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Type 2 Diabetes TBL for Medical Students Instructor Guide 1

Authors: Satoru K Nishimoto PhD, William F Brescia PhD, Russell W Chesney MD, Vicki M Park PhD, Melburn R Park PhD, Sunil K Sinha MD, Robert J Ferry Jr., MD

From: University of Tennessee Health Science Center, Departments of Microbiology Immunology Biochemistry, Department of Medical Education, Department of Pediatrics, Department of Anatomy and Neurobiology

Type 2 Diabetes TBL for M1 Students


Title: Type 2 Diabetes TBL for medical students

Purpose of Module:This session examines the impact of type 2 diabetes (T2D) on energy metabolism as covered in first year basic sciences for medical students. Knowledge of molecular mechanisms in energy metabolism and signal transduction are required. Knowledge of anatomy is integrated to apply anatomical knowledge to T2D. The team-based learning format includes a readiness assurance test (that is taken individually and by teams) and a worksheet that applies basic science knowledge into medical decision making. This TBL is intended to take place subsequent to carbohydrate metabolism and abdominal anatomy to reinforce knowledge of these subjects. In addition, there are reading assignments as specified for corresponding genetics and nutrition.

Type 2 Diabetes is an important and relevant metabolic disorder that is central to this TBL. The exercise focuses on normal processes related to diabetes. The TBL has been used in each of the last 3 years of the curriculum for first semester medical students. Each of our TBL sessions consists of 84 students in permanent 6-person teams plus several faculty facilitators. The session is repeated for the other half of the class.

Objectives:

1. Analyze metabolic consequences of carbohydrate metabolism related to the feed/fast cycle.

2. Given that both genes and environment contribute to complex disease risk, apply knowledge of risk genes to a case scenario involving T2D.

3. Apply knowledge of abdominal anatomy to circulatory function. 4. Be able to advise patients while maintaining a professional relationship.5. Develop a nutritional plan as it relates to treatment of individuals with T2D.


General Information:

Methods:As an interdisciplinary Team-Based Learning (TBL), the TBL is facilitated by a Medical Education Professional for the RAT events and teams of Basic Scientists and Clinicians for the application. Prior to TBL, the facilitator team met to plan alterations from the previous year, the logistics and timing. The exercise includes previously used RAT and Application questions which may need to be modified, and are informative for TBL faculty. The RAT assessments are completed within 30 minutes, with the rest of the time devoted to the clinical case and the application questions. A PowerPointTM/TurningPoint TM presentation and a Turning Technologies Response System captures individual iRAT responses, and printed sheets and scratch-off Immediate Feedback Assessment Technique (IF-AT) TM cards capture team tRAT responses. These are graded for the course. Teams have cards, and stands are present on team tables for application response simultaneous reveals. The application exercise is not graded or recorded.

The large class of approximately 170 students is split into 6-person teams with half of the teams participating in one of two 2-hour sessions. Teams are formed in the first “orientation” week of the M1 year. Students remain in the same teams throughout the M1 year. Team formation is transparent, with advanced degrees, medical experience, undergraduate college, geography as methods to line students up then divide them, distributing advanced degrees, experience, and school/geographic origin so that students are roughly equally represented. A final visual sorting to distribute students into teams by sex is performed in a practice TBL to prepare for TBL activities.

Advanced preparation: Suggested Materials:1. Students should have recently learned the concepts covered in the carbohydrate metabolism section of medical education. The relevant concepts would be: the feed fast cycle, blood glucose, carbohydrate digestion, glycogen metabolism, glycolysis, gluconeogenesis. Presentation of these concepts should precede scheduling of this TBL. An appropriate resource for knowledge acquired prior to the TBL is Marks’ Basic Medical Biochemistry A Clinical Approach Third Edition, by Michael Lieberman and Allan D. Marks, Chapters 1-3, 26-28, and 31. Any similar resource will be sufficient. In addition, students should have recently studied the gross anatomy of the abdominal organs. Specifically, they should be familiar with the positional relationships of liver, pancreas, spleen, and gastrointestinal tract to each other. They should be familiar with the arterial supply to these structures and with venous drainage of the pancreas, spleen and gastrointestinal tract to the liver via the hepatic portal system. Gray’s Anatomy for Students, 3rd edition, Chapter 4, pp. 310-365 is a suitable resource.

