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Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes: A Systematic Review and Meta-analysis FREE

Elizabeth Sumamo Schellenberg, BSc, MPH; Donna M. Dryden, PhD; Ben Vandermeer, MSc; Christine Ha, BSc; and Christina Korownyk, MD, CCFP
[+] Article and Author Information

From the University of Alberta Evidence-based Practice Center and Alberta Research Centre for Health Evidence, University of Alberta, Edmonton, Alberta, Canada.

Disclaimer: The findings and conclusions in this article are those of the authors, who are responsible for its content, and do not necessarily represent the views of the Agency for Healthcare Research and Quality. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Acknowledgment: The authors thank the following persons for their contributions: Carol Spooner (screening, data extraction, and research support), Tamara Durec (searching), Andrea Milne (searching), and Teodora Radisic (article retrieval).

Grant Support: By the Agency for Healthcare Research and Quality (contract 290-2007-10021-I).

Potential Conflicts of Interest: Mr. Vandermeer: Grant: Agency for Healthcare Research and Quality. Dr. Korownyk: Grant: Agency for Healthcare Research and Quality. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0950.

Requests for Single Reprints: Christina Korownyk, MD, CCFP, Department of Family Medicine, 1706 College Plaza, 8215 112 Street, University of Alberta, Edmonton, Alberta T6G 2C8, Canada; e-mail, cpoag@ualberta.ca.

Current Author Addresses: Ms. Sumamo Schellenberg: Edmonton Clinic Health Academy, 4-88D, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada.

Dr. Dryden: Edmonton Clinic Health Academy, 4-474, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada.

Mr. Vandermeer: Edmonton Clinic Health Academy, 4-496B, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada.

Ms. Ha: Edmonton Clinic Health Academy, 4th Floor, University of Alberta, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada.

Dr. Korownyk: Department of Family Medicine, 1706 College Plaza, 8215 112 Street, University of Alberta, Edmonton, Alberta T6G 2C8, Canada.

Author Contributions: Conception and design: E. Sumamo Schellenberg, D.M. Dryden, C. Ha, C. Korownyk.

Analysis and interpretation of the data: E. Sumamo Schellenberg, D.M. Dryden, B. Vandermeer, C. Ha, C. Korownyk.

Drafting of the article: E. Sumamo Schellenberg, D.M. Dryden, C. Korownyk.

Critical revision of the article for important intellectual content: E. Sumamo Schellenberg, D.M. Dryden, B. Vandermeer, C. Korownyk.

Final approval of the article: E. Sumamo Schellenberg, D.M. Dryden, B. Vandermeer, C. Ha, C. Korownyk.

Statistical expertise: B. Vandermeer.

Obtaining of funding: D.M. Dryden.

Administrative, technical, or logistic support: E. Sumamo Schellenberg, D.M. Dryden, C. Ha.

Collection and assembly of data: E. Sumamo Schellenberg, D.M. Dryden, C. Ha.


Ann Intern Med. 2013;159(8): 543-551. doi:10.7326/0003-4819-159-8-201310150-00007
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Background: The effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose is unclear.

Purpose: To systematically review the effectiveness of lifestyle interventions on minimizing progression to diabetes in high-risk patients or progression to clinical outcomes (such as cardiovascular disease and death) in patients with type 2 diabetes.

Data Sources: 5 electronic databases (1980 to June 2013), reference lists, and gray literature.

Study Selection: Two reviewers independently identified randomized, controlled trials of lifestyle interventions (≥3 months’ duration) that included exercise, diet, and at least 1 other component; the comparator was standard care.

Data Extraction: One reviewer extracted and a second verified data. Two reviewers independently assessed methodological quality.

Data Synthesis: Nine randomized, controlled trials with patients who were at risk for diabetes and 11 with patients who had diabetes were included. Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up.

Limitation: Most trials focused on surrogate measures (such as weight change, blood pressure, and lipids) for which clinical relevance was unclear.

Conclusion: Comprehensive lifestyle interventions effectively decrease the incidence of type 2 diabetes in high-risk patients. In patients who already have type 2 diabetes, there is no evidence of reduced all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes.

Primary Funding Source: Agency for Healthcare Research and Quality.


Type 2 diabetes is a major cause of illness and death. Diabetes was the seventh-leading cause of death in the United States in 2007 (1), and cardiovascular disease (CVD) accounted for more than 65% of all diabetic deaths (2). Diabetes is also the leading cause of new cases of kidney failure, lower extremity amputations, and blindness not related to injury among adults (1).

