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S H O R T R E P O R T
A Mathematical Model for the
Determination of Total Area
Under Glucose Tolerance and
Other Metabolic Curves
MARY M. TAI, MS, EDD
OBJECTIVE— To develop a mathematical model for the determination of total
areas under curves from various metabolic studies.
RESEARCH DESIGN AND METHODS— In Tai's Model, the total area under a
curve is computed by dividing the area under the curve between two designated
values on the X-axis (abscissas) into small segments (rectangles and triangles) whose
areas can be accurately calculated from their respective geometrical formulas. The
total sum of these individual areas thus represents the total area under the curve.
Validity of the model is established by comparing total areas obtained from this
model to these same areas obtained from graphic method Gess than ±0.4%). Other
formulas widely applied by researchers under- or overestimated total area under a
metabolic curve by a great margin.
RESULTS — Tai's model proves to be able to 1) determine total area under a curve
with precision; 2) calculate area with varied shapes that may or may not intercept on
one or both X/Y axes; 3) estimate total area under a curve plotted against varied time
intervals (abscissas), whereas other formulas only allow the same time interval; and
4) compare total areas of metabolic curves produced by different studies.
CONCLUSIONS — The Tai model allows flexibility in experimental conditions, which
means, in the case of the glucose-response curve, samples can be taken with differing time
intervals and total area under the curve can still be determined with precision.
E
stimation of total areas under curves
of metabolic studies has become an
increasingly popular tool for evalu-
ating results from clinical trials as well as
research investigations, such as total area
under a glucose-tolerance or an energy-
expenditure curve (1,2). Three formulas
have been developed by Alder (3), Vec-
chio et al. (4), and Wolever et al. (5) to
calculate the total area under a curve.
From the Obesity Research Center, St. Luke's-Roosevek Hospital Center, New York; and the
Department of Nutrition, New York University, New York, New York.
Address correspondence and reprint requests to Mary M. Tai, MS, EdD, Department of
Nutrition, New York University, Education Building #1077, 35 West 4th Street, New York,
NY 10012.
Received for publication 18 February 1993 and accepted in revised form 23 September
1993.
However, except for Wolever et al.'s for-
mula, other formulas tend to under- or
overestimate the total area under a met-
abolic curve by a large margin.
RESEARCH DESIGN AND
METHODS
Tai's mathematical model
Tai's model was developed to correct the
deficiency of under- or overestimation of
the total area under a metabolic curve.
This formula also allows calculating the
area under a curve with unequal units on
the X-axis. The strategy of this mathe-
matical model is to divide the total area
under a curve into individual small seg-
ments such as squares, rectangles, and tri-
angles, whose areas can be precisely deter-
mined according to existing geometric
formulas. The area of the individual seg-
ments are then added to obtain the total
area under the curve. As shown in Fig. 1,
the total area can be expressed as:
Total area = triangle a 4- rectangle b 4-
triangle c + rectangle d 4- triangle e 4-
rectangle/4- triangleg 4- rectangle h +...
If y = height, x = width
Area (square) = x2
or y2
(x = y);
Area (rectangle) = xy;
Area (triangle) = xy/2
Let: X: = x2 — xx X2= x3 — x2
.A.T — X^ X~) -^4 — X^ -^4>
•^n-1 = X
n ~ X
n-l
Total Area = ^Xl (y2 - y:) + X ^ 4-
x3 (3/4-3/3) 4- X33/3
 (Kyy1 + X1 y2 + X#2 4- X ^ 4- X33/3 +
4- X^4 4- X#5 4- ... 4- X ^ ^ - i
xn_, cr,,.! 4- yn)]
If the curve passes the origin,
should be added to above formula. If the
curve intercepts at y0 at the Y-axis, let
Xo = xt - XQ, l/2[X0(y0 4- yx)] should be
added to the above formula; Tai's formula
applied to different conditions:
152 DIABETES CARE, VOLUME 17, NUMBER 2, FEBRUARY 1994
©
Tai
0 x, x2 x
Figure 1—Total area under the curve is the
sum of individual areas of triangles a, c, e, and g
and rectangles b, d,f and h.
