1. Anatomy and physiology of t2d
Lesson Five
Today we will…
Make a human body poster that shows how t2d affects organs and body systems
Look at treatment options for different symptoms of t2d
Evaluate costs of prevention and treatment options for t2d

2. “If current trends continue, 1 in 3
Lesson 5
“If current trends continue, 1 in 3
U.S. adults will have diabetes by 2050.”
Center for Disease Control and Prevention

3. Many body organs are affected by type 2 diabetes.
Today’s lesson focuses on:
Heart
Kidneys
Brain
Eyes
Feet (limbs)
Image: Wikimedia Commons

4. Three mechanisms
Three ways type 2 diabetes damages cells and organs:
Polyol Pathway
Advanced Glycation End Products (AGEs)
Atherosclerosis

5. Polyol Pathway
Cells in the kidney, eye, and nerves take up glucose in the absence of insulin
Inside the cell, glucose is converted to a substance (sorbitol) which builds up because it cannot get out.
Water flows into the cell and can cause the cell to burst (think of a water balloon).
Research has focused on inhibiting the enzyme, aldose reductase, which converts glucose to sorbitol. Currently, there are no AR inhibitors approved for clinical use in the United States (Schemmel et al., 2010).
Best treatment to date is to lower blood sugar through diet (weight loss), exercise, and drugs (metformin and insulin).
Connection to Worm unit: In the dialysis activity in the worm unit, water moved out of the dialysis tubing containing low glycerol into the salt. In the polyol pathway, the sorbitol cannot move out of the cell, so in order to achieve balance on both sides of the cell membrane, water moves into the cell.
This is a key mechanism for nerve and retina damage

6. AGEs AGEs 2. Advanced Glycation End Products (AGEs)
AGEs cross-link proteins and contribute to tissue stiffness in heart, bone and muscle.
protein
Glucose attaches to proteins
protein
glucose
AGEs
Drugs that inhibit AGE formation have been tested in clinical trials, but none have yet to be shown to reduce kidney disease.
AGE damage can also make small blood vessels leaky
This is a key mechanism for eye and kidney damage.

7. 3. Atherosclerosis Large blood vessels also become leaky due to AGEs
Layers of fat and cholesterol start to accumulate along the vessel walls.
Prevention of peripheral arterial disease and cardiovascular disease includes: quit smoking, reduce blood glucose, lower blood pressure to less than 140/80 mmHg, lower LDL cholesterol below 100 mg/dl, possibly take aspirin or other antiplatelet meds, exercise, changing diet
Treatment: Balloon angioplasty; artery bypass
This makes the blood vessel stiff and narrows the channel.
Atherosclerosis leads to high blood pressure, causing the heart to work harder.
This is a key mechanism for heart failure and stroke. It also contributes to kidney failure.

8. Polyol Pathway TREATMENT
Cells in the kidney, eye, and nerves take up glucose in the absence of insulin
Inside the cell, glucose is converted to a substance (sorbitol) which builds up because it cannot get out.
Water flows into the cell and can cause the cell to burst (think of a water balloon).
Can the enzyme that converts glucose into sorbitol be inhibited?
Research has focused on inhibiting the enzyme, aldose reductase, which converts glucose to sorbitol. Currently, there are no AR inhibitors approved for clinical use in the United States (Schemmel et al., 2010).
Best treatment to date is to lower blood sugar through diet (weight loss), exercise, and drugs (metformin and insulin).
Connection to Worm unit: In the dialysis activity in the worm unit, water moved out of the dialysis tubing containing low glycerol into the salt. In the polyol pathway, the sorbitol cannot move out of the cell, so in order to achieve balance on both sides of the cell membrane, water moves into the cell.
Still working on it…
This is a key mechanism for nerve and retina damage

9. AGEs AGEs TREATMENT 2. Advanced Glycation End Products (AGEs)
AGEs cross-link proteins and contribute to tissue stiffness in heart, bone and muscle.
protein
Glucose attaches to proteins
protein
glucose
AGEs
AGE damage can also make small blood vessels leaky
Drugs that inhibit AGE formation have been tested in clinical trials, but none have yet to be shown to reduce kidney disease.
Currently, there are no AR inhibitors approved for clinical use in the United States (Schemmel et al., 2010).
Best treatment to date is to lower blood sugar through diet (weight loss), exercise, and drugs (metformin and insulin).
Drugs that inhibit the formation of AGEs have been tested, but…none have been shown to reduce kidney damage. Yet.
This is a key mechanism for eye and kidney damage.

10. 3. Atherosclerosis TREATMENT
Large blood vessels also become leaky due to AGEs
Layers of fat and cholesterol start to accumulate along the vessel walls.
Balloon angioplasty can help to open narrow vessels
Prevention of peripheral arterial disease and cardiovascular disease includes: quit smoking, reduce blood glucose, lower blood pressure to less than 140/80 mmHg, lower LDL cholesterol below 100 mg/dl, possibly take aspirin or other antiplatelet meds, exercise, changing diet
Treatment: Balloon angioplasty; artery bypass
This makes the blood vessel stiff and narrows the channel.
Atherosclerosis leads to high blood pressure, causing the heart to work harder.
This is a key mechanism for heart failure and stroke. It also contributes to kidney failure.

11. Chronic Elevated Blood Glucose
Pathways to organ damage
Chronic Elevated Blood Glucose
Nerve damage
Capillary damage
Large blood vessel damage
EYES LIMBS KIDNEYS HEART BRAIN

12. Where should money for treatment and/or prevention be spent?
Pathways to organ damage
Where should money for treatment and/or prevention be spent?
Chronic Elevated Blood Glucose
Nerve damage
Capillary damage
Large blood vessel damage
EYES LIMBS KIDNEYS HEART BRAIN

13. TYPE 2 DIABETES Elevated Blood Glucose = PREDIABETES
Prevention and Treatment $$
Normal Blood Glucose Levels
Elevated Blood Glucose =
PREDIABETES
More Reversible
Point out for students that the first arrows are bi-directional—a person can work to control elevated blood sugar and prediabetes
Fix pancreas animation
TYPE 2 DIABETES
with severe complications such as organ damage
$$$$$
Less Reversible