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thomas m s wolever bm phd glycemic index of foods david a jenkins dm dsc vladimir vuksan phd in individual subjects robert g josse md gerald s wong md alexandra ...

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                                                                                                                                       Thomas M.S. Wolever, BM, PhD
                  Glycemic Index of Foods                                                                                              David |.A. Jenkins, DM, DSc
                                                                                                                                       Vladimir Vuksan, PhD
                  in Individual Subjects                                                                                               Robert G. Josse, MD
                                                                                                                                       Gerald S. Wong, MD
                                                                                                                                       Alexandra L. Jenkins, BSc, RPDt
                                                                                                                                                                                        Downloaded from http://diabetesjournals.org/care/article-pdf/13/2/126/439321/13-2-126.pdf by guest on 04 January 2023
                 We studied 12 subjects with diabetes to determine                                  elusion is not necessarily valid if the subjects tested each
                  how well the glycemic index (Gl) predicted the ranking                            food only once, and the lack of consistency was due to
                 of glycemic responses of different foods in individuals.                           within-individual variability Therefore, repeated testing
                 All subjects ate three mixed meals (bread, rice, or                                of the same meal in each subject is required to deter-
                 spaghetti with GIs of 100, 79, and 61, respectively) four                          mine whether the variability of glycemic responses is
                 times in a randomized complete block design. The mean                              due to consistent differences between subjects or to day-
                 glycemic response areas of the different meals ranked                              to-day variability within individuals.
                 according to the predicted Gl in every individual. The                                Our objective was to determine whether different in-
                 observed mean ± SD Gl values of the meals were                                     dividuals shared common Gl values of foods, which
                 significantly different from each other (bread 100 ± 7,
                  rice 75 ± 9, spaghetti 54 ± 9), with no significant                               would allow the Gl to be used to predict the ranking of
                 difference in response between subjects. It is concluded                           glycemic responses in individual subjects. Therefore, we
                 that individuals share common mean Gl values for                                   determined the glycemic responses of different test meals
                 different foods. Within confidence limits determined                               with a range of Gl values taken on four occasions each
                 by the variability of glycemic responses, the number                               by a group of diabetic subjects.
                 of repeated tests conducted, and the expected Gl
                 difference, the Gl can be used to predict the ranking of
                 the mean glycemic responses of mixed meals taken by                                RESEARCH DESIGN AND METHODS
                 individuals. Diabetes Care 13:126-32, 1990
                                                                                                    Twelve patients with diabetes were studied on an out-
                                                                                                    patient basis on 12 separate occasions over a 3- to 6-
                           here is much controversy about the validity of                           mo period with procedures that had been approved by
                           classifying foods according to their glycemic re-                        the University of Toronto Ethical Review Committee on
                           sponses with the glycemic index (Gl) or relative                         the use of human subjects. Volunteers entered the test-
                 Tglucose area (RGA) (1-4). It has been pointed out                                 ing area at St. Michael's Hospital, Toronto, in the morn-
                 that the glycemic ranking of foods in individuals is not                           ing after overnight fasts. The subjects were chosen to be
                  always as expected (5-8), implying that glycemic re-                              dissimilar with respect to age, sex, body weight, treat-
                 sponses are idiosyncratic in different subjects. This con-                         ment, and type of diabetes to increase the chances of
                                                                                                    detecting differences between the individuals (Table 1).
                                                                                                    Only one of the seven patients taking insulin (subject 2)
                                                                                                    had a known history of ketosis and could be classified
                  From the Division of Endocrinology and Metabolism, St. Michael's Hospital,        on this basis as having insulin-dependent diabetes mel-
                 and the Department of Nutritional Sciences, Faculty of Medicine, University of     litus (IDDM). The other six patients on insulin were di-
                 Toronto, Toronto, Ontario, Canada.                                                 agnosed in other centers, and records of ketosis were
                    Address correspondence and reprint requests to Thomas M.S. Wolever, As-
                 sistant Professor, Department of Nutritional Sciences, Faculty of Medicine, Uni-   not available. In them, the diagnosis of IDDM or non-
                 versity of Toronto, Toronto, Ontario, Canada M5S 1A8.                              insulin-dependent diabetes mellitus (NIDDM) was based
                    Received for publication 7 June 1989 and accepted in revised form 13 Sep-       on a fasting serum C-peptide below the lower limit of
                 tember 1989.