2. Students should be provided with short readings on nutrition and on the genetics of T2D. The summary of the Evert, 2013 paper is included with this resource. Everything else is freely available online.

a. Nutrition summary “Nutrition therapy for management of adults with diabetes.docx” (summarized from the American Diabetes Association 2013 Position Statement, Evert et. al. Diabetes Care 2013;36:3821-3842 free access at care.diabetesjournals.org ).

b.Genetics of Type II Diabetes by the American Medical Association [one page summary available online at ama-assn.org; go to Resources page; Genetics and Molecular Medicine; Genetics of Common Disorders].


Readiness Assurance Questions [with answers and rationales in the following section]

Diabetes Readiness Assurance Test for Administration to Individuals (iRAT) and Teams (TRAT)

1. Human metabolism assessed 8 hours after a regular mixed meal is most likely to reflect:

A. High glycogenesis, high glycogenolysis B. High gluconeogenesis, high glycogenesisC. Low gluconeogenesis, high glycogenesisD. Low glycogenesis, high glycogenolysis

2. Your patient is an overweight woman with two first-degree relatives (her mother and her sister) with type 2 diabetes. Both affected family members also are overweight. How would you approach your patient about this issue?

A. Do not bring up the obesity, since such discussion will lower her self-esteem. B. Refer her to a dietitian.C. Suggest that the patient may have a “gland” problem.D. Have a frank discussion of diet and exercise.

3. Complex diseases incorporate both genetic and environmental risk factors. Of the following options, which one is true with regard to our current understanding of risks underlying T2D?

A. The increased prevalence of T2D suggests that many new mutations have arisen in diabetes risk genes over the past 50-100 years.B. Genetic association studies (GWAS) have identified a number of diabetes risk genes, but each gene accounts for only a small proportion of the risk to develop T2D.C. A goal of genomic research is to define a single mechanism to explain the pathophysiology of T2D.C. In recent years, proliferation of both physical fitness programs and weight reduction diets has failed to reverse the increasing incidence of T2D. This suggests that the role of environmental risk factors was overestimated previously.

4. Phosphofructokinase (PFK-1) and fructose -1,6-bisphosphatase are important regulatory enzymes in the glycolytic and gluconeogenic pathways. Which one of the compounds listed below controls the activity of both of these enzymes by acting as either an allosteric activator or inhibitor?

A. Acetyl-CoA B. CitrateC. Fructose-1,6-bisphosphateD. Fructose-2,6-bisphosphate

5. In diabetes (type 1 or type 2), what happens to hemoglobin in the red blood cells (erythrocytes)?

A. Non-enzymatic glycation of hemoglobinB. Increased destruction of hemoglobinC. Non-enzymatic methylation of hemoglobinD. Overactive hexose monophosphate shunt reduces hemoglobin

6. How does fast breathing (tachypnea termed Kussmaul respirations) help a dehydrated diabetic patient?


A. Loss of ketones in breath B. Increased removal of CO2

C. Decreased HCO3– production

D. Distracts the diabetic’s intense thirst

7. According to the ADA 2013 Position Statement, which of the following is a critical element of nutritional counseling for adults with diabetes? A. A successful counseling plan should be written for individuals with low health literacy in order to be easily accessible by all patients.B. Nutritional counseling should be individualized based on each patient’s needs and goals.C. Specific diet is less important than monitoring of total nutrients and/or nutritional supplements.D. Diet is less important than monitoring of glycemic load.


Answers to RAT Questions1.D. Low glycogenesis, high glycogenolysis8 hours after a meal, liver glycogen is being broken down to G-1-P to G-6-P to G for release into the blood to maintain blood glucose for tissues to use. Blood glucose is regulated primarily by low insulin/glucagon ratio in the early fasting state. This is the state in which we ask patients to come in and give blood for routine tests. Glycogenesis is shut down as glycogenolysis is up, to prevent a futile or substrate cycle, so A is incorrect. Shut down of glycogenesis makes B incorrect. Gluconeogenesis is ramping up in the liver to produce glucose for blood, and glycogenesis is low, so C is incorrect. E is incorrect because high gluconeogenesis is not coupled to high glycogenesis.

2.D. Have a frank discussion of diet and exercise The issue is that physicians need to diagnose obesity and confront its existence in the patient. Diet and exercise have been shown to improve glucose intolerance. Mincing around the issue will not help the patient who has a chronic condition and has a condition with serious renal, cardiovascular and retinal consequences. Doctors should counsel patients on lifestyle and risk factors so A is incorrect. A discussion with the patient about reasons to see a dietician should precede B. Suggesting a defect in gland function would be inappropriate and unclear so C is incorrect.

