diabetes research and clinical practice 111 (2016) 28–35

Contents available at ScienceDirect

Diabetes Research
and Clinical Practice
jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es

Glycemic load, exercise, and monitoring blood

glucose (GEM): A paradigm shift in the treatment
of type 2 diabetes mellitus

Daniel J. Cox a,*, Ann G. Taylor b, Harsimran Singh a, Matthew Moncrief a,

Anne Diamond a, William S. Yancy Jr.c, Shefali Hegde a, Anthony L. McCall d
a
Center for Behavioral Medicine Research, University of Virginia School of Medicine, PO Box 800223, Charlottesville,
VA 22908, USA
b
University of Virginia School of Nursing, PO Box 800782, Charlottesville, VA 22908, USA
c
Duke University School of Medicine, Durham Veterans Affairs Medical Center, 508 Fulton St # 3, Durham, NC 27705,
USA
d
Endocrinology and Metabolism, University of Virginia School of Medicine, PO Box 801407, Charlottesville, VA 22908,
USA

article info abstract

Article history: Aims: This preliminary RCT investigated whether an integrated lifestyle modification
Received 23 July 2015 program that focuses on reducing postprandial blood glucose through replacing high with
Received in revised form low glycemic load foods and increasing routine physical activities guided by systematic self-
1 September 2015 monitoring of blood glucose (GEM) could improve metabolic control of adults with type 2
Accepted 14 October 2015 diabetes mellitus, without compromising other physiological parameters.
Available online 21 October 2015 Methods: Forty-seven adults (mean age 55.3 years) who were diagnosed with type 2 diabetes
mellitus for less than 5 years (mean 2.1 years), had HbA1c 7% (mean 8.4%) and were not
Keywords: taking blood glucose lowering medications, were randomized to routine care or five 1-h
Type 2 diabetes mellitus instructional sessions of GEM. Assessments at baseline and 6 months included a physical
Glycemic load exam, metabolic and lipid panels, and psychological questionnaires.
Exercise Results: The GEM intervention led to significant improvements in HbA1c (decreasing from
Physical activities 8.4 to 7.4% [69–57 mmol/mol] compared with 8.3 to 8.3% [68–68 mmol/mol] for routine care;
Self-monitoring of blood glucose Interaction p < .01) and psychological functioning without compromising other physio-
Postprandial blood glucose logical parameters.
Conclusions: Consistent with a patient-centered approach, GEM appears to be an effective
lifestyle modification option for adults recently diagnosed with type 2 diabetes mellitus.
# 2015 Elsevier Ireland Ltd. All rights reserved.

recommended lifestyle modification (LM) as the sole initial

1. Introduction treatment for type 2 diabetes mellitus when diagnostic
glycosylated hemoglobin (HbA1c) is 7.5%. Specifically:
In 2012, the American Diabetes Association (ADA) and ‘‘Weight reduction, achieved through dietary means alone
the European Association for the Study of Diabetes [1] or with adjunctive medical or surgical intervention,

* Corresponding author. University of Virginia Health System, PO Box 800223, Charlottesville, VA 22908, USA. Tel.: +1 434 924 8021;
fax: +1 434 924 5314.
E-mail address: djc4f@virginia.edu (D.J. Cox).
http://dx.doi.org/10.1016/j.diabres.2015.10.021
0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.

