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Evaluating metabolic syndrome in a medical

physiology laboratory
Bruce Martin, John B. Watkins, III and J. W. Ramsey

Advan Physiol Educ 28:195-198, 2004. doi:10.1152/advan.00017.2004


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on the following topics:
Biochemistry .. Triglycerides
Medicine .. Fitness (Physical Activity)
Medicine .. Cholesterol
Medicine .. Metabolic Syndrome X
Medicine .. Exercise
Medicine .. Obesity

Adv Physiol Educ 28: 195198, 2004;


doi:10.1152/advan.00017.2004.

Teaching in the Laboratory

Evaluating metabolic syndrome in a medical physiology laboratory


Bruce Martin, John B. Watkins III, and J. W. Ramsey
Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana 47405
Submitted 1 June 2004; accepted in final form 23 August 2004.

obesity; cholesterol; electrolytes; malnutrition


THE METABOLIC SYNDROME, a condition characterized by central
obesity, hypertension, insulin resistance, and atherogenic dyslipidemia (4, 9, 14), is a major and increasingly prevalent
disorder in the developed world. For medical students, understanding the physiological and nutritional aspects of the metabolic syndrome is of fundamental importance for their future
medical practice (4). This condition is suitable for study in a
first-year medical physiology laboratory since the five variables used for diagnosis [fasting blood triglyceride, highdensity lipoprotein (HDL) cholesterol, and glucose levels,
blood pressure, and abdominal obesity (14)] are readily determined.
The two primary risk factors for development of the metabolic syndrome apart from genetic factors are overweight/
obesity and physical inactivity. We designed a laboratory that
also addressed each of the latter two factors by including
assessment of physical activity and body fatness, together with
a lunch that required complete nutritional analysis.
We incorporated nutritional analysis in part because 50%
of graduating medical students in the United States describe
their medical education coverage of nutrition as inadequate (7).
To address this issue, the National Heart, Lung, and Blood
Institute of the National Institutes of Health has initiated the
Nutrition Academic Award program to develop strategies for
implementation and integration of nutritional education into
the medical curricula (11). Improved nutritional training results

Address for reprint requests and other correspondence: B. Martin, Rm 200,


Jordan Hall, Indiana Univ., Bloomington, IN 47405 (E-mail: martin1@indiana.edu).

in physicians more secure in their nutritional knowledge (9).


The design of this laboratory allows new nutritional information to be readily integrated into existing curricula (13, 15).
Finally, this laboratory is well suited to a teaching strategy
designed to directly involve students. All measurements, including blood draws, physical activity estimates, meal selection and analysis, and determinations of body fatness, are made
by students on each other. This design creates personal as well
as professional ties to the material, goals that enhance student
interest and motivation (16).
METHODS

Informed consent. Thirty-five students signed informed consent


forms to allow their data, as obtained in a class laboratory exercise in
medical physiology, to be included in this publication. The class
consisted of first-year medical students and graduate students. Participants agreed to allow their data to be included in published mean
group data, with no individual data or identifiers to be used. Consent
was obtained after the completion and assignment of grades in this
course, and data analysis began only after obtaining consent. A third
party eliminated the data from those individuals who did not consent,
and then presented the investigators with the remaining data without
identifiers. These procedures were reviewed and approved by the
Bloomington campus Institutional Review Board of Indiana University.
Venous blood collection and analysis. The exercise takes place on
one afternoon of a 14-week physiology laboratory and problem-based
learning component of the first-year medical and graduate student
curriculum. During week two of this block, student-measured blood
pressure records are obtained and are later included in this laboratory.
During weeks four and five, students learn to draw venous blood
samples from each other, while under the supervision of a registered
nurse and a trained phlebotomist (5). Fasting blood samples from
weeks four and five are analyzed at Bloomington Hospital for a lipids
panel (cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglycerides), and a basic metabolic panel [including blood
urea nitrogen, creatinine, glucose, Na, K, Cl, Ca2, bicarbonate
(measured as total CO2), total protein, and albumin]. The data returned from Bloomington Hospital were given to students the next
week (week six), which is the exercise described in this study.
Student-selected lunch. On the morning before this afternoon laboratory, students are given a standard equation for estimation of daily
caloric expenditure (1). Their lunch caloric content is then restricted
to a maximum of one-third of estimated daily caloric expenditure.
One-third of the students are allowed any food choices whose total
caloric content does not exceed the allowable lunch total.
In contrast to the ad libitum food choices given to this first group,
meal composition is further constrained in the remainder of the class.
A second one-third of the class is asked to follow a Step I diet of the
National Cholesterol Education Program (NCEP). The Step I diet
limits saturated fat to 10% of total calories and cholesterol to 300
mg/day (100 mg for this meal). The diet should also contain 55%
carbohydrate calories and 15% of dietary calories as protein (14).
The final one-third of the class must comply with the NCEP Step
II diet, which limits saturated fat to 7% of total calories and
cholesterol to 200 mg/day (70 mg for this meal) (14). These basic

