1. Biology, Homeostasis, and Type 2 Diabetes
A one-week unit exploring how…
Type 2 diabetes is a growing concern and occurs frequently in our communities.
Type 2 diabetes is a complex condition that is heavily influenced by environmental factors such as access to resources, personal choice, product marketing, public policy, socio-economic status, and stress.
Most traits are determined by a combination of genetic and environmental factors, including complex diseases like type 2 diabetes.
Blood glucose levels are regulated to stay within a healthy range. Type 2 diabetes is the result of chronic high blood glucose levels over time as regulation of blood glucose levels fail.
Glucose, the major energy source for all human cells, is released primarily through digestion of carbohydrates. Food choices impact blood glucose levels.
Type 2 diabetes is a serious condition with negative health consequences if left untreated.
Type 2 diabetes can be prevented: factors contributing to a person’s risk include good nutrition and exercise.
Students can make a meaningful contribution to the prevention of type 2 diabetes.
These are the enduring understandings for the unit.

2. Lesson One Entrance Activity: What do you know about type 2 diabetes?
Biology, Homeostasis, and Type 2 Diabetes
Lesson One
Entrance Activity:
What do you know about type 2 diabetes?
Think about….
What is type 2 diabetes?
What causes it?
What happens to the body?
Who gets it?
Are there treatments available?
What social factors may contribute?

3. Color Percentage white No data cream <4.5 yellow 4.5-5.9 gold
Biology, Homeostasis, and Type 2 Diabetes
Diabetes: A Growing Concern
Color
Percentage
white
No data
cream
<4.5
yellow
gold
orange
red
> 9.0
The following slides show the percentage of adults who have been diagnosed with diabetes in the US between 1994 and This table shows the color key for percentages in the next sides.

4. 1994
Methodology
The percent of U.S. adults who have diagnosed diabetes was determined by using data from the Behavioral Risk Factor Surveillance System (BRFSS, available at An ongoing, yearly, state-based telephone survey of the non-institutionalized adult population in each state, the BRFSS provides state-specific information on behavioral risk factors for disease and on preventive health practices. Respondents who reported that a physician told them they had diabetes (other than during pregnancy) were considered to have diagnosed diabetes. Rates were age-adjusted using the 2000 U.S. Standard Population.

5. 1995

6. 1996

7. 1997

8. 1998

9. 1999

10. 2000

11. 2001

12. 2002

13. 2003

14. 2004

15. 2005

16. 2006

17. 2007

18. 2008

19. 2009

20. 2010

21. Major changes to the survey method in 2011
more detail at

22. 2011

23. 2012

24. 2013

25. 2014

26. 2015

27. Incidence and Prevention
Types of Diabetes
Incidence and Prevention
Type
Prevalence
Possible Prevention
Type 1 Diabetes 5%
none
Type 2 Diabetes
90-95%
for many, lifestyle changes
Gestational Diabetes
<1-2%
for some, lifestyle changes
other
1-5%
Data from the CDC

28. Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among US Adults
Obesity (BMI ≥30 kg/m2)
1994
2000
2015
No Data <14.0% %–17.9% %–21.9% %–25.9% > 26.0%
Diabetes
1994
2000
2015
No Data <4.5% %–5.9% %–7.4% %–8.9% >9.0%
CDC’s Division of Diabetes Translation. United States Surveillance System available at

29.
Part C
Part A
Part B

30. Lesson One What are the characteristics of type 2 diabetes?
Biology, Homeostasis, and Type 2 Diabetes
Lesson One
What are the characteristics of type 2 diabetes?
result of chronic (long-term) high blood glucose levels
can develop over time
body is unable to maintain healthy ranges of glucose
high glucose levels can damage nerves, heart, blood vessels, hands, feet, kidneys
complications can even lead to death
These are the enduring understandings for the unit.

31. Asking Questions Lesson One Type 2 Diabetes: What is glucose?
How does my diet matter?
Biological Concepts
Individual Choices
Does
exercise
matter?
How does the body balance glucose?
Type 2 Diabetes:
A Complex Disease
How do we market foods and drinks?
Social
Factors
How can we stop
the growth?
Treatments and Solutions
How are
resources distributed?
Nature vs. Nurture
What should
our priorities be?
Is it determined by genes,
the environment, or both?

