Advances in Bioscience and Biotechnology, 2013, 4, 1-10 ABB
http://dx.doi.org/10.4236/abb.2013.49A001 Published Online September 2013 (http://www.scirp.org/journal/abb/)
Glycemic responses to glycemia-targeted
specialized-nutrition beverages with varying
carbohydrates compared to a standard nutritional
beverage in adults with type 2 diabetes*
Amy A. Devitt#, Jennifer A. Williams, Yong S. Choe, Deborah S. Hustead, Vikkie A. Mustad
Abbott Nutrition, Abbott Laboratories, Columbus, USA
Received 11 July 2013; revised 12 August 2013; accepted 1 September 2013
Copyright © 2013 Amy A. Devitt et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: Postprandial plasma glucose concentra-
tion is an important diabetes management target.
Glycemia-targeted specialized-nutrition (GTSN) bev-
erages, containing various quantities and types of
carbohydrates (CHO), have been formulated to blunt
postprandial hyperglycemia. The objective of this
research was to evaluate the effectiveness of these
products on postprandial glycemic and hormonal
responses based on comparisons of GTSN with dif-
fering carbohydrate quantities or types. Methods: In
two randomized, double-blind, crossover studies, par-
ticipants (mean age 61 years) with type 2 diabetes
consumed GTSN in a meal tolerance test. In the CHO
Quantity Study, a standard nutritional beverage
(STD) was compared to a low carbohydrate nutri-
tional beverage with tapioca dextrin (GTSN-TDX)
and a balanced carbohydrate nutritional beverage
containing a blend of the slowly-digesting carbohy-
drates maltodextrin and sucromalt (GTSN-SDC). In
the CHO Type Study, the GTSN beverages had simi-
lar carbohydrate quantities but varied in carbohy-
drate composition with GTSN-SDC compared to a
formula with tapioca starch and fructose (GTSN-
TS&F), and one with isomaltulose and resistant
starch (GTSN-I&RS). Postprandial (0 - 240 min)
concentrations of blood glucose, insulin (CHO Quan-
tity Study only) and glucagon-like-peptide (GLP)-1
(CHO Quantity Study only) were measured. Results:
Despite having substantially different carbohydrate
quantities, the GTSN blunted the glucose positive
area under the curve (AUC0 - 240 min) by 65% to 82%
compared to the STD formulation (p < 0.001). GTSN
also elicited ~50% lower insulin positive AUC0 - 240 min
(p < 0.05), while postprandial GLP-1 responses were
increased (p = 0.018) vs. STD. In the CHO Type
Study, glucose positive AUC0 - 240 min tended to be
lower for GTSN-SDC (1477 ± 460) than GTSN-TS&F
(2203 ± 412 ; p = 0 .062) an d GTSN-I&RS ( 2190 ± 412;
p = 0.076). No differences were observed between
GTSN-TS&F and GTSN-I&RS. Conclusions: These
results demonstrate the effectiveness of several GTSN
products and suggest that both CHO quantity and
type play important roles in postprandial glycemic
response in men and women with type 2 diabetes.
Furthermore, GTSN products containing slow-di-
gesting carbohydrates can blunt postmeal glucose and
insulin concentration despite delivering greater total
grams of CHO, which provides a dietary benefit for
people with diabetes.
Keywords: Diabetes; Oral Nutritional Supplement;
Glycemia-Targeted Specialized-Nutrition;
Glucagon-Like Peptide 1; Glycemic Control;
Low-Glycemic/Slowly-Digested Carbohydrates
1. INTRODUCTION
In 2007, pre-diabetes and diabetes cost the United States
(US) an estimated $218 billion in medical expenditures
and lost productivity [1]. Higher rates of health care utili-
zation among individuals with diabetes may be attributed
to long-term complications including heart disease and
stroke, high blood pressure, blindness, kidney disease,
nervous system disease, amputations, dental disease,
*Author Disclosure Statement: AAD, JAW, YSC, DSH, and VAM are
employees of the sponsor company, Abbott Laboratories.
Funding: Abbott Nutrition, Abbott Laboratories funded both clinical
studies described herein.
#Corresponding author.

