European Journal of Internal Medicine 27 (2016) 3747

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European Journal of Internal Medicine

journal homepage: www.elsevier.com/locate/ejim

Original Article

Efcacy of lifestyle interventions in patients with type 2 diabetes: A

systematic review and meta-analysis
Xiao-Li Huang , Jian-Hua Pan, Dan Chen, Jing Chen, Fang Chen, Tao-Tao Hu
Department of Nephrology, The First Hospital of Wuhan, China

a r t i c l e i n f o a b s t r a c t

Article history: Background: The current meta-analysis evaluated the outcomes of various lifestyle interventions, including diet
Received 9 June 2015 modications (DIET), physical activity (PA), and patient education (EDU) in reducing the risk of cardiovascular
Received in revised form 3 November 2015 disease in patients with type 2 diabetes.
Accepted 16 November 2015 Methods: Randomized clinical trials comparing lifestyle intervention with usual care (control) in type 2 diabetes
Available online 3 December 2015
patients were hand-searched from medical databases by two independent reviewers using the terms diabetes, car-
diovascular risk, lifestyle, health education, dietary, exercise/physical activities, and behavior intervention.
Keywords:
Diabetes
Results: Of the 235 studies identied, 17 were chosen for the meta-analysis. The average age of patients ranged from
Cardiovascular 5067.3 years. Results reveal no signicant difference between the groups, with respect to BMI, while PA and DIET
Lifestyle yielded a greater reduction in HbA1c. Signicant reduction in both systolic and diastolic pressures in the DIET group,
Intervention and diastolic pressure in the PA group, was observed. HDL-c in the DIET group was signicantly higher than the con-
Meta-analysis trol group, while no change in LDL-c levels, was seen in all three intervention subtypes. There was no difference be-
tween the EDU vs. the control group in terms of HbA1c, blood pressure or HDL-c and LDL-c.
Conclusion: DIET intervention showed an improvement in HbA1c, systolic/diastolic blood pressure and HDL-c, with
an exception of LDL-c and BMI, suggesting that nutritional intervention had a signicant impact on the quality of life
by reducing the cardiovascular risk in type 2 diabetes patients.
2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

1. Introduction Furthermore, the expectation of strict adherence to dietary control, ex-

The global increase in the prevalence of diabetes seen in recent years
has been attributed mostly to obesity, poor diet, and lack of physical
activity. The World Health Organization projects diabetes as the 7th
leading cause of death and estimates that there will be 366 million
adults with diabetes in 2030 [1,2]. Of which, 90% of people will have
type 2 diabetes, resulting from the body's ineffective use of insulin [3]
and poor glycemic control. Reduced metabolic control of glucose can
in turn increase the risk of cardiovascular diseases (CVD). The common
cardiovascular risk factors associated with diabetes include, increased
body weight, glycemia, serum lipids, and blood pressure [4].
Improvement of glycemic control and reduction of cardiovascular
risk factors through diet and exercise has long been advocated [5,6].
However, with the introduction of many new oral hypoglycemic agents,
such as the glucagon-like peptide-1 receptor (GLP-1R) agonist and
dipeptidyl peptidase-4 (DPP-4) inhibitors, in addition to the conven-
tional metformin mono-therapy and increased use of insulin, the nutri-
tional control of diabetes seemed to have lost its relevance [79].
Corresponding author at: Department of Nephrology, The First Hospital of Wuhan,
Wuhan Qiaokou District Liji North Road No. 215, 430030 Wuhan, China. Tel.: + 86
13871101268.
E-mail address: 5051huangxiaoli@163.com (X.-L. Huang).
ercise regimen and other lifestyle changes is not as realistic as the drug
treatment in many patients. Besides, the evidence for dietary modica-
tions in glycemic control, though compelling, is often based on short
term studies, mostly one year or less [10,11]. Clinical trials with a longer
follow-up period are often necessary to conrm the positive impact of
lifestyle changes in reducing the CVD in type 2 diabetes patients.
Recently, the Look AHEAD study examined the effects of an intensive
lifestyle intervention (with diet modication and physical activity) over
a period of four years in a large cohort of overweight and obese individ-
uals with type 2 diabetes [12]. The results indicate that patients who
underwent intensive lifestyle intervention as opposed to diabetes sup-
port and education (control), had better glycemic control, blood pres-
sure, high density lipoprotein-cholesterol (HDL-C) and triglyceride
levels, thus lowering their cardiovascular disease risk. Though, the max-
imum benets were seen at one year, the intervention group had great-
er improvements over the control group even at 4 years.
In contrast, a long term behavioral intervention program, providing
a regular, personalized exercise prescription did not improve glycemic
control in sedentary, insulin treated type 2 patients during a 2 year in-
tervention period [13], indicating that a more strictly supervised exer-
cise training with personal coaching may be required to maximize the
adherence and to increase the physical activity status. Similarly, a ran-
domized clinical trial to determine the effect of case management in

