- Email: [email protected]
Lifestyle Modification for Metabolic Syndrome: A Systematic Review
Accepted Manuscript Lifestyle Modification for Metabolic Syndrome: A Systematic Review Nikhil Bassi, MD Ilya Karagodin, MD Serena Wang, MD Patricia Vassallo, MD Aparna Priyanath, MD Elaine Massaro, MS,RN Neil J. Stone, MD PII:
S0002-9343(14)00576-2
DOI:
10.1016/j.amjmed.2014.06.035
Reference:
AJM 12596
To appear in:
The American Journal of Medicine
Received Date: 29 April 2014 Revised Date:
7 June 2014
Accepted Date: 9 June 2014
Please cite this article as: Bassi N, Karagodin I, Wang S, Vassallo P, Priyanath A, Massaro E, Stone NJ, Lifestyle Modification for Metabolic Syndrome: A Systematic Review, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.06.035. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
*Manuscript Click here to view linked References
RI PT
Lifestyle Modification for Metabolic Syndrome: A Systematic Review
Authors: Nikhil Bassi, MD* Ilya Karagodin, MD* Serena Wang, MD* Patricia Vassallo, MD* Aparna Priyanath, MD* Elaine Massaro MS,RN**Neil J. Stone MD*
M AN U
SC
Departments of Cardiology and Medicine *, Department of Endocrinology** Feinberg School of Medicine Chicago, Illinois Words 1959 (excluding footnotes, endnotes)
TE D
Send Correspondence to: Neil J. Stone MD 676 N. St Clair; Suite 600 Chicago, Il 60611 Attn: Jill Thiel (administrative assistant): 312 695-0829
None of the authors have any disclosures except for our nurse Elaine Massaro who gets paid by BD for teaching injection techniques for insulin. Running head: Lifestyle Modification for Metabolic Syndrome
ABSTRACT
EP
Keywords: Metabolic Syndrome, Adherence, Motivation, Technology
AC C
Abstract: Background: All five components of Metabolic Syndrome have been shown to improve with lifestyle and diet modification. New strategies for achieving adherence to meaningful lifestyle change are needed to optimize atherosclerotic cardiovascular risk reduction. We performed a systematic literature review, based on the PRISMA framework (Preferred Reporting Items for Systematic Reviews and MetaAnalyses), investigating optimal methods for achieving lifestyle change in Metabolic Syndrome.
ACCEPTED MANUSCRIPT Methods: We submitted standardized search terms to the Pubmed Central, CINAHL, Web of Science, and Ovid databases. Within those results, we selected randomized controlled trials (RCTs) presenting unique methods of achieving lifestyle change in patients with one or more components of the Metabolic Syndrome. Data extraction using the PICO framework (population, intervention, comparator, outcome,
RI PT
and risk of bias) was used to compare the following endpoints: prevalence of Metabolic Syndrome, prevalence of individual Metabolic Syndrome components, mean number of Metabolic Syndrome
SC
components, and amount of weight loss achieved.
Results: Twenty-eight RCTs (6372 patients) were included. Eight RCTs demonstrated improvement in
M AN U
Metabolic Syndrome risk factors after one year. Team-based, interactive approaches with highfrequency contact with patients who are motivated made the largest and most lasting impact. Technology was found to be a useful tool in achieving lifestyle change, but ineffective when compared to personal contact.
Conclusion: Patient motivation leading to improved lifestyle adherence is a key factor in achieving
TE D
reduction in Metabolic Syndrome components. These elements can be enhanced via frequent encounters with the health-care system. Use of technologies such as mobile and Internet-based communication can increase the effectiveness of lifestyle change in Metabolic Syndrome, but should not
EP
replace personal contact as the cornerstone of therapy. Our ability to derive quantitative conclusions is limited by inconsistent outcome measures across studies, low power and homogeneity of individual
AC C
studies, largely motivated study populations, short follow-up periods, loss to follow-up, and lack of or incomplete blinding.
INTRODUCTION
The Metabolic Syndrome diagnosis requires three of five easily measured metabolic factors: increased abdominal circumference, low high-density lipoprotein (HDL) cholesterol levels by gender, elevated blood pressure, elevated fasting triglyceride levels, and elevated fasting glucose
ACCEPTED MANUSCRIPT levels (per the National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) criteria).1 Patients with Metabolic Syndrome are at increased risk for diabetes, atherosclerotic cardiovascular disease, non-alcoholic fatty liver disease, and all-cause mortality.2-3 Of concern,
RI PT
the National Health and Nutrition Examination Surveys (NHANES) reported an increase in the prevalence of Metabolic Syndrome in consecutive surveys.4
SC
We believe that Metabolic Syndrome is important to identify, not only because of the associated risks, but also to emphasize that lifestyle should be the initial focus of therapy. All five clinical
M AN U
markers of Metabolic Syndrome improve with therapeutic diet and physical activity.5 ATP III recommended lifestyle modification as the initial management.1,6 Behavioral lifestyle change as first-line treatment is even more salient due to recent reports that statin therapy is associated with a small, but increased, risk of diabetes, especially in subjects with metabolic risk factors.7
TE D
Studies have shown that intensive, short-term programs for weight loss are effective at controlling risk factors for Metabolic Syndrome.8 However, once these programs end, there are
EP
high rates of recidivism and many patients tend to regain their weight and reacquire or exacerbate components of Metabolic Syndrome.9-10
AC C
We were interested in the use of technology to help patients achieve lifestyle modification of Metabolic Syndrome risk factors. Previous studies demonstrated technology to be a useful tool in the areas of smoking cessation and Type I Diabetes.11-12
We theorized that a tailored lifestyle-change regimen with the help of peer support and modern technology may help patients with Metabolic Syndrome. We sought to answer the following
ACCEPTED MANUSCRIPT question: for patients with one or more components of Metabolic Syndrome, how can we deliver lifestyle change therapy in the most effective and resource-efficient manner? To answer this question, we reviewed randomized controlled trials (RCTs) that investigated different methods of
M AN U
SC
RI PT
achieving behavioral lifestyle change.
Methods
TE D
This systematic review was done in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and metaanalyses in health care interventions.13 Please see attached Appendix for a detailed description of
EP
the literature review, including results of each search strategy. Search terms were jointly proposed by two independent reviewers while under the guidance of
AC C
expert faculty. Three independent reviewers performed the literature search via PUBMED, CINAHL, Web of Science, and Ovid databases. The reviewers selected RCTs with at least 50 adult subjects that addressed adherence and technology. Additional landmark studies were also nominated and presented to all reviewers for approval. All trials were jointly assessed for validity using the Cochrane Risk of Bias tool.14 Bias was assessed based on the domains of sequence generation, allocation concealment, and
ACCEPTED MANUSCRIPT completeness of outcome data. A meta-analysis was not performed due to the high variability of study durations and methodology.
RI PT
Results
A total of twenty-eight RCTs were selected for the final systematic review (see Table 1).
SC
Compared to all trials screened, the selected trials were deemed to have an overall lower risk of bias based on the domains of sequence generation, allocation concealment, and completeness of
M AN U
outcome data.
Trials enrolled a median of 149.5 patients. The median age of participants was 50.5, and the median BMI (body mass index) was 31.4. 58.5% of participants were female. Median study duration was 12 months.
TE D
Risk of bias within studies was assessed by documenting the methodological quality parameters for each of the selected studies (see table 2). All 28 trials included in this review utilized a
EP
randomized controlled design, and seventeen attempted concealed allocation. Blinding of at least 1 study component was included in 14 out of 28 trials. Median loss to follow-up was 13.9%, and
AC C
none of the trials utilized a crossover design. Study outcomes Adherence
Real-time adherence monitoring strategies included tools such as questionnaires,15 attendance monitoring,16 and exercise diaries.17
ACCEPTED MANUSCRIPT Most studies utilized a resource-intensive model. More than half of the 28 studies explicitly used a nutritionist as part of the intervention. At least 12 studies used an exercise therapist or physiologist to work with patients. Five gave free membership to a gym or exercise
RI PT
facility.18,19,20,21,22 Pettman et al used interactive cooking sessions,20 Ma et al featured food tastings,23 and Spring et al provided monetary compensation for participants who achieved their goals.24
SC
Despite the intensive, focused nature of the intervention, few papers were designed to
demonstrate long-term amelioration of Metabolic Syndrome risk factors. Of the 28 trials
M AN U
included in this literature review, eight showed a benefit after one year.16,19,21,22,25,26,27,28 The studies that demonstrated successful adaptation of lifestyle modification after one year utilized a team-based approach. Bo showed that a lifestyle intervention program organized by trained professionals (nutritionists, endocrinologists, and internists) can significantly reduce the
TE D
prevalence of Metabolic Syndrome (OR = 0.28, 95% CI = 0.18-0.44, p<0.001).16 Den Boer demonstrated that an intervention led by a dietician trained in motivational interviewing led to a significantly lower prevalence of Metabolic Syndrome (52.6% in intervention group vs. 74.6% in
EP
the control group , p = 0.014), and this difference was maintained after four years (p=0.002).19 Digenio demonstrated that higher frequency interactions, whether in person or by telephone with
factors.29
AC C
health-care providers, were associated with a higher reduction in Metabolic Syndrome risk
A key element associated with better long-term results was the motivation of the patients to succeed. Dansinger found that the amount of weight loss achieved by study participants was
ACCEPTED MANUSCRIPT significantly associated with self-reported adherence levels (r=0.60, p<0.001), rather than with specific diet type (r=0.07, p=0.4).26 Sacks observed that attendance at group counseling sessions was strongly correlated with amount of weight loss, regardless of the diet prescribed.27 Busnello
RI PT
divided a roughly equal number of study participants into his intervention and control groups, and found that those who were motivated were more likely to have a lower BMI in the post-study period, regardless of whether the patient was in the intervention or control arm.17
SC
Adherence to a low-calorie regimen was key to weight loss, regardless of the specific diet chosen. Sacks found no difference in weight loss between four diet profiles after one year, but did find a
M AN U
strong curvilinear association between self-reported dietary adherence and overall weight loss (r=0.60, p<0.001).27
With regards to exercise, Kukkonen et al failed to demonstrate an additional benefit to exercise
TE D
when added to a low-energy diet (or = 0.10 vs 0.08, p>0.05).30 Other studies showed that a combination of aerobic and resistance training regimens is more effective than either alone, and that aerobic exercise may help prevent weight re-gain.22-23 Two studies separately found diet
AC C
EP
control to have a greater impact on Metabolic Syndrome components than exercise alone.28,31
Technology
Eight of twenty-eight trials were analyzed separately, as they primarily used technology to achieve their lifestyle intervention.25,30,32-36,43 Methods included pedometers,30,31 self-tracking websites,32 web-based education,30,33,34 e-mail feedback,34,36 and text messaging.35 Of these studies, two were designed to show follow-up after one year.32, 35
ACCEPTED MANUSCRIPT
A program utilizing computer-linked pedometers demonstrated significant improvements in body weight (-1.29±1.03 kg, p=0.01);33 and daily text message recipients lost significantly more
RI PT
weight (−1.97 ± 1.6kg, p=0.02) than participants receiving printed educational materials only.36 However, our literature review demonstrates challenges with a predominantly
technology-based approach for achieving successful lifestyle change. For instance, in one study,
SC
the personal contact group re-gained 4 kg post-weight loss intervention, whereas the web-based group regained 5.2 kg (p=0.008).35 Tate et al demonstrated that human e-mail counseling, but not
M AN U
automated e-mail counseling, resulted in significantly (p<0.001) more weight loss after 6 months (−7.3±6.2 kg) than the no counseling group (−2.6± 5.7 kg).34 A third study showed that high frequency face-to-face counseling and high-frequency telephone counseling resulted in a significantly (p = 0.024) higher percentage of participants (62±11% and 49±11%, respectively)
TE D
achieving 5% weight loss after 6 months, as compared to low frequency face-to-face counseling (42±11%), high-frequency e-mail counseling (38±11%), and self-help (39±11%).30
EP
Discussion
Reducing Metabolic Syndrome risk factors is challenging, and resource-intensive programs are
AC C
not necessarily more successful.31,35 Few papers demonstrated successful long-term intervention. Moreover, most studies were not of a large enough size to permit broad generalization. Nonetheless, insights emerged that can be useful in clinical practice.