3.B. Genetic association studies (GWAS) have identified a number of diabetes risk genes, but each gene accounts for only a small proportion of the risk to develop T2D.Although genomic research has been successful in identifying more than 35 genes associated with increased risk of T2D, the identified risk genes account for only a small proportion of attributable genetic risk. In the assigned AMA reading, 30-70% of T2D risk is attributed to combined effects of genes, and later the article alludes to the fact that known genes do not account for all of this heritable risk.) Option A is incorrect. It is unlikely that a single mechanism accounts for all cases of T2D.With regard to options C and D, it is fair to say that there has been little to no change in genetic makeup at the population level. Changes in lifestyle and related environmental influences presumably account for increased prevalence of T2D.

4. D. Fructose-2,6-bisphosphateF-2,6-BP can bind to the activation site of PFK-1 and therefore activate glycolytic pathway (even in presence of high ATP). However, when glucose is limiting the level of F-2, 6-BP is decreased, and therefore not activating PFK-1 and glycolysis. Low levels of F-2,6-BP promotes gluconeogenesis in liver. Acetyl-CoA, citrate, and F-1,6-BP do not affect both PFK-1 and F-1,6,-bisphosphatase, so A, B, and C are incorrect.

5. A. Non-enzymatic glycation of hemoglobin. This is the basis for the HemoglobinA1C test to look at long-term elevations in blood glucose. Proteins, including hemoglobin, have a higher level of glycation due to high blood sugar levels.A possible distractor is the increased destruction of hemoglobin (choice B). High glucose levels can deplete NADPH in red cells due to the increase in sorbitol production, which uses NADPH, and makes it less available for keeping reduced glutathione to scavenge free radicals. These can damage the cell membrane making red cells inflexible and more susceptible to lysis. Thus hemoglobin destruction would be secondary to red cell lysis (or glycation) so A is the best


answer. Another possible distractor is an increased hexose monophosphate shunt (choice D), which would provide NADPH for red cells. This does not result in significant hemoglobin reduction in cells. Choice C is incorrect. There is no non-enzymatic methylation of hemoglobin for diabetics.

6. B. Increased removal of CO2

The patient has low blood pH or acidosis as well as dehydration from high glucose. Exhaling CO2 actually serves to enhance acid removal since carbonic acid is produced when carbon dioxide and water react. Removal of acid by exhaling CO2 causes a rise in the pH and is useful in alleviating the acidosis. However, this is an adaptive response that cannot always overcome acidosis when ketogenesis is massive. A is not the best answer. Even though there is loss of ketones in breath, occurs as acetone (produced from non-enzymatic reactions from acetoacetate to acetone) is volatile and can be lost from breathing, but this is an insignificant compared to the amount of ketone bodies that lower pH. C is incorrect because decreased HCO3

- would lower pH, as it acts as a proton-accepting base for H+ in blood.

7. The best answer is B. The nutritional plan should be individualized for each patient’s needs. The ADA states there is “no one size fits all” approach. Nutrition therapy should be individualized based on health goals, personal and cultural preferences, health literacy and numeracy, access to healthful choices, and readiness, willingness, and ability to change.A is a potential common sense distractor based on good communication between counselor and patient. C is correct in that a specific diet to follow is not as important as the needs of the patient. For D, monitoring glycemic load can aid the nutritional plan, but may be more than some patient will need or wish to do.


Applications Exercises [with proposed best answers and rationale]

Type 2 Diabetes – Applications WorksheetTEAM NUMBER: __________

Case:……………………………………………………………………………………………

A 49 y/o African-American woman with a long history of obesity, type 2 diabetes (T2D), dyslipidemia, and mild asthma presents to the emergency department with a 5-day history of weakness, tactile fever, productive cough, abdominal pain, nausea, and vomiting. The patient’s report and chart review confirm that two years prior to this presentation, her T2D had been managed with diet alone. Over the past year, glipizide (Glucotrol), metformin (Glucophage), and detemir insulin (long-lasting insulin) were added because of poor glycemic control. Compliance with dietary recommendations and this medical regimen is uncertain.