Prediabetes, defined by the American Diabetes Association as impaired fasting glucose or impaired glucose tolerance, is considered a relatively high-risk state for diabetes (3). A combination of risk factors collectively known as the metabolic syndrome has also shown moderate predictive value in identifying persons at increased risk for diabetes (45). Both prediabetes and the metabolic syndrome have been associated with increased risk for vascular disease (67). Known modifiable risk factors for type 2 diabetes include obesity (8) and physical inactivity (9). Current guidelines recommend lifestyle changes for both prevention and management of type 2 diabetes (10).

Many systematic reviews have reported a benefit with exercise and dietary interventions in diabetes prevention (1115). However, we are not aware of any reviews that assessed the effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose.

The objective of this systematic review was to assess the effects of comprehensive lifestyle interventions in the prevention of diabetes in adults who have been identified as having increased risk for type 2 diabetes (for example, those with the metabolic syndrome or prediabetes) and the prevention of diabetic complications (such as microvascular and macrovascular outcomes) in adults diagnosed with type 2 diabetes.

We followed an a priori research protocol that met standards for conducting systematic reviews. A full technical report with detailed methods and evidence tables is available at www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id82TA.pdf.

Data Sources and Searches

A research librarian conducted searches in MEDLINE (Appendix Table 1), the Cochrane Central Register of Controlled Trials, CINAHL, EMBASE, and SCOPUS from 1980 to March 2010. Searches were updated in MEDLINE and the Cochrane Central Register of Controlled Trials in July 2012 and June 2013. Search filters for randomized, controlled trials (RCTs) and English-language studies were applied. We also hand-searched clinical trial registries and reference lists of relevant studies and reviews.

Table Jump PlaceholderAppendix Table 1. Search Strategy 
Study Selection

Two reviewers independently screened titles and abstracts using broad inclusion criteria. The full text of potentially relevant studies was assessed independently by 2 reviewers using a standardized form. Disagreements were resolved by consensus or third-party adjudication.

Randomized, controlled trials were included if they involved adults (≥18 years) who were diagnosed with type 2 diabetes or had risk factors suggesting increased risk for it. Our operational definition for patients at risk for diabetes included the metabolic syndrome, prediabetes, insulin resistance, impaired fasting glucose, impaired glucose tolerance, syndrome X, dysmetabolic syndrome X, and the Reaven syndrome. For simplicity, we refer to these patients as “high-risk patients.” The lifestyle intervention had to include an exercise component, a diet component, and at least 1 other component (such as counseling, smoking cessation, and behavior modification). The comparison could be usual care, diet or exercise components alone, or a wait list. A priori, the duration of the intervention was at least 3 months with a minimum 6-month follow-up. We made a post hoc modification also to include RCTs in which the duration of the intervention was at least 1 year even if there was no follow-up. The primary outcomes were progression to type 2 diabetes in patients at risk or development of macrovascular and microvascular complications (such as death, cardiovascular outcomes, nephropathy, retinopathy, or neuropathy) in those with type 2 diabetes. Secondary outcomes included surrogate markers for the development of vascular complications, including body composition, metabolic variables (such as fasting plasma glucose, hemoglobin A1c, and lipid levels), blood pressure, physical activity, and dietary or nutrient intake.

Data Extraction and Quality Assessment

One reviewer extracted data using a standardized form, and a second reviewer verified data for accuracy and completeness. Discrepancies were resolved through consensus or in consultation with a third party. We extracted study and patient characteristics, inclusion and exclusion criteria, interventions, and outcomes.

Two reviewers independently assessed the methodological quality of studies using the Cochrane Collaboration Risk-of-Bias tool (16). Discrepancies were resolved through consensus or third-party adjudication. The source of funding was recorded for all studies (17).

One reviewer graded the strength of evidence using the Agency for Healthcare Research and Quality Evidence-based Practice Center approach (18). Four domains were examined: risk of bias, consistency, directness, and precision. We assigned an overall strength of evidence grade of high, moderate, low, or insufficient. When only 1 study was available for an outcome, we rated the strength of evidence as insufficient.

Data Synthesis and Analysis

We described the results of studies qualitatively and in evidence tables. We did meta-analyses using a DerSimonian–Laird random-effects model (19) when the populations, interventions, time points, and outcomes were sufficiently similar. Statistical heterogeneity was quantified using the I2 statistic (20). We calculated mean differences or standardized mean differences for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. If no event was reported in 1 treatment group, a correction factor of 0.5 was added to each cell of the 2 × 2 table to obtain estimates of the RR. We reported all results with 95% CIs and used Review Manager, version 5.0 (The Cochrane Collaboration, Copenhagen, Denmark), to do meta-analyses.

Role of the Funding Source

The Agency for Healthcare Research and Quality suggested the initial questions and approved copyright assertion for this article but did not participate in the literature search, data analysis, or interpretation of the results.