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195

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Martin, Bruce, John B. Watkins III, and J. W. Ramsey. Evaluating metabolic syndrome in a medical physiology laboratory. Adv
Physiol Educ 28: 195198, 2004; doi:10.1152/advan.00017.2004.
The metabolic syndrome, a cluster of factors linked to obesity that
contribute to risk for atherosclerosis and Type 2 diabetes, may affect
2025% of the adults in the United States. We designed a medical
physiology laboratory to evaluate and discuss the physiological and
nutritional principles involved in the metabolic syndrome. The five
criteria used to diagnose this syndrome (fasting blood triglycerides,
high-density lipoprotein cholesterol, and glucose, blood pressure,
central obesity) were measured by students on each other either
previously or during this exercise. In addition, to illustrate nutritional
factors involved in causation and treatment of the metabolic syndrome, a meal was provided during the laboratory. Class members
were randomized to groups allowed ad libitum meal composition, or
constrained to the National Cholesterol Education Program Step I or
Step II diets. The composition of the diet (including saturated fat,
cholesterol, dietary fiber, and carbohydrate content) was discussed in
the context of blood cholesterol, triglyceride, and glucose levels. This
laboratory allows a comprehensive analysis of the physiological and
nutritional factors involved in the development of the metabolic
syndrome.

Teaching in the Laboratory


196

EVALUATING THE METABOLIC SYNDROME

Table 1. Blood lipid levels


Variable

Recommended Level or Metabolic Syndrome Diagnostic Criterion (14)

Class Mean

Triglycerides, serum; mg/dl


Cholesterol, total; serum; mg/dl
HDL cholesterol, serum; mg/dl
LDL cholesterol, serum; mg/dl

Diagnostic criterion: 150


Recommended: 200
Diagnostic criteria: Males 40; Females 50
Recommended 130

9952
16634
4812
9933

Values are means SD; n 35 subjects. HDL, high-density lipoprotein; LDL, low-density lipoprotein.

recommendations persist in the updated NCEP version of the Step II


diet, known as the TLC diet (14).
After lunch has been eaten in the laboratory, analysis of the
selected lunch items is carried out using nutrition facts provided by
the retailer. Because McDonalds USA provides the most extensive
nutritional information in the Bloomington, IN, area, they were
chosen as vendor. Students used McDonalds USA Nutrition Facts for
Popular Menu Items as obtained on the internet (6) for calculation of
lunch nutritional content. This list includes total calories and calories
from fat, saturated fat (g), carbohydrate (g), and protein (g), cholesterol (mg), sodium (mg), dietary fiber (g), and vitamins A and C,
calcium, and iron as the percentage of recommended daily value.
Body fatness and malnutrition estimates. During the afternoon
exercise, central obesity, as estimated from abdominal circumference,
was determined and the criteria for diagnosis of the metabolic syndrome were defined as 40 inches (102 cm) in males, and 35 inches
(88 cm) in females (3). Four other simple, noninvasive estimates of
body fatness or malnutrition were used. First, body mass index was
calculated as {weight (kg)/[height (m)]2} (2, 8). Second, triceps
skinfold was compared with standards obtained from the combined
National Health and Nutrition Examination Surveys of 19711974
and 19761980 (12). Third, body weight was compared with reference weights for various heights as derived from mortality experience
data, and expressed as a percentage of the weight-for-height median
values (12). Fourth, midarm muscle area, used to detect the presence
of malnutrition, was determined from arm circumference and triceps
skinfold and compared with data from National Health and Nutrition
Examination Surveys (12).

selected diets of persons assigned to the ad libitum, Step I, and


Step II groups.
Mean results from the basic metabolic panel are listed in
Table 3, and the class mean results from the five noninvasive
indexes of body fatness and malnutrition are shown in Table 4.

RESULTS

Central obesity [waist circumference 40 inches (males),


35 inches (females)].
Fasting blood triglycerides, 150 mg/dl.
Blood HDL cholesterol 40 mg/dl (males), 50 mg/dl
(females).
Blood pressure 130/85 mmHg.
Fasting glucose 110 mg/dl.