Area = -
i = 1
(Tai's formula)
When the curve passes the origin: XQ =
y0 = 0, Xo = Xl - 0;
When the curve intercepts Y-axis at y0:
Xo = Xl - 0
When the curve neither passes the origin
nor intercepts at y-axis: Xo = y0 = 0
Example using Tai's model:
Blood glucose determined at six time
periods: (6)
time (min) 0 30 60 90 120
Glucose (mg/dl) 95 147 124 111 101
Xo = x: - Xo = 30 - 0 = 30 ;
X1 = 60-30 = 30; X2 = X3 = 30
1
Area = - [30(95 + 147) 4- (147 + 124)
+ (124+ 111) +(111 + 101)]
= 14400 mg/dl/120 min
RESULTS
Comparison of Tai's formula to
other formulas
Five sets of laboratory data from the pre-
vious experiments of the author are used
here for calculating the total area under a
curve using the four different formulas as
indicated above. The validity of each
model was verified through comparison
of the total area obtained from the above
formulas to a standard (true value),
which is obtained by plotting the curve
on graph paper and counting the num-
ber of small units under the curve. The
sum of these units represents the actual
total area under the curve. Results are
presented in Table 1. From Table 1, it is
evident that total area I can not be ob-
tained from Alder's formula. Total area II
has underestimated the total area under a
metabolic curve by a large margin. Total
area III corresponds well (— 6.1%) with
the actual area estimated from the plot
(total area V). However, this formula
only permits a single t value, which means
the time interval has to be the same.
CONCLUSIONS
Verification of Tai's mathematical
model
From Table 1, it is clear that Tai's for-
mula (total area IV) has the most accu-
rate estimation of the total area under a
curve. Total area IV agrees extremely
well with actual total area obtained from
the graph (+ 0.1%). Because no statisti-
cally significant differences were found
between areas from these two methods,
the validity of Tai's model can thus be
established.
This formula also permits accu-
rate determination of total area under the
curve when the curve intercepts with
Y-axis, as well as when the curve passes
the origin. Furthermore, in this formula,
values on X-axis do not have to be the
same as the t in Wolever et al.'s formula. It
allows flexibility in experimental condi-
tions, which means, in the case of glucose-
response curve, samples can be taken with
differing time intervals and the total area
under the curve can still be determined
with precision. Thus, if different authors
estimate the total area under a curve from
Table 1—Summary
Total area
Test
Glucose
TEF (SM)
TEF (LM)
RMR(L)
RMR(O)
Ave
1
N.A.*
N.A.*
N.A.*
N.A.*
N.A.*
of results: (% area: (
II
480 (3.3%)
336 (3.2%)
452 (3.2%)
1157(3.9%)
1636 (4.6%)
(3.6%)
Yo of total area V)
III
13517 (94.3%)
9588 (92.6%)
13367 (94.7%)
N.A.t
N.A.t
(93.9%)
IV
14400 (100.4%)
10326 (99.8%)
14163 (100.3)
30040 (100.0%)
35733 (100.0%)
(100.1%)
V
14337
10349
14115
30047
35725
t tests: II:V P < 0.005; III:V NS; IV:V NS
Area 1: Alder (3)*; Area II: Vecchio et al. (4);
Area III: Wolever et al. (5); Area IV: Tai's Model
Area: V: Graphic Method;
Metabolic studies:
Test I
Blood glucose at six time periods before and after a glucose load: (blood glucose: x,
mg/dl; time interval between tests t = 30 min; obese women: n = 6) (6)
Test II and III
Thermic effect of food at ten time periods after one large meal (LM: 750 kcal) or six
small meals (SM: 125 kcal)
(TEF: x, 10 " 2
kcal • min ~ 1
• kg " 1
LBM; t = 30 min; lean women: n = 7) (2)
Test IV and V
Resting metabolic rate of lean (L) and obese (O) women.
