How do sulphonylureas work?
They act upon the beta cell to promote insulin secretion in response to glucose
What class of drug is Gliclazide?
What does the level of HbA1C indicate?
The blood glucose over the last 2-3 months
- 50% from last month
- 25% the month before
- 25% the month before that
Which groups of diabetic drugs are associated withhypoglycaemic attacks?
What DDP4 inhibitors are available for use in the treatment of type 2 diabetes?
What enzyme degrades both the incretin peptides?
Dipeptidyl peptidase-4 (DDP4)
What bacterial skin infections are diabetics more susceptible to?
Staphylococcal infections - boils in elderly etc
What class of drug is metformin?
How much insulin reaches the general circulation after its release from the pancreas
Which areas of the body are mainly affected by atherosclerosis in diabetics?
- Legs and feet
What are the 5 conditions that make up metabolic syndrome?
- Central obesity
- Decreased HDL cholesterol
- Elevated fasting glucose levels
What is the normal range of fasting blood glucose?
What is the increase in risk of diabetes if a person is obese?
What is the clinical use of C-peptide?
It can be used to study the beta cell activity
What molecule is converted into insulin before its release from the beta cells?
What are the blood test that can be used to diagnose diabetes?
- Fasting blood glucose
- Randon blood glucose
- Glucose tolerance test
- Capillary blood test
- Glycosylated haemoglobin test
What transporter is utilised in the uptake of glucose into the pancreatic beta cells?
How does type 2 diabetes affect pancreatic alpha cells?
It activates them so there is a higher basal level of glucagon released
How does the entry of glucose into the beta cell stimulate release of insulin??
As the glucose is used in glycolysis, ATP is produced, this closes the ATP-sensitive K+ channels
This leads to depolarisation of the cell and subsequent Ca2+ release
This leads to movement of the secretory granules containing preformed insulin to the cell memebrane and subsquent release of insulin
What functions of insulin are soley found in adipose cells?
- Triglyceride synthesis from glucose
- Inhibits intracellular breakdown of stored triglycerides
What cells in the intestine secreted GIP?
What currently are the 3 main pharmacological interventions used in type 2 diabetes?
How do elevated levels of free fatty acids affect adipose cells?
- Induces resistance of insulin
- Impair secretion of insulin
What are the side effects of metformin?
- Epigastric discomfort
What 2 peptides secreted from the intestine are involved in the incretin effect?
- Glucose-dependent Insulinotropic Peptide/ Gastric Inhibitory Peptide (GIP)
- Glucagon-like-peptide-1 (GLP-1)
What is the diagnositic criteria for diabetes using a fasting blood glucose test?
Glucose level > 7.0mmol/L on 1 occasion
What is the function of insulin in skeletal muscle and adipose tissue?
It promotes translocation of the glucose transporter GLUT-4 from an inactive intracellular site to the cell membrane
How does metformin help in type 2 diabetes?
- Reduces rate of hepatic gluconeogenesis
- Reduces hepatic glucose output
- Increases insulin sensitivity
What are the 2 molecules produced by the enzymatic cleavage of proinsulin?
What level of HbA1C would be diagnositic of diabetes?
Anything over 48mmol/mol
What effect do the incretin peptides have on the pancreas?
They increase the secretion of insulin from the beta cells
Which area of the brain does insulin act on, when suppressing appetite?
Ventromedial nuclei of the hypothalamus
What are the 2 glucose transporters found in the kidney?
- SGLT2 - proximal tubule, 90% of glucose
- SGLT1 - descending limb, 10% of glucose
What allows the early phase of insulin release to happen so quickly?
There is preformed insulin in secretory granules which can be released immediately
What are the main complications of diabetes?
- Predisposition to infection
- Increased severity of atherosclerosis and its complications
- Extensive small vessel damage
- Renal glomerular disease
- Retinal vascular disease
- Peripheral nerve damage
What are the 3 main functions of insulin?
- Promotes glucose uptake by target cells and provides it for glucose storage
- Prevents fat and glycogen breakdown
- Inhibits gluconeogenesis and increases protein synthesis
What cells in the intestine secrete GLP-1
What dysfunction of the liver is seen in type 2 diabetes?
There is overproduction of glucose in the presence of elevated insulin levels
What are the morbities associated with type 2 diabetes?
- Ischaemic heart disease
- Cerebrovascular disease
- Peripheral gangrene of lower limbs
- Chronic renal disease
- Reduced visual acuity
- Peripheral neuropathy
Briefly how do the Thiazolidinediones
They reduce insulin resistance by interacting with the PPAR-γ nuclear receptor
What are the advantages of metformin?
- Does not affect insulin secretion
- Does not induce hypoglycaemia
- Does not cause weight gain
What does the glycoslyated haemoglobin test measure?
The level of HbA1C in the blood
How do sulphonylureas cause an increase in insulin secretion?
They act on the ATP-sensing potassium channels which initiates the release of calcium and subsequent insulin secretion
What is the glucose tolerance test?
- 75g of glucose given and blood sugar monitored at 1 and 2 hours.
- Test the body's ability to store glucose by removing it from the blood
- Normal levels usually return within 2-3 hours
- Diabetics blood glucose rises higher than non-diabetics and remains higher for longer
What GLP-1 agonists are used in the treatment of type 2 diabetes?
What level of glucose is diagnostic of diabetes using a random blood glucose test?
Over 11.1mmol/L in the presence of classic symptoms of:
- Blurred vision