http://dx.doi.org/10.1016/j.ejim.2015.11.016
0953-6205/ 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
38 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747
the control of diabetes in type 2 diabetes patients did not yield any sig-
nicant difference between the case management and the control
groups [14]. There was no difference in the mean HbA1c level, or low
density lipoprotein-cholesterol (LDL-C) or blood pressure (BP) among
the groups, suggesting cautious use of resources on personalized inter-
ventions and case management in the treatment of type 2 diabetes.
Though exercise has been shown to have a positive effect on cardio-
vascular health, the effect of exercise on BP reduction in type 2 diabetic
patients is inconsistent. Recent ndings suggest that though there was
no reduction in BP, a modest reduction in the HbA1c levels (0.2%) was
observed in the exercise group [15], further substantiating the protec-
tive effect of exercise on glycemic control. Reports elsewhere further
corroborate the effectiveness of exercise intervention strategies in pro-
moting physical activity and improving HbA1c and cardiovascular risk
prole [16]. The above study also revealed that counseling alone, though
effective in achieving the recommended level of physical activity (PA),
was unsuccessful in minimizing the cardiovascular risk, suggesting the
need for a larger volume of PA in high-risk patients. Conversely, Kirk
et al. [17] reported that counseling improved glycemic control as well
as the status of cardiovascular risk factors in type 2 diabetic patients.
In reports elsewhere, regular drug-counseling through pharmacist
care program signicantly reduced the various CVD risk factors, includ-
ing stroke [18].
The aforementioned studies along with various other reports indi-
cate that structured reinforcement with diabetes health education,
counseling, physical activity programs, and nutritional control can con-
trol the risk of CVD in patients with type 2 diabetes [1926]. The aim of
the present meta-analysis is to compare the outcomes of intensive exer-
cise, dietary regimens, and comprehensive lifestyle interventions and its
signicance on clinical markers of cardiovascular disease in patients
with type 2 diabetes.
2. Methods
2.1. Selection criteria
We performed a literature search of PubMed Central and MEDLINE,
the Cochrane Central Register of Controlled Trials (CENTRAL),
EMBASE, and Google Scholar databases (until July 15, 2014) using the
terms diabetes, cardiovascular risk, lifestyle, health education, dietary,
exercise/physical activities, and behavior intervention. Prospective,
randomized controlled trials comparing lifestyle interventions with
the usual care control group were included in the current meta-
analysis. Only articles in English were considered for analysis. We ex-
cluded studies that did not recruit patients with type 2 diabetes or
those with no mention of lifestyle program/education relating to the pa-
tient dietary and exercise behavior/physical activities.
2.2. Study selection and data extraction
Studies identied by the search strategy were hand-selected and
data were extracted by two independent reviewers. Where there was
uncertainty regarding eligibility, a third reviewer was consulted.
The following information was extracted from studies that met the
inclusion criteria: the name of the rst author, year of publication,
study design, number of participants in each treatment group, partici-
pants' age and gender, diagnostic criteria, intervention regiment for
the study/control group, and results. The minimum number of partici-
pants was 30 in each study, while the minimum follow-up period was
6 months.
2.3. Outcomes
The primary outcome was the reduction in the risk factors for cardio-
vascular disease, such as, body mass index, HbA1c, blood pressure, and
the level of cholesterol.
2.4. Quality assessment
The included studies were assessed for the risk of bias using the Risk
of Bias assessment tool, Review Manager 5.1. Recommendations for
judging the risk of bias were provided in Chapter 8 of the Cochrane
Handbook for Systematic Reviews Interventions [27].
2.5. Statistical analysis
The reduction in the risk factors for cardiovascular disease, such as,
body mass index (BMI), HbA1c, systolic blood pressure (SBP), diastolic
blood pressure (DBP), high-density lipoprotein-c (HDL-c), and low-
density lipoprotein-c (LDL-c). BMI, HbA1c, SBP, DBP, HDL-c, and LDL-c
were compared between participants having an intensive lifestyle inter-
vention (intervention group) and the conventional intervention (con-
trol group). The intervention group was divided into 3 subgroups
according to the type of intervention and data were analyzed separately
according to 3 different programs, intensive physical activity (PA), in-
tensive dietary (DIET), and education program (EDU). For each outcome
measure, the standardized difference (Std. diff) in means with corre-
sponding 95% condence intervals was calculated for each individual
and study. Std. diff in means of b0 indicates that the intervention was
favored, showing a greater decrease in change of outcome than the con-
trol group. Conversely, Std. diff in means of N 0 indicates that the control
group was favored, which means that the intervention group had less
decrease in change of outcome than the control. Std. diff in means = 0