Examination discloses oral temperature 37.5°C (99.5°F), blood pressure 101/74 mmHg by automated measurement at the right arm, pulse 134 bpm, respirations 34/min, and fruity breath. Skin of the central nape over her posterior neck is deeply pigmented and thickened to an extent about 3” wide. The patient appears drowsy but cogent. More detailed exam of her head and neck reveals periodontal disease and poor dentition. Her lungs sound clear to auscultation posteriorly, without wheezes or rhonchi. Her anterior heart sounds appear normal. Mild epigastric tenderness is elicited by deep palpation, but without rebound tenderness or guarding. Extremities were well perfused with symmetric radial pulses.

Remarkable laboratory results on room air from an arterial blood sample include pH 7.12, pCO2

of 17 Torr, and bicarbonate 5.6 mEq/L. Clean-catch urinalysis reveals 4+ glucosuria and 3+ ketonuria. Serum chemistries reveal glucose 420 mg/dL, BUN 16 mg/dL, creatinine 1.3 mg/dL, sodium 139 mEq/L, chloride 112 mEq/L, CO2 of 11.2 mmol/L, and potassium 6.2 mEq/L. Plain radiograph of her chest reveals no infiltrate.

……………………………………………………………………………………………………1. A molecule of insulin is secreted by a pancreatic beta-cell. What are reasonable vascular paths that it could take to reach the liver?

A. Splenic vein, superior mesenteric vein, common hepatic vein, proper hepatic veinB. Splenic vein, portal veinC. Superior (anterior) pancreatico-duodenal vein, common hepatic vein, portal veinD. Superior (anterior) pancreatico-duodenal vein, portal veinE. Inferior (posterior) pancreatico-duodenal vein, superior (posterior) pancreatico-duodenal vein, portal vein

2. The patient with diabetes has a blood pH of 7.12 (normal 7.4). Why is the pH low?

A. Decreased fatty acid release from adipose tissueB. Elevated blood ketone bodiesC. Excessive drinking of fluid (polydypsia)D. VomitingE. Elevated blood glucose

3. After learning that he may be at increased risk to develop diabetes, the patient's 24-year-old son decides to pursue direct-to-consumer testing in order to assess his heritable risk. He submits a saliva sample and receives a report indicating that his genetic risk is in the average


range according to the company's algorithm. The report includes the information that he has the low risk genotype for the TCF7L2 (Transcription Factor 7-Like 2) gene (two copies of the low risk allele). Of the following options, which one is the best next step?

A. The genetic test should be repeated. Since the son's mother has diabetes, he should have inherited at least one high risk allele at the TCF7L2 locus.B. The son should be informed that direct to consumer testing is not legitimate medicine, and he should disregard the report.C. The son should be counseled that his positive family history supersedes the test result.D. The son should be reassured by his test result. As long as he maintains a healthy body weight, he avoids the elevated risk conferred by positive family history.E. Additional genetic testing is indicated to ensure that all diabetes risk genes are tested.

4. During her doctor’s visit, the patient admits she did not take her medications regularly because of their costs and her health literacy (she would take the meds when she felt bad). One month later the patient returns, having been adherent with her medications. Which of the following choices represents the most likely result of the workup done (fasting overnight) on the return morning visit after adherence to medications?

Answer Blood glucose

Blood ketones

Hemoglobin A1C

Urine glucose

Urine ketones

A High High High High HighB Low High Normal High HighC Normal High Normal Normal HighD Normal Normal High Normal NormalE Normal Normal Normal Normal Normal


Metabolic States and Diabetes Risk in Popular Media

5. The TV adventurer named Survivorman (Les Stroud) has not eaten due to inability to find edibles or catch/kill game for 2 days. He is feeling weaker but still alive and active. A check on a glucometer reveals his blood glucose is normal, 80 mg/dl. Of the following, the best source for blood glucose in Mr. Stroud at this time is from:

A. Muscle glycogenB. Adipose TriglycerideC. Muscle proteinD. Liver glycogenE. Red cell AcetylSCoA

6. Actor Tom Hanks has been diagnosed with T2D. There may have been clinical clues to his disorder in his acting career, if you imagine him as his character. Which of his roles in these movies provides a likely precursor for the T2D diagnosis?

A. BigB. A League of Their OwnC. CastawayD. Forrest GumpE. Saving Private Ryan


Type 2 Diabetes – Applications Worksheet(ANSWER KEY)

Case:……………………………………………………………………………………………

A 49-year-old African-American woman with a long history of obesity, type 2 diabetes (T2D), dyslipidemia, and mild asthma presents to the MED’s emergency department with a 5-day history of weakness, tactile fever, productive cough, abdominal pain, nausea, and vomiting. The patient’s report and chart review confirm that two years prior to this presentation, her T2D had been managed with diet alone. Over the past year, glipizide (Glucotrol), metformin (Glucophage), and detemir insulin were added because of poor glycemic control. Compliance with dietary recommendations and this medical regimen is uncertain.