32. Lesson Two Entrance Activity:
Biology, Homeostasis, and Type 2 Diabetes
Lesson Two
Entrance Activity:
What is glucose? Where does glucose come from in our diets?
Think about….
What foods/drinks contain glucose?
Where do other sugars come from?
What is glucose used for in the body?
Glucose can be described as both a fuel and a toxin. How can something so good also be so bad?

33. Lesson Two Where is glucose in food? Part I
Teacher note: Slides 1 -9 are introductory slides to be shown before the activity begins.

34. Lesson Two Glucose Monosaccharide Disaccharides Polysaccharides
Starch such as potatoes, wheat, corn, rice, cassava, sorghum
Fiber, such as indigestible cellulose
Table sugar, milk sugar
Including glucose, which is the primary energy molecule for the body.
Teacher note: Slides 1 -9 are introductory slides to be shown before the activity begins.

35. = C6H12O6 What does glucose have to do with type 2 diabetes?
Type 2 diabetes develops when blood glucose levels are too high for too long. The body is not maintaining blood glucose within a healthy range.
For the model we will be using next, glucose is represented by a pasta wheel. 1 2 3 6 5 4 = 1 2 3 4 6 5
Teacher note: Slides 1 -9 are introductory slides to be shown before the activity begins.
Paper model of Glucose
Pasta model of Glucose
C6H12O6

36. Balanced Blood Glucose
Homeostasis:
Maintaining balance by regulating internal conditions
HIGH Blood Glucose
Balanced Blood Glucose
LOW Blood Glucose
A balancing act happens many times a day—every time you have a meal or consume a drink with sugar. The ability of the body to maintain balance and regulate internal conditions is called homeostasis.

37. Homeostasis allows organisms to maintain balance (stability) even as the external environment changes.
You may have high blood glucose levels after eating a large meal, or low blood glucose levels between meals. Your body responds to how often you eat and what you eat in order to keep blood glucose levels within a healthy range.
Feedback mechanisms maintain homeostasis
Balance is maintained when different components of a system regulate each other.
Teacher note: Slides 1 -9 are introductory slides to be shown before the activity begins. A B

38. Insulin Glucagon How does the body balance blood glucose levels?
A feedback mechanism relying on two hormones:
Insulin
Allows glucose to leave the blood and enter some cells. Insulin is like a key that unlocks the cell membrane so that glucose can enter the cell. Without insulin, most glucose stays in the blood.
Glucagon
Allows glucose to leave some cells and enter the blood

39. 3 pasta wheels represent a balanced amount of blood glucose
Balanced Blood Glucose

40. Insulin Released
HIGH Blood Glucose
Feedback Mechanism

41. Feedback Mechanism HIGH Blood Glucose Insulin Released
Insulin causes glucose to leave the blood and enter cells
HIGH Blood Glucose
Feedback Mechanism

42. Feedback Mechanism LOW Blood Glucose Balance tips….
Glucose leaves cells to enter the blood
Glucagon Released
Feedback Mechanism

43. Balanced Blood Glucose
Feedback Mechanism
Balanced Blood Glucose
Insulin and glucagon work together to regulate blood sugar.
This feedback mechanism helps to maintain homeostasis in the system.

44. Feedback mechanisms are common in biology and nature.
Here’s an example with body temperature regulation
Normal Body Temperature

45. Body sweats, blood vessels dilate
HIGH Body Temp
Feedback Mechanism

46. Feedback Mechanism HIGH Body Temp Body sweats, blood vessels dilate
Temperature goes down
HIGH Body Temp
Feedback Mechanism

47. Feedback Mechanism LOW Body Temp Balance tips…. Temperature goes up
Shivering
Blood vessels constrict
Feedback Mechanism

48. Feedback mechanisms maintain homeostasis
Normal Body Temperature

49. Model Board

50. = Model Board Pieces Who’s who of diabetes:
Glucose! Carbohydrates are broken down during digestion to this simple sugar. Glucose is carried to every cell in our body by the blood stream, where it is used as the source of energy for our bodies. =
In our model, the 6-sided glucose sugar is represented by a round pasta piece.
Glycogen! The stored form of glucose is called glycogen. Glycogen is made up of many connected units of glucose.
In some tissues, insulin is required for glucose to enter the cell.

