Topic 3 - part 2

Question 1

How can you diagnose type 1 diabetes?

Answer 1

Glucosuria/ Ketonuria
- urine sample

Fasting plasma glucose concentration
> 7mmol/L

Oral glucose tolerance test
> 11 mmol/L

Glycated hemoglobin
> 6,5% (normal range 3,5-5,5%)

Question 2

What are some direct consequences of acute high blood glucose?

Answer 2

• Hyperglycemia
• Ketoacidosis
• Hyperosmolar coma - dehydration (diabetic coma)
• happens in untreated diabetes

Question 3

What is the problem in type 1 diabetes?

Answer 3

Cell-mediated destruction of B-cells producing insulin in pancrease

=> No production of insulin

Question 4

What is a long term consequence of glucose not being able to enter the cell?

Answer 4

Inapropriatly high rate of amino acid oxidation

Acetyl - CoA accumulation=> ketones in breath, blood, urine

Question 5

What is SGLT2?

Answer 5

transporter in cell membrane from lumen of renal tubule

Question 6

What is farxiga? how does it act, what consequences?

Answer 6

Inhibits SGLT2 => so inhibits reabsorption of glucose in the renal tubule. This leads to even more glucose spilled in urine. Could lead to severe dehydration, because glucose excretion pulls a lot of water. Also, could potentially loose weight because glucose (calories) excreted…

Question 7

What are chronic consequences of diabetes?

Answer 7

Microvascular problems => disease of small blood vessels

RETINOPATHY - Retina damaged => blindness (retina has fine blood vessels that could be damaged by high blood glucose)

NEPHROPATHY - Kidney damage due to long term exposure to high blood glucose => can become leaky. Watch for blood pressure…

NEUROPATHY - nerve damage- peripheral nerves damaged by high blood glucose

Macrovascular:

ATHEROSCLEROSIS
- more dominant in T2DM.. but still

Question 8

What is management solution for type 1 diabetes?

Answer 8

• Insulin injection ( intra muscular = the most popular, pump, nasal, islet transplant)
• Activity
• Balanced intake

Question 9

Insulin producing cells = ?

Glucagon producing cells =

Answer 9

Beta cells = insulin

Alpha cells = glucagon

Question 10

What are the steps in insulin synthesis?

Answer 10

1. translation and translocation => preinsulin
2. Folding, oxidation and SIGNAL PEPTIDE CLEAVAGE=> proinsulin
3. ER export, Golgi transport, vesicle packaging
4. Protease cleavage liberates C -peptide
5. Carboxypeptidase E produces insulin => insulin

*** take home message => progressively more cleavage, what looked like 2-3 polypeptide chain is actually one

Question 11

Explain how insulin is excreted.

Answer 11

• High influx of glucose inside Beta-cell using GLUT2
• Increase ATP production will close K+ channels, cause depolarization
• Depolarization will cause opening of Ca 2+ channels
• Calcium will change gene expression through CREBP (calcium responsive element binding protein)
• Increase gene expression to increase insulin production, and also increase insulin mobilization from stores because we don’t want to wait.

Question 12

What are the 4 anabolic effect of insulin?

Answer 12

• Glycogen synthesis
• Fat synthesis
• Protein synthesis
• Growth and gene expression

Question 13

Prevalence of T2DM has _____ since 2000

Answer 13

tripled

Question 14

What are some causes why number of people having T2DM is increasing? (prevalence…)

Answer 14

• Population aging
• Obesity rates are rising
• Canadian lifestyles are increasingly sedentary
• (indigenous people are 3-5 times more likely to develop T2DM than the general population…)

Question 15

2 risks factors for T2DM?

Answer 15

• Heredity

- Obesity

Question 16

What are some symptoms of T2DM?

Answer 16

• Glucosuria
• Blood glucose > 10mmol/L (hyperglycemia)
• Frequent urination, excessive thirst
• Ketonuria
• DEhydration => HHNKS
• Weight loss
• Increased appetite

Question 17

What does HHNKS stand for?

Answer 17

Hyperglycemic Hyperosmolar Nonketotic Syndrom

- Dehydration of cell due to high blood glucose…

Question 18

What is the first symptom in T2DM?

Answer 18

increased INSULIN! not increased blood glucose! because insensitivity to insulin…

Question 19

How is there insulin insensitivity?

Answer 19

GLUT 4 cells are insulin resistant

• Non GLUT 4 cells exposed to high concentration of glucose
• High insulin followed by Beta cell exhaustion
• Then requirement for exogenous insulin

Question 20

What is the effect of insulin insensitivity on GLUT 4 peripheral tissues?

Answer 20

• FAt based economy
• Low glycogen
• Increased muscle proteolysis to provide gluconeogenic a.a.
• Cori cycle

Question 21

What is the effect of lack of insulin sensitivity on liver?

Answer 21

• Gluconeogenesis (even if glucose levels are high!)
• Lipogenesis (increased VLDL)
• NAFLD (non-alcoholic fatty liver disease)

Question 22

What substrate is primarily going to be metabolized in GLUT 4 tissues?

Answer 22

fat! Since no glucose in cells, using fat for energy

• but other cells are going to be metabolizing CHO…

Question 23

What is one widely used drug used to treat T2DM, and how does it act?

Answer 23

Metformin

• Decreases hepatic gluconeogenesis
• Increased peripheral insulin sensitivity
• Increases GLUT 4 medicated glucose uptake
• Increases fatty acid oxidation (hepatic oxidation)

Question 24

What is really key in recommendations fo managing T2DM?

Answer 24

• Weight management

- Activity

Question 25

What is a potential better approach then fasting in monitoring blood glucose?

Answer 25

Focus more on the “not more than 7mmol/L blood glucose” instead of not more than 5mmol/L fasting glucose..