A. A. Devitt et al. / Advances in Bioscience and Biotechnology 4 (2013) 1-10 2
pregnancy complications, ketosis, and increased suscep-
tibility to other illnesses [2]. Epidemiological observa-
tions suggest that the risk of developing these complica-
tions, particularly those related to the macro- and mi-
crovasculature, in individuals with type 2 diabetes as
well impaired glucose tolerance can be dramatically re-
duced by improving glycemic control [3-5]. Both fasting
and postprandial glucose concentrations are important
targets for improving long-term outcomes [3-10]. Cur-
rent guidelines for treating diabetes recommend the use
of pharmacologic therapies that lower postprandial glu-
cose levels as well as adjunctive diet therapy, including
consumption of glycemia-targeted specialized-nutrition
(GTSN) products [4,5].
The use of diabetes-specific enteral nutrition formulas
is reported to be associated with improved glycemic con-
trol compared with standard enteral nutrition formulas
that are generally high in carbohydrate (mostly high gly-
cemic sources), and low in fat and fiber [11-23]. GTSN
products often utilize two distinct approaches to impart
glycemic control 1) manipulation of carbohydrate quan-
tity by providing less total carbohydrate (35% - 40% of
energy) and/or 2) manipulation of carbohydrate type by
utilization of specialized carbohydrates with differing
digestion and absorption profiles. The studies described
herein examined the glucose, insulin, and glucagon-like
peptide 1 (GLP-1) responses to consumption of several
commercially available US and non-US manufactured
GTSN beverages with different quantities or types of
glycemia-targeted carbohydrates, and a standard nutrition
beverage, in men and women with type 2 diabetes.
2. METHODS
2.1. Study Design
This paper describes the results from two separate ran-
domized, double-blind, three-treatment crossover studies
conducted at one clinical research site (Radiant Research,
Cincinnati, OH). Where one study assessed the impact of
the quantity of carbohydrate consumed (CHO Quantity
Study) and the other study assessed the type of carbohy-
drate consumed (CHO Type Study). The studies were
conducted according to Good Clinical Practice Guide-
lines, all applicable privacy regulations, Food and Drug
Administration regulations, and the ethical principles that
have their origin in the Declaration of Helsinki. An ex-
ternal institutional review board (Schulman Associates
IRB, Inc., Cincinnati, OH) approved each protocol be-
fore the study began. Informed consent was obtained
from all subjects prior to the initiation of any study-re-
lated procedures, and subjects were informed of their
right to withdraw from the study at any time. Subjects
completed a screening visit and, if eligible, three treat-
ment visits which were separated by 7 - 14 days. A meal
tolerance test was performed at each treatment visit.
2.2. Subjects
Both studies recruited men and women between 18 and
75 years of age, inclusive, who stated that they had type
2 diabetes [as evidenced by the use of oral hypoglycemic
medication(s) for at least two months prior to screening],
and who had a body mass index  18.5 kg/m2 and ≤ 35
kg/m2. Women of childbearing potential who were not
pregnant or lactating, and who were at least six weeks
postpartum prior to the screening visit, could enroll if
they were practicing an acceptable method of birth con-
trol. Individuals with type 1diabetes were excluded from
participation as were those using exogenous insulin or
exenitide, and anyone with a history of diabetic ketoaci-
dosis, congestive heart failure, severe gastroparesis, renal
disease, end-stage organ failure, or who had received an
organ transplant. The occurrence of a significant cardio-
vascular event, such as myocardial infarction or stroke,
less than six months prior to screening was also exclu-
sionary, as was having an active malignancy (excluding
basal and squamous cell carcinomas and carcinoma
in-situ of the cervix), clotting or bleeding disorder, he-
patic disease, or a chronic contagious infectious disease
(such as tuberculosis, hepatitis B or C, or HIV). Subjects
with a current infection requiring medication or hospi-
talization, or who had undergone surgery or received sys-
temic corticosteroid treatment in the past three months,
or antibiotics in the past three weeks, were not enrolled.
With the exception of oral hypoglycemic medication(s)
and stable-dose (for at least two months prior to screen-
ing) antihypertensive, lipid-lowering, thyroid, or hor-
mone therapy, all other medications and herbal and die-
tary supplements that could profoundly affect blood glu-
cose, were disallowed.
2.3. Test Products
To assess the impact of the quantity of carbohydrate
(CHO Quantity Study), eligible participants were ran-
domly assigned in a double-blind, crossover manner, to
receive a single serving of either 1) a standard nutri-
tional beverage [STD; Ensure®, Abbott Nutrition, Co-
lumbus, OH], 2) a GTSN beverage with tapioca dextrin
[GTSN-TDX; Boost Glucose Control®, Nestlé Health-
Care Nutrition, Ontario, Canada], or 3) a GTSN bever-
age with a proprietary blend of slow-digesting carbohy-
drates including resistant maltodextrin and sucromalt
[GTSN-SDC; Glucerna SR®, Abbott Nutrition] (Table 1).
Assessment of the impact of the type of carbohydrate
(CHO Type Study) was done by randomly assigning eli-
gible participants in a double-blind, crossover manner, to
receive a single serving of either 1) the same slow-di-
gesting carbohydrate GTSN beverage administered in the

A. A. Devitt et al. / Advances in Bioscience and Biotechnology 4 (2013) 1-10 3
first study [GTSN-SDC], 2) a GTSN beverage with
tapioca starch and fructose [GTSN-TS&F; Resource
Diabet®, Nestlé HealthCare Nutrition], or 3) a GTSN
beverage with isomaltulose and resistant starch [GTSN-
I&RS; Diasip®, Nutricia Advanced Medical Nutrition,
Dublin, Ireland] (Table 1). To maintain blinding, only
the assigned product coordinator saw the study products
in their original labeled packaging and the staff members
who had direct contact with study subjects remained
unaware of treatment assignment.
was necessary in order for the meal tolerance test to pro-
ceed. At the clinic, subjects were instructed to take their
usual morning dose of antihyperglycemic medication(s)
if applicable, and approximately 15 minutes later a base-
line venous blood sample was collected via an indwell-
ing catheter. The time of test beverage consumption was
standardized for each subject between visits. Not more
than 30 minutes later, the chilled test beverage was given
to the subjects in a styrofoam cup with a lid and straw
and the first mouthful of test beverage was considered as
time = 0 minutes. Subjects were asked to drink the entire
beverage within 10 minutes. The study staff assessed
treatment compliance by witnessing the subject drink the
study product. Subjects were given free access to water
throughout the remainder of the visit. Postprandial blood
samples were collected at 30, 60, 90, 120, 180, and 240
minutes (±5 minutes at each time point) after start of
consumption of test beverage. Upon completion of the
meal tolerance test, the subject’s capillary blood glucose
level was measured via finger-stick to ensure a level be-
tween 60 and 300 mg/dL, and a snack was provided be-
fore leaving the clinic.
2.4. Meal Tolerance Test Procedures
At the screening visit, subjects received specific instruc-
tions regarding the diet and physical activity restrictions
to follow prior to each treatment visit, including 1) fast
for approximately 8 - 14 hours, 2) consume at least an
average of 150 g carbohydrate per day for the three days
prior to visits, 3) avoid consumption of alcohol and do
not exercise strenuously in the 24 hours prior to the visits,
and 4) delay taking the morning dose of oral anti-hyper-
glycemic medications on the test days until instructed to
do so at the clinic. To confirm compliance with carbohy-
drate intake prior to the meal tolerance tests, subjects
were provided with diet records to complete for the three
days prior to each treatment visit. The study coordinator
reviewed these records prior to performing the meal tol-
erance test.
2.5. Laboratory Analyses and Calculations
Analyses of baseline and postprandial blood samples for
plasma glucose (both studies), serum insulin (CHO
Quantity Study only) was performed at a central labora-
tory (ICON Central Laboratories, Farmingdale, New
York, USA). Plasma glucose was analyzed by the glu-
cose hexokinase method at a central laboratory (UV,
Roche Hitachi Modular). The methodology and criteria
for measuring glycemic response was adapted from
A fasting capillary blood glucose measurement was
taken via a glucose meter (FreeStyle Flash® Meter, Ab-
bott Diabetes Care, Inc., Alameda, CA) at the beginning
of each treatment visit; a value  60 and < 300 mg/dL
Table 1. Nutrition information per serving of study producta.
CHO Quantity Study CHO Type St udy
STD GTSN-TDX GTSN-SDC GTSN-TS&F GTSN-I&RS
Serving size, mL 237 237 237 200 200
Calories, kcal 250 190 220 200 200
Protein, g 9 16 11 14 10
Fat, g 6 7 8 6 8
Total carbohydrate, g 40 16 29 24 23
Sugars, g 23 4 4 5 17
Dietary Fiber, g 0 3 6 — 4
Soluble, g 0 — — 4 3.4
Insoluble, g 0 — — — 0.6
Chromium, µg 30 60 200 20 24
aDashes indicate items that were not listed in the nutrition information. Abbreviations: GTSN-SDC = Glycemia-targeted specialized-nutrition-slow digesting
carbohydrates, GTSN-TDX = Glycemia-targeted specialized-nutrition-tapioca dextrin, GTSN-TS&F = Glycemia-targeted specialized-nutrition-tapioca starch &
fructose, GTSN-I&RS = Glycemia-targeted specialized-nutrition-isomaltulose and resistant starch, STD = standard nutritional formula.

A. A. Devitt et al. / Advances in Bioscience and Biotechnology 4 (2013) 1-10 4
criteria used in previous studies [31-33]. Serum insulin
was measured using immunometric assay (Siemens
Healthcare Diagnostics IMMULITE Series). Blood sam-
ples for plasma GLP-1 (6 - 36 amide; CHO Quantity
Study only) measurement were collected into dipeptidyl
peptidase IV protease inhibitorcontaining tubes are were
analyzed at Quest Diagnostics central laboratory (Teter-
boro, NJ, USA).
Calculations for area under the curve from 0 - 240
minutes (AUC0 - 240 min), positive AUC0 - 240 min, peak value,
adjusted peak value, and peak time, were completed for
glucose, insulin, and GLP-1. These calculations were
performed according to a priori rules, described briefly
here. AUC was calculated by the trapezoidal method for
each variable. Positive AUC0 - 240 min was also calculated
using the trapezoidal method for the area above the base-
line (time 0) value for a given variable and the area be-
low the baseline was considered as zero. Peak value was
the maximum value of all valid points over 0 - 240 min-
utes. Adjusted peak value was the peak value minus the
value at time = 0. Peak time was the first time point dur-
ing the 0 - 240 minute interval at which the peak value
was attained.
2.6. Statistical Analyses
Statistical analyses were generated using SAS version
9.1.3 (Cary, NC). The randomization scheme was deter-
mined according to Latin squares for a crossover study
balanced for carryover effect. Sample sizes were chosen
such that 18 evaluable subjects in CHO Quantity Study
had at least 80% power to detect a difference in means of
the primary outcome variable, adjusted peak value for
plasma glucose concentration over 0 - 240 minutes,
characterized by a standardized effect size of 0.2333. In
the CHO Type Study (a pilot study in nature), 18 evalu-
able subjects would have 80% power to detect a differ-
ence between GTSN-SDC and either of the other two
products (GTSN-TS&F or GTSN-I&RS) for adjusted
peak value for plasma glucose of 35% - 45% if variabil-
ity was large and 10% - 20% if variability was small.
Statistical analyses were performed on data from all sub-
jects who were randomized into the study, and on a sub-
set which included only those subjects who were deemed
to be protocol evaluable (i.e., those who met all entry
criteria, for whom there were no missing values for the
primary outcome variable, and who consumed all test
meals). The results from both sets of analyses were simi-
lar. The protocol evaluable data are presented herein.
Each continuous variable was analyzed with a three-
treatment three-period repeated measures analysis of
variance using SAS PROC MIXED with variance com-
ponents covariance structure and Satterthwaite degrees
of freedom, with treatment and period as fixed effects
and subjects as random effect. The three pairwise differ-
ences of the least squares means of the treatments were
tested using Tukey-Kramer p-value adjustments. The
residuals from the parametric analysis were utilized to
check for deviation from normality using the Shapiro-
Wilk test, and if the parametric approach was determined
to be inappropriate, then three pairwise treatment differ-
ences were analyzed using signed rank test with step
down Bonferroni p-value adjustments. Period effects
were not tested in the nonparametric analyses. A result
was declared to be statistically significant if the p-value
was less than 0.05.
3. RESULTS
The CHO Quantity Study enrolled 25 subjects, but four
were excluded from the evaluable analyses for the fol-
lowing reasons: withdrew for personal reasons (n = 1),
discontinued the study after a non-study product-related
hospitalization for pneumonia (n = 1), had a recent
change in oral hypoglycemic medication (n = 1), and
used an antibiotic (n = 1). The CHO Type Study enrolled
22 subjects and all completed the study, however because
one subject was missing data for the primary outcome
variable, 21 subjects were included in the protocol evalu-
able analysis. Demographic and other baseline charac-
teristics of the evaluable subjects in both studies were
similar (Table 2). Full compliance with treatment, i.e.,
complete beverage consumption, was confirmed for all
evaluable subjects in both studies. All study products
appeared to be well tolerated, and overall there were no
safety concerns and no clinical differences in signs or
symptoms associated with consumption of the study
products.
Table 2. Baseline characteristics of evaluable subjects.
Characteristic CHO Quantity Study
(n = 21) CHO Ty pe Study (n = 21)
n (%)
Sex
Male 15 (71) 14 (67)
Female 6 (29) 7 (33)
Ethnicity
Caucasian 19 (90) 20 (95)
African American2 (10) 1 (5)
Mean (SEM)
Age, years 61 (1.9) 61 (1.8)
Height, cm 172 (2) 171 (2)
Weight, kg 91 (3) 90 (3)
Body Mass Index,
kg/m2 31 (0.7) 31 (0.6)
Abbreviation: SEM = standard error of the mean.

A. A. Devitt et al. / Advances in Bioscience and Biotechnology 4 (2013) 1-10 5
Plasma glucose concentrations at each time point dur-
ing the meal tolerance tests are shown in Figure 1; over-
all metabolic responses are shown in Table 3. In the
CHO Quantity Study (Figure 2) a comparison of GTSN-
TDX, GTSN-SDC and STD, revealed that the adjusted
peak glucose responses were significantly lower with
GTSN-TDX and GTSN-SDC compared with STD (p <
0.001) and GTSN-TDX was significantly lower than
GTSN-SDC (p = 0.005). Consumption of GTSN-SDC
and GTSN-TDX also elicited significantly lower glucose
positive AUC0 - 240 min compared with STD (68% and
82%, respectively, p < 0.001 for both); although small,
the difference between GTSN-SDC and GTSN-TDX was
also statistically significant (p < 0.001). Peak time for
glucose was significantly shorter from GTSN-TDX
compared to STD, however no differences were observed
between GTSN-SDC and the other treatments.
Postprandial adjusted peak insulin was 48% and 44%
lower after GTSN-SDC and GTSN-TDX ingestion, re-
spectively, vs. STD (p < 0.001 for both) (Ta ble 3). Con-
sumption of the diabetes-specific products also elicited
52% (GTSN-SDC) and 50% (GTSN-TDX) lower insulin
positive AUC0 - 240 min vs. STD (p < 0.001 for both) (Ta-
ble 3). However, peak time for insulin was significantly
shorter from GTSN-TDX compared to GTSN-SDC and
STD.
GLP-1 positive AUC0 - 240 min responses were higher
after GTSN-SDC and GTSN-TDX consumption com-
pared with STD, but the difference was statistically sig-
Time (min) After Beverage Consumption
Glu cose (mg/dL)
100
150
200
250 STD
DSN-TDX
DSN-SDC - Stu dy 1
DSN-SDC - Stu dy 2
DSN-TS&F
DSN-I&RS
306090120 180 240
A
GTSN-I&RS - CHO T ype S tudy
GTSN-TDX - CHO Quantity Study
GTSN TS&F - CHO Type S tudy
STD - CHO Quantit
y
Stud
y
GTSN-SDC - CHO Quantity Study
GTSN-SDC - CHO Type Study
Figure 1. Mean (SEM) baseline and postprandial plasma glu-
cose concentrations.
Time (min) After Beverage Consumpt ion
Insulin (IU/mL)
0
20
40
60
80
100 STD
DSN-TDX
DSN-SDC
306090120 180 240
STD
GTSN - TDX
GTSN - SDC
Figure 2. Mean (SEM) baseline and postprandial serum insu-
linconcentrations (CHO Quantity Study).
nificant only for GTSN-TDX (p = 0.018) (Table 3). Peak
time for GLP-1 was significantly higher for GTSN-TDX
compared to STD while no differences were seen be-
tween GTSN-SDC and any other treatment.
Pair-wise comparisons between the three GTSN
treatments with differing carbohydrate composition in
the CHO Type Study revealed small but significant dif-
ferences (Tab le 3 ); consumption of GTSN-SDC led to a
significantly lower adjusted peak plasma glucose com-
pared to GTSN-TS&F (p < 0.001) and GTSN-I&RS (p =
0.005). No differences were observed between GTSN-
TS&F and GTSN-I&RS for adjusted peak plasma glu-
cose (p = 0.333). A similar pattern of a significantly
lower glucose peak value was observed from the com-
parison between GTSN-SDC and both GTSN-TS&F (p <
0.001) and GTSN-I&RS (p < 0.001) with no differences
seen from the comparison of GTSN-TS&F and GTSN-
I&RS (p = 0.344). Plasma glucose AUC0 - 240 min was sig-
nificantly smaller for GTSN-SDC compared to both
GTSN-TS&F (p = 0.028) and GTSN-I&RS (p = 0.003)
with no differences observed between the two latter
treatment comparisons (p = 0.653). However, though
GTSN-SDC tended to have a lower glucose positive
AUC0 - 240 min compared to GTSN-TS&F and GTSN-
I&RS no significant differences were observed from any
of the pair-wise treatment comparisons.
4. DISCUSSION
The American Diabetes Association (ADA) recommends
that postprandial glucose levels be targeted if glycosy-
lated hemoglobin goals are not met, despite reaching
preprandial glucose goals [4]. These results, in agree-
ment with previous examinations, indicate that consump-
tion of GTSN beverages, compared with a standard nu-
trition beverage, significantly attenuates postprandial
hyperglycemic and insulinemic responses in individuals
with type 2 diabetes [11-30]. The mean unadjusted peak
postprandial plasma glucose values elicited by all four of
the GTSN products ranged from ~148 mg/dL to 169
mg/dL, all within the ADA recommended target of <180
mg/dL at 1 - 2 hours postprandial for diabetic patients
who have premeal glucose values within target, but have
glycosylated hemoglobin values above target level [4].
However, the lower 1 - 2 hour postmeal glucose target
recommended by the International Diabetes Federation,
160 mg/dL, was achieved only after consumption of the
GTSN-TDX (CHO Quantity Study) and GTSN-SDC
(CHO Type Study) products [5].
Based on total carbohydrate content, it was to be
expected that STD containing 40 g carbohydrate would
result in the highest postprandial glucose response.
However, if considering total carbohydrate alone, one
ight have also expected a substantially higher glycemic m

A. A. Devitt et al. / Advances in Bioscience and Biotechnology 4 (2013) 1-10 6
Table 3. Glucose, insulin, and glucagon-like peptide-1 responses to meal tolerance tests1.
CHO Quantity Study2 (n = 21) CHO Type St udy3 (n = 21)
STD GTSN-TDXGTSN-SDC GTSN-SDC GTSN-TS&F GTSN-I&RS
Mean (SEM)
Plasma Glucose
AUC0 - 240 min 36309 (2134)NA 31136 (1827)NA 32294 (2161)NA 29924 (1593)x31413 (1749)y 31851 (1743)y
Positive AUC0 - 240 min 6266 (747)a 1144(252)b 2000(339)c 1477(460) 2203(412) 2190(412)
Unadjusted Peak, mg/dL 206.6 (9.2)NA 156.1 (8.6)NA 162.1 (9.4)NA 148.3 (7.5)x 169.3 (8.7)y 164.0 (8.5)y
Adjusted Peak, mg/dL 71.7 (5.8)a 18.4 (2.5)b 25.9 (2.7)b 17.9 (3.4)x 32.8 (4.1)y 28.6 (3.7)y
Peak time, min 70.0 (5.2)a 48.6 (3.9)b 58.6 (5.3)ab 60.0 (5.9) 52.9 (4.6) 58.6 (4.8)
Serum Insulin
AUC0 - 240 min 11764 (1313)NA 7632 (697)NA 7848 (865)NA DNC DNC DNC
Positive AUC0 - 240 min 7286 (930)a 3635 (492)b 3488 (602)b DNC DNC DNC
Unadjusted Peak, µIU/mL 96.6 (11.3)NA 60.1 (7.8)NA 58.8 (9.1)NA DNC DNC DNC
Adjusted Peak, µIU/mL 77.0 (9.9)a 42.8 (7.2)b 40.1 (8.4)b DNC DNC DNC
Peak time, min 75.0 (5.1)a 52.5 (4.3)b 74.3 (7.1)a DNC DNC DNC
Plasma GLP-1
AUC0 - 240 min 3967 (512)NA 5085 (532)NA 5435 (689)NA DNC DNC DNC
Positive AUC0 - 240 min 1367 (213)a 2580 (322)b 2075 (372)ab DNC DNC DNC
Unadjusted Peak, pmol/L 28.1 (3.4)NA 34.2 (3.5)NA 37.2 (5.4)NA DNC DNC DNC
Adjusted Peak, pmol/L 16.6 (2.5) 23.5 (2.9) 21.8 (3.7) DNC DNC DNC
Peak time, min 52.1 (8.5)a 97.9 (14.8)b 72.6 (9.3)ab DNC DNC DNC
1Abbreviations: GTSN-IR&S = Glycemia-targeted specialized-nutrition-isomaltulose, GTSN-SDC = Glycemia-targeted specialized-nutrition-slow digesting
carbohydrates, GTSN-TDX = Glycemia-targeted specialized-nutrition-tapioca dextrin, GTSN-TS&F = Glycemia-targeted specialized-nutrition-tapioca starch &
fructose, GLP-1 = glucagon-like peptide-1, SEM = standard error of the mean, STD = standard nutritional formula, DNC = data not collected. 2In the CHO
Quantity Study, significant differences between treatments are denoted by differing superscripts (a,b,c; when p < 0.05), NA = Not Analyzed. 3In the CHO Type
Study, significant differences between treatments are denoted by differing superscripts (x,y; when p < 0.05).
response for GTSN-SDC, containing 29 g total carbohy-
drate, compared with the other GTSN, containing lower
carbohydrate levels (16 - 23 g). These results point to the
importance of not only the quantity of carbohydrate, but
also its type on the resulting glycemic response [15,34-
40].
The differences in postprandial glycemic responses
among the GTSN beverages assessed in the CHO Type
Study were a result of the carbohydrate sources in each
formula. GTSN-SDC contained a blend of low glycemic
index, slowly digestible carbohydrates including sucro-
malt (a natural analog of sucrose) [41]. and a form of
maltodextrin that is resistant to amylase digestion in the
small intestine [42]. Isomaltulose, found in the GTSN-
I&RS beverage, is another low-glycemic index, slowly
digestible carbohydrate [43-47] which has a hydrolyza-
tion rate of 20% - 25% that of sucrose [48]. The GTSN-
TS&F product contained added fructose which has a
very low-glycemic index and is often recommended, in
limited quantities, in diabetes because it does not stimu-
late pancreatic beta-cell insulin secretion, and aids in
glucose clearance through the liver [49]. In the present
head-to-head comparison, ingestion of GTSN-SDC was
superior to both GTSN-I&RS and GTSN-TS&F for
blunting postprandial hyperglycemia.
In addition to the various carbohydrate blends in the
nutritional beverages examined in these studies, differ-
ences in caloric density and other nutrients may have
also contributed to the postprandial glycemic responses.