The literature search identified 1289 citations. Twenty unique studies in 58 publications were included (Figure 1).Nine studies addressed patients at increased risk for type 2 diabetes; 11 studies addressed patients diagnosed with type 2 diabetes. A list of excluded studies and reasons for exclusion is available from the authors.

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Figure 1.

Summary of evidence search and selection.

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Description of Included Studies

Many included trials were associated with several publications that either expanded on the main results, reported secondary outcomes that were not included in the primary report, or reported different follow-up time points. The publication that was the first to report outcome data was considered the primary study. Relevant baseline and outcome data were taken from the primary publication and supplemented with data from the associated publications. Even if reported data were from a follow-up study, the primary article is cited. See Table 1 of the Supplement for a list of the sentinel and associated publications.

High-Risk Patients

The duration of the interventions ranged from 6 to 72 months, with follow-ups between 3 and 20 years for5 RCTs (2125) (Table 2 of the Supplement). Four trials had long-term interventions ranging from 12 to 36 months but with no follow-up (2629). For all studies, the number of participants ranged from 39 to 3234 (median, 210; interquartile range [IQR], 78 to 522). The mean age was between 44 and 85 years. The mean body mass index (BMI) ranged from 26.2 kg/m2 (SD, 3.9) to 38.3 kg/m2 (SD, 5.9).

Although all lifestyle interventions included diet and exercise components, additional components were diverse (Appendix Table 2). Five studies included both individual and group counseling (2124, 26), 1 incorporated only group counseling (27), and 1 had only individual counseling (28). Other components included behavior modification (22, 28), a smoking cessation program (23, 26), regular telephone contact (2223), individual goal setting (21), and cooking lessons (23). One study (28) included medication (orlistat) as an intervention component.

Table Jump PlaceholderAppendix Table 2. Descriptions of Lifestyle Interventions for Patients at Risk for Diabetes 

The interventions were administered or delivered by dietitians (2124, 2628), exercise advisors (2223), physiotherapists (27), nurse managers (2223), nurses (21, 24), physicians (2224), endocrinologists (21), psychologists (22), and technicians (24).

The comparison group received various interventions, including usual care by a family physician (21, 27), educational materials or advice on diet or exercise (2226), wait-list controls (28), food diaries (23), and annual diabetes education sessions (29).

Three trials (22, 26, 28) were assessed as having high risk of bias, and 6 (21, 2325, 27, 29) had unclear risk of bias. Most had inadequate allocation concealment. All but 1 study (24) had high or unclear risk of bias for lack of blinding for subjective or self-reported outcomes (such as hours of exercise per week). Two studies (22, 28) received funding from industry.

Patients With Diabetes

The interventions ranged from 6 to 48 months with follow-up between 6 and 93 months for 5 trials (3034) (Table 3 of the Supplement). Six trials (3540) had interventions that lasted 1 year but had no follow-up after intervention. For all 11 trials, the number of participants ranged from 72 to 5145 (median, 200 [IQR, 149 to 280]). The mean ages were between 53.0 and 62.4 years.

All studies included diet and exercise components plus at least 1 additional component (Appendix Table 3). Five studies used both group and individual counseling (3132, 35, 3738), 3 incorporated only group counseling (30, 34, 39), and 2 had only individual counseling (33, 36). Other components included a smoking cessation course (30), regular telephone contact (3233), individual goal setting (3436, 38), regular blood glucose and blood pressure monitoring (38), and stress management (34, 38). In 1 study (34), participants went on a 3-day nonresidential retreat at the beginning of the intervention. In another study (39), physicians were responsible for motivating the participants. Four studies had medication as one of the intervention components if treatment targets were not met: orlistat (31) and stepwise use of medications (30, 33, 35).

Table Jump PlaceholderAppendix Table 3. Descriptions of Lifestyle Interventions for Patients With Type 2 Diabetes 

The interventions were administered or delivered by dietitians (3032, 3435, 3739), case managers or nurses (3031, 35, 3839), physicians (3031, 3536, 39), qualified exercise advisors or trainers (31, 3435), behavioral therapists or physiologists (31, 34), health or nonprofessional peer counselors (32), lay leaders and trained support group leaders (34), and lifestyle counselors (31). One study (33) reported that a multidisplinary team delivered the intervention but did not specify the individual members.

The comparison group received standard care from their physician (30, 34, 40) or standard care plus a range of other components, including educational materials (32, 36), general health advice at regular laboratory visits (33), encouragement to take diabetes education classes (35), group support sessions (31), a nutrition training session (37), visits to a diabetes outpatient clinic (39), and encouragement to visit community health centers (39).

Two trials (35, 37) were assessed as having high risk of bias; 9 (3034, 36, 3840) were assessed as unclear. Most individual domains had low risk of bias; however, all studies had unclear or high risk of bias for blinding of subjective or self-reported outcomes. Two studies stated that outcome assessors were blinded to treatment allocation (3031). Two studies received funding from industry (31, 33).