(RMR: x 10 ~ 2
kg • min ~ x
• kg " x
LBM; L: n = 7, O: n = 8; tY = t2 = 20 min; t3 = 25
min; t4 = t5 = t6 = 30 min) (6)
*Nonapplicable because of the irregular shape of the curve.
tNonapplicable because of the uneven time intervals.
DIABETES CARE, VOLUME 17, NUMBER 2, FEBRUARY 1994 153
©
A mathematical model for total area under curves
Tai's formula, comparisons can be made
between areas under curves produced un-
der different experimental conditions.
Acknowledgments—I would like to dedi-
cate Tai's Model to my late parents Mr. and
Mrs. T. C. Tai. I gratefully acknowledge Dr. F.
X. Pi-Sunyer and Dr. H. Dowling from the
Obesity Research Center for their support
and encouragement, Dr. R. Kuc from Yale
University for his expert review and Mrs. Y.
Dam for her artwork.
References
1. Wolever TMS: How important is predic-
tion of glycemic responses? Diabetes Care
12:591-93, 1989
2. Tai MM, Castillo P, Pi-Sunyer EX Meal size
and frequency: effect on the thermic effect
of food. Am] Clin Nutr 54:783-87, 1991
3. Alder I: A New Look at Geometry. New
York, The John Day Company, 1966
4. Vecchio TJ, Oster HL, Smith D: Oral so-
dium, tolbutamide and glucose tolerance
tests. Arch Intern Med 115:161-66, 1965
5. Wolever TMS, Jenkins DJA, Jenkins AL,
Josse AG: The glycemic index: method-
ology and clinical implications. Am] Clin
Nutr 54:846-54, 1991
6. Tai MM, Pi-Sunyer FX: Effect of exercise
on thermic effect of food (TEF) in lean
(L) and obese (O) women (Abstract). Int
J Obesity 1L461A, 1987
154 DIABETES CARE, VOLUME 17, NUMBER 2, FEBRUARY 1994
©

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  • 1. S H O R T R E P O R T A Mathematical Model for the Determination of Total Area Under Glucose Tolerance and Other Metabolic Curves MARY M. TAI, MS, EDD OBJECTIVE— To develop a mathematical model for the determination of total areas under curves from various metabolic studies. RESEARCH DESIGN AND METHODS— In Tai's Model, the total area under a curve is computed by dividing the area under the curve between two designated values on the X-axis (abscissas) into small segments (rectangles and triangles) whose areas can be accurately calculated from their respective geometrical formulas. The total sum of these individual areas thus represents the total area under the curve. Validity of the model is established by comparing total areas obtained from this model to these same areas obtained from graphic method Gess than ±0.4%). Other formulas widely applied by researchers under- or overestimated total area under a metabolic curve by a great margin. RESULTS — Tai's model proves to be able to 1) determine total area under a curve with precision; 2) calculate area with varied shapes that may or may not intercept on one or both X/Y axes; 3) estimate total area under a curve plotted against varied time intervals (abscissas), whereas other formulas only allow the same time interval; and 4) compare total areas of metabolic curves produced by different studies. CONCLUSIONS — The Tai model allows flexibility in experimental conditions, which means, in the case of the glucose-response curve, samples can be taken with differing time intervals and total area under the curve can still be determined with precision. E stimation of total areas under curves of metabolic studies has become an increasingly popular tool for evalu- ating results from clinical trials as well as research investigations, such as total area under a glucose-tolerance or an energy- expenditure curve (1,2). Three formulas have been developed by Alder (3), Vec- chio et al. (4), and Wolever et al. (5) to calculate the total area