Examination discloses oral temperature 99.5°F, blood pressure 101/74 mmHg by automated measurement at the right arm, pulse 134 bpm, respirations 34/min, and fruity breath. Skin of the central nape over her posterior neck is deeply pigmented and thickened to an extent about 3” wide. The patient appears drowsy but cogent. More detailed exam of her head and neck reveals periodontal disease and poor dentition. Her lungs sound clear to auscultation posteriorly, without wheezes or rhonchi. Her anterior heart sounds appear normal. Mild epigastric tenderness is elicited by deep palpation, but without rebound tenderness or guarding. Extremities were well perfused with symmetric radial pulses.

Remarkable laboratory results on room air from an arterial blood sample include pH 7.12, pCO2

of 17 Torr, and bicarbonate 5.6 mEq/L. Clean-catch urinalysis reveals 4+ glucosuria and 3+ ketonuria. Serum chemistries reveal glucose 420 mg/dL, BUN 16 mg/dL, creatinine 1.3 mg/dL, sodium 139 mEq/L, chloride 112 mEq/L, CO2 of 11.2 mmol/L, and potassium 6.2 mEq/L. Plain radiograph of her chest reveals no infiltrate.

……………………………………………………………………………………………………1. A molecule of insulin is secreted by a pancreatic beta-cell. What are reasonable vascular paths that it could take to reach the liver?

A. Splenic vein, superior mesenteric vein, common hepatic vein, proper hepatic veinB. Splenic vein, portal veinC. Superior (anterior) pancreatico-duodenal vein, common hepatic vein, portal veinD. Superior (anterior) pancreatico-duodenal vein, portal veinE. Inferior (posterior) pancreatico-duodenal vein, superior (posterior) pancreatico-duodenal vein, portal vein

B is the best, most direct answer. Likely to be the major path taken by most insulin.D is correct, a more circuitous route. E could be correct. Least likely to be the path taken, most circuitous.A & C are incorrect. They are not paths to the liver.


2. The patient with diabetes has a blood pH of 7.12 (normal 7.4). Why is the pH low?

A. Decreased fatty acid release from adipose tissueB. Elevated blood ketone bodiesC. Excessive drinking of fluid (polydypsia)D. VomitingE. Elevated blood glucose

Correct answer B. Ketone bodies are elevated, ketone bodies are organic acids that would lower the pH.For answer A, Fatty acids are bound by albumin and do not reach concentrations high enough to alter blood pH. For answer C, drinking of fluid would not alter blood pH. For answer D, vomiting increases blood pH (opposite from what is seen) as stomach acids are lost to vomiting. Answer E, Elevated blood glucose, this causes osmotic problems (dehydration of tissues, including the brain) and modifies activity of proteins by glycosylation, but would not alter blood pH.

3. After learning that he may be at increased risk to develop diabetes, the patient's 24-year-old son decides to pursue direct-to-consumer testing in order to assess his heritable risk. He submits a saliva sample and receives a report indicating that his genetic risk is in the average range according to the company's algorithm. The report includes the information that he has the low risk genotype for the TCF7L2 (Transcription Factor 7-Like 2) gene (two copies of the low risk allele). Of the following options, which one is the best next step?

A. The genetic test should be repeated. Since the son's mother has diabetes, he should have inherited at least one high risk allele at the TCF7L2 locus.B. The son should be informed that direct to consumer testing is not legitimate medicine, and he should disregard the report.C. The son should be counseled that his positive family history supersedes the test result.D. The son should be reassured by his test result. As long as he maintains a healthy body weight, he avoids the elevated risk conferred by positive family history.E. Additional genetic testing is indicated to ensure that all diabetes risk genes are tested.

Answer “C” is the best answer.As stated in the assigned AMA reading, TCF7L2 genotype may increase diabetes risk 1.5 to 2.4-fold. However, the strongest predictors remain positive family history, increased BMI and other factors. The MBNBF lecture on complex disease included information from the Framingham study (Talmud et al., 2010) demonstrating that standard clinical measures were much better predictors of T2D risk than genotype scores. Therefore, option C, based on established family history, provides the best advice.Options A and D are not valid, since it is well established that many people have T2D in spite of having the low risk genotype at TCF7L2.Option B has some merit in that clinical utility of T2D genotyping (and direct-to-consumer testing for complex disease, in general) has not been demonstrated. However, as a freestanding response, it fails to address the son’s risk.Option E is incorrect, not all risk genes are known. Cost to patient should be considered.

