and second line medications used in the treatment of diabetes mellitus.
Metformin (biguanide) Sulphonylureas TZDs (glitazones) Gliptins (DPP4 inhibitors) GLP-1 agonists Meglitinides Acarbose
What oral hypoglycaemic agent works at the renal tubules?
Sodium-glucose linked transporter 1 inhibitors
What is orlistat and what are the indications for use?
Orlistat is a pancreatic lipase inhibitor which can be used as an OTC treatment for obesity. It is only available to patients with a BMI of over 28. It is indicated as an anti-obesity agent in combination with a healthy eating plan, or prior to bariatric surgery.
Outline the mechanism by which metformin acts as an oral hypoglycaemic agent
Metformin functions by reducing hepatic gluconeogenesis in diabetic patients, while also increasing the expression of GLUT-4 channels in (adipocytes and skeletal myocytes), thereby increasing insulin sensitivity. This is generally only used where pancreatic insulin output is sufficient and when renal function is maintained to prevent lactic acidosis.
Describe the diet and life style changes which should be suggested to a T2 diabetic patient prior to commencing oral hypoglycaemic therapy.
Diet: increase intake of fibre (oats, plant based foods, nuts), lean meats and fish. Reduce the amount of sugar and saturated fat intake.
Lifestyle: increase aerobic and weight lifting exercise, loose weight gradually. Stop smoking, reduce cholesterol. Manage hypertension/reduce salt intake.
What advantages can diet and lifestyle changes provide a T2 diabetic patient?
Diet and lifestyle changes will reduce blood glucose levels, decreasing the risk of diabetic complications i.e. Micro and macro vascular complications). Managing weight, hypertension, reducing cholesterol and stopping smoking will also decrease the risk of cardiovascular disease. Exercise will reduce blood pressure.
What order of hypoglycaemic therapy is recommended by NICE?
First line treatment is metformin, the dose of which should be gradually increased over week to minimise GI symptoms. Gliptins, sulphonyureas and/or glitazones are then used in combination with metformin or each other.
Monotherapy -> duel therapy -> triple therapy -> insulin
What are the common side effects of metformin treatment for diabetes?
GI symptoms including abdominal pain, diarrhoea, nausea and vomiting are more common. Metformin dose is started low and titrated upward in order to minimise GI upset.
Lactic acidosis is also common and can cause fast/shallow breathing, dizziness, tiredness and muscle pain as well as GI symptoms. This is due to reduced hepatic uptake of lactate due to reduced gluconeogenesis.
Note that metformin is very unlikely to cause hypoglycaemia since it does not increase insulin production, but rather increases insulin sensitivity and reduces additional glucose production.
What are the contraindications of metformin therapy?
The major contraindication of metformin theory is renal impairment, with a GFR <30 ml/min. This is due to the risk of lactic acidosis associated with metformin therapy, since renal reabsorption and production of HCO3- is important in maintaining blood pH.
Lactic acidosis is thought to result from reduced hepatic uptake of lactate.
What are the symptoms of hypoglycaemia?
Dizziness Slurred speech Loss of coordination Hunger Headache Sweating Impatience/irritability
How do sulphonyureas act as hypoglycaemic agents?
Sulphonyureas act by increasing the pancreatic secretion of insulin. They do this by inhibiting the ATP-gated K ion channel, hence causing depolarisation of the membrane, causing calcium entry into the cell and the release of insulin from storage vesicles.
What are the side effects of sulphonylureas in the treatment of diabetes mellitus?
Hypoglycaemia - due to the increase in insulin secretion
Weight gain - due to the increased level of insulin increasing storage of glucose as fat. For this reason sulphonyureas are not recommended for patients who are overweight.
How do the glitazones (TZDs) act as hypoglycaemics?
Glitazones work by agonising the PPARs, a class of receptors involved in carbohydrate and lipid metabolism control. PPARs are a class of nuclear receptors whose natural ligand is fatty acids. Activation of the receptors cause an alteration of transcription pattern. The glitazones bind the receptor and simulate an increase in fatty acids, causing an increase in their storage in adipocytees. As a result cells switch to carbohydrate metabolism due to their decreased available lit your in the blood. This works to increase muscle and adipose sensitivity to insulin. It also decreases hepatic glucose output.
What are the side effects of glitazone (TZD) treatment?
Weight gain is one of the most notable side effects of glitazone treatment, due to the increased storage of fatty acids in adipose.
Other side effects can relate to fluid retention, e.g. Decreased urine output, oedema in face, ankles and arms, exacerbation of heart failure.
There is also a risk of bladder cancer, about 1%.
What are the contraindications to TZD/glitazone treatment?
Existing bladder cancer, obesity, renal failure, existing fluid retention (e.g. Liver disease, nephrotic syndrome, heart failure), existing heart failure/congestive heart failure.