indicates that the intervention and control groups had a similar change
in outcomes. Additionally, for changes in the levels of HDL-c, the effect
was identied as the Std. diff in means of N 0, indicating that the inter-
vention group was favored with greater increase in the change of
HDL-c than the control; whereas Std. diff in means of b 0 indicates that
the control group was favored, with greater increase in the change of
HDL-c than the intervention group.
A 2 based test of homogeneity was performed using Cochran's Q
statistic and I2. I2 illustrates the percentage of the total variability in ef-
fect estimates among trials resulting from heterogeneity rather than
chance. Random effect models of analysis were used if heterogeneity
was detected (I2 N 50%). Otherwise, xed effect models were used. For
each outcome measure, the standardized difference in means with cor-
responding 95% condence intervals was calculated for each individual
and study.
A two-sided P value of b 0.05 indicated statistical signicance for one
comparison group over the other. Sensitivity analysis was carried out
for the outcome HbA1c using the leave one-out approach. A funnel
plot, the fail-safe N (which indicates whether the observed signicance
is spurious or not), and Egger's test (which detects whether the ob-
served studies is asymmetry or not) were used to assess possible publi-
cation bias in EDU subgroup only. Since ve or fewer studies are
insufcient to detect funnel plot asymmetry [28], publication bias for
the other two subgroups was not assessed. All analyses were performed
using Comprehensive Meta-analysis statistical software, version 2.0
(Biostat, Englewood, NJ, USA).
3. Results
3.1. Literature search
After the removal of duplicates, a total of 235 studies were identied
through the database search, of which 167 studies were excluded due to
lack of relevancy. After full text reviewing of 68 articles, we excluded 51
studies. The reasons for elimination being, eight articles were from the
same trial that was included in the meta-analysis; while eight articles
did not contain the outcome of interest; fourteen articles adopted inter-
vention programs that were shorter than 6 months; and twelve articles
had other interventions involved, for example, pharmacological inter-
vention; while two articles only studied one gender in the trial; and
 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747
six articles were 3 or 4 arm RCTs. One study [29] was initially included,
however, it later had to be excluded because of the variability in BMI,
LDL-c and HDL-c analyses, as compared with other included studies.
The inclusion of this study would have skewed the meta-analysis by in-
creasing the discrepancy in both sensitivity and publication bias analy-
ses. 17 studies were included in the nal meta-analysis. The owchart
for the selection of trials is shown in Fig. 1.
3.2. Study characteristics
The number of patients in each group per study ranged from 23 to
2575 (Table 1). The mean (SD) age was similar across the studies
(range, 50 [12.4] to 67.3 [19]) and between the intervention and control
groups (Table 1). The proportion of male patients ranged from 29% to
98%, and the length of the study ranged from 6 months to 8 years
(Table 1). There were 10 studies in the EDU group, 5 in the PA group,
and 3 in the DIET group. The Look AHEAD Research Group [12] study
used intervention containing both intensive physical activity and
dietary programs; therefore, the data in this study were included and
analyzed separately in PA and DIET groups. The changes in outcome
measures from the baseline for the studies included in this meta-
analysis are summarized in the Supplementary Table S1.
Fig. 2 represents the assessed outcomes of the included studies. For
each trial, the risk of bias was detailed in the risk of bias summary
Fig. 1. A owchart showing the selection of studies.
39
(Fig. 2A). In addition, an overall assessment of risk of bias was presented
in Fig. 2B. All studies utilized random sequence generation, thus
avoiding any selection bias. However, only 65% (11/17) studies had allo-
cation concealment, leaving the rest of the 35% of the studies with un-
clear risk of bias. Blinding of participants and personnel was not
followed through in 15/17 (88%) studies, thus resulting in a higher
risk of performance bias. In addition, some of these study results are
further biased by not blinding the outcome assessment (detection
bias; 6/17 studies; 38%). Only 47% of the studies included had intent-
to-treat analysis (Fig. 2A, B).
3.3. Clinical outcome measures
3.3.1. Body mass index (BMI)
Twelve of the included studies reported change from baseline in
BMI. There was heterogeneity for this outcome across studies in the
PA group, but it was homogeneous in both DIET and EDU groups (PA:
Q statistic = 35.77, I2 = 94.41%, P b 0.001; DIET: Q statistic = 5.54,
I2 = 0%, P = 0.477; EDU: Q statistic = 5.20, I2 = 0%, P = 0.635). There-
fore, the random effect analysis was applied to the PA group, and the
xed effect analyses in the DIET and EDU groups, respectively. The stan-
dardized differences in the means of change from baseline in BMI
showed similar changes between the intervention and control groups
for all three subgroups (PA: standardized difference in means, 0.77;
40 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747