                 126                                                                                                     DIABETES CARE, VOL. 13, NO. 2, FEBRUARY 1990
                                                                                                       T.M.S. WOLEVER AND ASSOCIATES
              TABLE 1
              Clinical details of subjects studied
                                                                                     Serum C-
                                                             Fasting blood          peptide (pM)
                           Age    Years     BMI     Type of    glucose
                                                2
              Subject Sex   (yr) diabetic  (kg/m ) diabetes     (mM)       HbA    Fasting 90 min                   Treatment
                                                                               lc
                 1                          27.2       I           t 1.7   0.108     33      106   20 L a.m., 3-5 L p.m.
                       F    62      13                         5.3 d
                 2     M    36      22      19.1       I       6.8 dt 2.8  0.065     60       83   8 L + 7-10 R a.m., 8-10 L + 7-15 R p.m.
                 3     F    67      12      21.4      N        8.1 it 3.4  0.079    311      371   35 La.m.
                 4     F    63       4      24.2      N        7 A dt 3.1  0.077    877     3970   35 L + 5 Ra.m.
                 5     F    66       8      24.2      N        8.6 it 1.2  0.064    258      662   5 mg G
                                                      N            t 2.1   0.072             570   38 L + 8 R a.m.
                 6     M    72      20      21.0               8.8 1                311
                 7                                                 t 1.1   0.047
                       F    66       8      26.2      N        7.3 H                513     1523   15-19 La.m.
                 8     F    53      13      30.8       I       7.4 dt 2.7  0.078    252      238   40-52 N a.m.
                 9      F   48       4      33.7      N       10.7 ± 1.8   0.097    334      351   10 mgC                                        Downloaded from http://diabetesjournals.org/care/article-pdf/13/2/126/439321/13-2-126.pdf by guest on 04 January 2023
                10     M    71       4      23.8      N        9.6 ± 0.6   0.061    358      517   20 mgC
                11     M    80       9      23.9      N        6.7 ± 0.4   0.061   3510     5300   Diet alone
                12      F   83       8      25.2      N        8.2 ± 0.4   0.054   1490     3050   5 L a.m.
              I, IDDM; N, NIDDM; units insulin (L, lente; R, regular; N, NPH); C, glyburide. Values are means ± SD.
              normal for our laboratory (200 pM) or on no rise at 90          meals on four different occasions according to a ran-
              min after a test meal containing 50 g carbohydrate as           domized complete block design (11). The meals con-
             white bread (Table 1).                                           sisted of a 50-g carbohydrate portion of either white
                We wanted to have an 80% chance of detecting an               bread (B), polished white rice (R), or white spaghetti (S)
             extreme range of Gl values of 20 between subjects. The           to which cheese and tomato were added, so that fat and
              pooled coefficient of variation (C.V.) of glycemic re-          protein comprised 31 and 19% of calories. Duplicate
             sponses for our nine NIDDM and three IDDM subjects               test meals were analyzed for macronutrient composition
             was estimated to be 18.7% based on published C.V.s of            (12; Table 2). Test meals were served with 1-2 cups of
             glycemic responses in NIDDM and IDDM patients (9).               coffee or tea with or without 30 ml 2% butterfat milk
             With this degree of variation, power analysis suggested          (beverage standard for each subject).
