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European Journal of Internal Medicine 27 (2016) 3747

Contents lists available at ScienceDirect

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-


ercise regimen and other lifestyle changes is not as realistic as the drug
The global increase in the prevalence of diabetes seen in recent years treatment in many patients. Besides, the evidence for dietary modica-
has been attributed mostly to obesity, poor diet, and lack of physical tions in glycemic control, though compelling, is often based on short
activity. The World Health Organization projects diabetes as the 7th term studies, mostly one year or less [10,11]. Clinical trials with a longer
leading cause of death and estimates that there will be 366 million follow-up period are often necessary to conrm the positive impact of
adults with diabetes in 2030 [1,2]. Of which, 90% of people will have lifestyle changes in reducing the CVD in type 2 diabetes patients.
type 2 diabetes, resulting from the body's ineffective use of insulin [3] Recently, the Look AHEAD study examined the effects of an intensive
and poor glycemic control. Reduced metabolic control of glucose can lifestyle intervention (with diet modication and physical activity) over
in turn increase the risk of cardiovascular diseases (CVD). The common a period of four years in a large cohort of overweight and obese individ-
cardiovascular risk factors associated with diabetes include, increased uals with type 2 diabetes [12]. The results indicate that patients who
body weight, glycemia, serum lipids, and blood pressure [4]. underwent intensive lifestyle intervention as opposed to diabetes sup-
Improvement of glycemic control and reduction of cardiovascular port and education (control), had better glycemic control, blood pres-
risk factors through diet and exercise has long been advocated [5,6]. sure, high density lipoprotein-cholesterol (HDL-C) and triglyceride
However, with the introduction of many new oral hypoglycemic agents, levels, thus lowering their cardiovascular disease risk. Though, the max-
such as the glucagon-like peptide-1 receptor (GLP-1R) agonist and imum benets were seen at one year, the intervention group had great-
dipeptidyl peptidase-4 (DPP-4) inhibitors, in addition to the conven- er improvements over the control group even at 4 years.
tional metformin mono-therapy and increased use of insulin, the nutri- In contrast, a long term behavioral intervention program, providing
tional control of diabetes seemed to have lost its relevance [79]. 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-
Corresponding author at: Department of Nephrology, The First Hospital of Wuhan,
Wuhan Qiaokou District Liji North Road No. 215, 430030 Wuhan, China. Tel.: + 86
cise training with personal coaching may be required to maximize the
13871101268. adherence and to increase the physical activity status. Similarly, a ran-
E-mail address: 5051huangxiaoli@163.com (X.-L. Huang). 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- 2.4. Quality assessment
nicant difference between the case management and the control
groups [14]. There was no difference in the mean HbA1c level, or low The included studies were assessed for the risk of bias using the Risk
density lipoprotein-cholesterol (LDL-C) or blood pressure (BP) among of Bias assessment tool, Review Manager 5.1. Recommendations for
the groups, suggesting cautious use of resources on personalized inter- judging the risk of bias were provided in Chapter 8 of the Cochrane
ventions and case management in the treatment of type 2 diabetes. Handbook for Systematic Reviews Interventions [27].