Table 1
Baseline characteristics of studies included in the meta-analysis.

Study Type of Totala Group Description of groups Patientb Age, years Sex/males Length of
study (mean SD) (n, %) program

Intensive physical activity and dietary program

The Look AHEAD RCT 5145 Intervention Intensive lifestyle intervention (ILI) 2570 58.6 6.8 1044, 40.7% 4 years
Research Group [12] Control Diabetes support and education (DSE) 2575 58.9 6.9 1038, 40.4%

Intensive physical activity program

Dobrosielski DA [15] RCT 140 Intervention Supervised exercise 70 57 6 41, 59% 26 weeks
Control General advice about physical activity 70 56 6 40, 57%
Wisse W [13] RCT 74 Intervention Regular, structured and personalized 32 54.3 1.4 20, 62% 2 years
exercise prescription
Control Usual care 29 51.3 1.8 18, 62%
Balducci S [16] RCT 606 Intervention Supervised training plus structured exercise 303 NA NA 12 months
counseling
Control Standard care (counseling only) 303 NA NA
Kirk A [17] RCT 70 Intervention Physical activity counseling with a trained 35 57.6 7.9d 35, 50%d 12 months
research assistant
Control Standard exercise leaet 35

Intensive dietary program

Coppell KJ [22] RCT 93 Intervention Intensive individualized dietary intervention 45 56.6 8.8 17,38% 6 months
Control Usual care 48 58.4 8.8 21, 44%
Uusitupa M [30] RCT 86 Intervention Intensive individualized dietary intervention 40 NA NA 15 months
Control Usual care 46 NA NA

