Insulin

Question 1

What si teh role of insulin

Answer 1

• Stimulates uptake of glucose into liver, muscle and adipose tissue
• Decreases hepatic glucose output via inhibition of gluconeogenesis
• Inhibits glycogenolysis
• Promotes uptake of fats
• Ideal insulin treatment would be to reinstate the normal daily insulin profile to prevent both hyperglycaemia and hypoglycaemia

Question 2

What are types of insulin available

Answer 2

Animal Porcine and Bovine
Recombinant DNA technology
• Human short acting insulins
• Human rapid acting insulin analogues
• Isophane intermediate acting insulin
• Long acting basal analogue insulins
• Very long acting basal analogue insulins

Question 3

What affectstheduraton of action ofisulins

Answer 3

Once absorbed, duration o action 4-5 minutes. Only difference - rate at which absorbed. Some take time to break down. Fast acti ones are more momnomeric. Some ar more bound together so slow breakdown.

Question 4

Describe recombinant dna technology

Answer 4

• Has allowed for the development and production of analogues – the insulin molecule structure is modified to alter the pharmacokinetic properties, primarily affecting the absorption of the drug from subcutaneous tissue
• B26-30 region altered

Question 5

How many types of insulin are there

Answer 5

Over 20 different types are insulin in use in various strengths and forms (vials, cartridges, disposable pens)
U100. 100 units per ml. Obesity a problem need to use u200, u300 etc
Liable to prescribing error s- could accidnetllay give too much

Question 6

What are the 6 mai insulin categories and how are they absorbed

Answer 6

• Ultrafast acting
• Rapid acting
• Short acting
• Intermediate acting
• Long acting
• Very long acting
• Absorption into blood stream via subcutaneous
injection
• Formulation of insulin influences rate of absorption

Question 7

Describe ultra fast acting insulin apart

Answer 7

Ss

Question 8

Describe rapid acting insulin

Answer 8

• Rapid onset of action 5 to 15 minutes • Inject just before eating
• Peaks ~ 60 minutes
• Duration 4 to 6 hours

Humalog, Novorapid, Apidra)

Question 9

Describe short acting insulin

Answer 9

Actrapid, Humulin S, Hypurin Bovine and Porcine Neutral)
• Starts to work 30 to 60 minutes
• Need to inject at least 15 to 30 minutes before
eating several times daily to cover meals • Peaks at 2 to 3 hours
• Duration 8 to 10hours

Question 10

Describe intermediate acting insulin

Answer 10

Intermediate acting insulin (Insulatard, Humulin I and Insuman Basal, Hypurin Bovine and Porcine Isophane)
• Slower onset 2 to 4 hours
• Peaks 4 to 8 hours
• Duration up to 12 to 20 hours

Question 11

Describe long and very on acting insuin

Answer 11

Long and very acting insulin (Glargine, Detemir, Degludec)
• Slow onset 2 to 6 hours
• Duration up to 24 hours
• Very long up to 50+ hours (DEGLUDEC insulin)

Question 12

What are fixed. combination

Answer 12

• Novomix 30
• Humulin M3
• Humalog Mix 25 and 50
• Hypurin Porcine 30/70
• Insuman Comb 15 and 25 and 50
• And modes of delivery using syringes, insulin Pens, insulin pumps

Question 13

Describe insulin pump therapy

Answer 13

Sensor augmented pump therapy with threshold suspend

Question 14

What are the adverse effects of insulin

Answer 14

• Hypoglycaemia
• Hyperglycaemia
• Lipodystrophy – lipohypertrophy or lipoatrophy
• Painful injections - hypertrophy of adipose, and scarring if you keep injecting into same space
• Insulin allergies

Question 15

Describe the safer administration of insulin

Answer 15

• In UK 4 to 5% population has diabetes
• 30 to 40% treated with insulin
• Insulin errors are very common in UK with approximately prescribing errors in ~20% cases
• Why? Too much will lead to hypoglycaemia and too little to hyperglycaemia
• Look online for Safer Insulin Prescribing module

Question 16

Why does blood glucose rise

Answer 16

• Inability to produce insulin due to beta cell failure and / or
• Insulin production adequate but insulin resistance prevents insulin working effectively

Question 17

How do we treat type 2 diabetes

Answer 17

Type2
– Lifestyle plus non-insulin therapies
• Biguanides, sulphonylureas, thiazolidinediones, DPP4 inhibitors, α- Glucosidase inhibitors, SGLT2s, GLP1 analogues and Insulin
• Plus non pharmacologic methods via bariatric surgery and very low calorie diets
• Above require patient education and ability to monitor results of therapy

Question 18

What are the key challenges for patient with type 2 diabetes

Answer 18

Ss

Question 19

What are the nice targets in typ 2 diabetes

Answer 19

• In general target for all is HbA1c 6.5 to 7.5%
• HbA1c 6.5%:Diet and first 2 treatment steps
• HbA1c 7.5%:Beyond this or if at risk of severe hypoglycaemia
• Common sense: Limited life expectancy and Co morbid conditions

Question 20

Describe metformin

Answer 20

• decrease Insulin resistance leading to increased glucose by tissues
• decrease hepatic glucose production (reduces hepatic
gluconeogenesis)
• Limits weight gain
• decrease CVS events (UKPDS)
• Can be combined with all other diabetes medications
• Side effects include GI symptoms
• Lacticacidosisrare
• Vitamin B12 deficiency uncommon
• Stop if CKD < 30ml/min or significant comorbidities
• Dose range typically 500mg to 2.5g (also Modified Release available) and Cost low

Question 21

Describe sulphonylureas

Answer 21

Stimulate beta cell to release insulin
• Extensive experiencedecrease Microvascular risk
(UKPDS)
• Side effects
• Weight gain
• Hypoglycaemia
• Cost low
• Commonly used include Gliclazide (Modified Release too) (hepatic metabolism so can be used in renal impairment), Glimepiride

Question 22

Wha is acarbose

Answer 22

Acarbose: α glucosidase inhibitor
• Only 1 available in the class
• Inhibits breakdown of carbohydrates to glucose by blocking action of the enzyme α Glucosidase
• Side effects are predictable! Flatulence, loose stools and diarrhoea
• Modest reduction in HbA1c ~ 0.5%
• Rarely if ever used nowadays

Question 23

What are glitazones

Answer 23

Glitazones [Pioglitazone]
• increase insulin sensitivity in muscle and adipose tissue and decrease hepatic glucose output
• They bind to and activate one or more peroxisome proliferator-activated receptors (PPARs)
• Can be used in combination with other oral agents
• Cardiovascular concerns with Rosiglitazone - Weight gain, fluid retention, cvs events such as angina - increase cholesterol.
• Pioglitazone still available but concerns regarding weight gain, fluid retention and heart failure, effects on bone metabolism and bladder cancer
• Rarely used nowadays

Question 24

Describe glucagon like peptide 1 therapies

Answer 24

• Alternative hormone system influencing glucose metabolism
• High glucose in Type 2 diabetes due to insufficient release of insulin and over production of glucagon
• GLP1therapy(Exenatide,Liraglutide, Lixisenatide)
• Increase insulin secretion from the beta cells
• Decreases production of Glucagon from alpha cells
Switches off desire to eat - safety centre in hypothalamus - promote weight loss and improve control. A to fo former medicines promote weight gain

Question 25

Descrive the physiological effects of gulp-1

Answer 25

Ss

Question 26

Describe gliptis or dpp4 inhibitors

Answer 26

Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin • Inhibits DPP-4 activity increasing postprandial active GLP-1 concentrations • Side effects include GI symptoms, ?pancreatitis • Low risk of hypoglycaemia • Weight neutral • Modest HbA1c reduction • Cost high

Question 27

What are the adverse effects o glp1 agonists

Answer 27

* Gastrointestinal symptoms, nausea, loose stools or diarrhoea * Gastro oesophageal reflux * Low risk of hypoglycaemia * Occasional painful to inject * ? Pancreatitis and pancreatic carcinoma * NICE and FDA found no evidence of pancreatitis in the reported studies * Generally perceived to be safe and well tolerated agents * Widely used * Avoid if eGFR < 30ml/min

Question 28

Descrive dapagliflozin

Answer 28

A novel insulin-independent approach to remove excess glucose Dapagliflozin selectively inhibits SGLT2 in the renal proximal tubule *Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with Type 2 diabetes.4 Sodium-Glucose Co -Transp

Question 29

What are the adverse effects f glifozins

Answer 29

Glifozins: adverse side effects • Can be used for patients with Type1 and Type 2 diabetes as add on therapy • Dapagliflozin, Canagliflozin and Empagliflozin available • Side effects can be predicted • Increase risk of lower urinary tract symptoms including genital and urinary infections especially in women (5%) • Polyuria • Hypoglycaemia risk low