51. Model Board Pieces Who’s who of diabetes:
Insulin! This hormone is released into the blood when blood glucose levels are high. It enables glucose to be transported into the cell in some tissues.
In our model, insulin is represented by a piece of I-shaped pasta
Glucagon! This hormone is released into the blood when blood glucose levels are low. It enables glucose to be released from some tissues back into the blood stream.
Teacher note: Slides 1 -9 are introductory slides to be shown before the activity begins.
In our model, glucagon is represented by a piece of curvy-shaped pasta

52. Model Board Organs The body organs:
Pancreas: One of the major players in glucose homeostasis, the pancreas releases the hormones, insulin and glucagon, that control blood glucose. The cells in the pancreas that produce insulin are called β (beta) cells.
Liver: This organ takes up glucose when levels are high and releases glucose when levels are low. It stores glucose in chains as glycogen. It is key for glucose regulation.

53. Model Board Organs More body organs:
Muscles: Our muscles are able to take up and store lots of glucose when insulin is present. More muscles mass means more of a reservoir for glucose.
Fat cells: Fat cells take up glucose when insulin is present. Fat cells use glucose to make more fat.
Brain: The brain takes up glucose whenever it needs energy, and doesn’t require insulin. Glucose is the fuel the brain normally uses.
I changed the last line.

54. Balanced Blood Glucose
Homeostasis:
Maintaining balance by regulating internal conditions
HIGH Blood Glucose
Balanced Blood Glucose
LOW Blood Glucose
All of these systems work together to keep our blood glucose level balanced.

55. Maintaining Blood Glucose
Blood vessels carry insulin and glucose to cells
High Blood Glucose
Pancreas releases insulin
High blood glucose triggers the pancreas to release insulin.

56. Maintaining Blood Glucose
In the presence of insulin, glucose enters the cells and leaves the blood.
Blood glucose levels fall.
High Blood Glucose
Pancreas releases insulin

57. Maintaining Blood Glucose
Pancreas releases glucagon
Balance tips….
Low Blood Glucose
Low blood glucose triggers the pancreas to release glucagon

58. Maintaining Blood Glucose
Blood vessels carry glucagon to the cells which trigger the release of stored glucose back into the blood. Blood glucose levels rise.
Pancreas releases glucagon
Low Blood Glucose
Low blood glucose triggers the pancreas to release glucagon

59. Balanced Blood Glucose
Balance tips….

60. Glucose responses for two different foods.
What kind of food might be represented by Line A?
A sugary food or drink the releases glucose into the blood quickly, such as soda, candy, or cookies. White bread, white rice and other starches without much fiber can also release glucose quickly.
What kind of food might be represented by Line B?
A food with a higher fiber content, such as whole grains, whole fruit, and legumes.
How would insulin release be different for Lines A and B? Line A foods would trigger more insulin.

61. A B Which graph best represents healthy blood glucose levels?
Graph A represents a feedback mechanism that maintains homeostasis. This keeps blood glucose levels within a range. It is okay for blood glucose levels to go up (within a range) as long as they come back down. A B

62. A graph for a person that is becoming diabetic may look like this, as blood glucose levels begin to rise:
A graph of blood glucose levels that are well- controlled would look something like this:
Note: Glucose levels are not constant, but they vary within a range.

63. Lesson Three Entrance Activity:
Biology, Homeostasis, and Type 2 Diabetes
Lesson Three
Entrance Activity:
We know that a healthy body keeps blood glucose levels regulated within a range, as homeostasis “tips the balance” many times a day.
What factors can contribute to a loss of control of blood glucose?
Think about….
What is the role of the pancreas?
What is the role of diet?
What is the role of exercise?

64. Glucose out of balance
How is diabetes diagnosed? By measuring blood glucose levels.
Fasting glucose test: After fasting for at least 12 hours, a person’s blood is drawn and tested for glucose. A healthy person would have a fasting blood glucose level of about mg/dL.
Oral Glucose Tolerance Test: After measuring fasting glucose, a person is given a glucose-rich drink. Blood is then drawn at time intervals to see how that person’s body is processing the glucose.
A third test, the A1C test, measures how much of a person’s hemoglobin is coated with sugar. Since red blood cells (which carry hemoglobin) turn over every few months, the A1C test gives an average blood sugar level over the past 2-3 months.