Education program
Ali M [25] RCT 48 Intervention Pharmacist care package (about diabetes, its 23 66.4 12.7 10, 43.5% 12 months
treatment and associated cardiovascular risk
factors)
Control Usual care (seen by a pharmacist only at the 23 66.8 10.2 13, 56.5%
beginning of the study and then after 12
months)
Mohamed H [23] RCT 290 Intervention Structured group counseling sessions in 109 53.1 12.4 40, 36.7% 12 months
addition to educational toolkit
Control Diabetes educational toolkit only 181 50 12.4 50, 27.6%
Chan CW [18] RCT 120 Intervention Pharmacist care package (about 51 63.2 9.5 30, 58.8% 9 months
drug-counseling and cardiovascular risks)
Control Without pharmacist interventions 54 61.7 11.2 28, 51.9%
Sevick MA [26] RCT 265 Intervention Group counseling sessions over the diabetes 132 NA 38, 29% 6 months
self-management regimen
Control Monthly contact with the study team 133 NA 46, 34.8%
Crasto W [20] RCT 189 Intervention Education medication optimization group 94 62.6 10.3 71, 75.5% 18 months
(a structured self-management education
program)
Control Usual care by their own clinician 95 60.3 10.7 72, 75.8%
Salinero-Fort MA [21] RCT 608 Intervention Precede Health Promotion Education (PHPE) 300 66.06 8 139, 46.2% 2 years
Control Conventional Health Promotion Education 300 67.28 19 152, 50.7%
(CHPE)
Sone H [35] RCT 2033 Intervention Lifestyle intervention (education on lifestyle 1017 58.5 6.9 549, 54.0% 8 years
modication)
Control Conventional treatment 1016 58.6 7.0 538, 53.0%
Ko GT [19] RCT 180 Intervention Structured health program 90 55.0 9.0 44, 48.9% 1 year
Control Usual care 88 56.0 10.2 34, 38.6%
Krein SL [14] RCT 246 Intervention Care by a signed case manager 123 61 10 121, 98% 18 months
Control Usual care 123 61 11 117, 95%
Trento M [24] RCT 112 Intervention Systemic education program in group and 56 62.0 (35 to 80)c 27, 48.2% 4 years
individual sessions
Control Usual care 56 61.0 (43 to 78)c 34, 60.7%

Abbreviations: RCT, randomized control trial; NA, not available.

a
Total number of patients enrolled.
b
Number of patients in each group.
c
Median (range: min. to max.)
d
Represented data for the entire group.

95% CI, 1.94 to 0.39, P = 0.194; DIET: standardized difference in
means, 0.20; 95% CI, 0.63 to 0.22, P = 0.354; EDU: standardized dif-
ference in means, 0.06; 95% CI, 0.14 to 0.01, P = 0.082; Figs. 3, 4, 5).
3.3.2. HbA1c
All 17 studies provided data for the change in HbA1c from the base-
line. Owing to the evidence of heterogeneity among the studies, a ran-
dom effect analysis was applied to PA and EDU groups and a xed
effect analysis to the DIET group (PA: Q statistic = 90.60, I2 = 95.59%,
P b 0.001; DIET: Q statistic = 1.96, I2 = 0%, P = 0.375; EDU: Q
statistic = 76.48 I2 = 88.23%, P b 0.001). The standardized difference
in means of change from baseline in HbA1c signicantly favored the in-
tervention group, as compared with the control groups, in the PA and
DIET intervention (PA: standardized difference in means, 1.02; 95%
CI, 1.80 to 0.23, P = 0.011; DIET: standardized difference in
means, 0.30; 95% CI, 0.35 to 0.24, P b 0.001) (Figs. 3 and 4).
 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747 41

Fig. 2. The quality assessment for each included study was summarized in (A) risk of bias summary or (B) as percentages across all included studies in the risk of bias graph.

However, no difference between the intervention and control groups in 3.3.3. Blood pressure (SBP and DBP)
the EDU patient group was seen (standardized difference in means, Sixteen of the 17 studies reported values for systolic (SBP) and dia-
0.08; 95% CI, 0.3 to 0.15, P = 0.509; Fig. 5). stolic (DBP) blood pressure at the baseline and following intervention.
42 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747

Fig. 3. Forest plot comparing the intervention and control groups. Changes from the baseline (top to bottom) in BMI, HbA1c, SBP, DBP, LDL-c, and HDL-c for patients in the intensive
physical activity program are given. Abbreviations: CI, condence interval; std diff, standardized difference.