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 diabetes research and clinical practice 111 (2016) 28–35
improves glycemic control and other cardiovascular risk
factors. Modest weight loss (5–10%) contributes meaningful-
ly to achieving improved glucose control . . . Foods high in
fiber (such as vegetables, fruits, whole grains, and legumes),
low-fat dairy products, and fresh fish should be emphasized.
High-energy foods, including those rich in saturated
fats, and sweet desserts and snacks should be eaten less
frequently and in lower amounts . . . As much physical
activity as possible should be promoted, aiming for at
least 150 min/week of moderate activity, including aerobic,
resistance, and flexibility training.’’. Thus, the ADA recom-
mends weight loss, less consumption of high-energy
foods, and at least 150 min/week of moderate physical
activity. It does not specify the role of self-monitoring of
blood glucose (SMBG) in the management of type 2 diabetes
mellitus [2].
Consistent with the ADA recommendations, a major NIH-
funded, multi-center trial (Look AHEAD) [3] randomized 5145
overweight adults with poorly controlled type 2 diabetes
mellitus to either 42 sessions of an intensive lifestyle
modification intervention promoting weight loss through
decreased caloric intake and increased exercise or to a
diabetes support group. The weight loss group experienced
an 8% reduction in weight and a 0.64% reduction in HbA1c,
both significantly greater than the support group.
Since the conclusion of the Look AHEAD project, several
investigations have focused on specific diets, exercise, and
blood glucose (BG) monitoring strategies. Our review of this
literature [7] suggests an optimal LM program should empha-
size a low glycemic load (GL) diet [8], an exercise program
combining aerobic and strength activities, and structured
SMBG [2]. To the authors’ knowledge, an integrated combina-
tion of these three approaches has not been published.
Therefore, we have devised a program called the Glycemic
load, Exercise, and Monitoring blood glucose program (GEM)
that incorporates these strategies.
This represents a paradigm shift from conventional
approaches in that GEM:
1. Focuses on reducing postprandial BG elevations, not weight
loss.
2. Emphasizes avoidance of high GL foods, not restriction of
calories or macronutrients.
3. Encourages eating a variety of available, culturally appro-
priate, affordable foods that do not produce large elevations
in BG, rather than focusing on a specific diet.
4. Recommends increasing physical activities during one’s
daily routine as opposed to following a structured exercise
program.
5. Relies heavily on systematic BG monitoring to [4–6]:
a. Educate individuals about their routine foods that
significantly raise their BG levels and therefore should
be avoided (e.g., banana, energy bars, corn), about
familiar and new foods that do not significantly impact
their BG and therefore should be encouraged, and about
types of physical activities (plus the timing and duration
during the day) that promote lowering BG.
b. Motivate individuals to repeat choices that led to desired
BG levels and avoid choices that led to personally
unacceptably high BG levels.
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29
c. Activate individuals to eat foods and engage in physical
activities based upon selected BG parameters.
This study used a randomized, 2 between (GEM vs. Routine
Care [RC])  2 within (0- and 6-month assessments) design to
test the primary hypothesis that GEM would lower HbA1c more
than RC of adults with type 2 diabetes mellitus diagnosed
within the past 5 years. The secondary hypotheses were that
GEM would lead to more frequent SMBG, more physical
activities, and ingestion of fewer high GL foods than would
occur with RC. Ancillary benefits of better psychological
functioning without worsening hyperlipidemia were also
expected. The study was approved by the University of Virginia
Institutional Review Board for Health Sciences Research.
2. Subjects, materials and methods
The general public was informed of the project through
newspaper, Internet, and radio announcements, and physician
referrals. Forty-seven individuals who satisfied the inclusion/
exclusion criteria were consented. Given that enrollment was
ongoing, three individuals who completed RC were subsequent-
ly crossed over to the GEM group. Inclusion criteria were: (1)
Diagnosed with type 2 diabetes mellitus within the past 5 years,
(2) Age >24 and <80 years, (3) HbA1c 7.0%, (4) Approval of
primary care physician to participate. Exclusion criteria were: (1)
Currently using, or used within the last 3 months, medications
that directly lower BG (e.g., insulin, sulfonylureas, glinides; note
that patients were allowed to take medications like metformin
that did not directly lower BG and lead to hypoglycemia), (2)
Currently using, or used within the last 3 months, thiazide
diuretics at doses above HCTZ 25 mg or equivalent, or loop
diuretics above furosemide 20 mg or equivalent, (3) Currently
pregnant or contemplating pregnancy in the coming year, (4)
Currently using, or used within the last 3 months, medications
that impede weight loss (e.g., prednisone), (5) Having
conditions that preclude increasing physical activities (e.g.,
severe neuropathy, active cardiovascular disease, emphysema,
osteoarthritis, stroke), (6) Undergoing treatment for cancer, (7)
History of lactic acidosis, (8) Diagnosed with renal impairment.
Five subjects were excluded because baseline HbA1c was
<7%, one person dropped out after electing gastric bypass
surgery, and two were lost to follow-up. Two of the dropouts
were from RC and one was from GEM. This resulted in 21 GEM
and 18 RC participants whose pre–post-data were analyzed.
The final sample consisted of 18 men and 21 women, with a
mean age of 55.3  9.9 years, mean type 2 diabetes mellitus
duration of 2.1  1.7 years, mean HbA1c of 8.4 [69 mmol/
mol]  1.2%, and a mean BMI of 37.9  10. Following randomi-
zation to GEM or RC respectively, 29% and 28% were not taking
diabetes medication, 38% and 56% were taking one medication
(primarily Metformin), 19% and 16% were taking two medica-
tions, and 14% and 0% were taking three diabetic medicines.
2.1. Overview
Interested individuals were initially screened over the
telephone and informed of study requirements. Their treating
physician provided a letter affirming the patient met the
30 diabetes research and clinical practice 111 (2016) 28–35