65. Oral Glucose Tolerance Test
Blood Glucose levels (mg/dl)
Glucose given
Blood Insulin levels (µU/ml)
300
140
120
250
Diabetes (n=100)
100
200
Prediabetes (n=191) 80
150
Healthy (n=240) 60
100 40
Point out for students that the fasting blood glucose levels are different for each of the three conditions, even before glucose is given.
The data are from people who are first degree relatives (parent, siblings, and/or children). 50 20 20 40 60 80
100
120 20 40 60 80
100
120
Fasting
Time (min)
Time (min)
Jensen CC et al: Diabetes 51: ; 2002

66. TYPE 2 DIABETES High Blood Glucose Levels = PREDIABETES
Contributions to type 2 diabetes
Insulin Resistance
in cells and organs
Beta Cell Damage
less insulin produced in the pancreas
High Blood Glucose Levels =
PREDIABETES
Point out for students that the first arrows are bi-directional—a person can work to control elevated blood sugar and prediabetes. At a certain point however, treatments are the only options.
TYPE 2 DIABETES

67. Lesson Three Extension: Three mechanisms
Three ways type 2 diabetes damages cells and organs:
Polyol Pathway
Advanced Glycation End Products (AGEs)
Atherosclerosis
LESSON THREE EXTENSION

68. 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).
LESSON THREE EXTENSION
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

69. Polyol Pathway TREATMENT
Cells in the kidney, eye, and nerves take up glucose in the absence of insulin
Water flows into the cell and can cause the cell to burst (think of a water balloon).
Inside the cell, glucose is converted to a substance (sorbitol) which builds up because it cannot get out.
Can the enzyme that converts glucose into sorbitol be inhibited?
LESSON THREE EXTENSION
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

70. AGEs AGEs 2. Advanced Glycation End Products (AGEs) protein
AGEs cross-link proteins and contribute to tissue stiffness in heart, bone and muscle.
protein
Glucose attaches to proteins
protein
glucose
AGEs
LESSON THREE EXTENSION
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.

71. AGEs AGEs TREATMENT 2. Advanced Glycation End Products (AGEs) protein
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
LESSON THREE EXTENSION
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.

72. 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.

73. 3. Atherosclerosis TREATMENT
Large blood vessels also become leaky due to AGEs
Layers of fat and cholesterol start to accumulate along the vessel walls.
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.
Balloon angioplasty can help to open narrow vessels
LESSON THREE EXTENSION
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

74. Chronic Elevated Blood Glucose
Pathways to organ damage
Chronic Elevated Blood Glucose
LESSON THREE EXTENSION
Nerve damage
Capillary damage
Large blood vessel damage
EYES LIMBS KIDNEYS HEART BRAIN

75. 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
LESSON THREE EXTENSION
Nerve damage
Capillary damage
Large blood vessel damage
EYES LIMBS KIDNEYS HEART BRAIN

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

77. Lesson Four A Taste of Home Entrance Activity: By Monica
Biology, Homeostasis, and Type 2 Diabetes
Lesson Four
Entrance Activity:
A Taste of Home
By Monica
What are some environmental risk factors for type 2 diabetes in Monica’s family?
To think about….
How does culture impact risk?
How does product marketing impact risk?
How have these changed over time?

78. Student Sheet 4.1: Genetic risk factors
The beans in the bag represent the gene pool
of the population.
For each gene you will draw from 2 possible alleles
You could draw…
Color Combinations
2 white beans
1 of each color
(2 combinations)
1W 1R or 1R 1W
2 red beans
Probability
25% or ¼
50% or ½
Term
Homozygous
Heterozygous or

79. - 1 or Student Sheet 4.1: Genetic risk factors
Egg carton represents 12 genes that contribute to type 2 diabetes
Each gene contains 2 alleles
Possible Allele Combinations:
Two white beans increase RISK
One of each color is neutral or
- 1
Two red beans are PROTECTIVE
(decrease risk)