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 2.5. Statistical analysis
patients is inconsistent. Recent ndings suggest that though there was
no reduction in BP, a modest reduction in the HbA1c levels (0.2%) was The reduction in the risk factors for cardiovascular disease, such as,
observed in the exercise group [15], further substantiating the protec- body mass index (BMI), HbA1c, systolic blood pressure (SBP), diastolic
tive effect of exercise on glycemic control. Reports elsewhere further blood pressure (DBP), high-density lipoprotein-c (HDL-c), and low-
corroborate the effectiveness of exercise intervention strategies in pro- density lipoprotein-c (LDL-c). BMI, HbA1c, SBP, DBP, HDL-c, and LDL-c
moting physical activity and improving HbA1c and cardiovascular risk were compared between participants having an intensive lifestyle inter-
prole [16]. The above study also revealed that counseling alone, though vention (intervention group) and the conventional intervention (con-
effective in achieving the recommended level of physical activity (PA), trol group). The intervention group was divided into 3 subgroups
was unsuccessful in minimizing the cardiovascular risk, suggesting the according to the type of intervention and data were analyzed separately
need for a larger volume of PA in high-risk patients. Conversely, Kirk according to 3 different programs, intensive physical activity (PA), in-
et al. [17] reported that counseling improved glycemic control as well tensive dietary (DIET), and education program (EDU). For each outcome
as the status of cardiovascular risk factors in type 2 diabetic patients. measure, the standardized difference (Std. diff) in means with corre-
In reports elsewhere, regular drug-counseling through pharmacist sponding 95% condence intervals was calculated for each individual
care program signicantly reduced the various CVD risk factors, includ- and study. Std. diff in means of b0 indicates that the intervention was
ing stroke [18]. favored, showing a greater decrease in change of outcome than the con-
The aforementioned studies along with various other reports indi- trol group. Conversely, Std. diff in means of N 0 indicates that the control
cate that structured reinforcement with diabetes health education, group was favored, which means that the intervention group had less
counseling, physical activity programs, and nutritional control can con- decrease in change of outcome than the control. Std. diff in means = 0
trol the risk of CVD in patients with type 2 diabetes [1926]. The aim of indicates that the intervention and control groups had a similar change
the present meta-analysis is to compare the outcomes of intensive exer- in outcomes. Additionally, for changes in the levels of HDL-c, the effect
cise, dietary regimens, and comprehensive lifestyle interventions and its was identied as the Std. diff in means of N 0, indicating that the inter-
signicance on clinical markers of cardiovascular disease in patients vention group was favored with greater increase in the change of
with type 2 diabetes. 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
2. Methods HDL-c than the intervention group.
A 2 based test of homogeneity was performed using Cochran's Q
2.1. Selection criteria statistic and I2. I2 illustrates the percentage of the total variability in ef-
fect estimates among trials resulting from heterogeneity rather than
We performed a literature search of PubMed Central and MEDLINE, chance. Random effect models of analysis were used if heterogeneity
the Cochrane Central Register of Controlled Trials (CENTRAL), was detected (I2 N 50%). Otherwise, xed effect models were used. For
EMBASE, and Google Scholar databases (until July 15, 2014) using the each outcome measure, the standardized difference in means with cor-
terms diabetes, cardiovascular risk, lifestyle, health education, dietary, responding 95% condence intervals was calculated for each individual
exercise/physical activities, and behavior intervention. Prospective, and study.
randomized controlled trials comparing lifestyle interventions with A two-sided P value of b 0.05 indicated statistical signicance for one
the usual care control group were included in the current meta- comparison group over the other. Sensitivity analysis was carried out
analysis. Only articles in English were considered for analysis. We ex- for the outcome HbA1c using the leave one-out approach. A funnel
cluded studies that did not recruit patients with type 2 diabetes or plot, the fail-safe N (which indicates whether the observed signicance
those with no mention of lifestyle program/education relating to the pa- is spurious or not), and Egger's test (which detects whether the ob-
tient dietary and exercise behavior/physical activities. served studies is asymmetry or not) were used to assess possible publi-
cation bias in EDU subgroup only. Since ve or fewer studies are
2.2. Study selection and data extraction insufcient to detect funnel plot asymmetry [28], publication bias for
the other two subgroups was not assessed. All analyses were performed
Studies identied by the search strategy were hand-selected and using Comprehensive Meta-analysis statistical software, version 2.0
data were extracted by two independent reviewers. Where there was (Biostat, Englewood, NJ, USA).
uncertainty regarding eligibility, a third reviewer was consulted.