             that each subject should be tested 12 times (10).                   Subjects began to eat their test meals 5-10 min after
                Each subject consumed each of three different test            taking their usual dose of insulin or oral hypoglycemic
             TABLE 2
             Test meal composition based on proximate analysis
                    Test meal                Weight (g)          Carbohydrate (g)          Fat (g)          ProteiYi (g)        Energy (kcal)
              Bread
                White bread                     118                    50.0                 0.3                 8.6                 237
                Cheddar cheese                   41                     0.6                13.7                10.3                 166
                Stewed tomato*                   60                     2.1                 0.01                0.4                  10
                Total                                                  52.7                14.0                19.3                 413
                Percentage of energy                                   51                  31                  19
              Rice
                Polished white ricet             65                    50.0                 0.1                 4.6                 219
                Cheddar cheese                   42                     0.6                14.0               10.5                  170
                Skim cheese                      11                     0.4                 0.4                 3.7                  20
                Stewed tomato*                   60                     2.1                 0.01                0.4                  10
                Total                                                  53.1                14.5                19.2                 419
                Percentage of energy                                   51                  31                  19
              Spaghetti
                White spaghetti                  72                    50.0                 0.1                 8.6                 236
                Cheddar cheese                   42                     0.6                14.0                10.5                 170
                Stewed tomato*                   60                     2.1                 0.01                0.4                  10
                Total                                                  52.7                14.1                19.5                 416
                Percentage of energy                                   51                  31                  19
              *Del Monte-brand canned stewed tomato.
              tWeighed raw.
             DIABETES CARE, VOL. 13, NO. 2, FEBRUARY 1990                                                                                127
                GLYCEMIC INDEX IN INDIVIDUALS
                agent (if any). Meals were eaten within 5-10 min. Fin-                               First Repeat                   Second Repeat
                ger-stick capillary blood samples were obtained at fast-
                ing and at 30-min intervals for 3 h after the start of the
                test meal for analysis of glucose with a YSI model 27AM                  —7 8
                glucose analyzer (Yellow Springs, OH).
                  Subject 8 did not complete her last two tests because
               of an exacerbation of her irritable bowel. The missing
               values (1 B and 1 R test) were estimated in the analysis
               of variance by use of the means of the other three re-                   LU
                spective test meals.                                                    cr
                   Incremental areas under the glycemic response curves                              Third Repeat                   Fourth Repeat
               were calculated geometrically (13). To assess differ-                    LU
                                                                                        en
               ences between test meals and between subjects, anal-                     o
                                                                                        C_3
               ysis of variance with repeated measures (ANOVARM),
               with subject and test meal as the variables, was per-                    o
               formed on all the glycemic response areas and on the                     o                                                                          Downloaded from http://diabetesjournals.org/care/article-pdf/13/2/126/439321/13-2-126.pdf by guest on 04 January 2023
                                                                                        o
               GIs, i.e., the glycemic response areas expressed as a                    ^4
                percentage of each subject's own mean response to the
                B meal (9). To assess the significance of differences within
               subjects, the glycemic areas and CIs of each subject
               were analyzed by ANOVARM with test meal as the vari-                             0 60 120 180 0 60 120 180
               able. After demonstration of significant heterogeneity,                                                 TIME (min)
               the significance of differences between foods was de-
               termined by Tukey's Q method to adjust for multiple                       FIG. 1. Mean blood glucose increments of 12 patients with
               comparisons (14).                                                         non-insulin-dependent diabetes mellitus for 1st, 2nd, 3rd,
                  The ranking of glycemic responses was assessed within                 and 4th repeats of bread (solid lines), rice {dashed lines),
               each subject by making all possible three-way compar-                    and spaghetti (dotted lines) test meals.
                isons between the glycemic responses of the B, R, and
                S meals. For each subject taking four B, four R, and four
               S meals, there were 64 possible comparisons of individ-                  other, whether expressed as incremental areas (1105 ±
                ual areas (36 in subject 8). To determine the effect of                 246, 819 ± 204, and 581 ± 142 mM • min, F(222) =
                increasing the number of repeated tests performed on                    29.21, P < 0.01) or GIs (100 ± 7, 75 ± 9, and 54 ±
               the proportion of correct predictions, the means of all                  9 mM • min, F           = 88.49, P < 0.01).
