Treatment and management of diabetes Flashcards
Insulin
A hormone secreted by the beta cells of the pancreas, found within the islets of Langerhans. Stimulates glucose uptake by liver, muscle and fat tissues, while simultaneously suppressing glucose production and lipolysis.
Insulin release
Insulin release is biphasic; consisting of a transient first phase followed by a sustained second phase. In type 1 diabetes, no insulin is released, while in type 2 diabetes the first phase of insulin secretion is lost.
Insulin receptor
A ligand-activated tyrosine kinase receptor, found in liver, muscle and fat tissues. It is composed of 2 extracellular alpha-subunit proteins, which act as the insulin binding site, and 2 transmembrane beta-subunit proteins, which is the tyrosine kinase component. They are coupled with glucose transporters (Glut-4) in the target cell membrane.
Insulin receptor signalling
When insulin binds to its receptor, it triggers the autophosphorylation as well as phosporylation of insulin receptor substrate (IRS) proteins. These activate enzymes and promote the transcription of genes which increase glucose uptake and glycogen synthesis.
Oral agents for treatment of diabetes
- biguanides
- sulfonylureas
- thiazolidinediones
- gliptins
- glucose transport inhibitors
Agents given by injection for treatment of diabetes
- insulin
- incretin mimetics
Exogenous insulin
Insulin may be administered by injection, mainly in patients with type 1 diabetes but also in some patients with type 2. There are many different types (eg. human, porcine, bovine), which may be modified to have different durations of action and rates of onset. Dose regimes vary from patient to patient, and are managed to minimise glucose fluctuations from factors such as diet and exercise. Complications include hypo/hyperglycaemia, allergy and lipodystrophy.
Management of type 1 diabetes
Patients with type 1 diabetes manage their condition with carbohydrate counting, a balanced diet, and exercise. They may have to adjust their insulin dose according to these factors. Regular HbA1c measurements are taken to monitor blood glucose levels, and self-monitoring can be done using finger-prick testing or continuous monitoring devices.
Management of type 2 diabetes
Patients with type 2 diabetes are advised to manage their condition with lifestyle modification, including a balanced diet, exercise, and interventions such as intermittent fasting or very low calorie diets. If these are not successful, they may require treatment with drugs or insulin.
Biguanides eg. metformin
Acts by reducing gluconeogenesis in the liver, increasing glucose uptake in skeletal muscle, reducing carbohydrate absorption and increasing fatty acid oxidation. It is the first choice drug in patients with type 2 diabetes, and can be used in combination with other drugs or insulin. It does not cause hypoglycaemia. Side effects include gastrointestinal disturbances and lactic acidosis, so it should not be given to patients with hepatic or renal disease.
Sulfonylureas eg. tolbutamide, glibenclamide, glipizide
Act by binding to KATP channels within beta cell membranes, blocking potassium exit. The resulting depolarisation causes calcium entry, promoting exocytosis and the secretion of insulin. They are usually well tolerated, but can cause hypoglycaemia and should be avoided in patients with impaired renal function. Other unwanted side effects include increased appetite leading to weight gain.
Other SUR modulators eg. repaglinide, nateglinide
Have a similar mechanism of action to sulfonylureas, but are much less potent and have a shorter duration of action. They are more selective for the KATP channels in pancreatic beta cells. The risk of hypoglycaemia is lower and they may cause less weight gain than sulfonylureas.
Thiazolinedinediones eg. pioglitazone
Bind to nuclear receptors and alter gene expression, enhancing the effect of endogenous insulin in target tissues, and reducing hepatic glucose output. Act on adipose tissue by increasing fatty acid uptake and lipogenesis, leading to weight gain. Have a very slow onset of action, generally 1-2 months.
Incretins
Peptide hormones released from the gut, which stimulate insulin secretion, inhibit glucagon secretion and reduce gastric emptying to slow the rate of food absorption. They are also involved in the control of food intake via appetite and satiety.
Glucagon-like peptides eg. exenatide
Incretin mimetics, which bind to GLP-1 receptors on the beta cells of the pancreas. They reduce blood glucose after a meal by stimulating insulin secretion, inhibiting glucagon secretion, and reducting gastric emptying. They also reduce food intake by promoting satiety, leading to weight loss.