Additionally, in the EDU group, Krein study [14] DBP was not considered
for analysis due to the observed 95% CI (2.0 to 4.0) being not symme-
try relative to the mean of 0.85. Hence, only 9 studies were retained for
analysis. There was heterogeneity across the studies for both SBP and
DBP in PA and EDU groups, but homogeneity in the DIET group (PA: Q
statistic = 18.24, I2 = 83.56%, P b 0.001 for SBP; Q statistic = 49.55,
I2 = 93.95%, P b 0.001 for DBP; DIET: Q statistic = 0.41, I2 = 0%, P =
0.817 for SBP; Q statistic = 2.94, I2 = 31.09%, P = 0.230 for DBP;
EDU: Q statistic = 42.62, I2 = 78.88%, P b 0.001 for SBP; Q statistic =
24.06, I2 = 66.75%, P = 0.002 for DBP). Consequently, a random effect
analysis was used for PA and EDU groups and a xed analysis for the
DIET group. The standardized difference in means of change from base-
line in both SBP and DBP signicantly favored the intervention in the
DIET group (SBP: standardized difference in means, 0.19: 95% CI,
0.25 to 0.14, P b 0.001; DBP: standardized difference in means:
0.08, 95% CI = 0.13 to 0.02, P = 0.005; Fig. 4). However, there
was no signicance in means of change from baseline in both SBP and
DBP in the EDU group (SBP: standardized difference in means, 0.17:
95% CI, 0.34 to 0, P = 0.056; DBP: standardized difference in means,
0.08: 95% CI, 0.23 to 0.06, P = 0.267; Fig. 5), suggesting the limited
impact of EDU alone strategy. In PA group, the intervention showed a
signicant decrease in DBP, but no signicant change in SBP (SBP: stan-
dardized difference in means, 0.05: 95% CI, 0.46 to 0.35, P = 0.792;
DBP: standardized difference in means, 0.76: 95% CI, 1.45 to 0.07,
P = 0.030; Fig. 3).
3.3.4. LDL-c and HDL-c
Of the 17 studies, 13 reported change from the baseline in LDL-c and
15 reported change from the baseline in HDL-c. In LDL-c, four studies
belonged to the PA program, two in the DIET program, and eight in
the EDU program. A random effect analysis was applied to LDL-c, as
there was evidence of heterogeneity among the studies in all 3 groups.
In HDL-c, four studies belonged to the PA program, three to the DIET
program, and nine to the EDU program. Additionally, in EDU group,
the Crasto study [20] was not considered, as the observed 95% CI
( 0.07, 0.04) was not symmetry relative to the mean of 0.01. Hence,
 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747
Fig. 4. Forest plot comparing intervention and control groups, for changes from the baseline in (top to bottom) BMI, HbA1c, SBP, DBP, LDL-c and HDL-c for those in the intensive dietary
program are shown. Abbreviations: CI, condence interval; std diff, standardized difference.
only 8 studies were retained for analysis in the EDU group. A xed effect
analysis was applied to HDL-c in the DIET group, but a random effect
analysis was used in the PA and EDU groups (PA: Q statistic = 17.10,
I2 = 82.46%, P = 0.001 for LDL-c; Q statistic = 13.54, I2 = 77.84%,
P = 0.004 for HDL-c; DIET: Q statistic = 3.17, I2 = 68.42%, P = 0.075
for LDL-c; Q statistic = 0.97, I2 = 0%, P = 0.616 for HDL-c; EDU: Q
statistic = 36.53, I2 = 80.84%, P b 0.001 for LDL-c; Q statistic = 25.42,
I2 = 72.46%, P = 0.001 for HDL-c). According to the analysis, standard-
ized difference in the mean change from the baseline favored the inter-
vention group for HDL-c in the DIET program, suggesting that the
intervention group had a higher increase in the HDL-c level, as com-
pared with the control group (standardized difference in means,
0.026; 95% CI, 0.21 to 0.32, P b 0.001). But, there was no signicant dif-
ference in the PA and EDU groups. The difference in LDL-c between the
intervention and control groups was not signicant in all 3 groups,
either.
3.4. Sensitivity analysis
Sensitivity analysis was performed in which the results were ana-
lyzed using leave-one-out approach, with each study removed in turn
for HbA1c results for those in the PA, DIET, and the EDU programs, sep-
arately. The direction and magnitude of the combined estimates did not
markedly change with the exclusion of individual studies, indicating
that no one study dominated the ndings (Fig. 6).
43
3.5. Publication bias
Funnel plot analysis for publication bias was performed for the
HbA1c education program only. It was found that the combined effect
size yielded Z values of 0.53 for HbA1c (P = 0.597). The Eggar's test
demonstrated marked evidence of symmetry, indicating that there
was no signicant evidence of publication bias (one tailed P = 0.428
for HbA1c; Fig. 7). The publication bias was not done in the physical ac-
tivity and dietary programs, as at least ve studies were required for
funnel plot analysis.
4. Discussion
The signicance of intensive lifestyle intervention for weight loss
and reduction in cardiovascular morbidity and mortality among type 2
diabetic or pre-diabetic patients have been demonstrated [3032].
Though, comprehensive lifestyle interventions effectively decrease the
incidence of type 2 diabetes in high-risk patients, its effect in patients
who already have type 2 diabetes are variable among trials [33,34]. Fur-
thermore, lowering blood glucose through lifestyle modication may
improve cardio-metabolic risk factors, but may not affect CVD event
rates [32]. Sone et al. have reported that lifestyle interventions had lim-
ited effects on typical cardiovascular risk factors, but had a signicant ef-
fect on stroke incidence in patients with established type 2 diabetes
44 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747
 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747 45