                                                                                                           (2;22)
                possible combinations of four tests taken two at a time                 Comparison of glycemic responses between sub-
               were calculated for each test meal. This gave six values                 jects. There were highly significant differences between
               for each test meal and 216 possible comparisons be-                      the incremental glycemic response areas of the different
               tween B, R, and S (54 in subject 8). Next, the means of                  subjects (F(11(106) = 54.64, P < 0.01, Table 3). In addi-
               all the combinations of the four tests taken three at a                  tion, there was a significant interaction between the ef-
               time were calculated, resulting in 64 comparisons be-                    fects of test meal and subject (F         6) = 3.90, P < 0.01),
                                                                                                                               (22J0
               tween B, R, and S (4 in subject 8). Finally, there was                   indicating that the differences between the test meals'
               one comparison in each subject between the means of                      incremental glycemic response areas varied in the dif-
               the four tests of B, R, and S. For each group of com-                    ferent subjects. However, when the results were ex-
                parisons there were six possible outcomes: B > R > S,                   pressed as the Gl, there was no significant difference
                B>S>R, R>B>S, R>S>B, S>B>R, andS between the subjects (F                                                     = 1.57, NS) and no inter-
                                                                                                                      (11106)
                > R > B. If the glycemic responses of B, R, and S were                  action between the effects of test meal and subject
                randomly distributed, 17% of the total comparisons would                F(22,io6) = 1-12, NS, Table 3).
                be correct (i.e., B > R > S) and 83% incorrect. The                     Comparison of different meals within subjects. In all
               observed number of correct rankings in each subject                       12 subjects, the mean glycemic response area for B was
                                                                                   2    greater than R, which was greater than S (Table 3). The
               was compared with that expected by chance with x -
               analysis (14).                                                           differences between test meals were not statistically sig-
                                                                                        nificant in subjects 2, 8, and 11 because of large within-
                                                                                         individual variability of glycemic responses. For the re-
               RESULTS                                                                  maining 9 subjects, B was significantly greater than R
                                                                                         in 5 and greater than S in all 9, with R being significantly
               The mean glycemic responses for the first, second, third,                greater than S in 4 (Table 3).
                and fourth repeats of the three test meals are shown in                  Ranking of glycemic responses within subjects. The
                Fig. 1. The pattern of the mean glycemic responses was                  overall proportion of correct rankings of individual tests
                similar in every case with B > R > S. The overall                       was 71 % (P < 0.001, Table 4). In 11 of 12 subjects, the
                mean ± SD glycemic responses of B, R, and S test meals,                  proportion of correct rankings was significantly greater
                respectively, were all significantly different from each                than would have been expected by chance (Table 4).
               128                                                                                         DIABETES CARE, VOL. 13, NO. 2, FEBRUARY 1990
                                                                                                T.M.S. WOLLVER AND ASSOCIATES
            TABLE 3
             Incremental areas under the curve and glycemic index values for four test meals of bread, rice, and spaghetti taken
             by each subject
                                        Area under the curve mM • min                                 Glycemic index
             Subject           Bread               Rice              Spaghetti           Bread             Rice           Spaghetti
                1           1925 ± 98          1493 ± 153*          802 ± 129t          100 ± 5          78 ± 8*          42 ± 7t
                2           1740 ± 78          1373 ± 531          1243 ± 206           100 ± 4          79 ± 31          72 ± 12
                3           1709 ± 197         1133 ± 281*          696 ± 83t           100 ± 12         66 ± 16*         41 ± 5+
                4           1196 ± 115          855 ± 199*          111 ± 92*           100 ± 10         72 ± 17*         65 ± 8*
                5           1224 ± 148          761 ± 268*          472 ± 148*          100 ± 12         62 ± 22*         39 ± 12*
                6           1214 ± 236         1033 ± 107           544 ± 151t          100 ± 19         85 ± 9           45 ± 12t
                7            970 ± 101          620 ± 68*           567 ± 83*           100 ± 10         64 ± 7*          59 ± 9*
                8            748 ± 341          607 ± 204           553 ± 184           100 ± 46         81 ± 27          74 ± 25
                9            909 ± 96           730 ± 150           365 ± 25t           100 ± 11         80 ± 16          40 ± 3t      Downloaded from http://diabetesjournals.org/care/article-pdf/13/2/126/439321/13-2-126.pdf by guest on 04 January 2023
               10            601 ± 76           420 ± 114           282 ± 90*           100 ± 13         70 ± 19*         47 ± 15*
               11            603 ±115           451 ± 131           413 ± 101           100 ± 19         75 ± 22          69 ± 17
               12            420 ± 117          350 ± 42            258 ± 43*           100 ± 28         83 ± 10          62 ± 10*
             Values are means ± SD.