80. What is the probability of inheriting ONLY risk alleles (white beans) for these 12 genes?
For each cup, the chance of drawing two white beans is ¼, or 25%.
To get two white beans in two cups, the probability is ¼ x ¼ = 1/16
For all 12 cups…
¼ x ¼ x ¼ x ¼ x ¼ x ¼ x ¼ x ¼ x ¼ x ¼ x ¼ x ¼ =
1 in 16,777,216 or ~ % chance
3 possible allele combinations per egg cup (RR, RW, WW).
3 x 12 cups per dozen = 36 possible combinations per container
36 x 216 = 648 combinations

81. Over 150 genes have been associated with type 2 diabetes.
That is a lot of different allele combinations!
These combinations lead to tremendous variation of traits in a population.
Limitations in the model: 1) Each allele associated with type 2 diabetes is present in the population at the same frequency (50:50), and alleles vary in frequency in a population. 2) Alleles are sometimes linked and don’t always sort independently of each other. 3) Environmental impacts on genes are not addressed.

82. Environmental and Genetic Risk Factors
Student Sheet 4.2: Environmental Risk Factors

83. For complex diseases, variations in many genes may add to risk of getting that disease.
People without t2d
People with t2d
Low-risk allele
High-risk allele
Fraction of people
More risk alleles for type 2 diabetes
Genetic factors:
Small variations in many genes
Many different gene variants may contribute to a complex condition like type 2 diabetes. Environmental risk factors may “push” the curve over meaning more people in a population will have the condition.
Fletcher & Houlston (2010) Nat Rev Cancer

84. GENETICS ENVIRONMENT GENETICS ENVIRONMENT GENETICS ENVIRONMENT
(Little) Likelihood of getting Type 2 Diabetes (Lots)
GENETICS
ENVIRONMENT
Person A
GENETICS
ENVIRONMENT
Person B
GENETICS
Person C
Many different gene variants may contribute to a complex condition like type 2 diabetes. Environmental risk factors may “push” the curve over meaning more people in a population will have the condition.
ENVIRONMENT

85. Diabetes Prevention Program Data
Allele combinations:
Diabetes incidence rate
EXTENSION SLIDE: Scientists are studying the gene alleles that increase the likelihood that a person will develop type 2 diabetes (risk alleles). The alleles at the location in question come in three combinations: CC, CT, and TT.
Note: People all have the same genes, but the genes of any two people are slightly different. This is why no two people are exactly the same. The different forms of a gene are called alleles.
Incidence proportion is the number of new cases within a specified time period divided by the size of the population initially at risk.
For example, if a population initially contains 100 non-diseased persons and 8 develop a condition (diabetes) over one year of observation, the incidence proportion is 8 cases per 100 persons over 1 year
Instead of following 1 person for 100 years, researchers follow 100 people for one year. If 8 people go from pre-diabetes to diabetes, then the incidence rate is 8 cases/100 person-years.  (Or they follow them for 5 years, but convert to the same units)
Jablonski K A et al. 2010; Diabetes 59:
Copyright © 2011 American Diabetes Association, Inc.

86. Biology, Homeostasis, and Type 2 Diabetes
Lesson Five
Entrance Activity
If current trends continue, 1 in 3 U.S. adults will have diabetes by 2050.
How would you distribute money and resources towards prevention and/or treatment of diabetes?
To think about….
How old will you be in 2050?
Will you be at risk for type 2 diabetes?
How and when should your future self take steps to prevent you from developing type 2 diabetes?
Source: Center for Disease Control and Prevention

87. Infographic from the American Diabetes Association, diabetes.org

88. Four Options Food Labelling and Marketing Lifestyle Changes
Is this a treatment, a prevention, or both?
Food Labelling and Marketing
Lifestyle Changes
Medications
Surgery
Is this driven by individuals or society?
Who benefits? What is the cost? Who is harmed?
Prevention or Treatment? Is the goal of this option prevention (keeping people from becoming diabetic) or treatment (providing interventions for people already living with type 2 diabetes)? Or both?
Individual or Social? Is the option driven by the choices and decision-making of individuals, or at a societal level in which people need to work together to create change? Are there ways social interactions and group behaviors contribute to health in this option?
Who benefits? What is the cost? Who is harmed? What kinds of harms and benefits might come from different options? Costs associated are not only monetary, but could be harm to some groups or people.

89. Back to the Beginning
I think that solutions to the growth of type 2 diabetes lie mostly with:
Individuals
Society
Environment
Genes
I think developing type 2 diabetes is mostly due to: