Treatment of diabetes

Question 1

What is the natural progression of diabetes due to?

Answer 1

A disruption of an individual’s ability to metabolise glucose, progressive beta cell failure, low/falling insulin and low insulin sensitivity

Question 2

What is the NICE guideline for measuring blood glucose?

Answer 2

Measure blood glucose at least 4 times a day (before and after each meal and at bedtime)

Question 3

What measurements are indicative of diabetes?

Answer 3

• Fasting levels above 7mM
• Random glucose measurement over 11.1mM
• HbA1c - levels above 7%

Question 4

At which level of glucose does the renal system get overloaded?

Answer 4

Blood glucose levels >10mM

Question 5

What glucose levels should be maintained in those with type 1 diabetes on insulin replacement therapy?

Answer 5

• 4-7mM

* <7.8mM

Question 6

How is insulin administered and why?

Answer 6

• Parentally/ subcutaneously/ IV

* It is a protein that would be digested/destroyed by the gut if taken orally

Question 7

What are the rapid acting soluble insulins?

Answer 7

• Insulin lispro
• Insulin aspart
• Insulin Glulisine

Question 8

What are the different insulin regimes?

Answer 8

• 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

Question 9

What are the pros/ cons of fixed dose insulin therapy?

Answer 9

• 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

Question 10

What are the pros/cons of flexible insulin therapy?

Answer 10

• Allows doses to be varied in response to different carbohydrate quantities in meals
• Requires a good understanding of glucose metabolism - requires time and commitment

Question 11

what is the main adverse effect of insulin therapy?

Answer 11

Hypoglycaemia

Question 12

What type of drug is metformin?

Answer 12

• Biguanide

* Oral hypoglycaemic agent

Question 13

How does metformin work?

Answer 13

• 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

Question 14

What are incretins?

Answer 14

• 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

Question 15

What secretes glucagon like peptide 1?

Answer 15

L cells in the gut

Question 16

What secretes gastric inhibitory peptide?

Answer 16

K cells in the gut

Question 17

What are incretins rapidly degraded by?

Answer 17

Dipeptidyl peptidase 4 (DPP-4)

Question 18

name 3 incretin mimetics

Answer 18

• Exenatide
• Exenatide LAR
• Liraglutide

Question 19

How do incretin analogues work to treat diabetes?

Answer 19

• Lower blood glucose after a meal by increasing insulin secretion
• Suppresses glucagon secretion

Question 20

How are incretin analogues administrated?

Answer 20

Subcutaneously

Question 21

What are gliptins?

Answer 21

• DPP-4 inhibitors
• Enhances endogenous incretin effects
• Lowers blood glucose by increasing first phase of insulin response after meals

Question 22

Name 2 gliptins

Answer 22

• Sitagliptin

* Vildagliptin

Question 23

What are the insulin secretagogues?

Answer 23

• Sulphonylureas

* Meglitinides

Question 24

Describe sulphonylureas

Answer 24

• Interfere with beta cell ion channels to potentiate insulin secretion
• Increase appetite so can lead to weight gain
• Requires functional beta cells

Question 25

Name 4 sulphonylureas

Answer 25

*  Tolbutamide *  Chloropropamide *  Glibenclamide *  Glipizide

Question 26

Describe meglitinides

Answer 26

*  Block K-ATP channel to increase insulin release | *  short duration of activity leads to lower risk of hypoglycaemia

Question 27

Name 2 meglitinides

Answer 27

*  Repaglinide | *  Nateglinide

Question 28

Why must you monitor patients of sulphonylureas closely?

Answer 28

Can interact with other drugs to produce severe hypoglycaemia due to competition for metabolising enzymes, plasma binding proteins and excretory pathways

Question 29

What is the mechanism of action of Sulphonylureas?

Answer 29

*  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

Question 30

Name 3 selective sodium glucose cotransporter 2 (SGLT2) inhibitors

Answer 30

*  Canagliflozin *  Dapagliflozen *  Empagliflozin

Question 31

What is the mechanism of action of SGLT 2 inhibitors?

Answer 31

• Block glucose reabsorption in the proximal tubules leading to therapeutic glycosuria

Question 32

When are SGLT 2 inhibitors used?

Answer 32

mono-therapy in type 2 diabetics when exercise or diet alone is not adequate and for whom metformin is contraindicated or inappropriate

Question 33

What are the risks of SGLT 2 inhibitors?

Answer 33

They increase the chance of getting an urinary tract infection

Question 34

What are thiazolidinediones?

Answer 34

*  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

Question 35

Describe physiological effects of thiazolidinediones

Answer 35

*  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

Question 36

What have thiazolidinediones been linked to?

Answer 36

*  bladder cancer *  Heart failure *  Osteoporotic fractures

Question 37

Describe the mechanism of pioglitazone

Answer 37

• PPAR- gamma ligands promote transcription of genes important in insulin signalling: lipoprotein lipase, fatty acid transporters, Glut 4 and others

Question 38

What are alpha glucosidase inhibitors?

Answer 38

*  competitive inhibitors of intestinal alpha-glucosidase | *  Delay carbohydrate absorption in the small intestine reducing postprandial spike in glucose

Question 39

what are the side effects of alpha glucosidases?

Answer 39

*  Flatulence | *  Diarrhoea

Question 40

What are the risk factors for gestational diabetes?

Answer 40

*  Family history of diabetes *  History of glucose intolerance *  Ethnicity *  Previous pregnancy where baby weights >4.5 kg *  BMI > 30 *  Age

Question 41

What are complications for babies whose mothers have diabetes?

Answer 41

*  Stillbirth *  Congential malformation *  macrosomia *  Birth injury *  Perinatal mortality

Question 42

How does the WHO define prediabetes?

Answer 42

*  Impaired fasting glucose: 6.1-6.9mmol | *  Impaired glucose tolerance: 7.8-11.0mmol after ingestion fo 75g of glucose

Question 43

What causes impaired fasting glycaemia?

Answer 43

*  Reduced hepatic insulin sensitivity *  Low beta cell mass *  Inappropriately elevated glucagon secretion

Question 44

What causes impaired glucose tolerance?

Answer 44

*  Reduced peripheral insulin sensitivity *  Loss of beta cell function *  Reduced incretin secretion