Fig. 6. Sensitivity analysis using the leave-one-out approach, showing the inuence of each individual study on the pooled estimate of HbA1c in patients in the intensive physical activity,
dietary, and education programs are given. Abbreviations: CI, condence interval; std diff, standardized difference.

[35]. The present meta-analysis evaluated the effects of intensive phys-
ical activity (PA), diet control (DIET) and education and counseling
(EDU) interventions, in reducing the risk of cardiovascular disease in
patients with type 2 diabetes.
Our analysis revealed that weight loss, as indicated by the reduction
in BMI, was similar between the intervention and the control groups, ir-
respective of the nature of intervention (PA, DIET or EDU). Interestingly,
the intensive PA and DIET intervention yielded a greater reduction in
glycated hemoglobin (HbA1c) than the control group, while no signi-
cant difference was observed in the EDU group (Figs. 3, 4, 5). In terms
of blood pressure, signicant improvement in both systolic and diastolic
blood pressure (SBP and DBP) was observed in the DIET intervention
group, while intensive PA was able to reduce the DBP signicantly,
with little or no effect on the SBP levels. No signicant difference in
blood pressure was seen in the EDU intervention vs. the control group.
Regarding serum lipids, the HDL-c level in the DIET group was signi-
cantly higher than the non-intervention control group, thereby lower-
ing the risk of CVD in the DIET intervention group. However, there
was no signicant difference in LDL-c levels between the intervention
and control groups in all three intervention subtypes.
Our current analysis is in agreement with other studies where even
small to moderate weight loss and a change in fatty acid composition
of diet achieved a good metabolic control in the majority of obese,
middle-aged patients with recent type 2 diabetes [30]. Likewise, the
LOADD (Lifestyle Over and Above Drugs in Diabetes) study also have
demonstrated a signicant difference in HbA1c, body weight, BMI, and
waist circumference, after adjusting for age, sex and baseline measure-
ments in type 2 diabetic patients [22]. Participants in the intensive life-
style intervention in the Look AHEAD study (diet modication, calorie
goal of 12001800 based on initial weight; and physical activity, at
least 175 min/week) achieved and maintained signicant weight loss
and had better glycemic control, blood pressure, HDL-c, and triglycerides,
thus reducing their CVD risk [11].
Our results also reveal that PA intervention had a signicant impact
on HbA1c and diastolic blood pressure (Fig. 3). However, unlike an Ital-
ian Diabetes and Exercise study (IDES) [16], it did not have any effect on
other risk factors, including BMI, SBP, LDL-c, and HDL-c. Though the out-
come of HDL-c favored intervention group with intensive physical activ-
ity, it was not statistically different from the control (Fig. 3). While two
of the studies favored the intervention group [12,16], two other studies
had no signicant outcome [13,17]. The presence of heterogeneity along
with small sample size, might have led to no signicance in the pooled
overall data. Besides, physical activity could be inuenced by many fac-
tors, including motivation, reinforcement, intensity, and adherence to
the PA program. In addition, reports elsewhere indicate that a personal-
ized exercise prescription program provided by physical therapist every
6 weeks for 2 years did not alter the physical activity levels or improve
glycemic control in sedentary, insulin treated type 2 diabetes patients
[13]. Counseling alone, though successful in achieving the recommend-
ed amount of physical activity, was of limited efcacy on cardiovascular