inclusion/exclusion criteria and could participate in the study.
Subsequently, individuals came to the lab for informed
consent and baseline assessment. Using a random number
generator, participants were randomized to either RC or GEM.
Participants in both groups continued with routine care as
determined by their treating physicians. During the assess-
ment, a 24-h food recall was performed using the ASA24 [9].
The following week, subjects wore an accelerometer and
pedometer to quantify their routine activity. Upon return of
the activity equipment, participants were given a Verio IQ
glucose meter and testing supplies for six months. Subse-
quently, a 24-h 7-point BG profile (pre–post-breakfast, lunch
and dinner and bedtime readings) [10] was collected. Follow-
ing this, GEM subjects began treatment. Post-assessment was
conducted 6 months after baseline assessment.
2.2. Assessment
1. Understand the management and treatment options for
type 2 diabetes mellitus.
2. Learn how to use the Verio IQ meter to educate the individual
concerning how certain foods and physical activities
influence BG, motivate the individual to avoid those foods
that raise BG to a personally unacceptable level and
embrace those activities that lower BG, and activate the
individual to engage in the BG-lowering behaviors.
3. Choose foods that have low GL or net carbohydrate content
and that slow carbohydrate digestion.
4. Engage in sustainable routine activities of daily living that
lower BG directly by ‘‘burning’’ glucose and decreasing
insulin resistance for future BG elevations.
5. Review the gains made (e.g., lower BG, increased energy,
weight loss) that are consistent with one’s preferences,
habits, and environment to sustain BG optimization in the
future.

Identical assessments were carried out at baseline and at 6 Study fidelity was maintained throughout the study design
months. These included a physical exam, blood tests, a 6-min by training staff, holding weekly team meetings, having
walk test to assess physical fitness [11], and psychological participants keep study logs and checklists, and using
questionnaires. These assessments were carried out by nurse participant trainer manuals. The GEM topics discussed in
practitioners, supervised by A.G.T. and A.D. The psychological the five one-on-one sessions were delivered according to the
questionnaires included four brief, psychometrically validated participant manual.
measures of: (1) Quality of life, 26-item WHOQOL-BREF [12], (2)
Empowerment, 8-item Michigan Diabetes Empowerment 2.4. Outcome variables
Scale [13], (3) Depressive symptoms, 9-item PHQ-9 [14], (4)
Problem Areas in Diabetes, 5-item PAID-5 [15]. In addition, Researchers need to operationalize concepts with specific
three unique questionnaires were developed specifically for measures, with no one measure comprehensively describing
this study: (1) A food questionnaire that listed 16 common high that concept. This preliminary RCT operationalized each
GL and 12 common low GL foods (test–retest reliability = 0.93). concept with multiple measures:
Subjects reported how many servings of each food item they
ate in an average week. (2) A physical activities questionnaire  Metabolic Control
that assessed the hours of daily sedentary activity, such as  HbA1c
reading, watching television, or using a computer. (3) A  % participants achieving ADA’s Standards of Medical Care
diabetes knowledge questionnaire, based on content from the general goal of HbA1c 7.0%
GEM manual.  7-point BG profile [10]
Blood tests included: HbA1c TOSOH G7 (HPLC), HDL Abbott  Behavior Change
Architect (solubilization/cholesterol esterase/oxidase), LDL  Eating behaviors
Calculated (Friderwald), Total cholesterol Abbott Architect  Food questionnaire
(Cholesterol esterase/oxidase), Triglyceride Abbott Architect  24-h food recall diary
(glycerol to glycerol-3-P with glycerol kinase, not blanked),  Physical activities
CRP-HS Abbott Architect (Latex Immunoassay), and Insulin  Pedometer
Immulite 2000 (Sandwich immunoassay).  Accelerometer
 6-min walk test
2.3. GEM intervention  BG monitoring
 Verio IQ meter memory
The GEM intervention was based on the principles of active  SMBG questions
learning and was modeled after the successful Blood Glucose  Ancillary Benefits
Awareness Training (BGAT) [16]. The GEM topics were discussed  Blood tests
in five one-on-one sessions with either a diabetes educator (A.D.)  Vital sign and physical functioning
or a clinical psychologist (D.J.C.). There was a one week interval  Psychological questionnaires
between classes 1 and 2, and a three week interval between
classes 2 and 3, 3 and 4, and 4 and 5 to allow experimentation 3. Results
with food choices and physical activities. Each chapter had
specific objectives and homework assignments designed to help 3.1. Overview
individuals apply the chapter’s content to their daily routine.
The GEM manual was reviewed for clarity and readability by 2 between (Group)  2 within (Time) Mixed-Model ANOVA’s
professional and lay advisory boards (see Acknowledgments). were used for continuous variables to determine change in
The objectives of the five chapters were to help participants: variables (Time) and a differential effect of GEM (Interaction).