under a curve. From the Obesity Research Center, St. Luke's-Roosevek Hospital Center, New York; and the Department of Nutrition, New York University, New York, New York. Address correspondence and reprint requests to Mary M. Tai, MS, EdD, Department of Nutrition, New York University, Education Building #1077, 35 West 4th Street, New York, NY 10012. Received for publication 18 February 1993 and accepted in revised form 23 September 1993. However, except for Wolever et al.'s for- mula, other formulas tend to under- or overestimate the total area under a met- abolic curve by a large margin. RESEARCH DESIGN AND METHODS Tai's mathematical model Tai's model was developed to correct the deficiency of under- or overestimation of the total area under a metabolic curve. This formula also allows calculating the area under a curve with unequal units on the X-axis. The strategy of this mathe- matical model is to divide the total area under a curve into individual small seg- ments such as squares, rectangles, and tri- angles, whose areas can be precisely deter- mined according to existing geometric formulas. The area of the individual seg- ments are then added to obtain the total area under the curve. As shown in Fig. 1, the total area can be expressed as: Total area = triangle a 4- rectangle b 4- triangle c + rectangle d 4- triangle e 4- rectangle/4- triangleg 4- rectangle h +... If y = height, x = width Area (square) = x2 or y2 (x = y); Area (rectangle) = xy; Area (triangle) = xy/2 Let: X: = x2 — xx X2= x3 — x2 .A.T — X^ X~) -^4 — X^ -^4> •^n-1 = X n ~ X n-l Total Area = ^Xl (y2 - y:) + X ^ 4- x3 (3/4-3/3) 4- X33/3 (Kyy1 + X1 y2 + X#2 4- X ^ 4- X33/3 + 4- X^4 4- X#5 4- ... 4- X ^ ^ - i xn_, cr,,.! 4- yn)] If the curve passes the origin, should be added to above formula. If the curve intercepts at y0 at the Y-axis, let Xo = xt - XQ, l/2[X0(y0 4- yx)] should be added to the above formula; Tai's formula applied to different conditions: 152 DIABETES CARE, VOLUME 17, NUMBER 2, FEBRUARY 1994 ©
  • 2. Tai 0 x, x2 x Figure 1—Total area under the curve is the sum of individual areas of triangles a, c, e, and g and rectangles b, d,f and h. Area = - i = 1 (Tai's formula) When the curve passes the origin: XQ = y0 = 0, Xo = Xl - 0; When the curve intercepts Y-axis at y0: Xo = Xl - 0 When the curve neither passes the origin nor intercepts at y-axis: Xo = y0 = 0 Example using Tai's model: Blood glucose determined at six time periods: (6) time (min) 0 30 60 90 120 Glucose (mg/dl) 95 147 124 111 101 Xo = x: - Xo = 30 - 0 = 30 ; X1 = 60-30 = 30; X2 = X3 = 30 1 Area = - [30(95 + 147) 4- (147 + 124) + (124+ 111) +(111 + 101)] = 14400 mg/dl/120 min RESULTS Comparison of Tai's formula to other formulas Five sets of laboratory data from the pre- vious experiments of the author are used here for calculating the total area under a curve using the four different formulas as indicated above. The validity of each model was verified through comparison of the total area obtained from the above formulas to a standard (true value), which is obtained by plotting the curve on graph paper and counting the num- ber of small units under the curve. The sum of these units represents the actual total area under the curve. Results are presented in Table 1. From Table 1, it is evident that total area I can not be ob- tained from Alder's formula. Total area II has underestimated the total area under a metabolic curve by a large margin. Total area III corresponds well (— 6.1%) with the actual area estimated from the plot (total area V). However, this formula only permits a single t value, which means the time