             *P < 0.05 vs. bread.
             +P < 0.05 vs. bread and rice.
            The proportion of incorrect rankings was greater for sub-    proportion of correct predictions increased to 83, 92,
            jects with the most variable glycemic responses (r =         and 100%, respectively.
            0.644, P < 0.05). However, none of the clinical char-
            acteristics of the subjects were significantly related to
            the proportion of correct rankings (age, r = 0.379; du-      DISCUSSION
             ration of diabetes, r = -0.383; fasting C-peptide, r =
             -0.318; postprandial C-peptide, r = -0.328; treat-                 he results demonstrate that different individuals
             ment with insulin, r = 0.239; classification of diabetes,          share the same mean Gl values of foods. Thus,
            r = 0.392; mean fasting blood glucose, r = 0.346; SD                differences in Gl observed when individual tests
            of fasting blood glucose, r = -0.210; HbA , r = 0.338).      Tare compared are due largely to day-to-day var-
                                                       1c
            When comparisons were made between the means of              iability within the same subject. When tests of B, R, and
            two, three, and four repeated tests of each meal, the        S were repeated four times by each subject, the Gl cor-
            TABLE 4
             Pooled SD of glycemic index values for each subject and number (percentage) of 3-way comparisons for which ranking
             of glycemic responses in each individual was as predicted by Gl (i.e., bread > rice > spaghetti)
                                                                            Number of area values averaged for comparisons
             Subject                       Pooled SD               1                    2                   3                  4
                1                             6.6               64 (100)*           216 (100)            64 (100)             (100)
                2                            19.1               16(25)              126 (58)             48 (75)              (100)
                3                            11.9               60 (94)*            216 (100)            64 (100)             (100)
                4                            12.0               36 (56)*            156 (72)             56 (88)              (100)
                5                            16.0               60 (94)*            210(97)              64 (100)             (100)
               6                             14.3               48 (75)*            192 (89)             64 (100)             (100)
                7                             8.8               44 (69)*            186 (86)             56 (88)              (100)
               8                             29.5               14 (39)*             24 (44)              3(75)               (100)
               9                             11.4               56 (88)*            210(97)              64(100)              (100)
               10                            15.7               56 (88)*            204 (94)             64(100)              (100)
               11                            19.4               28 (44)*            144 (67)             48 (75)              (100)
               12                            18.1               48 (75)*            198 (92)             64 (100)             (100)
             Mean percentage
               correct predictions                                 71                  83                  92                 100
             Comparisons were conducted with individual area values and all possible combinations of means of 2, 3, and 4 values for each meal. Values
             in parentheses are percentages.
             *P < 0.001.
            DIABETES CARE, VOL. 13, NO. 2, FEBRUARY 1990                                                                       129
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...Thomas m s wolever bm phd glycemic index of foods david a jenkins dm dsc vladimir vuksan in individual subjects robert g josse md gerald wong alexandra l bsc rpdt downloaded from http diabetesjournals org care article pdf by guest on january we studied with diabetes to determine elusion is not necessarily valid if the tested each how well gl predicted ranking food only once and lack consistency was due responses different individuals within variability therefore repeated testing all ate three mixed meals bread rice or same meal subject required deter spaghetti gis respectively four mine whether times randomized complete block design mean consistent differences between day response areas ranked according every our objective observed sd values were dividuals shared common which significantly other no significant would allow be used predict difference it concluded that share for determined test confidence limits range taken occasions number group diabetic tests conducted expected can rese...

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