It has previously been demonstrated that achieving a reduction in caloric consumption can be effective in decreasing Metabolic Syndrome components.12 However, two high-quality studies included in our review show that adherence, not the specific dietary prescription, contributes
ACCEPTED MANUSCRIPT most to successful weight loss programs.24-25 Patient motivation was found to be critical for improved adherence. This should be a key element of any successful strategy.
RI PT
Three replicable strategies can be implemented in the primary-care setting. Interactive programs, such as group sessions, engage patients much more effectively than passive strategies.16
Adherence improves when patients are held personally accountable with frequent personal
SC
feedback.35 A team-based approach, with dieticians trained in motivational interviewing, can
M AN U
improve adherence.19
We found technology to be a useful adjunct in improving patient motivation. Internet-based therapies can be successful in reducing the mean number of Metabolic Syndrome components,30,34,35 while mobile technology helped achieve weight loss in a small, short-term RCT.36 Many studies provided pedometers for study participants. This is a cost-effective way to
TE D
both monitor and encourage physical activity.18-23,36-37
EP
However, technology should not substitute for a face-to-face relationship. Frequent telephone encounters and automated primary care physician messages did not demonstrate improvement in
AC C
glycemic control.32 A head-to-head comparison between high-frequency telephone intervention and high-frequency email communication revealed better results via telephone, suggesting the power of personal contact. This strategy was shown to be most effective when it came to weight loss and reduction in Metabolic Syndrome risk factors.29 Moreover, more weight is re-gained in a primarily technology-based approach as compared to personal contact.35
ACCEPTED MANUSCRIPT If adherence or resources are an issue, prioritizing a diet-based program may be more effort and cost-efficient. Allowing patients to choose their own calorie-controlled diets may help increase acceptability and adherence. Likewise, addition of regular aerobic exercise further improves
RI PT
control of Metabolic Syndrome components.23
The best overall strategy should include individual patient characteristics and preferences. Based
SC
upon available literature, we believe a multi-disciplinary team, trained in motivational feedback, utilizing group support16 with instruction in internet monitoring, pedometer usage, and regular
M AN U
personal feedback is likely to achieve the best results. Our review supports recent findings for both short and long-term potential benefit for lifestyle coaches to address individual barriers to success.38
TE D
Limitations:
There are a number of important limitations to our systematic review. Many of the studies, though well designed, were underpowered to reveal statistically significant differences between
EP
intervention and control groups. Several of the studies were conducted overseas among
AC C
ethnically homogenous populations that may not extrapolate well to individuals in the United States. The majority of studies had short follow-up periods, which limits conclusions about maintenance of lifestyle change.
If motivation is the key factor in adherence, then the motivation level of the study population matters. The subjects selected for these studies were recruited from clinics and/or media
ACCEPTED MANUSCRIPT advertisements, resulting in a largely educated and motivated cohort. Perhaps not surprisingly,
RI PT
the subjects who attended the most sessions had the best outcomes. 26, 27
Conclusion:
A successful lifestyle intervention for the Metabolic Syndrome, paradoxically, does not depend
SC
much on the exact prescription of diet and exercise, but rather, on the patient's motivation to change as reflected in improved adherence. A focus solely on the specifics of the lifestyle
M AN U
regimen may not be sufficient. We found evidence that expanding the focus to include methods of increasing patient participation and motivation through specifics of delivery (use of technology and promotion of personalized feedback and individualized goals) as well as setting (group-based strategies; team-based approach) can enhance the realization of a cost-efficient and
TE D
effective program. Although technology is an exciting advance, our review could not endorse technology alone for the needed improvement in lifestyle to treat the Metabolic Syndrome. We conclude that technology enhances, rather than replaces, personal contact for continued
AC C
Funding
EP
successful control of Metabolic Syndrome risk factors.
No funding sources were utilized for the compilation of this review.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
1 Grundy SM, Brewer HB Jr., Cleeman JI, et al. American Heart Association, National Heart, Lung, and Blood Institute. Definition of Metabolic Syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:43. 2 Ford ES, et al; Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the Metabolic Syndrome: a summary of the evidence. Diabetes Care. 2005;28(7):1769-1778. 3 Hamaguchi M, Kojima T, Takeda N, et al; The Metabolic Syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143(10):722. 4 Mozumdar A, Liguori G, et al; Persistent Increase of Prevalence of Metabolic Syndrome Among U.S. Adults: NHANES III to NHANES 1999-2006. Diabetes Care. 2011;34(1):216-219. 5 Grundy, S. Point: The Metabolic Syndrome Still Lives. Clinical Chemistry. 2005;51:1352-1354. 6 Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the Metabolic Syndrome. Circulation. 2005;112:2735–2752. 7 Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):56571. 8 Dunn AL, Marcus BH, Kampert JB, et al. Comparison of Lifestyle and Structured Interventions to Increase Physical Activity and Cardiorespiratory Fitness: A Randomized Trial. JAMA. 1999;281(4):327334. 9 Stunkard AJ, McLaren-Hume M. The results of treatment for obesity. Arch Int Med 1959;103:79–85. 10 Kassirer J, Angell M. Losing weight—an ill-fated New Year's resolution. N Engl J Med 1998;338:52–4. 11 Obermayer J, Riley W, Asif O, et al. College smoking-cessation using cell phone text messaging. J Am Coll Health. 2004;53(2):71–8. 12 Franklin V L, Waller A, Pagliari C, et al. A randomized controlled trial of Sweet Talk, a text messaging system to support young people with diabetes. Diabet Med. 2006 12;23(12):1332–8. 13 Moher D, Liberati A, Tetzlaff J. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009 Jul 21;6(7):e1000097. 14 Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18; 343:d5928. 15 Bo S, Ciccone G, Baldi C, Benini L, et al. Effectiveness of a lifestyle intervention on Metabolic Syndrome A randomized controlled trial. J Gen Intern Med. 2007 Dec;22(12):1695-703. 16 Busnello FM, Bodanese LC, Pellanda LC, et al. Nutritional intervention and the impact on adherence to treatment in patients with Metabolic Syndrome. Arq Bras Cardiol. 2011 Sep; 97(3): 217-24. 17 Nishijima H, Satake K, Igarashi K, et al. Effects of exercise in overweight Japanese with multiple cardiovascular risk factors. Med Sci Sports Exerc. 2007 Jun;39(6):926-33. 18 den Boer AT, Herraets IJ, Stegen J, et al. Prevention of the Metabolic Syndrome in IGT subjects in a lifestyle intervention: results from the SLIM study. Nutr Metab Cardiovasc Dis. 2013 Nov;23(11):114753. 19 Pettman TL, Misan GM, Owen K, et al. Self-management for obesity and cardio-metabolic fitness: description and evaluation of the lifestyle modification program of a randomised controlled trial. Int J Behav Nutr Phys Act. 2008 Oct 27;5:53.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
20 Yamashiro T, Nishikawa T, Isami S, et al. The effect of group-based lifestyle interventions on risk factors and insulin resistance in subjects at risk for Metabolic Syndrome: the Tabaruzaka Study 1. Diabetes Obes Metab. 2010 Sep;12(9):790-7. 21 Kemmler W, Von Stengel S, Engelke K, et al. Exercise decreases the risk of Metabolic Syndrome in elderly females. Med Sci Sports Exerc. 2009 Feb;41(2):297-305. 22 Thomas TR, Warner SO, Dellsperger KC, et al. Exercise and the Metabolic Syndrome with weight regain. J Appl Physiol 2010 Jul;109(1):3-10. 23 Ma J, Yank V, Xiao L, et al. Translating the Diabetes Prevention Program lifestyle intervention for weight loss into primary care: a randomized trial. JAMA Intern Med. 2013 Jan 28;173(2):113-21. 24 Spring B, Schneider K, McFadden HG, et al. Multiple behavior changes in diet and activity: a randomized controlled trial using mobile technology. Arch Intern Med. 2012 May 28;172(10):789-96. 25 Dansinger ML, Gleason JA, Griffith JL, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005 Jan 5;293(1):43-53. 26 Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859-873. 27 Jacobs DR Jr, Sluik D, Rokling-Andersen MH, et al. Association of 1-y changes in diet pattern with cardiovascular disease risk factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise Study. Am J Clin Nutr. 2009 Feb;89(2):509-17. 28 Weinstock RS, Trief PM, Cibula D, Morin PC, Delahanty LM. Weight loss success in Metabolic Syndrome by telephone interventions: results from the SHINE study. J Gen Intern Med 28(12):1620–8. 29 Digenio AG, Mancuso JP, Gerber RA, et al. Comparison of methods for delivering a lifestyle modification program for obese patients: a randomized trial. Ann Intern Med. 2009 Feb 17;150(4):25562. 30 Kukkonen-Harjula KT, Borg PT, Nenonen AM, et al. Effects of a weight maintenance program with or without exercise on the Metabolic Syndrome: a randomized trial in obese men. Prev Med. 2005 SepOct;41(3-4):784-90. 