Table 2. Meal composition


Kilocalories
Fat calories, % total Kcal
Saturated fat calories, % total Kcal
Protein, g
Carbohydrate, g
Na content, mg
Cholesterol, mg
Dietary fiber, g
Ad libitum diet
Saturated fat, % total Kcal
Cholesterol, mg
Step 1 diet
Saturated fat, % total Kcal
Cholesterol, mg
Step 2 diet
Saturated fat, % total Kcal
Cholesterol, mg
Values are means SD; n 35 subjects.

680200
2911
104
2411
8237
1,037333
7434
42
142
10345
82
8841
63
345

The metabolic syndrome (or syndrome X) consists of a


constellation of factors, including central obesity, atherogenic
dyslipidemia, hypertension, and insulin resistance (4, 9, 14).
These clustered factors contribute substantially to risk for both
Type 2 diabetes and atherosclerotic cardiovascular disease (9).
The metabolic syndrome is increasing in incidence in the US,
and is said to afflict as many as 2025% of the adults in this
country (4, 14). The primary causes of and treatments for the
metabolic syndrome include dietary and nutritional factors,
making this issue an ideal site for a nutrition-physiology
connection in medical education (13, 15).
Evaluating criteria for presence of metabolic syndrome. In
2002, the National Heart, Lung, and Blood Institute of the
National Institutes of Health issued its Third Report of the
Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults (14). This report defines the
metabolic syndrome as the presence of three or more of the
following (14):

Because each of these criteria is readily evaluated, this


laboratory allows a complete analysis and discussion of a
condition that is epidemic across much of the developed world.
Diet composition. Evaluation of the features of the metabolic
syndrome leads directly to consideration of the triglycerideand cholesterol-lowering diets followed by the students. Our
experience has been that students enjoy being randomized into
the three diets and then searching the menu to meet the given
dietary requirements. For many young adults this is their first
exposure to a therapeutic diet. Discussion of diet composition,
cholesterol transport and regulation, risk factors for insulin
resistance, and potential medications used for treatment of
hyperlipidemia, hypertension, or hyperglycemia make this area
fertile soil indeed for conversation with medical students.
The National Heart, Lung, and Blood Institute has recently
amended and expanded its definition of the former Step II diet.
This diet is now known as the Therapeutic Lifestyle Changes

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The mean lipid levels in the class of 35, obtained from


analysis of fasting venous blood samples, are shown in Table
1. Table 2 lists mean meal composition from the entire class. It
also shows saturated fat and cholesterol contents of self-

DISCUSSION

Teaching in the Laboratory


EVALUATING THE METABOLIC SYNDROME

Table 3. Blood levels of electrolytes, glucose, protein,


and protein breakdown products
Variable

[Na] plasma, mEq/l


[Cl] plasma, mEq/l
[Ca2], total plasma, mg/dl
[K] plasma, mEq/l
[HCO
3 ], plasma, mEq/l
Glucose, blood, mg/dl
Protein, total, blood, g/dl
Albumin, blood, g/dl
Creatinine, plasma, mg/dl
Urea nitrogen, plasma, mg/dl

Normal Range

Class Mean

136146
143.02.4
98106
103.02.2
8.410.2
9.30.3
3.55.1
4.10.3
2329
26.22.0
70105
7714
6.48.3
8.00.5
3.55.0
4.50.4
Males 0.71.3; Females 0.61.1
0.90.2
718
143

Values are means SD; n 35. [HCO


3 ] is measured as total CO2.

