Treatment of diabetes Flashcards
What is the natural progression of diabetes due to?
A disruption of an individual’s ability to metabolise glucose, progressive beta cell failure, low/falling insulin and low insulin sensitivity
What is the NICE guideline for measuring blood glucose?
Measure blood glucose at least 4 times a day (before and after each meal and at bedtime)
What measurements are indicative of diabetes?
- Fasting levels above 7mM
- Random glucose measurement over 11.1mM
- HbA1c - levels above 7%
At which level of glucose does the renal system get overloaded?
Blood glucose levels >10mM
What glucose levels should be maintained in those with type 1 diabetes on insulin replacement therapy?
- 4-7mM
* <7.8mM
How is insulin administered and why?
- Parentally/ subcutaneously/ IV
* It is a protein that would be digested/destroyed by the gut if taken orally
What are the rapid acting soluble insulins?
- Insulin lispro
- Insulin aspart
- Insulin Glulisine
What are the different insulin regimes?
- Fixed does= amount of insulin taken at each meal doesn’t vary day to day
- Flexible insulin therapy: gives patients more control of what they eat and how they balance their blood glucose levels
What are the pros/ cons of fixed dose insulin therapy?
- can help to simplify a patient’s understanding of glucose metabolism
- doesn’t offer flexibility of how much carbohydrates a patient may chose to consume at each meal - must be fixed
What are the pros/cons of flexible insulin therapy?
- Allows doses to be varied in response to different carbohydrate quantities in meals
- Requires a good understanding of glucose metabolism - requires time and commitment
what is the main adverse effect of insulin therapy?
Hypoglycaemia
What type of drug is metformin?
- Biguanide
* Oral hypoglycaemic agent
How does metformin work?
- Increases insulin sensitivity
- Reduces gluconeogenesis in the liver and opposes the action of glucagon
- Increases glucose uptake and utilisation in skeletal muscle
- Slightly delays carbohydrate absorption in the gut
- Increases fatty acid oxidation - reducing circulating LDL and VLDL (can help in obesity related diabetes and with atherosclerosis)
- Suppresses apetite
What are incretins?
- Stimulate insulin biosynthesis/secretion, inhibit glucagon secretion in the pancreas, delay gastric emptying, increase cardiac output and increase Brain satiety signals
- Indirectly increases insulin sensitivity in muscle and decreases gluconeogenesis in the liver
- Glucagon like peptide- 1 and Gastric inhibitory peptide
What secretes glucagon like peptide 1?
L cells in the gut
What secretes gastric inhibitory peptide?
K cells in the gut
What are incretins rapidly degraded by?
Dipeptidyl peptidase 4 (DPP-4)
name 3 incretin mimetics
- Exenatide
- Exenatide LAR
- Liraglutide
How do incretin analogues work to treat diabetes?
- Lower blood glucose after a meal by increasing insulin secretion
- Suppresses glucagon secretion
How are incretin analogues administrated?
Subcutaneously
What are gliptins?
- DPP-4 inhibitors
- Enhances endogenous incretin effects
- Lowers blood glucose by increasing first phase of insulin response after meals
Name 2 gliptins
- Sitagliptin
* Vildagliptin
What are the insulin secretagogues?
- Sulphonylureas
* Meglitinides
Describe sulphonylureas
- Interfere with beta cell ion channels to potentiate insulin secretion
- Increase appetite so can lead to weight gain
- Requires functional beta cells
Name 4 sulphonylureas
- Tolbutamide
- Chloropropamide
- Glibenclamide
- Glipizide
Describe meglitinides
- Block K-ATP channel to increase insulin release
* short duration of activity leads to lower risk of hypoglycaemia
Name 2 meglitinides
- Repaglinide
* Nateglinide
Why must you monitor patients of sulphonylureas closely?
Can interact with other drugs to produce severe hypoglycaemia due to competition for metabolising enzymes, plasma binding proteins and excretory pathways
What is the mechanism of action of Sulphonylureas?
- High affinity receptors present in beta cell membranes
- Block ATP sensitive potassium channels in the beta cells
- Causes beta cell depolarisation which leads to insulin secretion
Name 3 selective sodium glucose cotransporter 2 (SGLT2) inhibitors
- Canagliflozin
- Dapagliflozen
- Empagliflozin
What is the mechanism of action of SGLT 2 inhibitors?
•Block glucose reabsorption in the proximal tubules leading to therapeutic glycosuria
When are SGLT 2 inhibitors used?
mono-therapy in type 2 diabetics when exercise or diet alone is not adequate and for whom metformin is contraindicated or inappropriate
What are the risks of SGLT 2 inhibitors?
They increase the chance of getting an urinary tract infection
What are thiazolidinediones?
- Also called glitazones
- Peroxisome proliferator activated receptor - gamma agonist
- Increase insulin sensitivity, lowers blood glucose and promotes esterification/storage of free fatty acids in the adipose tissue
Describe physiological effects of thiazolidinediones
- Reduces amount of exogenous insulin needed by 30%
- Promotes the transcription of several genes that increase the storage of fatty acids in adipocytes, decreasing the amount of circulating FFAs
- cells become more dependent on the oxidation of carbohydrates, reducing blood glucose levels
- Can cause weight gain and fluid retention
What have thiazolidinediones been linked to?
- bladder cancer
- Heart failure
- Osteoporotic fractures
Describe the mechanism of pioglitazone
•PPAR- gamma ligands promote transcription of genes important in insulin signalling: lipoprotein lipase, fatty acid transporters, Glut 4 and others
What are alpha glucosidase inhibitors?
- competitive inhibitors of intestinal alpha-glucosidase
* Delay carbohydrate absorption in the small intestine reducing postprandial spike in glucose
what are the side effects of alpha glucosidases?
- Flatulence
* Diarrhoea
What are the risk factors for gestational diabetes?
- Family history of diabetes
- History of glucose intolerance
- Ethnicity
- Previous pregnancy where baby weights >4.5 kg
- BMI > 30
- Age
What are complications for babies whose mothers have diabetes?
- Stillbirth
- Congential malformation
- macrosomia
- Birth injury
- Perinatal mortality
How does the WHO define prediabetes?
- Impaired fasting glucose: 6.1-6.9mmol
* Impaired glucose tolerance: 7.8-11.0mmol after ingestion fo 75g of glucose
What causes impaired fasting glycaemia?
- Reduced hepatic insulin sensitivity
- Low beta cell mass
- Inappropriately elevated glucagon secretion
What causes impaired glucose tolerance?
- Reduced peripheral insulin sensitivity
- Loss of beta cell function
- Reduced incretin secretion