31 Morey MC, Pieper CF, Edelman DE, et al. Enhanced fitness: a randomized controlled trial of the effects of home-based physical activity counseling on glycemic control in older adults with prediabetes mellitus. J Am Geriatr Soc. 2012 Sep;60(9):1655-62. 32 Maruyama C, Kimura M, Okumura H, et al. Effect of a worksite-based intervention program on metabolic parameters in middle-aged male white- workers: a randomized controlled trial. Prev Med. 2010 Jul;51(1):11-7. 33 Tate DF, Jackvony EH, Wing RR. A randomized trial comparing human e-mail counseling, computer-automated tailored counseling, and no counseling in an Internet weight loss program. Arch Intern Med. 2006 Aug 14-28;166(15):1620-5. 34 Svetkey LP, Stevens VJ, Brantley PJ, et al. Weight Loss Maintenance Collaborative Research Group. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA. 2008 Mar 12;299(10):1139-48. 35 Patrick K, Raab F, Adams MA, et al. A text message-based intervention for weight loss: randomized controlled trial. J Med Internet Res. 2009 Jan 13;11(1):e1. 36 Oh EG, Bang SY, Hyun SS, et al. Effects of a 6-month lifestyle modification intervention on the cardiometabolic risk factors and health-related qualities of life in women with Metabolic Syndrome. Metabolism. 2010 Jul;59(7):1035-43. 37 Nanri A, Tomita K, Matsushita Y, et al. Effect of six months lifestyle intervention in Japanese men with Metabolic Syndrome: randomized controlled trial. J Occup Health. 2012;54(3):215-22. 38 Venditti EM, Wylie-Rosett J, Delahanty LM, Mele L, Hoskin MA, Edelstein SL;Diabetes Prevention Program Research Group. Short and long-term lifestyle coaching approaches used to address
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
diverse participant barriers to weight loss and physical activity adherence. Int J Behav Nutr Phys Act. 2014 Feb 12;11:16. 39 Munakata M, Honma H, Akasi M, et al. Repeated counseling improves the antidiabetic effects of limited individualized lifestyle guidance in Metabolic Syndrome: J-STOP-Metabolic Syndrome final results. Hypertens Res. 2011 May;34(5):612-6. 40 Fappa E, Yannakoulia M, Ioannidou M, et al. Telephone counseling intervention improves dietary habits and metabolic parameters of patients with the Metabolic Syndrome: a randomized controlled trial. Rev Diabet Stud. 2012 Spring;9(1):36-45. 41 Melanson KJ, Summers A, Nguyen V, et al. Body composition, dietary composition, and components of Metabolic Syndrome in overweight and obese adults after a 12-week trial on dietary treatments focused on portion control, energy density, or glycemic index. Nutr J. 2012 Aug 27;11:57. 42 Chen YC, Tsao LI, Huang CH, et al. An Internet-based health management platform may effectively reduce the risk factors of Metabolic Syndrome among career women. Taiwan J Obstet Gynecol. 2013 Jun;52(2):215-21.
ACCEPTED Table 1 – Characteristics of Included StudiesMANUSCRIPT Study
Population
Intervention
Comparator
Main Relevant Outcome
ADHERENCE
4 diet programs (Atkins, Zone, Weight Watchers, Ornish)
None
KukkonenHarjula, et al (2005)
N= 90 (middleaged men with BMI 30-40 and waist girth > 100cm)
All men participated in a weight loss program for two months.
Usual care (patients could be randomized to control arm after they completed two month weight reduction phase).
Bo, et al (2007)
N = 335 (at least two components of Metabolic Syndrome)
Lifestyle intervention program (5 sessions) with team-based approach and group sessions
Nishijima, et al (2007)
N=561 Japanese adults with two or more CVD risk factors (HTN, HL, or glucose intolerance)
Exercise two-four times per week for 6 months under supervision of personal trainer
187 men w/ risk factors for DMII (~50% with Metabolic Syndrome)
N = 95 (elderly females w/ Metabolic Syndrome)
Kemmler, et al (2009)
In the combined intervention, the odds ratio of Metabolic Syndrome was 0.10 after the weight reduction phase, 0.08 after the weight maintenance phase, and 0.29 at the 23 months follow up. (p>0.05). Thus, adding exercise to lowenergy diet did not result in statistically significant reduction in Metabolic Syndrome over longterm.
M AN U
Lifestyle intervention significantly reduced prevalence of Metabolic Syndrome (OR = 0.28, 95% CI = 0.18-0.44, NNT = 3.2, p<0.001) at 12 months.
Lifestyle modification advice
BP, body weight, waist circumference, and triglycerides were all significantly improved in intervention vs. control group (p<0.05) at 6 months. Reductions in LDL and HbA1C were not significant.
Randomized to three arms: -Diet group, -exercise group, or -diet and exercise group
No change in diet or exercise
Weight change was -3.5 kg per 10 point change in diet score (p<0.0001), independent of change in energy intake. Subjects with better adherence to diet had significantly more improvement in weight, SBP, lipid profile, and glucose tolerance.
High intensity aerobic/resistance exercises focusing on bone strength
Low-intensity training (60 min/wk)
After 12 months, number of Metabolic Syndrome components significantly decreased in the exercise group (p = 0.002) vs.
TE D
Standard PCP-based counseling
EP
AC C
Jacobs, et al (2009)
Then randomized into 2 interventions (if not randomized to control arm): -Resistance training -Walking
Amount of weight loss was significantly associated with adherence level (r=0.60, p<0.001) at 12 months.
RI PT
N = 160 (BMI = 27-42 and at least 1 Metabolic Syndrome component)
SC
Dansinger, et al (2005)
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT
Main Relevant Outcome slightly in the control group (p = 0.34). Prevalence of Metabolic Syndrome decreased by 30.3% in exercise group vs. 15.6% in control group (p = 0.15)
N = 153 overweight adults with Metabolic Syndrome
16-week lifestyle program that provided strategies in diet, exercise, and behavior, as well as peer group support and free gym access. Also included one 45-60 min supervised exercise session each week
No intervention: national guidelines for healthy eating offered
Sacks, et al (2009)
N = 683 (BMI = 25-40)
4 diet programs: 1) Low fat, average protein 2) High fat, average protein 3) Low fat, high protein 4) High fat, high protein
None
Oh, et al (2010)
N = 52 (Korean females with Metabolic Syndrome)
Nurse-led therapeutic lifestyle change program
No treatment
Intervention group showed significantly greater reductions in body weight and waist circumference (p<0.001), which were maintained 6 months following intervention.
Thomas, et al (2010)
N = 102 (BMI 25.0-39.9 with at least two Metabolic Syndrome components)
10% body weight loss with supervised jogging and caloric restriction x 46 months, followed by programmed weight regain, split into exercise vs. no exercise groups
No exercise during weight regain period
Following weight regain, the aerobic intervention group maintained significant improvements in VO2 max, BP, glucose homeostasis, HDL, LDL, and inflammatory markers that were achieved during weight loss period, while control group showed worsening of most metabolic markers, suggesting that exercise can counter effects of partial weight regain on many disease markers.
Yamashiro, et al (2010)
N = 137 (Japanese cohort with at least 1 Metabolic Syndrome component)
Adherence to diet was strongly associated with weight loss. All four diet programs were equally successful in achieving and maintaining weight loss over two years. Attendance at group sessions was associated with weight loss (p=0.22).
SC
M AN U
TE D
EP
AC C 4-month and 10-month No treatment group-based lifestyle
intervention
Greater attendance at information sessions was correlated with significantly greater reductions in body fat (p<0.001), SBP (p=0.01), total cholesterol (p<0.001), and plasma glucose (p<0.001).
RI PT
Pettman, et al (2009)
At month 34, mean # of Metabolic Syndrome components (4-month: .17±0.17, 10-month: -0.29±0.16, and control: +0.54±0.24) significantly lower in both intervention groups vs. control
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT
Main Relevant Outcome (p<0.05)
N = 80 (Brazilian cohort with Metabolic Syndrome)
Diet, telephone counseling, and education
Diet alone
Patients in both groups who arrived more motivated had significantly higher reductions in BMI after 4 months than those subjects who arrived less motivated (p<0.001)
Munakata, et al (2011)
N = 109 (previously untreated Japanese Metabolic Syndrome patients)
Multiple lifestyle counseling sessions
Single counseling session
Multiple guidance group showed significantly greater reduction in waist circumference (-4.8±5.6 vs. 1.9±5.7 cm, p=0.02) and FBS (9.0±14.0 vs. -2.5±14.1 mg/dl, p=0.03) than single guidance group at 6 months.
Wu (2011)
N = 135 adults with at least one DMII risk factor (overweight, HTN, dyslipidemia, impaired glucose tolerance, etc.)
Home-based exercise group
Usual care group (oral instruction and general lifestyle education)
While the intervention group showed significantly increased physical activity vs. the control group (p<0.001), no intervention effect was found for metabolic risk factors or components of Metabolic Syndrome.
Fappa, et al (2012)
N= 87 (Metabolic Syndrome patients)
1) Face-to face dietary counseling x7 2) Telephone dietary counseling x7
One-time dietary counseling
Metabolic Syndrome reduction rate was 52% in the face-to-face group, 54% in the telephone group, and 21% in control group (p = 0.024).
Melanson, et al (2012)
N = 157 (sedentary adults with BMI 27-35)
Portion control, low energy, or low glycemic index diet with weekly weight loss meetings x 12 wks
None
All three groups had significant improvements in waist circumference, total cholesterol, and LDL (p<0.001). The changes were not significantly different between groups (p>0.05).