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 diabetes research and clinical practice 111 (2016) 28–35 31

Dichotomous variables were analyzed with Chi Square Tests
for Independence. Pearson’s correlations were used to explore
relationships between behavior change variables and change
in HbA1c for GEM subjects. Tables 1 and 2 show the pre- and
post-intervention means and standard deviations of the
outcome variables, the Time effect (Assessment 0 vs. 6
months ANOVA), the Time  Group Interaction (differential
impact of GEM), and the GEM pre–post-Contrast (change in the
GEM group scores). Because this is a preliminary RCT, both the
significant findings and trends are discussed.
3.2. Metabolic control
GEM participants demonstrated a greater reduction in
HbA1c than the RC participants. Mean HbA1c dropped
1.03% for GEM (from 8.4% to 7.4% [69–57 mmol/mol]), and
0.01% for RC (8.3% to 8.3% [68–68 mmol/mol]) (Interaction
p = .03, Contrast p < .01). Additionally, more GEM partici-
pants (52%) had an HbA1c 7 at the six month assessment
than RC participants (12%) ( p = .02). On the 7-point BG
profiles, GEM participants demonstrated a significant re-
duction in their pre-dinner to post-dinner BG (Interaction
p = .03).
3.3. Behavior change
On the pre–post-food questionnaires, GEM participants
reported eating fewer high GL foods (Interaction = 03, Contrast
p < .001), but not more low GL foods. On the ASA 24-h food
recall, GEM participants reported eating fewer grams of
carbohydrate (Interaction p = .05, Contrast p = .01) and fewer
calories (Interaction p = 13, Contrast p = .01), although there

Table 1 – ANOVAs comparing GEM to RC.

Variable Routine care means GEM means Time effect Interaction GEM 0–6 m
contrast
Pre Post Pre Post F p F p
Metabolic control
HbA1c 8.4  1.1 8.3  1.6 8.4  1.3 7.4  1.3 6.89 0.01 4.98 0.03 0.01
7-Point change @ breakfast 22.4  54.4 36.6  48.2 16  41.5 -4.9  35.9 0.05 0.83 1.25 0.28 0.28
7-Point change @ lunch 47.4  34.8 2.4  43 25.4  31.3 18.9  43.3 4.85 .04 2.69 0.12 0.72
7-Point change @ dinner 20.3  44.4 50.1  26 21.9  39.8 -11.1  66.6 0.02 0.91 5.7 .03 0.11
7-Point daily average 185.7  46.2 164.5  28.1 172.7  62 143  40.4 2.88 0.11 0.08 0.78 0.28