interval has to be the same. CONCLUSIONS Verification of Tai's mathematical model From Table 1, it is clear that Tai's for- mula (total area IV) has the most accu- rate estimation of the total area under a curve. Total area IV agrees extremely well with actual total area obtained from the graph (+ 0.1%). Because no statisti- cally significant differences were found between areas from these two methods, the validity of Tai's model can thus be established. This formula also permits accu- rate determination of total area under the curve when the curve intercepts with Y-axis, as well as when the curve passes the origin. Furthermore, in this formula, values on X-axis do not have to be the same as the t in Wolever et al.'s formula. It allows flexibility in experimental condi- tions, which means, in the case of glucose- response curve, samples can be taken with differing time intervals and the total area under the curve can still be determined with precision. Thus, if different authors estimate the total area under a curve from Table 1—Summary Total area Test Glucose TEF (SM) TEF (LM) RMR(L) RMR(O) Ave 1 N.A.* N.A.* N.A.* N.A.* N.A.* of results: (% area: ( II 480 (3.3%) 336 (3.2%) 452 (3.2%) 1157(3.9%) 1636 (4.6%) (3.6%) Yo of total area V) III 13517 (94.3%) 9588 (92.6%) 13367 (94.7%) N.A.t N.A.t (93.9%) IV 14400 (100.4%) 10326 (99.8%) 14163 (100.3) 30040 (100.0%) 35733 (100.0%) (100.1%) V 14337 10349 14115 30047 35725 t tests: II:V P < 0.005; III:V NS; IV:V NS Area 1: Alder (3)*; Area II: Vecchio et al. (4); Area III: Wolever et al. (5); Area IV: Tai's Model Area: V: Graphic Method; Metabolic studies: Test I Blood glucose at six time periods before and after a glucose load: (blood glucose: x, mg/dl; time interval between tests t = 30 min; obese women: n = 6) (6) Test II and III Thermic effect of food at ten time periods after one large meal (LM: 750 kcal) or six small meals (SM: 125 kcal) (TEF: x, 10 " 2 kcal • min ~ 1 • kg " 1 LBM; t = 30 min; lean women: n = 7) (2) Test IV and V Resting metabolic rate of lean (L) and obese (O) women. (RMR: x 10 ~ 2 kg • min ~ x • kg " x LBM; L: n = 7, O: n = 8; tY = t2 = 20 min; t3 = 25 min; t4 = t5 = t6 = 30 min) (6) *Nonapplicable because of the irregular shape of the curve. tNonapplicable because of the uneven time intervals. DIABETES CARE, VOLUME 17, NUMBER 2, FEBRUARY 1994 153 ©
  • 3. A mathematical model for total area under curves Tai's formula, comparisons can be made between areas under curves produced un- der different experimental conditions. Acknowledgments—I would like to dedi- cate Tai's Model to my late parents Mr. and Mrs. T. C. Tai. I gratefully acknowledge Dr. F. X. Pi-Sunyer and Dr. H. Dowling from the Obesity Research Center for their support and encouragement, Dr. R. Kuc from Yale University for his expert review and Mrs. Y. Dam for her artwork. References 1. Wolever TMS: How important is predic- tion of glycemic responses? Diabetes Care 12:591-93, 1989 2. Tai MM, Castillo P, Pi-Sunyer EX Meal size and frequency: effect on the thermic effect of food. Am] Clin Nutr 54:783-87, 1991 3. Alder I: A New Look at Geometry. New York, The John Day Company, 1966 4. Vecchio TJ, Oster HL, Smith D: Oral so- dium, tolbutamide and glucose tolerance tests. Arch Intern Med 115:161-66, 1965 5. Wolever TMS, Jenkins DJA, Jenkins AL, Josse AG: The glycemic index: method- ology and clinical implications. Am] Clin Nutr 54:846-54, 1991 6. Tai MM, Pi-Sunyer FX: Effect of exercise on thermic effect of food (TEF) in lean (L) and obese (O) women (Abstract). Int J Obesity 1L461A, 1987 154 DIABETES CARE, VOLUME 17, NUMBER 2, FEBRUARY 1994 ©