Nanri, et al (2012)
N= 107 (Japanese males with Metabolic Syndrome)
Lifestyle modification program focused on diet and exercise from trained occupational health nurse at baseline, one, and three months
Standard health guidance via an educational leaflet
Metabolic Syndrome prevalence decreased by 65.3% in intervention group, and 62.3% in control group (p=0.75). Intervention group had statistically significant decreases in weight, waist circumference, and HgA1C (p<0.001)
Den Boer, et al (2013)
N = 146 adults with impaired
Diet and exercise as moderated by dietician trained in motivational
General information about benefits of
Prevalence of Metabolic Syndrome was significantly lower in intervention group vs. control group
SC
M AN U
TE D
EP
AC C
RI PT
Busnello, et al (2011)
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT interviewing, voluntary participation in supervised aerobic and resistance training for mean of 4.2 yrs, assessed 4 years later
diet and exercise
Ma, et al (2013)
N = 241 (pre-DM or Metabolic Syndrome)
(1) a coach-led, groupdelivered intervention or (2) a self-directed DVD intervention
Usual care
Weinstock, et al (2013)
N= 257 (Metabolic Syndrome patients with BMI>30 and without diabetes)
Telephone delivery of the DPP lifestyle intervention delivered individually
Telephone delivery of the DPP lifestyle intervention (up to 8 participants/call) delivered in conference calls
N = 1032 (BMI = 25-45 & on meds for HTN and/or dyslipidemia)
After losing at least 4 kg in 6-month weight loss program, randomized to…
Svetkey, et al (2008)
Self-directed control
EP
1) Monthly personal contact 2) Monthly interactive web-based intervention
Patrick, et al (2009)
N = 376 (BMI = 30-40)
AC C
Digenio, et al (2009)
N = 65 (BMI = 2539.9)
Both interventions achieved significantly decreased waist circumference (p<0.001 for both interventions) and fasting plasma glucose (p<0.001 for coach-led and p=0.01 for self-directed vs usual care).
SC
M AN U
TE D
TECHNOLOG Y
Both arms: 16 sessions during year 1, 12 sessions during year 2, plus coaching sessions with dieticians
(52.6% vs 74.6%, respectively, p = 0.014) after active intervention. Four years later, reduced prevalence of Metabolic Syndrome between groups was maintained (p=0.268). In patients without Metabolic Syndrome at baseline, the incidence of developing it was 18.2% in the intervention group and 73.7% in the control group (p=0.011).
RI PT
glucose tolerance (66% had Metabolic Syndrome)
Main Relevant Outcome
1) High-frequency (HF) face-to-face (FTF) lifestyle modification counseling 2) Low-frequency (LF) FTF counseling 3) HF phone counseling 4) HF e-mail counseling
Self-help control group
SMS-based weight loss program (2-5x/day)
Printed educational materials only
Both interventions resulted in statistically significant weight loss. At year 2, mean weight loss was 6.2 kg in the conference call group and 2.2 kg in the individual group (p<0.001), suggesting that groupbased intervention may be more effective at achieving weight loss.
At 30 months, personal contact group re-gained less weight (4.0 kg) than self-directed group (5.5 kg, p=0.001) and web-based group (5.2 kg, p=0.008).
After 6 months, a significantly (p = 0.024) larger percentage of patients in the HF-FTF (62±11%) and HFphone group (49±11%) achieved weight loss of at least 5% compared to other three groups. Note: all patients received sibutramine. After 4 months, SMS group lost more weight than printed
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT
Main Relevant Outcome
Maruyama, et al (2010)
N = 101 (Japanese cohort with any MS component)
Lifestyle modification program (four counseling sessions & monthly website advice)
No treatment control
Significant improvement in body weight (-1.29±1.03kg, p=0.01), BMI (-0.47±0.36, p=0.01), and FPG (-5.2±4.2, p=0.02) in intervention group vs. control group at 4 months
Morey, et al (2012)
N = 302 (ages 60-80, BMI 25-45 with impaired glucose tolerance)
12-month home based counseling: in-person baseline counseling session, regular phone counseling, monthly automated encouragement, physician endorsement in clinic
Consultation with VA weight management program (for all participants)
RI PT
materials group (−1.97±1.6kg, p=0.02).
Spring, et al (2012)
N = 204 (sedentary individuals with low fruit and vegetable (F/V) intake, high sat fat intake, and low physical activity)
1) Increased F/V intake and increased physical activity 2) Decreased fat intake and sedentary leisure 3) Decreased fat intake and increased physical activity 4) Increased F/V intake and decreased sedentary leisure
None
M AN U
SC
Endurance physical activity increased significantly in intervention group vs. control (p<0.001). Both groups had similar decreases in FBG (~6%, p<0.001), while other glycemic markers remained stable Group #4 (increased F/V intake + decreased sedentary leisure) achieved the most significant lifestyle change compared to the other three groups (p<0.001). Differences between groups were maintained throughout the 20week follow-up.
Internet-based health management platform (software gave nutrition and exercise advice x1.5 months)
EP
N = 66 Taiwanese female (with one or more Metabolic Syndrome components)
AC C
Chen, et al (2013)
TE D
All groups utilized remote coaching via mobile technology.
No intervention
Significant improvement in waist circumference, fasting glucose, and mean # of Metabolic Syndrome components in intervention group (p<0.05) vs. control group
Table 2 – Methodological Quality Parameters
ACCEPTED MANUSCRIPT
Randomized
Concealed Allocation
Blinding (of at least 1 study component)
Dansinger, et al (2005)
Yes
Yes
Yes
41.9%
0
KukkonenHarjula, et al (2005)
Yes
No
No
24.4%
0
Bo, et al (2007)
Yes
Yes
Yes
10.7%
0
Yes
Yes
Yes
Jacobs Jr (2009)
Yes
No
No
Kemmler, et al (2009)
Yes
Yes
Yes
Pettman, et al (2009)
Yes
No
No
Sacks, et al (2009)
Yes
Yes
Oh, et al (2010)
Yes
No
Thomas (2010)
Yes
0
M AN U
Nishijima (2007)
SC
10.7%
0
31.6%
0
0%
0
Yes
20.5%
0
No
9.2%
0
No
Yes
34.3%
0
TE D
14.6%
EP
AC C
RI PT
ADHERENCE
Loss to Cross-over, % followup, %
Yamashiro, et al (2010)
Yes
No
No
19.0%
0
Busnello, et al (2011)
Yes
Yes
Yes
3.7%
0
Munakata, et al (2011)
Yes
No
No
12.8%
0
Wu, et al (2011)
Yes
Yes
Yes
12.6% 0
Fappa, et al (2012)
46.0%
Yes
ACCEPTED Yes Yes
Yes
No
No
Nanri, et al (2012) Yes
No
No
Den Boer, et al (2013)
Yes
No
No
Ma, et al (2013)
Yes
Yes
Yes
Weinstock, et al (2013)
Yes
Yes
No
Tate, et al (2006)
Yes
Yes
Yes
19.3%
Svetkey, et al (2008)
Yes
Yes
Yes
6.6%
Digenio, et al (2009)
Yes
Yes
No
Patrick, et al (2009)
Yes
Yes
No
Maruyama, et al (2010)
Yes
Yes
Morey, et al (2012)
Yes
Yes
Spring, et al (2012)
Yes
Chen, et al (2013)
Yes
Melanson et al (2012)
MANUSCRIPT 0 14% 0 4.7% 0 58.9% 0
0 47.5% 0
0
M AN U
0
0
13.3%
0
Yes
13.9%
0
Yes
13.2%
0
Yes
No
2.0%
0
No
No
4.6%
0
TE D
29.5%
EP
AC C
SC
TECHNOLOGY
RI PT
8.3%
ACCEPTED MANUSCRIPT
Appendix. Search results.
RI PT
a. We utilized the following search terms within PUBMED. All search terms included “Metabolic Syndrome” AND one of the following: Adherence – 41 results; Monitoring – 59 results; Strategy – 33 results; Lifestyle – 222 results; Program – 301 results; Intervention – 440 results
SC
b. We utilized the following search terms within CINAHL. All search terms included "Metabolic Syndrome" AND one of the following: Adherence - 3 results; Monitoring - 2 results; Strategy - 2 results; Lifestyle - 10 results; Program - 11 results); Intervention -29 results
M AN U
c. We utilized the following search terms within Web of Science. All search terms included "Metabolic Syndrome" AND one of the following: Adherence - 64 results; Monitoring - 99 results; Strategy - 197 results; Lifestyle - 349 results; Program - 351 results; Intervention - 773 results d. We utilized the following search terms within Ovid. All search terms included "Metabolic Syndrome" AND one of the following: Adherence - 13 results; Monitoring - 19 results; Strategy - 10 results; Lifestyle - 45 results; Program - 106 results; Intervention - 110 results.
TE D
Details of Search Strategy All eligible studies were published in English between Nov 14th, 2002 and January 31st, 2014. We excluded articles published before 2002. This was the year the Diabetes Prevention Program (DPP) was published. 1
AC C
EP
Eligible studies had to pertain to primarily non-pharmacological and non-surgical methods of decreasing cardiovascular risk for patients at risk for Metabolic Syndrome (with 1 or more Metabolic Syndrome components) or patients with Metabolic Syndrome as defined by the ATP III criteria. Of note, we considered overweight, obese, and sedentary adults to be at increased risk for Metabolic Syndrome, and therefore, also included studies that recruited these groups of individuals (BMI ≥ 25). We chose to exclude studies that solely examined nutritional supplements, surgery, pharmacological treatments, and special populations (such as those with HIV or on chemotherapy) outside the aforementioned inclusion criteria. Endpoints were variable across studies, and included changes in prevalence of Metabolic Syndrome and individual components of Metabolic Syndrome, changes in weight/BMI, HDL, LDL, TG, and waist circumference, as well as rate of adverse cardiovascular events, rate of death, and adherence to intervention.
ACCEPTED MANUSCRIPT
RI PT
Data was jointly extracted by all 3 reviewers. Data extraction followed the PICO framework and included: Population (size, mean age, mean BMI, % female), Intervention, Comparator, Outcome, Design, Duration, Percent Lost to Follow-Up, Presence of Randomization, Use of Blinding, Use of Concealed Allocation, and Percent Cross-Over.
Nominated Studies
M AN U
SC
-Weinstock, et al -Dansinger, et al -Sacks, et al -Tate, et al -Svetkey, et al -Patrick, et al -DiGenio, et al -Spring, et al
AC C
EP
TE D
1 Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
ACCEPTED MANUSCRIPT
Clinical significance •
Patient motivation and adherence are the key elements of successful lifestyle change
programs for Metabolic Syndrome. A team-based, interactive approach that holds patients accountable and provides
RI PT
•
regular personalized feedback results in increased adherence and more effective behavioral change.