4. During her doctor’s visit, the patient admits she did not take her medications regularly because of their costs and her health literacy (she would take the meds when she felt bad). . . . One month later the patient returns, having been adherent with her medications. Which of the


following choices represents the most likely result of the workup done (fasting overnight) on the return morning visit after adherence to medications?

Answer Blood glucose

Blood ketones

Hemoglobin A1C

Urine glucose

Urine ketones

A High High High High HighB Low High Normal High HighC Normal High Normal Normal HighD Normal Normal High Normal NormalE Normal Normal Normal Normal Normal

Best answer D. Medications should return glucose and ketones to normal, (choices A, B, and C are incorrect). 1 month is not long enough time for HgA1C to return to normal but they would be better than 1 month ago. Thus choice E is close but not as good as answer D.

Metabolic States and Diabetes Risk in Popular Media

5. The TV adventurer named Survivorman (Les Stroud) has not eaten due to inability to find edibles or catch/kill game for 2 days. He is feeling weaker but still alive and active. A check on a glucometer reveals he is at the low level of normal blood glucose, 80 mg/dl. Of the following, the best source for blood glucose in Mr. Stroud at this time is from:

A. Muscle glycogenB. Adipose TriglycerideC. Muscle proteinD. Liver glycogenE. Red cell AcetylSCoA

Answer C: Muscle protein breakdown makes amino acids, a major source of carbon for liver gluconeogenesis. Muscle loss is still high at 2 days, as the adaptive response to switch to ketone body metabolism has not yet fully activated sufficient to provide the brain with ketone bodies.Choice B would be a good answer, as TG breakdown in adipose tissue releases glycerol for gluconeogenesis by the liver. This would become a higher proportion of the total after ketone bodies increase high enough to supply the brain and muscle breakdown decreases after 3 days, thus, the argument for muscle protein as the best source here (choice C is best).Choice A is wrong, as there is no Glucose-6-phosphatase in muscles to allow release of glucose from muscle to blood. Choice D is wrong, as glycogen stores are most likely depleted or gone. Mr. Stroud would have needed to eat a meal providing glucose for storage as liver glycogen. Choice E is a red herring, as AcSCoA is not a precursor for gluconeogenesis, (unless you are a plant running the glyoxylate pathway).

6. Actor Tom Hanks has been diagnosed with T2D. There may have been clinical clues to his disorder in his acting career, if you imagine him as his character. Which of his roles in these movies provides a likely precursor for the T2D diagnosis?

A. BigB. A League of Their Own


C. CastawayD. Forrest GumpE. Saving Private Ryan

Best response: A League of Their Own TH gains weight for this role, playing a manager who is more corpulent, with a pear shaped body (abdominal obesity), overweight, and in relatively poor physical condition. We would imagine a relatively poor diet of ball park foods.Big is a movie of a child moving into an adult body. Though age is a risk factor for T2D the adult is a young healthy adult body, not likely to be a clue to TH’s later T2D.Castaway is a movie of isolation and survival with a dual meaning for social castaway as well. In this role, TH loses body mass, and is forced to forage for food, becoming leaner and in shape. Though the social castaway could have suffered from stress and high Glucocorticoids, overall not necessarily a clue to T2D.Forrest Gump, a mentally challenged, man has many amazing heroic and challenging adventures, including long distance running across the USA, football hero, and financial success. Not a clue to later T2D.In Saving Private Ryan, an officer leads his men through the North African campaign, Invasion of Europe (D-Day) and through enemy territory for a special mission. Stressful situations may have made him hypoglycemic, and we imagine army food would not have been healthy, but his early death by bullet holes precludes clues to T2D. Tom Hanks appeared on David Letterman’s show October 7, 2013. Tom Hanks discussed his recent diagnosis with T2D, and said that his role in A League of Their Own probably contributed to his T2D the most.


Context:This is one of five team-based learning experiences in the first semester of the M1 year

delivered in the Molecular Basis of Normal Body Function Course. This Team-Based Learning program is designed as an integration activity of the first year Molecular Basis of Normal Body Function course and the Structural Basis of Normal Body Function course. The exercise is meant to cover a set of problems related to the ongoing courses early in the first year of medical school instruction. The TBL has been used in 3 successive years with minor modifications which are briefly described below.