Self-regulatory behaviors
Knowledge 14  3.3 14.5  2.8 15.5  2.3 16.9  2.4 4.9 0.03 1.19 0.28 0.06
High GL foods 33.9  16.4 28.2  15 30.7  11.1 14.9  8 23 0.00 5.1 .03 .00
Low GL foods 35.9  15.2 37.2  16.6 42.4  21.7 37.5  21.7 0.3 0.59 0.87 0.36 0.35
Total Carbs 270.2  107.2 254.5  92.7 223.3  127.3 131.1  57.3 8.21 .01 4.12 .05 .01
Total fiber 17.9  12.5 19.3  9.4 19.9  13.4 15.9  11.2 0.27 0.61 1.25 0.27 0.31
Total fat 84.2  50.3 79  20.2 93.6  56.7 77.7  47.5 1.66 0.21 0.42 0.52 0.12
Saturated fat 27.6  15.5 25.5  11.5 28.9  19.3 23.9  17.3 1.82 0.19 0.29 0.59 0.12
Protein 91.8  35.4 82.4  24.1 88.8  38.5 83.3  35.3 1.33 0.26 0.09 0.77 0.57
Calories 2170  773.7 2025  572.1 2085  1059.8 1545  649.3 7.21 .01 2.4 0.13 .01
Accelerometer 17.06 14.97 24.65 38.96 1.43 0.23 1.67 0.2 0.02
Pedometer 1.81 3 20.08 35.44 1.24 0.27 0.82 0.37 .003
Questionnaire, sedentary 89.4  38.7 82.1  50.5 111.1  55.4 104.7  39.6 1.13 0.3 0 0.95 0.46
behavior
SMBG 1.6  1.7 1.1  1.1 2.9  2.9 1.6  1.4 5.92 0.02 1.41 0.24 .05

Physiological impact
6 min walk test, distance 1347  229.4 1244.7  603.7 1444.9  234.5 1434.9  281.6 0.57 0.45 0.39 0.54 0.89
walked/ft.
SBP 133.8  14.4 132.6  14.6 124.4  34.4 128.4  14.8 0.09 0.77 0.29 0.59 0.62
DBP 81.2  6 83.2  7.8 79.1  19.8 81.4  9.3 0.67 0.42 0 0.95 0.61
Weight 244.3  45.1 238.5  37.6 221  58.1 213.2  58.9 10.6 .01 0.24 0.62 .02
Waist 44.8  12 45.8  4.5 42.8  11.5 42.8  6.5 0.16 0.69 0.13 0.73 0.98

Blood test
HDL 41.4  10.1 42.6  10.6 38.8  8.1 41.8  11.7 6.01 .02 1.14 0.29 0.03
LDL 100.9  28.7 93.6  24.5 101.9  27.3 110  34.1 0.01 0.92 4.94 .03 0.14
Total cholesterol 174.4 169.1 166.5 177.9 0.47 0.49 3.4 0.07 0.12
Triglyceride 163.8  100.9 160.6  111.9 161.9  79 175.3  141 0.11 0.75 0.28 0.6 0.62
Insulin 19.7  13.1 20.8  19.9 16  11.2 14.5  10.5 0.01 0.94 0.3 0.59 0.45
CRP-HS 7.7  6.5 7.5  7.5 7  7.2 7.02  8.3 0.01 0.92 0.01 0.94 0.99
HOMA IR 3  1.8 2.8  1.9 2.4  1.5 2  1.4 1.02 0.32 0.18 0.67 0.29
ASCVD 10 year risk % 18.5  12.7 17.6  12.4 13.6  12.3 13.3  11.7 0.94 0.34 0.23 0.64 0.61

Psychological
WHO-BREF physical 15.7  2.8 15.3  3 15.1  2.8 16.2  3.1 1.14 0.29 5.06 .03 .04
WHO-BREF psychological 15.3  2.1 15.4  1.6 14.6  2.3 15.5  2.1 3.22 0.08 1.93 0.17 0.07
WHO-BREF social 14.3  3.2 14.9  2.5 14.3  2.3 14.4  2.9 0.59 0.45 0.35 0.56 0.91
WHO-BREF environment 15.7  2.3 16.3  2 16.3  2.3 17.1  2 6.39 0.02 0.05 0.82 0.14
PHQ-9, depression 2.6  2.4 3.4  3.8 4.6  3.4 3.4  4 0.07 0.8 2.4 0.13 0.32
Diabetes empowerment 25.7  7.2 29.4  5.7 28.9  9.1 34.7  4.5 9.75 .01 0.48 0.49 .02
PAID-5 7.1  4.7 7.6  6 7.9  4.7 5.8  4.9 0.87 0.34 2.26 0.14 .04

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32 diabetes research and clinical practice 111 (2016) 28–35

Table 2 – Chi square analyses comparing GEM to RC.