The following information was extracted from studies that met the 3. Results
inclusion criteria: the name of the rst author, year of publication,
study design, number of participants in each treatment group, partici- 3.1. Literature search
pants' age and gender, diagnostic criteria, intervention regiment for
the study/control group, and results. The minimum number of partici- After the removal of duplicates, a total of 235 studies were identied
pants was 30 in each study, while the minimum follow-up period was through the database search, of which 167 studies were excluded due to
6 months. lack of relevancy. After full text reviewing of 68 articles, we excluded 51
studies. The reasons for elimination being, eight articles were from the
2.3. Outcomes same trial that was included in the meta-analysis; while eight articles
did not contain the outcome of interest; fourteen articles adopted inter-
The primary outcome was the reduction in the risk factors for cardio- vention programs that were shorter than 6 months; and twelve articles
vascular disease, such as, body mass index, HbA1c, blood pressure, and had other interventions involved, for example, pharmacological inter-
the level of cholesterol. 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 39

six articles were 3 or 4 arm RCTs. One study [29] was initially included, (Fig. 2A). In addition, an overall assessment of risk of bias was presented
however, it later had to be excluded because of the variability in BMI, in Fig. 2B. All studies utilized random sequence generation, thus
LDL-c and HDL-c analyses, as compared with other included studies. avoiding any selection bias. However, only 65% (11/17) studies had allo-
The inclusion of this study would have skewed the meta-analysis by in- cation concealment, leaving the rest of the 35% of the studies with un-
creasing the discrepancy in both sensitivity and publication bias analy- clear risk of bias. Blinding of participants and personnel was not
ses. 17 studies were included in the nal meta-analysis. The owchart followed through in 15/17 (88%) studies, thus resulting in a higher
for the selection of trials is shown in Fig. 1. risk of performance bias. In addition, some of these study results are
further biased by not blinding the outcome assessment (detection
3.2. Study characteristics bias; 6/17 studies; 38%). Only 47% of the studies included had intent-
to-treat analysis (Fig. 2A, B).
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 3.3. Clinical outcome measures
(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 3.3.1. Body mass index (BMI)
98%, and the length of the study ranged from 6 months to 8 years Twelve of the included studies reported change from baseline in
(Table 1). There were 10 studies in the EDU group, 5 in the PA group, BMI. There was heterogeneity for this outcome across studies in the
and 3 in the DIET group. The Look AHEAD Research Group [12] study PA group, but it was homogeneous in both DIET and EDU groups (PA:
used intervention containing both intensive physical activity and Q statistic = 35.77, I2 = 94.41%, P b 0.001; DIET: Q statistic = 5.54,
dietary programs; therefore, the data in this study were included and I2 = 0%, P = 0.477; EDU: Q statistic = 5.20, I2 = 0%, P = 0.635). There-
analyzed separately in PA and DIET groups. The changes in outcome fore, the random effect analysis was applied to the PA group, and the
measures from the baseline for the studies included in this meta- xed effect analyses in the DIET and EDU groups, respectively. The stan-
analysis are summarized in the Supplementary Table S1. dardized differences in the means of change from baseline in BMI
Fig. 2 represents the assessed outcomes of the included studies. For showed similar changes between the intervention and control groups
each trial, the risk of bias was detailed in the risk of bias summary for all three subgroups (PA: standardized difference in means, 0.77;

Fig. 1. A owchart showing the selection of studies.


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 effect analysis to the DIET group (PA: Q statistic = 90.60, I2 = 95.59%,
means, 0.20; 95% CI, 0.63 to 0.22, P = 0.354; EDU: standardized dif- P b 0.001; DIET: Q statistic = 1.96, I2 = 0%, P = 0.375; EDU: Q
ference in means, 0.06; 95% CI, 0.14 to 0.01, P = 0.082; Figs. 3, 4, 5). 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-
3.3.2. HbA1c tervention group, as compared with the control groups, in the PA and
All 17 studies provided data for the change in HbA1c from the base- DIET intervention (PA: standardized difference in means, 1.02; 95%
line. Owing to the evidence of heterogeneity among the studies, a ran- CI, 1.80 to 0.23, P = 0.011; DIET: standardized difference in
dom effect analysis was applied to PA and EDU groups and a xed 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 95% CI, 0.34 to 0, P = 0.056; DBP: standardized difference in means,
for analysis due to the observed 95% CI (2.0 to 4.0) being not symme- 0.08: 95% CI, 0.23 to 0.06, P = 0.267; Fig. 5), suggesting the limited
try relative to the mean of 0.85. Hence, only 9 studies were retained for impact of EDU alone strategy. In PA group, the intervention showed a
analysis. There was heterogeneity across the studies for both SBP and signicant decrease in DBP, but no signicant change in SBP (SBP: stan-
DBP in PA and EDU groups, but homogeneity in the DIET group (PA: Q dardized difference in means, 0.05: 95% CI, 0.46 to 0.35, P = 0.792;
statistic = 18.24, I2 = 83.56%, P b 0.001 for SBP; Q statistic = 49.55, DBP: standardized difference in means, 0.76: 95% CI, 1.45 to 0.07,
I2 = 93.95%, P b 0.001 for DBP; DIET: Q statistic = 0.41, I2 = 0%, P = P = 0.030; Fig. 3).
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 = 3.3.4. LDL-c and HDL-c
24.06, I2 = 66.75%, P = 0.002 for DBP). Consequently, a random effect Of the 17 studies, 13 reported change from the baseline in LDL-c and
analysis was used for PA and EDU groups and a xed analysis for the 15 reported change from the baseline in HDL-c. In LDL-c, four studies
DIET group. The standardized difference in means of change from base- belonged to the PA program, two in the DIET program, and eight in
line in both SBP and DBP signicantly favored the intervention in the the EDU program. A random effect analysis was applied to LDL-c, as
DIET group (SBP: standardized difference in means, 0.19: 95% CI, there was evidence of heterogeneity among the studies in all 3 groups.
0.25 to 0.14, P b 0.001; DBP: standardized difference in means: In HDL-c, four studies belonged to the PA program, three to the DIET
0.08, 95% CI = 0.13 to 0.02, P = 0.005; Fig. 4). However, there program, and nine to the EDU program. Additionally, in EDU group,
was no signicance in means of change from baseline in both SBP and the Crasto study [20] was not considered, as the observed 95% CI
DBP in the EDU group (SBP: standardized difference in means, 0.17: ( 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 43

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 3.5. Publication bias
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, Funnel plot analysis for publication bias was performed for the
I2 = 82.46%, P = 0.001 for LDL-c; Q statistic = 13.54, I2 = 77.84%, HbA1c education program only. It was found that the combined effect
P = 0.004 for HDL-c; DIET: Q statistic = 3.17, I2 = 68.42%, P = 0.075 size yielded Z values of 0.53 for HbA1c (P = 0.597). The Eggar's test
for LDL-c; Q statistic = 0.97, I2 = 0%, P = 0.616 for HDL-c; EDU: Q demonstrated marked evidence of symmetry, indicating that there
statistic = 36.53, I2 = 80.84%, P b 0.001 for LDL-c; Q statistic = 25.42, was no signicant evidence of publication bias (one tailed P = 0.428
I2 = 72.46%, P = 0.001 for HDL-c). According to the analysis, standard- for HbA1c; Fig. 7). The publication bias was not done in the physical ac-
ized difference in the mean change from the baseline favored the inter- tivity and dietary programs, as at least ve studies were required for
vention group for HDL-c in the DIET program, suggesting that the funnel plot analysis.
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- 4. Discussion
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, The signicance of intensive lifestyle intervention for weight loss
either. and reduction in cardiovascular morbidity and mortality among type 2
diabetic or pre-diabetic patients have been demonstrated [3032].
3.4. Sensitivity analysis Though, comprehensive lifestyle interventions effectively decrease the
incidence of type 2 diabetes in high-risk patients, its effect in patients
Sensitivity analysis was performed in which the results were ana- who already have type 2 diabetes are variable among trials [33,34]. Fur-
lyzed using leave-one-out approach, with each study removed in turn thermore, lowering blood glucose through lifestyle modication may
for HbA1c results for those in the PA, DIET, and the EDU programs, sep- improve cardio-metabolic risk factors, but may not affect CVD event
arately. The direction and magnitude of the combined estimates did not rates [32]. Sone et al. have reported that lifestyle interventions had lim-
markedly change with the exclusion of individual studies, indicating ited effects on typical cardiovascular risk factors, but had a signicant ef-
that no one study dominated the ndings (Fig. 6). 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- demonstrated a signicant difference in HbA1c, body weight, BMI, and
ical activity (PA), diet control (DIET) and education and counseling waist circumference, after adjusting for age, sex and baseline measure-
(EDU) interventions, in reducing the risk of cardiovascular disease in ments in type 2 diabetic patients [22]. Participants in the intensive life-
patients with type 2 diabetes. style intervention in the Look AHEAD study (diet modication, calorie
Our analysis revealed that weight loss, as indicated by the reduction goal of 12001800 based on initial weight; and physical activity, at
in BMI, was similar between the intervention and the control groups, ir- least 175 min/week) achieved and maintained signicant weight loss
respective of the nature of intervention (PA, DIET or EDU). Interestingly, and had better glycemic control, blood pressure, HDL-c, and triglycerides,
the intensive PA and DIET intervention yielded a greater reduction in thus reducing their CVD risk [11].
glycated hemoglobin (HbA1c) than the control group, while no signi- Our results also reveal that PA intervention had a signicant impact
cant difference was observed in the EDU group (Figs. 3, 4, 5). In terms on HbA1c and diastolic blood pressure (Fig. 3). However, unlike an Ital-
of blood pressure, signicant improvement in both systolic and diastolic ian Diabetes and Exercise study (IDES) [16], it did not have any effect on
blood pressure (SBP and DBP) was observed in the DIET intervention other risk factors, including BMI, SBP, LDL-c, and HDL-c. Though the out-
group, while intensive PA was able to reduce the DBP signicantly, come of HDL-c favored intervention group with intensive physical activ-
with little or no effect on the SBP levels. No signicant difference in ity, it was not statistically different from the control (Fig. 3). While two
blood pressure was seen in the EDU intervention vs. the control group. of the studies favored the intervention group [12,16], two other studies
Regarding serum lipids, the HDL-c level in the DIET group was signi- had no signicant outcome [13,17]. The presence of heterogeneity along
cantly higher than the non-intervention control group, thereby lower- with small sample size, might have led to no signicance in the pooled
ing the risk of CVD in the DIET intervention group. However, there overall data. Besides, physical activity could be inuenced by many fac-
was no signicant difference in LDL-c levels between the intervention tors, including motivation, reinforcement, intensity, and adherence to
and control groups in all three intervention subtypes. the PA program. In addition, reports elsewhere indicate that a personal-
Our current analysis is in agreement with other studies where even ized exercise prescription program provided by physical therapist every
small to moderate weight loss and a change in fatty acid composition 6 weeks for 2 years did not alter the physical activity levels or improve
of diet achieved a good metabolic control in the majority of obese, glycemic control in sedentary, insulin treated type 2 diabetes patients
middle-aged patients with recent type 2 diabetes [30]. Likewise, the [13]. Counseling alone, though successful in achieving the recommend-
LOADD (Lifestyle Over and Above Drugs in Diabetes) study also have 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 that none of the studies dominated the current ndings. Finally, though
be always feasible on a long-term basis, however, it may improve the interventions involving pharmacological methods were excluded from
outcome and reduce the CVD risk in these patients. this meta-analysis, the use of medications in routine medical care in
Contrary to the popular belief in patient education and counseling, most studies may have made the relative benet of the intensive life-
no difference in glycated hemoglobin, blood pressure or triglyceride style interventions more difcult to demonstrate.
levels was seen between the intervention and control groups in the In summary, the current analysis indicates that in patients with type
EDU alone group in our analysis (Fig. 5). This is in agreement with stud- 2 diabetes, nutritional intervention (DIET group) had a better impact on
ies by Baker et al. where the absence of intensive individualized advice the quality of life by reducing their risk of CVD, as opposed to EDU or PA
or information only was very ineffective [36]. Further, results from case alone. DIET group showed a signicant improvement in all major car-
management studies also indicate that no signicant improvement in diovascular risk factors associated with diabetes, such as the HbA1c,
outcomes was observed [14,16]. Though, some studies have reported SBP, DBP, and HDL-c, except for LDL-c and BMI. The PA intervention
positive effects of case management in the reduction of CVD risk factors showed a signicant impact on HbA1c and DBP, but not on the other
[18,25]. It should be noted that multiple factors, like the ethnicity of pa- risk factors (BMI, SBP, LDL-c, and HDL-c). The EDU program, on the
tients, culture, and organizational structure of the program are critical other hand, did not show any difference in all the risk factors assessed
factors in determining the effectiveness of an intervention. in the study.
The existing evidence for multiple lifestyle interventions in reducing Supplementary data to this article can be found online at http://dx.
the CVD risk may be variable. Our meta-analysis included only RCTs in doi.org/10.1016/j.ejim.2015.11.016.
adults with type 2 diabetes. Clinical trials in children and adolescents
were excluded to maintain the homogeneity of the studies. Care was Conict of interests
also taken to choose only intervention programs longer than 6 months,
thus avoiding the inuence of short-term effect on the measured out- The authors state that they have no conicts of interest.
comes. Short-term interventions may not represent real life situations,
where patients may fail to follow strict adherence and where compli- Acknowledgments
ance cannot be enforced beyond the intervention period.
However, there are several limitations to the present analysis. The None.
authors fully acknowledge that the difference in the formats of lifestyle
intervention is diverse, and there was a high risk of performance bias in
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