Per serving, STD provided the greatest number of
calories (250 kcal) followed by GTSN-SDC (220 kcal),
GTSN-TS&F and GTSN-I&RS (both 200 kcal), and
GTSN-TDX (190 kcal). The quantity and type of protein
ingested may also have some effect on postprandial
hyperglycemia [50-52]. As the addition of protein to an
oral glucose load has been shown to slow gastric empty-
ing [52]. Proteins also enhance insulin secretion [53,54].
The STD beverage contained the least amount of protein
(9 g/serving), and the GTSN-TDX beverage contained the
largest amount (16 g/serving). Dietary fiber also plays an
important role in postprandial glycemic response [55,56].
Consumption of some dietary fibers (mainly viscous,
soluble fibers) can diminish postprandial glucose excur-
sions by their effects on intestinal motility and gastro-
intestinal hormones and enzymes [56]. The STD bever-
age provided no dietary fiber; and, among the diabetes-

A. A. Devitt et al. / Advances in Bioscience and Biotechnology 4 (2013) 1-10 7
specific beverages, GTSN-SDC contained the greatest
amount of dietary fiber (6 g soluble fiber/serving) com-
pared with GTSN-TDX (3 g dietary fiber/serving, type
not specified on the label), GTSN-TS&F (4 g soluble
fiber/serving), and GTSN-I&RS (3.4 soluble and 0.6
insoluble fiber/serving).
As shown previously [21], postprandial GLP-1, an in-
cretin hormone that is released from gut endocrine cells
during meals, and induces glucose-dependent stimulation
of insulin secretion, while suppressing glucagon secre-
tion, [57,58] responded in the opposite direction to post-
prandial insulin. Postive AUC0 - 240 min for GLP-1 was
increased after ingestion of GTSN-SDC but only signifi-
cantly after consumption of GTSN-TDX, vs. STD, de-
spite this difference postprandial insulin was signifi-
cantly lower from both GTSN-SDC and GTSN-TDX
compared to STD. This suggests that the GLP-1 positive
AUC from GTSN-TDX wasn’t sufficient to elicit meta-
bolic changes beyondGTSN-SDC. The exact mechanism
for the effects of GLP-1 on glucose control remains to be
determined [21]. Nevertheless, incretin-based therapies,
such as GLP-1 agonists and dipeptidyl peptidase-4 in-
hibitors that slow the removal of GLP-1 from the circu-
lation, are becoming more widely used in the treatment
of diabetes [59].
Although the study design of administering a single
bolus of each beverage on separate days is typical for
assessing postmeal glucose and insulin responses, it does
not allow application of these findings to what might
occur with long-term consumption. More studies exam-
ining the impact of GTSN formulations on long-term
glycemic control, as well as their effects on body weight,
are needed. There is relatively large variability in glucose
responses within (day-to-day) and among individual pa-
tients consuming enteral feeding products [11]. Although
variability was minimized by the use of a crossover study
design, inter-subject variability might explain the
difference between the two studies in the glycemic re-
sponses to GTSN-SDC ingestion. Another potential
limitation on the interpretation of these findings was the
fact that STD was not examined in the second study.
However, standard nutrition beverages have previously,
and consistently, been shown to result in higher post-
prandial glucose than diabetes-specific products [11-23].
so the side-by-side comparison of responses to STD
consumption in the CHO Quantity Study with the re-
sponses to ingestion of diabetes-specific beverages in the
CHO Type Study, was not unreasonable.
5. CONCLUSION
These results confirm the efficacy of GTSN products,
compared with a standard nutritional beverage, for at-
tenuating postprandial hyperglycemia in men and women
with type 2 diabetes, and further demonstrate the impor-
tance of carbohydrate amount and type on this effect.
Among the GTSN products, the beverage containing a
mixture of slowly-digestible carbohydrates including
sucromalt and resistant maltodextrin was superior as it
elicited glycemic control without reducing the quantity
of carbohydrate consumed. Reducing postprandial blood
glucose excursions by the use of GTSN is important for
overall glycemic control, and would be expected to im-
prove clinical outcomes in diabetic patients [3].
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