analysis would separate data from males and females, and this
is easily done during an actual class exercise.
This study of obesity and its origins and risks often begins
with students remarking on the small size of the allowed lunch
in kcalthe simple calculation of estimated daily caloric expenditure is often a first careful exploration into basic issues of
energy balance for these students. The midarm muscle area
(12) is used to estimate the possible presence of malnutrition,
as may occur, for example, during anorexia nervosa. The
physiological responses to malnutrition are readily expanded to
include assessment of meal caloric content, protein content,
and the levels of total protein, albumin, and urea nitrogen in the
blood. Finally, although its full explication belongs in a laboratory devoted to renal function, the blood levels of urea
nitrogen and creatinine can also properly be included in this
overarching review of protein anabolism and catabolism during
malnutrition.
Other possible points for emphasis. The low coefficient of
variation (SD/mean) for plasma levels of Na and Cl, as
contrasted with the very wide range of individual levels of Na
intake, is a useful starting point for a dialogue about extracellular fluid Na regulation and its complex relationship to Na
intake. McDonalds USA is not a preferred source for a wide
range of foods low in Na, and here a meal prepared in a
metabolic kitchen could provide a broader array of foods low
in Na content.
Although our chosen vendor does not provide potassium
levels in the nutritional tables provided, these could be calculated and then contrasted with the numbers seen in the normal
plasma range. Similarly, we chose not to emphasize Ca2
intake and Ca2 plasma regulation, but Ca2 intake levels are
directly available from the restaurant and easily could be
included in class discussion. Most clinical laboratory panels
also include bicarbonate and anion gap readings, and dialogue
can readily be generated that helps integrate these readings into
the broader understanding of extracelluar fluid and acid-base
regulation. We also chose to de-emphasize the vendor-provided nutritional information regarding vitamin A, vitamin C,
and iron content, but these also represent possible areas for
exploration. Many major restaurant chains provide this nutritional information.
Engaging student interest and personal ties to material.
Stimulating student involvement, interest, and personal investment is essential to any successful teaching laboratory (16).
We do this in part by simply using the students themselves as
subjects. By having them estimate their daily caloric expenditure, by having them draw each others blood and then interpret
their own results, by allowing them to choose their own lunch
in full view of its nutritional content, and by randomizing them
into clinically relevant therapeutic diets, we generate consid-

Table 4. Estimates of fatness and malnutrition


Variable

Normal Range or Metabolic Syndrome Diagnostic Criterion (14)

Class Mean

Waist, inches
Body mass index, weight (kg)/[height (m)]2
Triceps skinfold, %standard
Weight, %median
Mid-arm muscle area, %standard

Diagnostic criteria: Males 40; Females 35


Overweight: 2530; Obese: 30
Malnutrition: 50; Obesity: 150
Normal range: 85115
Malnutrition: 70

324
22.73.3
7823
10114
8923

Values are means SD; n 35 subjects.


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(TLC) diet (14). The TLC diet includes several additional


lifestyle and dietary changes that can be mentioned and discussed during this portion of the laboratory. In addition to
those issues directly commented on thus far (the need for
adjustment of total caloric intake to maintain a desirable body
weight, the maintenance of saturated fat intake 7% of dietary
calories, and limiting cholesterol to 200 mg/day) several
other recommendations can be considered.
One of these recommendations is that persons increase
viscous (soluble) fiber intake to 1025 g/day. This number far
exceeds that contained in the lunches chosen by our students
(Table 2). In addition, the nutritional information provided by
McDonalds USA lists only total fiber, and fails to distinguish
soluble from insoluble fiber. To more directly address the issue
of soluble fiber and its important role in the lowering of blood
cholesterol, further information could be added from standard
nutritional tables. Another alternative would be to prepare a
lunch, designed to comply with all TLC diet guidelines, in a
metabolic kitchen.
The recent dietary guidelines also suggest an intake of 2 g
per day of plant stanols/sterols, recommend enough exercise
each day to expend at least 200 kcal (14), and advocate
replacement of animal proteins with soy protein in some
situations. We have found that all of these dietary and lifestyle
issues are made highly relevant and engaging in this laboratory.
Body fatness and malnutrition estimates. We chose to supplement measures of waist circumference with four other rapid,
simple, noninvasive estimates of body fatness or malnutrition.
Contrasting the results obtained from body mass index (2, 8),
weight for height compared with the midpoint of an acceptable
range (12), and triceps skinfold (12) helps students understand
various methods for and problems with noninvasive determination of fatness. Our results show only the whole-class means,
which include both males and females. A more meaningful

197

Teaching in the Laboratory


198

EVALUATING THE METABOLIC SYNDROME

erable personal stake in the results. In addition, during the


course of the laboratory, we create a large table on the board in
full view of all class members. On it we have students (who are
randomly assigned a number) enter their blood results, and
their analyses of nutritional content of the meals they chose.
This table allows immediate visual inspection of all of the
individual data, comparison of generated means, and some
immediate feedback regarding intersubject variability.
In summary, the clustered diet- and activity-linked factors
that confer risk for Type 2 diabetes and atherosclerosis constitute the metabolic syndrome. By evaluating all of the factors
involved in this syndrome in a single setting, this laboratory
helps medical students grasp the nature of the disorder, its
relationship to dietary factors, and its link to physiological
principles. The increasing importance of these measurements
as obesity and its related disorders increase in prevalence
makes this a laboratory exercise of enormous significance.

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