X2 p Counts
Diabetes control
Participants with good HbA1c (7) 5.37 0.02 HbA1c > 7 HbA1c 7
RC 15 3
GEM 10 11
Participant changes in medications 0.94 0.63 No change Up Down
RC 16 3 1
GEM 15 6 1
Participant lost 7% of body weight 2.48 0.12 Yes No
RC 1 17
GEM 5 16
Additional questions
Do you have a target blood sugar? 5.8 0.055 Yes No Not sure
RC 11 4 3
GEM 18 0 2
How often do you actually test your BG? 15.18 0.002 Infrequent Weekly Daily Often
RC 7 0 9 2
GEM 1 6 5 8
To what extent do you use your meter 8.05 0.15 N/A 0 (Not at all) 1 2 3 4 (Very much)
to understand how different activities RC 1 1 5 2 5 4
affect your BG? GEM 0 0 1 3 5 11
To what extent do you use your meter 18.57 0.001 N/A 0 (Not at all) 1 2 3 4 (Very much)
to decide what to do to manage your RC 0 7 3 5 1 2
diabetes? GEM 0 0 3 1 7 9

was no change in consumption of total fiber, total fat,
saturated fat, or protein.
Pre- and post-Contrasts of 1-week accelerometer and
pedometer use revealed that GEM participants significantly
increased their minutes of daily aerobic walking (Contrast
p < .03), although the GEM participants did not report engaging
in significantly less sedentary behavior.
There was a trend for GEM participants to use their Verio IQ
meters more often than the RC participants during months 1
and 6 (Group p = .077). Additionally, at month 6 the GEM
participants were more likely to report that they had BG
targets for which to strive ( p = .055, see Table 2) and that they
used their meters more often to make lifestyle decisions
( p < .001) than to understand the effects of foods on their type
2 diabetes mellitus ( p = .15).
3.4. Ancillary benefits
From a physical perspective, HDL improved (Time p = .02) and
weight (pounds) was reduced (Time p = .01) in both groups,
and for GEM participants (Contrast p = .03 and .02 respective-
ly). The GEM intervention did not jeopardize nor improve
many of the participants’ physical parameters, including
blood pressure, total cholesterol, triglycerides, CRP-HS,
insulin sensitivity, and 10-year cardiovascular risk. GEM
participants demonstrated a non-statistically significant
increase in LDL from 102 to 110 mg/dL (Contrast p = .14),
although there was a significant interaction indicating LDL
increased for GEM participants compared with RC (Inter-
action p = .03).
From a psychological perspective, GEM participants reduced
their diabetes-related problems (PAID Interaction p = .14,
Contrast p = .04), improved their sense of empowerment
(Interaction p = 49, Contrast p = .02), and demonstrated a
greater improvement in quality of life in terms of their
physical activities (Interaction p = .03, Contrast p = .04) than
did those receiving RC only. GEM participants also trended
toward improvement in quality of life with respect to
psychological conditions (Interaction p = 17, Contrast p = .07).
3.5. Post hoc analyses
The authors were interested in whether improvement in the
behaviors targeted by GEM (i.e., food selection, physical
activities performed, and blood glucose self-monitoring)
directly related to reductions in participants’ HbA1c. There-
fore, the relationships between change in HbA1c and the self-
regulation dependent variables were explored for the GEM
group. A reduction in HbA1c was associated with a trend
toward improvement in knowledge (r = .47, p = .058), reduc-
tion in breakfast BG (r = .55, p = .098), an increase in physical
fitness as quantified by distance walked during the 6-min walk
test (r = .44, p < .046), and a reduction in self-reported
sedentary behaviors (r = .5, p = .04) (see Table 3).
3.6. Safety and confidentiality
No adverse events or breaches of the study protocol were
reported. All participants assigned to the GEM intervention
group completed the intervention, and none experienced any
untoward study-related physical or psychological events.
4. Discussion
4.1. Conclusions
The findings of this preliminary study demonstrate that this
five-session, 15-week GEM program had a significant and
robust effect on metabolic control. Most notable is the 1.03%

