Type 2 Diabetes

Question 1

What is type 2 Diabetes?

Answer 1

• Relative insulin deficiency (impaired B-cell function) and/or insulin resistance
• Onset >40 years (>25 years Black, S.Asian)
• Gradual Onset (link to overweight/obesity)

Question 2

What are current drug therapies for Type 2?

Answer 2

Aims to:
* Inc glucose uptake into tissues
* Stimulate the release of insulin
* Red glucose uptake from GI tract
* Red glucose reabsorption from kidney

Question 3

What is Metformoin?

Answer 3

• Increases glucose uptake into tissues
• Inhibits production of glucose in the body (Gluconeogenesis)
• Acts through AMP kinase

Question 4

What is Sulphonylureas?

Answer 4

• Stimulate insulin secretion from pancreatic B-cells
• Require functional B-cells
• Bind to SUR

Question 5

How does glucose interact with insulin release?

Answer 5

• Glucose increases exocytosis
  1. By inc ATP, resulting in a dec in potassium influx
• Results in increased insulin release

Question 6

How does Sulphonylureas interact with insulin release?

Answer 6

• Inhibits the ATP-sensitive K+ channels so mimics the process of glucose
• But misses step of inc ATP

Question 7

What are the issues with Sulphonylureas?

Answer 7

• Stimulate release of insulin independent of plasma glucose levels
• Risk of hypOglycaemia
• Also, weight gain- Inc appetite

Question 8

What are Meglitinides?

Answer 8

• Inhibit K.ATP channel similar to sulphonylureas
• Different binding site
• Stimulate insulin secretion from pancreatic B-cells
• Rapid onset and shorter duration of action
• Taken before each meal
• Less likely to cause hypoglycaemia

Question 9

What are Thiazolinediones?

Answer 9

• Agonists at PPARy receptor
• Peroxisome proliferator-activated receptor y
• Nuclear receptor- regulates expression of genes inv in glucose homeostasis e.g. GLUT-4 glucose transporter
• Incd uptake of glucose into liver and skeletal muscle
• Slow action 1-2 months for max effort

Question 10

What are the GLP-1 targeted drugs?

Answer 10

• GLP-1 glucagon like peptide 1
• Acts at GLP-1 receptor on B-cells–Stimulates insulin secretion in glucose dependent manner
• Inhibit glucagon release from a-cells (glucogon has opposite effect to Insulin)
• Broken down by DPP

Question 11

What is Exenatide?

Answer 11

• Resistant to degredation by DPP4-mimics the effect of GLP-1

Question 12

What are GLP-1 receptor agonists?

Answer 12

• Stimulate GLP-1 receptor
• Also, inhibits appetite

Question 13

What are DPP4 inhibitors?

Answer 13

• Prevents the breakdown of incretins
• Competitive inhibitors
• Prolongs the effect of endogenous GLP-1

Question 14

What are sodium-glucose co-transporter 2 inhibitors?

Answer 14

• Inhibits glucose reabsorption in the kidney?

Question 15

What is Acarbose?

Answer 15

• Alpha-glucosidase inhibitor
• Prevents the digestion of carbs in GI tract
• Red absorption of glucose from the diet
• Problem–Diarrhoea

Question 16

Explain insulin therapies.

Answer 16

• May be needed in the long term due to a gradual decline in insulin release.

Question 17

Summarise Strategies to manage diabetes.

Answer 17

• Inc Glucose uptake into tissues–
  1. Metformin,PPARgamma agonist
• Stimulate release of insulin–
  1. Sulphonylureas, GLP-1 agonists/incretin mimetics/DPP4 inhibitors
• Red glucose uptake from GI tract–
  1. Alpha-glucosidase inhibitors
• Red glucose reabsorption from the kideny
  1. SGLT2 inhibitors