Technology is a useful adjunct in achieving lifestyle change in Metabolic Syndrome, but
SC
•
AC C
EP
TE D
M AN U
does not replace personal contact as the cornerstone of successful therapy.
S0002-9343(14)00576-2
DOI:
10.1016/j.amjmed.2014.06.035
Reference:
AJM 12596
To appear in:
The American Journal of Medicine
Received Date: 29 April 2014 Revised Date:
7 June 2014
Accepted Date: 9 June 2014
Please cite this article as: Bassi N, Karagodin I, Wang S, Vassallo P, Priyanath A, Massaro E, Stone NJ, Lifestyle Modification for Metabolic Syndrome: A Systematic Review, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.06.035. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
*Manuscript Click here to view linked References
RI PT
Lifestyle Modification for Metabolic Syndrome: A Systematic Review
Authors: Nikhil Bassi, MD* Ilya Karagodin, MD* Serena Wang, MD* Patricia Vassallo, MD* Aparna Priyanath, MD* Elaine Massaro MS,RN**Neil J. Stone MD*
M AN U
SC
Departments of Cardiology and Medicine *, Department of Endocrinology** Feinberg School of Medicine Chicago, Illinois Words 1959 (excluding footnotes, endnotes)
TE D
Send Correspondence to: Neil J. Stone MD 676 N. St Clair; Suite 600 Chicago, Il 60611 Attn: Jill Thiel (administrative assistant): 312 695-0829
None of the authors have any disclosures except for our nurse Elaine Massaro who gets paid by BD for teaching injection techniques for insulin. Running head: Lifestyle Modification for Metabolic Syndrome
ABSTRACT
EP
Keywords: Metabolic Syndrome, Adherence, Motivation, Technology
AC C
Abstract: Background: All five components of Metabolic Syndrome have been shown to improve with lifestyle and diet modification. New strategies for achieving adherence to meaningful lifestyle change are needed to optimize atherosclerotic cardiovascular risk reduction. We performed a systematic literature review, based on the PRISMA framework (Preferred Reporting Items for Systematic Reviews and MetaAnalyses), investigating optimal methods for achieving lifestyle change in Metabolic Syndrome.
ACCEPTED MANUSCRIPT Methods: We submitted standardized search terms to the Pubmed Central, CINAHL, Web of Science, and Ovid databases. Within those results, we selected randomized controlled trials (RCTs) presenting unique methods of achieving lifestyle change in patients with one or more components of the Metabolic Syndrome. Data extraction using the PICO framework (population, intervention, comparator, outcome,
RI PT
and risk of bias) was used to compare the following endpoints: prevalence of Metabolic Syndrome, prevalence of individual Metabolic Syndrome components, mean number of Metabolic Syndrome
SC
components, and amount of weight loss achieved.
Results: Twenty-eight RCTs (6372 patients) were included. Eight RCTs demonstrated improvement in
M AN U
Metabolic Syndrome risk factors after one year. Team-based, interactive approaches with highfrequency contact with patients who are motivated made the largest and most lasting impact. Technology was found to be a useful tool in achieving lifestyle change, but ineffective when compared to personal contact.
Conclusion: Patient motivation leading to improved lifestyle adherence is a key factor in achieving
TE D
reduction in Metabolic Syndrome components. These elements can be enhanced via frequent encounters with the health-care system. Use of technologies such as mobile and Internet-based communication can increase the effectiveness of lifestyle change in Metabolic Syndrome, but should not
EP
replace personal contact as the cornerstone of therapy. Our ability to derive quantitative conclusions is limited by inconsistent outcome measures across studies, low power and homogeneity of individual
AC C
studies, largely motivated study populations, short follow-up periods, loss to follow-up, and lack of or incomplete blinding.
INTRODUCTION
The Metabolic Syndrome diagnosis requires three of five easily measured metabolic factors: increased abdominal circumference, low high-density lipoprotein (HDL) cholesterol levels by gender, elevated blood pressure, elevated fasting triglyceride levels, and elevated fasting glucose
ACCEPTED MANUSCRIPT levels (per the National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) criteria).1 Patients with Metabolic Syndrome are at increased risk for diabetes, atherosclerotic cardiovascular disease, non-alcoholic fatty liver disease, and all-cause mortality.2-3 Of concern,
RI PT
the National Health and Nutrition Examination Surveys (NHANES) reported an increase in the prevalence of Metabolic Syndrome in consecutive surveys.4
SC
We believe that Metabolic Syndrome is important to identify, not only because of the associated risks, but also to emphasize that lifestyle should be the initial focus of therapy. All five clinical
M AN U
markers of Metabolic Syndrome improve with therapeutic diet and physical activity.5 ATP III recommended lifestyle modification as the initial management.1,6 Behavioral lifestyle change as first-line treatment is even more salient due to recent reports that statin therapy is associated with a small, but increased, risk of diabetes, especially in subjects with metabolic risk factors.7
TE D
Studies have shown that intensive, short-term programs for weight loss are effective at controlling risk factors for Metabolic Syndrome.8 However, once these programs end, there are
EP
high rates of recidivism and many patients tend to regain their weight and reacquire or exacerbate components of Metabolic Syndrome.9-10
AC C
We were interested in the use of technology to help patients achieve lifestyle modification of Metabolic Syndrome risk factors. Previous studies demonstrated technology to be a useful tool in the areas of smoking cessation and Type I Diabetes.11-12
We theorized that a tailored lifestyle-change regimen with the help of peer support and modern technology may help patients with Metabolic Syndrome. We sought to answer the following
ACCEPTED MANUSCRIPT question: for patients with one or more components of Metabolic Syndrome, how can we deliver lifestyle change therapy in the most effective and resource-efficient manner? To answer this question, we reviewed randomized controlled trials (RCTs) that investigated different methods of
M AN U
SC
RI PT
achieving behavioral lifestyle change.
Methods
TE D
This systematic review was done in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and metaanalyses in health care interventions.13 Please see attached Appendix for a detailed description of
EP
the literature review, including results of each search strategy. Search terms were jointly proposed by two independent reviewers while under the guidance of
AC C
expert faculty. Three independent reviewers performed the literature search via PUBMED, CINAHL, Web of Science, and Ovid databases. The reviewers selected RCTs with at least 50 adult subjects that addressed adherence and technology. Additional landmark studies were also nominated and presented to all reviewers for approval. All trials were jointly assessed for validity using the Cochrane Risk of Bias tool.14 Bias was assessed based on the domains of sequence generation, allocation concealment, and
ACCEPTED MANUSCRIPT completeness of outcome data. A meta-analysis was not performed due to the high variability of study durations and methodology.
RI PT
Results
A total of twenty-eight RCTs were selected for the final systematic review (see Table 1).
SC
Compared to all trials screened, the selected trials were deemed to have an overall lower risk of bias based on the domains of sequence generation, allocation concealment, and completeness of
M AN U
outcome data.
Trials enrolled a median of 149.5 patients. The median age of participants was 50.5, and the median BMI (body mass index) was 31.4. 58.5% of participants were female. Median study duration was 12 months.
TE D
Risk of bias within studies was assessed by documenting the methodological quality parameters for each of the selected studies (see table 2). All 28 trials included in this review utilized a
EP
randomized controlled design, and seventeen attempted concealed allocation. Blinding of at least 1 study component was included in 14 out of 28 trials. Median loss to follow-up was 13.9%, and
AC C
none of the trials utilized a crossover design. Study outcomes Adherence
Real-time adherence monitoring strategies included tools such as questionnaires,15 attendance monitoring,16 and exercise diaries.17
ACCEPTED MANUSCRIPT Most studies utilized a resource-intensive model. More than half of the 28 studies explicitly used a nutritionist as part of the intervention. At least 12 studies used an exercise therapist or physiologist to work with patients. Five gave free membership to a gym or exercise
RI PT
facility.18,19,20,21,22 Pettman et al used interactive cooking sessions,20 Ma et al featured food tastings,23 and Spring et al provided monetary compensation for participants who achieved their goals.24
SC
Despite the intensive, focused nature of the intervention, few papers were designed to
demonstrate long-term amelioration of Metabolic Syndrome risk factors. Of the 28 trials
M AN U
included in this literature review, eight showed a benefit after one year.16,19,21,22,25,26,27,28 The studies that demonstrated successful adaptation of lifestyle modification after one year utilized a team-based approach. Bo showed that a lifestyle intervention program organized by trained professionals (nutritionists, endocrinologists, and internists) can significantly reduce the
TE D
prevalence of Metabolic Syndrome (OR = 0.28, 95% CI = 0.18-0.44, p<0.001).16 Den Boer demonstrated that an intervention led by a dietician trained in motivational interviewing led to a significantly lower prevalence of Metabolic Syndrome (52.6% in intervention group vs. 74.6% in
EP
the control group , p = 0.014), and this difference was maintained after four years (p=0.002).19 Digenio demonstrated that higher frequency interactions, whether in person or by telephone with
factors.29
AC C
health-care providers, were associated with a higher reduction in Metabolic Syndrome risk
A key element associated with better long-term results was the motivation of the patients to succeed. Dansinger found that the amount of weight loss achieved by study participants was
ACCEPTED MANUSCRIPT significantly associated with self-reported adherence levels (r=0.60, p<0.001), rather than with specific diet type (r=0.07, p=0.4).26 Sacks observed that attendance at group counseling sessions was strongly correlated with amount of weight loss, regardless of the diet prescribed.27 Busnello
RI PT
divided a roughly equal number of study participants into his intervention and control groups, and found that those who were motivated were more likely to have a lower BMI in the post-study period, regardless of whether the patient was in the intervention or control arm.17
SC
Adherence to a low-calorie regimen was key to weight loss, regardless of the specific diet chosen. Sacks found no difference in weight loss between four diet profiles after one year, but did find a
M AN U
strong curvilinear association between self-reported dietary adherence and overall weight loss (r=0.60, p<0.001).27
With regards to exercise, Kukkonen et al failed to demonstrate an additional benefit to exercise
TE D
when added to a low-energy diet (or = 0.10 vs 0.08, p>0.05).30 Other studies showed that a combination of aerobic and resistance training regimens is more effective than either alone, and that aerobic exercise may help prevent weight re-gain.22-23 Two studies separately found diet
AC C
EP
control to have a greater impact on Metabolic Syndrome components than exercise alone.28,31
Technology
Eight of twenty-eight trials were analyzed separately, as they primarily used technology to achieve their lifestyle intervention.25,30,32-36,43 Methods included pedometers,30,31 self-tracking websites,32 web-based education,30,33,34 e-mail feedback,34,36 and text messaging.35 Of these studies, two were designed to show follow-up after one year.32, 35
ACCEPTED MANUSCRIPT
A program utilizing computer-linked pedometers demonstrated significant improvements in body weight (-1.29±1.03 kg, p=0.01);33 and daily text message recipients lost significantly more
RI PT
weight (−1.97 ± 1.6kg, p=0.02) than participants receiving printed educational materials only.36 However, our literature review demonstrates challenges with a predominantly
technology-based approach for achieving successful lifestyle change. For instance, in one study,
SC
the personal contact group re-gained 4 kg post-weight loss intervention, whereas the web-based group regained 5.2 kg (p=0.008).35 Tate et al demonstrated that human e-mail counseling, but not
M AN U
automated e-mail counseling, resulted in significantly (p<0.001) more weight loss after 6 months (−7.3±6.2 kg) than the no counseling group (−2.6± 5.7 kg).34 A third study showed that high frequency face-to-face counseling and high-frequency telephone counseling resulted in a significantly (p = 0.024) higher percentage of participants (62±11% and 49±11%, respectively)
TE D
achieving 5% weight loss after 6 months, as compared to low frequency face-to-face counseling (42±11%), high-frequency e-mail counseling (38±11%), and self-help (39±11%).30
EP
Discussion
Reducing Metabolic Syndrome risk factors is challenging, and resource-intensive programs are
AC C
not necessarily more successful.31,35 Few papers demonstrated successful long-term intervention. Moreover, most studies were not of a large enough size to permit broad generalization. Nonetheless, insights emerged that can be useful in clinical practice.
It has previously been demonstrated that achieving a reduction in caloric consumption can be effective in decreasing Metabolic Syndrome components.12 However, two high-quality studies included in our review show that adherence, not the specific dietary prescription, contributes
ACCEPTED MANUSCRIPT most to successful weight loss programs.24-25 Patient motivation was found to be critical for improved adherence. This should be a key element of any successful strategy.
RI PT
Three replicable strategies can be implemented in the primary-care setting. Interactive programs, such as group sessions, engage patients much more effectively than passive strategies.16
Adherence improves when patients are held personally accountable with frequent personal
SC
feedback.35 A team-based approach, with dieticians trained in motivational interviewing, can
M AN U
improve adherence.19
We found technology to be a useful adjunct in improving patient motivation. Internet-based therapies can be successful in reducing the mean number of Metabolic Syndrome components,30,34,35 while mobile technology helped achieve weight loss in a small, short-term RCT.36 Many studies provided pedometers for study participants. This is a cost-effective way to
TE D
both monitor and encourage physical activity.18-23,36-37
EP
However, technology should not substitute for a face-to-face relationship. Frequent telephone encounters and automated primary care physician messages did not demonstrate improvement in
AC C
glycemic control.32 A head-to-head comparison between high-frequency telephone intervention and high-frequency email communication revealed better results via telephone, suggesting the power of personal contact. This strategy was shown to be most effective when it came to weight loss and reduction in Metabolic Syndrome risk factors.29 Moreover, more weight is re-gained in a primarily technology-based approach as compared to personal contact.35
ACCEPTED MANUSCRIPT If adherence or resources are an issue, prioritizing a diet-based program may be more effort and cost-efficient. Allowing patients to choose their own calorie-controlled diets may help increase acceptability and adherence. Likewise, addition of regular aerobic exercise further improves
RI PT
control of Metabolic Syndrome components.23
The best overall strategy should include individual patient characteristics and preferences. Based
SC
upon available literature, we believe a multi-disciplinary team, trained in motivational feedback, utilizing group support16 with instruction in internet monitoring, pedometer usage, and regular
M AN U
personal feedback is likely to achieve the best results. Our review supports recent findings for both short and long-term potential benefit for lifestyle coaches to address individual barriers to success.38
TE D
Limitations:
There are a number of important limitations to our systematic review. Many of the studies, though well designed, were underpowered to reveal statistically significant differences between
EP
intervention and control groups. Several of the studies were conducted overseas among
AC C
ethnically homogenous populations that may not extrapolate well to individuals in the United States. The majority of studies had short follow-up periods, which limits conclusions about maintenance of lifestyle change.
If motivation is the key factor in adherence, then the motivation level of the study population matters. The subjects selected for these studies were recruited from clinics and/or media
ACCEPTED MANUSCRIPT advertisements, resulting in a largely educated and motivated cohort. Perhaps not surprisingly,
RI PT
the subjects who attended the most sessions had the best outcomes. 26, 27
Conclusion:
A successful lifestyle intervention for the Metabolic Syndrome, paradoxically, does not depend
SC
much on the exact prescription of diet and exercise, but rather, on the patient's motivation to change as reflected in improved adherence. A focus solely on the specifics of the lifestyle
M AN U
regimen may not be sufficient. We found evidence that expanding the focus to include methods of increasing patient participation and motivation through specifics of delivery (use of technology and promotion of personalized feedback and individualized goals) as well as setting (group-based strategies; team-based approach) can enhance the realization of a cost-efficient and
TE D
effective program. Although technology is an exciting advance, our review could not endorse technology alone for the needed improvement in lifestyle to treat the Metabolic Syndrome. We conclude that technology enhances, rather than replaces, personal contact for continued
AC C
Funding
EP
successful control of Metabolic Syndrome risk factors.
No funding sources were utilized for the compilation of this review.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
1 Grundy SM, Brewer HB Jr., Cleeman JI, et al. American Heart Association, National Heart, Lung, and Blood Institute. Definition of Metabolic Syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:43. 2 Ford ES, et al; Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the Metabolic Syndrome: a summary of the evidence. Diabetes Care. 2005;28(7):1769-1778. 3 Hamaguchi M, Kojima T, Takeda N, et al; The Metabolic Syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143(10):722. 4 Mozumdar A, Liguori G, et al; Persistent Increase of Prevalence of Metabolic Syndrome Among U.S. Adults: NHANES III to NHANES 1999-2006. Diabetes Care. 2011;34(1):216-219. 5 Grundy, S. Point: The Metabolic Syndrome Still Lives. Clinical Chemistry. 2005;51:1352-1354. 6 Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the Metabolic Syndrome. Circulation. 2005;112:2735–2752. 7 Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 Aug 11;380(9841):56571. 8 Dunn AL, Marcus BH, Kampert JB, et al. Comparison of Lifestyle and Structured Interventions to Increase Physical Activity and Cardiorespiratory Fitness: A Randomized Trial. JAMA. 1999;281(4):327334. 9 Stunkard AJ, McLaren-Hume M. The results of treatment for obesity. Arch Int Med 1959;103:79–85. 10 Kassirer J, Angell M. Losing weight—an ill-fated New Year's resolution. N Engl J Med 1998;338:52–4. 11 Obermayer J, Riley W, Asif O, et al. College smoking-cessation using cell phone text messaging. J Am Coll Health. 2004;53(2):71–8. 12 Franklin V L, Waller A, Pagliari C, et al. A randomized controlled trial of Sweet Talk, a text messaging system to support young people with diabetes. Diabet Med. 2006 12;23(12):1332–8. 13 Moher D, Liberati A, Tetzlaff J. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009 Jul 21;6(7):e1000097. 14 Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18; 343:d5928. 15 Bo S, Ciccone G, Baldi C, Benini L, et al. Effectiveness of a lifestyle intervention on Metabolic Syndrome A randomized controlled trial. J Gen Intern Med. 2007 Dec;22(12):1695-703. 16 Busnello FM, Bodanese LC, Pellanda LC, et al. Nutritional intervention and the impact on adherence to treatment in patients with Metabolic Syndrome. Arq Bras Cardiol. 2011 Sep; 97(3): 217-24. 17 Nishijima H, Satake K, Igarashi K, et al. Effects of exercise in overweight Japanese with multiple cardiovascular risk factors. Med Sci Sports Exerc. 2007 Jun;39(6):926-33. 18 den Boer AT, Herraets IJ, Stegen J, et al. Prevention of the Metabolic Syndrome in IGT subjects in a lifestyle intervention: results from the SLIM study. Nutr Metab Cardiovasc Dis. 2013 Nov;23(11):114753. 19 Pettman TL, Misan GM, Owen K, et al. Self-management for obesity and cardio-metabolic fitness: description and evaluation of the lifestyle modification program of a randomised controlled trial. Int J Behav Nutr Phys Act. 2008 Oct 27;5:53.
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
20 Yamashiro T, Nishikawa T, Isami S, et al. The effect of group-based lifestyle interventions on risk factors and insulin resistance in subjects at risk for Metabolic Syndrome: the Tabaruzaka Study 1. Diabetes Obes Metab. 2010 Sep;12(9):790-7. 21 Kemmler W, Von Stengel S, Engelke K, et al. Exercise decreases the risk of Metabolic Syndrome in elderly females. Med Sci Sports Exerc. 2009 Feb;41(2):297-305. 22 Thomas TR, Warner SO, Dellsperger KC, et al. Exercise and the Metabolic Syndrome with weight regain. J Appl Physiol 2010 Jul;109(1):3-10. 23 Ma J, Yank V, Xiao L, et al. Translating the Diabetes Prevention Program lifestyle intervention for weight loss into primary care: a randomized trial. JAMA Intern Med. 2013 Jan 28;173(2):113-21. 24 Spring B, Schneider K, McFadden HG, et al. Multiple behavior changes in diet and activity: a randomized controlled trial using mobile technology. Arch Intern Med. 2012 May 28;172(10):789-96. 25 Dansinger ML, Gleason JA, Griffith JL, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005 Jan 5;293(1):43-53. 26 Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859-873. 27 Jacobs DR Jr, Sluik D, Rokling-Andersen MH, et al. Association of 1-y changes in diet pattern with cardiovascular disease risk factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise Study. Am J Clin Nutr. 2009 Feb;89(2):509-17. 28 Weinstock RS, Trief PM, Cibula D, Morin PC, Delahanty LM. Weight loss success in Metabolic Syndrome by telephone interventions: results from the SHINE study. J Gen Intern Med 28(12):1620–8. 29 Digenio AG, Mancuso JP, Gerber RA, et al. Comparison of methods for delivering a lifestyle modification program for obese patients: a randomized trial. Ann Intern Med. 2009 Feb 17;150(4):25562. 30 Kukkonen-Harjula KT, Borg PT, Nenonen AM, et al. Effects of a weight maintenance program with or without exercise on the Metabolic Syndrome: a randomized trial in obese men. Prev Med. 2005 SepOct;41(3-4):784-90. 31 Morey MC, Pieper CF, Edelman DE, et al. Enhanced fitness: a randomized controlled trial of the effects of home-based physical activity counseling on glycemic control in older adults with prediabetes mellitus. J Am Geriatr Soc. 2012 Sep;60(9):1655-62. 32 Maruyama C, Kimura M, Okumura H, et al. Effect of a worksite-based intervention program on metabolic parameters in middle-aged male white- workers: a randomized controlled trial. Prev Med. 2010 Jul;51(1):11-7. 33 Tate DF, Jackvony EH, Wing RR. A randomized trial comparing human e-mail counseling, computer-automated tailored counseling, and no counseling in an Internet weight loss program. Arch Intern Med. 2006 Aug 14-28;166(15):1620-5. 34 Svetkey LP, Stevens VJ, Brantley PJ, et al. Weight Loss Maintenance Collaborative Research Group. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA. 2008 Mar 12;299(10):1139-48. 35 Patrick K, Raab F, Adams MA, et al. A text message-based intervention for weight loss: randomized controlled trial. J Med Internet Res. 2009 Jan 13;11(1):e1. 36 Oh EG, Bang SY, Hyun SS, et al. Effects of a 6-month lifestyle modification intervention on the cardiometabolic risk factors and health-related qualities of life in women with Metabolic Syndrome. Metabolism. 2010 Jul;59(7):1035-43. 37 Nanri A, Tomita K, Matsushita Y, et al. Effect of six months lifestyle intervention in Japanese men with Metabolic Syndrome: randomized controlled trial. J Occup Health. 2012;54(3):215-22. 38 Venditti EM, Wylie-Rosett J, Delahanty LM, Mele L, Hoskin MA, Edelstein SL;Diabetes Prevention Program Research Group. Short and long-term lifestyle coaching approaches used to address
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
diverse participant barriers to weight loss and physical activity adherence. Int J Behav Nutr Phys Act. 2014 Feb 12;11:16. 39 Munakata M, Honma H, Akasi M, et al. Repeated counseling improves the antidiabetic effects of limited individualized lifestyle guidance in Metabolic Syndrome: J-STOP-Metabolic Syndrome final results. Hypertens Res. 2011 May;34(5):612-6. 40 Fappa E, Yannakoulia M, Ioannidou M, et al. Telephone counseling intervention improves dietary habits and metabolic parameters of patients with the Metabolic Syndrome: a randomized controlled trial. Rev Diabet Stud. 2012 Spring;9(1):36-45. 41 Melanson KJ, Summers A, Nguyen V, et al. Body composition, dietary composition, and components of Metabolic Syndrome in overweight and obese adults after a 12-week trial on dietary treatments focused on portion control, energy density, or glycemic index. Nutr J. 2012 Aug 27;11:57. 42 Chen YC, Tsao LI, Huang CH, et al. An Internet-based health management platform may effectively reduce the risk factors of Metabolic Syndrome among career women. Taiwan J Obstet Gynecol. 2013 Jun;52(2):215-21.
ACCEPTED Table 1 – Characteristics of Included StudiesMANUSCRIPT Study
Population
Intervention
Comparator
Main Relevant Outcome
ADHERENCE
4 diet programs (Atkins, Zone, Weight Watchers, Ornish)
None
KukkonenHarjula, et al (2005)
N= 90 (middleaged men with BMI 30-40 and waist girth > 100cm)
All men participated in a weight loss program for two months.
Usual care (patients could be randomized to control arm after they completed two month weight reduction phase).
Bo, et al (2007)
N = 335 (at least two components of Metabolic Syndrome)
Lifestyle intervention program (5 sessions) with team-based approach and group sessions
Nishijima, et al (2007)
N=561 Japanese adults with two or more CVD risk factors (HTN, HL, or glucose intolerance)
Exercise two-four times per week for 6 months under supervision of personal trainer
187 men w/ risk factors for DMII (~50% with Metabolic Syndrome)
N = 95 (elderly females w/ Metabolic Syndrome)
Kemmler, et al (2009)
In the combined intervention, the odds ratio of Metabolic Syndrome was 0.10 after the weight reduction phase, 0.08 after the weight maintenance phase, and 0.29 at the 23 months follow up. (p>0.05). Thus, adding exercise to lowenergy diet did not result in statistically significant reduction in Metabolic Syndrome over longterm.
M AN U
Lifestyle intervention significantly reduced prevalence of Metabolic Syndrome (OR = 0.28, 95% CI = 0.18-0.44, NNT = 3.2, p<0.001) at 12 months.
Lifestyle modification advice
BP, body weight, waist circumference, and triglycerides were all significantly improved in intervention vs. control group (p<0.05) at 6 months. Reductions in LDL and HbA1C were not significant.
Randomized to three arms: -Diet group, -exercise group, or -diet and exercise group
No change in diet or exercise
Weight change was -3.5 kg per 10 point change in diet score (p<0.0001), independent of change in energy intake. Subjects with better adherence to diet had significantly more improvement in weight, SBP, lipid profile, and glucose tolerance.
High intensity aerobic/resistance exercises focusing on bone strength
Low-intensity training (60 min/wk)
After 12 months, number of Metabolic Syndrome components significantly decreased in the exercise group (p = 0.002) vs.
TE D
Standard PCP-based counseling
EP
AC C
Jacobs, et al (2009)
Then randomized into 2 interventions (if not randomized to control arm): -Resistance training -Walking
Amount of weight loss was significantly associated with adherence level (r=0.60, p<0.001) at 12 months.
RI PT
N = 160 (BMI = 27-42 and at least 1 Metabolic Syndrome component)
SC
Dansinger, et al (2005)
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT
Main Relevant Outcome slightly in the control group (p = 0.34). Prevalence of Metabolic Syndrome decreased by 30.3% in exercise group vs. 15.6% in control group (p = 0.15)
N = 153 overweight adults with Metabolic Syndrome
16-week lifestyle program that provided strategies in diet, exercise, and behavior, as well as peer group support and free gym access. Also included one 45-60 min supervised exercise session each week
No intervention: national guidelines for healthy eating offered
Sacks, et al (2009)
N = 683 (BMI = 25-40)
4 diet programs: 1) Low fat, average protein 2) High fat, average protein 3) Low fat, high protein 4) High fat, high protein
None
Oh, et al (2010)
N = 52 (Korean females with Metabolic Syndrome)
Nurse-led therapeutic lifestyle change program
No treatment
Intervention group showed significantly greater reductions in body weight and waist circumference (p<0.001), which were maintained 6 months following intervention.
Thomas, et al (2010)
N = 102 (BMI 25.0-39.9 with at least two Metabolic Syndrome components)
10% body weight loss with supervised jogging and caloric restriction x 46 months, followed by programmed weight regain, split into exercise vs. no exercise groups
No exercise during weight regain period
Following weight regain, the aerobic intervention group maintained significant improvements in VO2 max, BP, glucose homeostasis, HDL, LDL, and inflammatory markers that were achieved during weight loss period, while control group showed worsening of most metabolic markers, suggesting that exercise can counter effects of partial weight regain on many disease markers.
Yamashiro, et al (2010)
N = 137 (Japanese cohort with at least 1 Metabolic Syndrome component)
Adherence to diet was strongly associated with weight loss. All four diet programs were equally successful in achieving and maintaining weight loss over two years. Attendance at group sessions was associated with weight loss (p=0.22).
SC
M AN U
TE D
EP
AC C 4-month and 10-month No treatment group-based lifestyle
intervention
Greater attendance at information sessions was correlated with significantly greater reductions in body fat (p<0.001), SBP (p=0.01), total cholesterol (p<0.001), and plasma glucose (p<0.001).
RI PT
Pettman, et al (2009)
At month 34, mean # of Metabolic Syndrome components (4-month: .17±0.17, 10-month: -0.29±0.16, and control: +0.54±0.24) significantly lower in both intervention groups vs. control
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT
Main Relevant Outcome (p<0.05)
N = 80 (Brazilian cohort with Metabolic Syndrome)
Diet, telephone counseling, and education
Diet alone
Patients in both groups who arrived more motivated had significantly higher reductions in BMI after 4 months than those subjects who arrived less motivated (p<0.001)
Munakata, et al (2011)
N = 109 (previously untreated Japanese Metabolic Syndrome patients)
Multiple lifestyle counseling sessions
Single counseling session
Multiple guidance group showed significantly greater reduction in waist circumference (-4.8±5.6 vs. 1.9±5.7 cm, p=0.02) and FBS (9.0±14.0 vs. -2.5±14.1 mg/dl, p=0.03) than single guidance group at 6 months.
Wu (2011)
N = 135 adults with at least one DMII risk factor (overweight, HTN, dyslipidemia, impaired glucose tolerance, etc.)
Home-based exercise group
Usual care group (oral instruction and general lifestyle education)
While the intervention group showed significantly increased physical activity vs. the control group (p<0.001), no intervention effect was found for metabolic risk factors or components of Metabolic Syndrome.
Fappa, et al (2012)
N= 87 (Metabolic Syndrome patients)
1) Face-to face dietary counseling x7 2) Telephone dietary counseling x7
One-time dietary counseling
Metabolic Syndrome reduction rate was 52% in the face-to-face group, 54% in the telephone group, and 21% in control group (p = 0.024).
Melanson, et al (2012)
N = 157 (sedentary adults with BMI 27-35)
Portion control, low energy, or low glycemic index diet with weekly weight loss meetings x 12 wks
None
All three groups had significant improvements in waist circumference, total cholesterol, and LDL (p<0.001). The changes were not significantly different between groups (p>0.05).