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 diabetes research and clinical practice 111 (2016) 28–35
Table 3 – Relationship between change in target beha-
viors and HbA1c from pre- to post-treatment.
Independent variables GEM
r p
Increases in knowledge .47
Reducing high GL foods .09
Increasing low GL foods .13
Reducing total carbohydrates .06
Increasing total fiber .09
Decreasing total calories .18
Reducing weight .023
Post-7-point change @ breakfast .55
Post-7-point change @ lunch .33
Post-7-point change @ dinner .11
Increasing distance in 6-min walk test .44
Increasing accelerometer .28
Increasing pedometer .2
Reducing sedentary behavior .5
Baseline SMBG .09
reduction in HbA1c over the last 3 months of the 6-month
observation period when there was no study-directed inter-
vention being offered. This reduction compares favorably to
the Look AHEAD program in terms of the magnitude of
improvement in HbA1c (1.03 vs. 0.64%), number of treatment
sessions (5 vs. 42), and length of non-intervention follow-up (3
months vs. 0 months). Additionally, the impact of the GEM
intervention compares favorably to the average improvement
seen with the introduction of metformin to the regimen of
persons with diabetes (1.03% vs. 0.9% reductions in HbA1c)
[17].
The reduction in HbA1c (1.03%) in the GEM participants was
accomplished without intensification of medication manage-
ment: post hoc comparison of GEM and RC participants who
reduced, maintained or increased their diabetes medication
showed no difference (chi square p = .51). This differed from
Polonsky’s Structured Blood Glucose Monitoring [6] study, in
which measuring participants’ BG seven times a day for 3 days
prior to a physician visit led to a 0.3% reduction in HbA1c and a
significant increase in medication management. Also, the GEM
study was unique in its psychological benefits, which included
participants reporting a higher perceived quality of life, a
greater sense of empowerment, and reduced common con-
cerns about their type 2 diabetes mellitus. All of these gains
were achieved without compromising specific physiological
parameters or increasing participants’ risk of cardiovascular
disease.
This study suggests that the GEM intervention led
participants to increase their physical activities and to
reduce their intake of high GL foods. Additionally, there was
a trend for GEM participants to perform more SMBG than
those participants in the RC group (Group effect p = .077).
The sample size was too small to perform a formal path
analysis confirming the process that GEM led to behavior
changes that resulted in reduced post-prandial BG, and
culminated in reduced HbA1c. Nevertheless, when consid-
ering possible mechanisms for the improvement in HbA1c
levels for the GEM participants, it is noteworthy that
improvements in knowledge ( p = .058), physical fitness as
determined by the 6-min walk test, reductions in sedentary
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33
behaviors, and lower pre- to post-breakfast BG elevations all
correlated with improvements in HbA1c. We did not
anticipate the frequency of SMBG to be directly related to
the reduction of HbA1c, given that it does not directly
impact metabolism as does ingested food/drink or engage-
.058 ment in physical activities. As a source of education,
.719
motivation, and activation, the impact of SMBG on HbA1c
.607
is mediated through food selection and increased activity.
.828
.752 This suggests that future GEM interventions should focus on
.506 ensuring that users comprehend the information about type
.920 2 diabetes mellitus in the GEM manual, reduce postprandial
.098 BG levels, and pursue physical fitness through moderate and
.323 vigorous physical activities.
.78
Although the GEM intervention does not emphasize weight
.046
.3
loss as the Look AHEAD program and the ADA do, GEM
.61 participants significantly reduced their weight from 100  26.4
.04 to 96.7  26.7 kg, which is a 4% weight loss. Weight lost did not
.679 significantly correlate with improvements in HbA1c, but
achieving the ADA guideline of losing >7% body weight did
appear to be helpful. Participants who lost 7% of their body
weight had a greater reduction in HbA1c than the participants
who lost <7% of their weight (HbA1c reductions of 1.7% and
0.4%, respectively, p < .03).
4.2. Limitations and strengths
There are limitations to consider when considering the
findings of this preliminary RCT. First, the sample size is
small, which limits power and external validity. Second,
although the GEM intervention is a manual-based treatment
intervention that exposes all participants to similar content
with similar homework activities, it was delivered by
developers of the program, which might have made the
findings vulnerable to a possible Hawthorne effect [18]. Third,