Fig. 5. Forest plot comparing intervention and control groups, for changes from the baseline in (top to bottom) BMI, HbA1c, SBP, DBP, LDL-c and HDL-c for patients in the education pro-
gram are shown. Abbreviations: CI, condence interval; std diff, standardized difference.
46 X.-L. Huang et al. / European Journal of Internal Medicine 27 (2016) 3747
Fig. 7. Funnel plots for the publication bias in HbA1c in patients undergoing intensive education program. Abbreviations: std diff, standardized difference.
risk factors [16]. A strictly supervised exercise training program may not
be always feasible on a long-term basis, however, it may improve the
outcome and reduce the CVD risk in these patients.
Contrary to the popular belief in patient education and counseling,
no difference in glycated hemoglobin, blood pressure or triglyceride
levels was seen between the intervention and control groups in the
EDU alone group in our analysis (Fig. 5). This is in agreement with stud-
ies by Baker et al. where the absence of intensive individualized advice
or information only was very ineffective [36]. Further, results from case
management studies also indicate that no signicant improvement in
outcomes was observed [14,16]. Though, some studies have reported
positive effects of case management in the reduction of CVD risk factors
[18,25]. It should be noted that multiple factors, like the ethnicity of pa-
tients, culture, and organizational structure of the program are critical
factors in determining the effectiveness of an intervention.
The existing evidence for multiple lifestyle interventions in reducing
the CVD risk may be variable. Our meta-analysis included only RCTs in
adults with type 2 diabetes. Clinical trials in children and adolescents
were excluded to maintain the homogeneity of the studies. Care was
also taken to choose only intervention programs longer than 6 months,
thus avoiding the inuence of short-term effect on the measured out-
comes. Short-term interventions may not represent real life situations,
where patients may fail to follow strict adherence and where compli-
ance cannot be enforced beyond the intervention period.
However, there are several limitations to the present analysis. The
authors fully acknowledge that the difference in the formats of lifestyle
intervention is diverse, and there was a high risk of performance bias in
the studies included. Although data were analyzed according to the in-
tervention subtypes, the delivery of the education programs was vari-
ous, including group sessions, self-management, and pharmacist care,
which may have a major impact on the cardiovascular risk. Moreover,
the intensity of the exercise and dietary regimens might also affect the
clinical outcomes. In addition, the wide range of variability in age, sex,
and duration of follow-up included in this meta-analysis could have
confounded our ndings. Ideally, we would have used subgroup analy-
sis to address this problem. However, due to the limitation of extracting
sufcient data for each confounder, it was not possible to perform this
type of analysis. Another factor which could affect the outcomes of
this study is that the Look AHEAD study constituted the majority of
the patients (5145 subjects) and had a longer follow-up period (4
years), thus reducing the overall impact of other studies included in
the analysis. However, the leave-one-out sensitivity analysis indicates
that none of the studies dominated the current ndings. Finally, though
interventions involving pharmacological methods were excluded from
this meta-analysis, the use of medications in routine medical care in
most studies may have made the relative benet of the intensive life-
style interventions more difcult to demonstrate.
In summary, the current analysis indicates that in patients with type
2 diabetes, nutritional intervention (DIET group) had a better impact on
the quality of life by reducing their risk of CVD, as opposed to EDU or PA
alone. DIET group showed a signicant improvement in all major car-
diovascular risk factors associated with diabetes, such as the HbA1c,
SBP, DBP, and HDL-c, except for LDL-c and BMI. The PA intervention
showed a signicant impact on HbA1c and DBP, but not on the other
risk factors (BMI, SBP, LDL-c, and HDL-c). The EDU program, on the
other hand, did not show any difference in all the risk factors assessed
in the study.
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.ejim.2015.11.016.
Conict of interests
The authors state that they have no conicts of interest.
Acknowledgments
None.
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