Nanri, et al (2012)
N= 107 (Japanese males with Metabolic Syndrome)
Lifestyle modification program focused on diet and exercise from trained occupational health nurse at baseline, one, and three months
Standard health guidance via an educational leaflet
Metabolic Syndrome prevalence decreased by 65.3% in intervention group, and 62.3% in control group (p=0.75). Intervention group had statistically significant decreases in weight, waist circumference, and HgA1C (p<0.001)
Den Boer, et al (2013)
N = 146 adults with impaired
Diet and exercise as moderated by dietician trained in motivational
General information about benefits of
Prevalence of Metabolic Syndrome was significantly lower in intervention group vs. control group
SC
M AN U
TE D
EP
AC C
RI PT
Busnello, et al (2011)
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT interviewing, voluntary participation in supervised aerobic and resistance training for mean of 4.2 yrs, assessed 4 years later
diet and exercise
Ma, et al (2013)
N = 241 (pre-DM or Metabolic Syndrome)
(1) a coach-led, groupdelivered intervention or (2) a self-directed DVD intervention
Usual care
Weinstock, et al (2013)
N= 257 (Metabolic Syndrome patients with BMI>30 and without diabetes)
Telephone delivery of the DPP lifestyle intervention delivered individually
Telephone delivery of the DPP lifestyle intervention (up to 8 participants/call) delivered in conference calls
N = 1032 (BMI = 25-45 & on meds for HTN and/or dyslipidemia)
After losing at least 4 kg in 6-month weight loss program, randomized to…
Svetkey, et al (2008)
Self-directed control
EP
1) Monthly personal contact 2) Monthly interactive web-based intervention
Patrick, et al (2009)
N = 376 (BMI = 30-40)
AC C
Digenio, et al (2009)
N = 65 (BMI = 2539.9)
Both interventions achieved significantly decreased waist circumference (p<0.001 for both interventions) and fasting plasma glucose (p<0.001 for coach-led and p=0.01 for self-directed vs usual care).
SC
M AN U
TE D
TECHNOLOG Y
Both arms: 16 sessions during year 1, 12 sessions during year 2, plus coaching sessions with dieticians
(52.6% vs 74.6%, respectively, p = 0.014) after active intervention. Four years later, reduced prevalence of Metabolic Syndrome between groups was maintained (p=0.268). In patients without Metabolic Syndrome at baseline, the incidence of developing it was 18.2% in the intervention group and 73.7% in the control group (p=0.011).
RI PT
glucose tolerance (66% had Metabolic Syndrome)
Main Relevant Outcome
1) High-frequency (HF) face-to-face (FTF) lifestyle modification counseling 2) Low-frequency (LF) FTF counseling 3) HF phone counseling 4) HF e-mail counseling
Self-help control group
SMS-based weight loss program (2-5x/day)
Printed educational materials only
Both interventions resulted in statistically significant weight loss. At year 2, mean weight loss was 6.2 kg in the conference call group and 2.2 kg in the individual group (p<0.001), suggesting that groupbased intervention may be more effective at achieving weight loss.
At 30 months, personal contact group re-gained less weight (4.0 kg) than self-directed group (5.5 kg, p=0.001) and web-based group (5.2 kg, p=0.008).
After 6 months, a significantly (p = 0.024) larger percentage of patients in the HF-FTF (62±11%) and HFphone group (49±11%) achieved weight loss of at least 5% compared to other three groups. Note: all patients received sibutramine. After 4 months, SMS group lost more weight than printed
Study
Population
Intervention Comparator ACCEPTED MANUSCRIPT
Main Relevant Outcome
Maruyama, et al (2010)
N = 101 (Japanese cohort with any MS component)
Lifestyle modification program (four counseling sessions & monthly website advice)
No treatment control
Significant improvement in body weight (-1.29±1.03kg, p=0.01), BMI (-0.47±0.36, p=0.01), and FPG (-5.2±4.2, p=0.02) in intervention group vs. control group at 4 months
Morey, et al (2012)
N = 302 (ages 60-80, BMI 25-45 with impaired glucose tolerance)
12-month home based counseling: in-person baseline counseling session, regular phone counseling, monthly automated encouragement, physician endorsement in clinic
Consultation with VA weight management program (for all participants)
RI PT
materials group (−1.97±1.6kg, p=0.02).
Spring, et al (2012)
N = 204 (sedentary individuals with low fruit and vegetable (F/V) intake, high sat fat intake, and low physical activity)
1) Increased F/V intake and increased physical activity 2) Decreased fat intake and sedentary leisure 3) Decreased fat intake and increased physical activity 4) Increased F/V intake and decreased sedentary leisure
None
M AN U
SC
Endurance physical activity increased significantly in intervention group vs. control (p<0.001). Both groups had similar decreases in FBG (~6%, p<0.001), while other glycemic markers remained stable Group #4 (increased F/V intake + decreased sedentary leisure) achieved the most significant lifestyle change compared to the other three groups (p<0.001). Differences between groups were maintained throughout the 20week follow-up.
Internet-based health management platform (software gave nutrition and exercise advice x1.5 months)
EP
N = 66 Taiwanese female (with one or more Metabolic Syndrome components)
AC C
Chen, et al (2013)
TE D
All groups utilized remote coaching via mobile technology.
No intervention
Significant improvement in waist circumference, fasting glucose, and mean # of Metabolic Syndrome components in intervention group (p<0.05) vs. control group
Table 2 – Methodological Quality Parameters
ACCEPTED MANUSCRIPT
Randomized
Concealed Allocation
Blinding (of at least 1 study component)
Dansinger, et al (2005)
Yes
Yes
Yes
41.9%
0
KukkonenHarjula, et al (2005)
Yes
No
No
24.4%
0
Bo, et al (2007)
Yes
Yes
Yes
10.7%
0
Yes
Yes
Yes
Jacobs Jr (2009)
Yes
No
No
Kemmler, et al (2009)
Yes
Yes
Yes
Pettman, et al (2009)
Yes
No
No
Sacks, et al (2009)
Yes
Yes
Oh, et al (2010)
Yes
No
Thomas (2010)
Yes
0
M AN U
Nishijima (2007)
SC
10.7%
0
31.6%
0
0%
0
Yes
20.5%
0
No
9.2%
0
No
Yes
34.3%
0
TE D
14.6%
EP
AC C
RI PT
ADHERENCE
Loss to Cross-over, % followup, %
Yamashiro, et al (2010)
Yes
No
No
19.0%
0
Busnello, et al (2011)
Yes
Yes
Yes
3.7%
0
Munakata, et al (2011)
Yes
No
No
12.8%
0
Wu, et al (2011)
Yes
Yes
Yes
12.6% 0
Fappa, et al (2012)
46.0%
Yes
ACCEPTED Yes Yes
Yes
No
No
Nanri, et al (2012) Yes
No
No
Den Boer, et al (2013)
Yes
No
No
Ma, et al (2013)
Yes
Yes
Yes
Weinstock, et al (2013)
Yes
Yes
No
Tate, et al (2006)
Yes
Yes
Yes
19.3%
Svetkey, et al (2008)
Yes
Yes
Yes
6.6%
Digenio, et al (2009)
Yes
Yes
No
Patrick, et al (2009)
Yes
Yes
No
Maruyama, et al (2010)
Yes
Yes
Morey, et al (2012)
Yes
Yes
Spring, et al (2012)
Yes
Chen, et al (2013)
Yes
Melanson et al (2012)
MANUSCRIPT 0 14% 0 4.7% 0 58.9% 0
0 47.5% 0
0
M AN U
0
0
13.3%
0
Yes
13.9%
0
Yes
13.2%
0
Yes
No
2.0%
0
No
No
4.6%
0
TE D
29.5%
EP
AC C
SC
TECHNOLOGY
RI PT
8.3%
ACCEPTED MANUSCRIPT
Appendix. Search results.
RI PT
a. We utilized the following search terms within PUBMED. All search terms included “Metabolic Syndrome” AND one of the following: Adherence – 41 results; Monitoring – 59 results; Strategy – 33 results; Lifestyle – 222 results; Program – 301 results; Intervention – 440 results
SC
b. We utilized the following search terms within CINAHL. All search terms included "Metabolic Syndrome" AND one of the following: Adherence - 3 results; Monitoring - 2 results; Strategy - 2 results; Lifestyle - 10 results; Program - 11 results); Intervention -29 results
M AN U
c. We utilized the following search terms within Web of Science. All search terms included "Metabolic Syndrome" AND one of the following: Adherence - 64 results; Monitoring - 99 results; Strategy - 197 results; Lifestyle - 349 results; Program - 351 results; Intervention - 773 results d. We utilized the following search terms within Ovid. All search terms included "Metabolic Syndrome" AND one of the following: Adherence - 13 results; Monitoring - 19 results; Strategy - 10 results; Lifestyle - 45 results; Program - 106 results; Intervention - 110 results.
TE D
Details of Search Strategy All eligible studies were published in English between Nov 14th, 2002 and January 31st, 2014. We excluded articles published before 2002. This was the year the Diabetes Prevention Program (DPP) was published. 1
AC C
EP
Eligible studies had to pertain to primarily non-pharmacological and non-surgical methods of decreasing cardiovascular risk for patients at risk for Metabolic Syndrome (with 1 or more Metabolic Syndrome components) or patients with Metabolic Syndrome as defined by the ATP III criteria. Of note, we considered overweight, obese, and sedentary adults to be at increased risk for Metabolic Syndrome, and therefore, also included studies that recruited these groups of individuals (BMI ≥ 25). We chose to exclude studies that solely examined nutritional supplements, surgery, pharmacological treatments, and special populations (such as those with HIV or on chemotherapy) outside the aforementioned inclusion criteria. Endpoints were variable across studies, and included changes in prevalence of Metabolic Syndrome and individual components of Metabolic Syndrome, changes in weight/BMI, HDL, LDL, TG, and waist circumference, as well as rate of adverse cardiovascular events, rate of death, and adherence to intervention.
ACCEPTED MANUSCRIPT
RI PT
Data was jointly extracted by all 3 reviewers. Data extraction followed the PICO framework and included: Population (size, mean age, mean BMI, % female), Intervention, Comparator, Outcome, Design, Duration, Percent Lost to Follow-Up, Presence of Randomization, Use of Blinding, Use of Concealed Allocation, and Percent Cross-Over.
Nominated Studies
M AN U
SC
-Weinstock, et al -Dansinger, et al -Sacks, et al -Tate, et al -Svetkey, et al -Patrick, et al -DiGenio, et al -Spring, et al
AC C
EP
TE D
1 Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
ACCEPTED MANUSCRIPT
Clinical significance •
Patient motivation and adherence are the key elements of successful lifestyle change
programs for Metabolic Syndrome. A team-based, interactive approach that holds patients accountable and provides
RI PT
•
regular personalized feedback results in increased adherence and more effective behavioral change.
Technology is a useful adjunct in achieving lifestyle change in Metabolic Syndrome, but
SC
•
AC C
EP
TE D
M AN U
does not replace personal contact as the cornerstone of successful therapy.