there was no attention control group. Fourth, the follow-up
period was limited to 3 months beyond the final treatment
session, and a longer follow-up period to evaluate sustain-
ability of study benefits would be beneficial. While we used
fasting insulin levels and BG readings to estimate insulin
sensitivity using the HOMA IR 2004, this is only an indirect
measure of the process and largely reflects insulin resistance
of the liver. The oral glucose tolerance test [19] would be a
more direct measure, especially of muscle insulin resistance.
Similarly, the 6-min walk test is a less direct measure of
physical fitness than a VO2 max test [20]. Using multiple
outcome variables and comparisons renders the results
vulnerable to Type II error, but it also allows convergent
validation, e.g., the agreement between: mean HbA1c and
number of participants achieving 7% weight loss, acceler-
ometer and pedometer findings, total carbohydrates and total
calories, and multiple psychological benefits, all confirm the
efficacy of GEM.
The strengths of this trial include (a) using a sample of
patients with poor glycemic control; (b) using an objective
outcome of glycemic control (HbA1c); (c) having no dropouts in
the GEM group during treatment, suggesting that the
intervention is well tolerated; (d) using multiple outcome
variables for each concept measured, allowing for convergent
validation, and (e) using a participant manual that allows for
standardized dissemination of the intervention.
34 diabetes research and clinical practice 111 (2016) 28–35
4.3. Future directions
The proportion of the general population of people with type 2
diabetes mellitus who would wish to and are able to use GEM
and who might achieve similar results to those in this
preliminary study needs to be determined. Further work is
also required to identify whether a shorter intervention might
be equally clinically effective and potentially more cost-
effective, or whether ongoing GEM intervention sessions are
required to maintain the effect. An additional group that only
employed instructions to use low GL foods and increase
routine physical activities would provide data to determine/
justify the contribution of systematic BG monitoring.
4.4. Summary
This preliminary evidence suggests that the GEM intervention
results in clinically meaningful improvements in people who
have type 2 diabetes mellitus and are in sub-optimal control.
The findings suggest that the GEM intervention, with its focus
on reducing postprandial BG levels by avoiding high GL foods,
increasing routine moderate to vigorous physical activities,
and using systematic SMBG is a promising option for
improving metabolic control while providing ancillary physi-
cal and psychological benefits. From a patient-centered
perspective [21,22], GEM may provide a treatment option
potentially more palatable to a portion of those with type 2
diabetes mellitus than conventional programs focused pri-
marily on weight loss. This is important when considering
some individuals with T2D do not need to lose weight, do not
want to lose weight, are not able to lose weight, or are not able
to sustain weight loss over a lifetime.
Conflict of interest
D.J.C. received a grant from LifeScan, Inc., which provided
Verio IQ meters, supplies, and partial financial support to
A.L.M., H.S., and A.D. for this project. The sponsor was not
involved in the design or conduct of the study, or in the
preparation of this manuscript. D.J.C. has served as a
consultant to Pfizer, Merck, and Sanofi. The University of
Virginia received support for contract research from Eli Lilly
and Sanofi conducted by A.L.M. No other potential conflicts of
interest relevant to this article exist.
Acknowledgments
Funding: A grant from LifeScan, Inc. (Totality 126392) provided
Verio IQ meters, supplies, and partial financial support to
conduct this project.
Assistance: The authors are indebted to the professional
advisory board members who reviewed the content of the GEM
manual: Bob Anderson, Sheri Colberg-Och, Lawrence Fisher,
Kate Lorig, Carla Miller, William Polonsky, Donna Rice, John R.
Sirard, Barbara Stetson, Heather Stuckey, and Diane E.
Whaley; the following nurse practitioner students who
conducted the physical exams: Elizabeth S. Dunning, Mary
C. Winston, Debra R. Brunk, Amy Nowakowski, and Maria T.
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Pescatore; and the research assistants who helped manage
this study: Ingrid L. Luk Van, Sarah Cain, and Addison Walker.
Special acknowledgment goes to cardiologist Rob Thompson,
for his personal and professional insights, his encouragement
for this project, and his writings for those who live with type 2
diabetes mellitus.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
diabres.2015.10.021.
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