Students prepare in advance of this session with content from prior and ongoing exercises and lectures in metabolism covering the concepts of the feed fast cycle, blood glucose, carbohydrate digestion, glycogen metabolism, glycolysis, and gluconeogenesis. Students are assessed on these concepts separately. The TBL gives another reason to review material prior to assessment in preparation for the in-class event. It is not intended that reference material in the Mark’s textbook be read in the week prior to the in-class session. The textbook is a reference that corresponds to content covered preceding the TBL that can be found in the text. The additional TBL-specific directed reading in genetics and nutrition are done in the prior to the in-class session.

The RAT in the current TBL has been modified. Replaced questions related to signal transduction (activation of cAMP-dependent protein kinase A regulating glycogen synthase) and carbohydrate metabolism pathways activated 1 hour after a carbohydrate rich meal. These questions were replaced when the number of RAT questions were decreased from 9 to 7 in the second iteration to shorten time needed for RAT and increase time for application questions. The % correct in the iRAT was also drove question evolution. The stem or distractors were modified if faculty decided an item was inappropriate for a RAT question. A guide was that iRAT responses for the class of less than 50% or more than 90% stimulated question item evolution. An advantage of TBL has been the ability to make modifications in RAT questions to match the content covered.

The application questions in the current TBL have also been modified. A genetic risk question was eliminated when schedule changes placed the TBL prior to the relevant genetics content in the course, and an anatomy question was eliminated for similar reasons. In addition, application questions were modified to promote discussion and cause the students to use some higher order thinking skills. Faculty monitored team responses to application questions. For example, team responses to application questions were captured in that each team must reveal their answer and defend their answer. This process captures the essence of instructor-student interaction, because the team member called upon to present the team’s decision must concisely verbalize their rationale in selecting and answer and must do so for all the class to hear. Instructors meet later to reflect on the answers and the quality and validity of questions. If an application question elicits a unanimous response, the question was modified to change distractors, or rephrase the question.

Examples of popular answers and the rationale generally matched expected rationales and the faculties “best choice” for an answer. However, students did come up with rationales that made faculty agree that it was a good rationale. Some examples are: Application question #6 was that many students remembered that in “Big”, the adult character continued to eat candy and sugary beverages as if he were much younger. The high refined sugar intake was the rationale for choosing “Big” rather than “A League of their own”. #5 Students generally split over the choice for Triglyceride glycerol and muscle protein as a source for gluconeogenesis, because they could not decide which source was the most abundant at 2 days of fasting, and data is not provided. We acknowledged that bothTriglyceride and protein are sources of gluconeogenesis and opine that at 2 days amino acids are more abundant precursor of glucose.


Application #1 promotes different answers because there are multiple paths for an insulin molecule. Review of anatomy notes, textbook and internet sources and intense intra-team discussion is common for this question.


Facilitation Schema

The TBL is designed for completion in 1 hour and 50 minutes, as indicated by the arrow and 1.8 hours. Approximate time to complete subsections of the TBL are indicated.

Preparation (pre Class) - Student materials provided from the Instructor Guide are the “Purpose” and “Objectives” on page 2 and the “Advanced Preparation” on page 3. Materials for part 1 of Advanced Preparation are in the content preceding the TBL, which includes metabolic biochemistry content corresponding to reading from Mark’s Biochemistry textbook. Students are preparing for an assessment covering the material. The short readings on nutrition and genetics that are not covered in the course are made available 2 weeks prior to the TBL.

Readiness Assurance - The RAT is the scored and graded portion of the TBL. There is also a short time for brief feedback on correct responses as RAT and IF-AT cards are collected. This is indicated as “instructor feedback” in the schema. Any written team appeal (to challenge a question) is also collected during instructor feedback. Written appeals must be turned in prior to the Application Exercise. Appeals are assessed by faculty scoring the IF-AT scratch off cards during the application. Only the team filing an appeal is eligible for re-scores.

Application Exercises - The application is not graded or scored. Teams open their packets to reveal sets of 2 questions at a time. The application discussion is the team discussion to arrive at a consensus answer prior to the simultaneous reveal of the team choice. Each application question has a “reveal” to indicate team choice. Inter-team discussion with faculty facilitation follows. For the TBL, 6 application questions are discussed in 3 sets, first 1&2, then 3&4, then 5&6 as indicated in the schema.


Results of the deployment of the Type 2 Diabetes TBL from 2011 to 2013 are shown below:

Table of RAT results from 2011, 2012, 2013.*students with excused absence or malfunction of ARS devices were given class average iRAT score.

Year %iRAT %tRAT Combined All TBL

2011 68.7* 99.8 94.6 95.1

2012 75.9* 100 94.0 93.7

2013 80.1* 99.0 94.7 93.2

The results of the RAT overall are consistent from year to year. The iRAT scores have steadily increased while the tRAT scores have consistently remained high. Students vote each year on the percentage of RAT score from the individual RAT compared to the team RAT, and each year they have chosen the highest percent allowed on the tRAT, 75%, with the iRAT counting 25% of the TBL score. Combined indicates the result of ((0.25iRAT)+(0.75tRAT)) scores. All TBL indicates the average score on all 5 combined RAT scores for 5 TBL/year.

There is a need for faculty to keep track of the time. A common pitfall is a failure to pace properly so that there is sufficient time to discuss the last application question. This is most commonly a pitfall for the first of the two sessions. Facilitators are eager for students to challenge and discuss questions. For the RAT, team challenges can be verbally discussed, but we have found that facilitators handling challenges at the level of grading tRATS on a case-by-case basis is best. This keeps the class moving on to the application questions. Keeping on track for application questions should involve minimal discussion for questions where there is a consensus among the teams. There is an added logistical problem when the two sessions are both scheduled for one morning or afternoon to accommodate 164-168 students in 84-89 person sessions. The facilities for TBL seat approximately 100 students. There is a two-hour window to complete the TBL. The first session must finish 10 minutes prior to the second session to exit half of the class, set up stations for new teams and seat the next group. Compounding the problem is the fact that students must access the 6th floor, which involves the buildings four elevators for both exiting and entering students. Part of the solution has been to exit students out one door, down one hallway to the elevators while the next class enters through a different doorway. It is not unusual to shorten the time for discussion of the last application question or for the second TBL to start later.

The Diabetes TBL is an active learning experience that is given in the first semester of the M1 year, following initial content on energy metabolism, with the minimum being carbohydrate metabolism and an overview of the feed/fast cycle. Students are assessed after approximately four weeks of content covering molecular, structural and clinical foundations courses that run concurrently. The TBL is an application of some of the basic science content in the four week block of content. Content in the TBL has been adjusted to accommodate schedule changes in the structural, molecular, and clinical courses when appropriate scheduling of content has not been possible. The TBL precedes discussion of lipid and fatty acid metabolism, amino acid and nitrogen metabolism. The questions and discussion are limited to carbohydrates and the introductory material in the overview of metabolism and the feed/fast cycle which is covered in


more detail later. In many iterations of the course, human genetics and nutrition content precede the material on energy metabolism. But in some years the content has been modified, or a new reading assignment is given to provide students with content tools to attack RAT and application questions.

Limitations of Type 2 Diabetes TBL and ideas for improving/expanding.

The curriculum has evolved in the 3 years the Diabetes TBL has been an in-class session. Questions in the RAT and Applications have been changed. Continued change is likely. The faculty facilitators must be able to respond with the content in the TBL as curriculum content and delivery of content evolves. In the molecular course, TBL has proven to be a flexible active learning experience for M1 students.

Over the years, the TBL is attended by facilitators from the molecular course, structural course, and medical education professionals. There have been 2 different clinicians who have been the main facilitator of the application. The event is also usually attended by the clinical co-course director (an MD) who has been extremely helpful in maintaining continuity between clinical facilitators. It is clear that students respect and appreciate the presence of clinicians in the in-class session. The clinicians provide students with reinforcement for the relevance of content covered in the basic sciences. They also provide a preview of future interactions with medical faculty and the knowledge base for diagnosis and treatment. The retention of clinician involvement is very important to future success of the in-class event. TBL has proven to be an effective way to incorporate clinicians to reinforce the basic science concepts.

There is little clinical application content at 8 weeks of the first year medical school curriculum. The TBL focuses on reinforcement of basic sciences and thus there are missed opportunities to discuss important therapeutics and treatment issues. A second Type 2 diabetes TBL is offered to M4 students as part of a capstone course to revisit basic science concepts. The M4 TBL discusses therapeutics, treatment options and side effects, as well as underlying basic science, thus, a missed opportunity in the M1 Diabetes TBL is covered in the M4 TBL.

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