Efficacy
High-Risk Patients

The findings are summarized in Appendix Table 4. Two studies (2324) reported CVD events. At 10 years after the intervention, the Finnish Diabetes Prevention Study (23, 41) reported no difference between groups (RR, 1.02 [95% CI, 0.73 to 1.42]). The Da Qing Diabetes Prevention Trial reported first CVD events at 6-year (24) and 20-year (42) follow-up and found no differences between the groups at either time point (hazard ratio [HR], 0.96 [CI, 0.76 to 1.44] and 0.98 [CI, 0.71 to 1.37], respectively). The strength of evidence is insufficient for the effect of comprehensive lifestyle interventions to prevent CVD events.

Table Jump PlaceholderAppendix Table 4. Summary of Results for Patients at Risk for Diabetes 

A 20-year follow-up study from the Da Qing Diabetes Prevention Trial (24, 42) reported that lifestyle interventions had no benefit in severe nephropathy or neuropathy, although incidence of severe retinopathy (defined as a history of photocoagulation, blindness, or proliferative retinopathy) was 47% lower. Severe retinopathy occurred in 31 participants (9.2%) in the intervention group and 17 (16.2%) in the control group. The 20-year follow-up data had limitations, including the number of patients lost to follow-up and the fact that many patients diagnosed with severe retinopathy did not have formal retinal examinations (42). Overall, the strength of evidence for benefit of lifestyle interventions on retinopathy is insufficient.

Seven studies (2124, 2627, 29) reported the development of type 2 diabetes from the end of intervention up to 10 years after it (Figure 2).At the end of intervention, there was an important difference in favor of the lifestyle intervention (RR, 0.35 [CI, 0.14 to 0.85]). The difference was maintained at up to 10 years of follow-up (Figure 2). The Da Qing Diabetes Prevention Trial (24, 42) also reported a difference in the development of type 2 diabetes in favor of lifestyle interventions at both 6 and 20 years (HR, 0.49 [CI, 0.33 to 0.73] and 0.57 [CI, 0.41 to 0.81], respectively); however, these results combine several intervention groups, including a lifestyle intervention with both diet and exercise components, a diet-only intervention, and an exercise-only intervention. The strength of evidence was moderate for development of type 2 diabetes.

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Figure 2.

Effect of lifestyle interventions versus usual care on development of diabetes for high-risk patients.

M–H = Mantel–Haenszel.

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Most studies reported positive effects for secondary outcomes, including changes in body composition, metabolic variables, physical activity, and dietary intake (Appendix Table 4). The results were not always statistically or clinically significant or sustained after the end of the active intervention.

Patients With Diabetes

The results are summarized in Appendix Table 5. Two trials, Steno-2 and Look AHEAD (Action for Health in Diabetes) (3031, 47), reported on macrovascular outcomes, and both included pharmacotherapy as an adjunct to the lifestyle interventions. For all-cause mortality, the pooled results showed no difference between the intervention and control groups at more than 10 years of follow-up (RR, 0.75 [CI, 0.53 to 1.06]) (Figure 3).The strength of evidence was low for this outcome.

Table Jump PlaceholderAppendix Table 5. Summary of Results for Patients With Type 2 Diabetes 
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Figure 3.

Effect of lifestyle interventions versus usual care on all-cause mortality for patients with type 2 diabetes.

M–H = Mantel–Haenszel.

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Both trials reported on a composite outcome of CVD events; however, the makeup of the outcomes was different, and we did not pool the results. The Look AHEAD trial (31, 47) found no difference between groups for their primary outcomes, which included death due to cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for angina (RR, 0.96 [CI, 0.85 to 1.09]). However, Steno-2 (30) found a difference (RR, 0.51 [CI, 0.36 to 0.74]) for their outcomes, which included death due to cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, coronary artery bypass grafting, percutaneous coronary intervention or revascularization for peripheral atherosclerotic arterial disease, and amputation due to ischemia.

Steno-2 (30) reported a reduction in the development of nephropathy, retinopathy, and progression of autonomic neuropathy in favor of the lifestyle intervention. No difference was seen in the progression of peripheral neuropathy.

Although many studies reported positive effects for lifestyle interventions on secondary outcomes, the results were not always statistically significant, and clinical significance remains unclear. In addition, the improvements in secondary outcomes were generally not sustained beyond the end of the active intervention (Appendix Table 5). The strength of evidence was low for improvement in BMI and weight at the end of the interventions. Increased physical activity levels were sustained at all time points up to 10 years after the intervention (standardized mean difference, 0.17 [CI, 0.11 to 0.22]; I2 = 0%) in favor of the lifestyle intervention, and the strength of evidence was low. Strength of evidence was also low for reduced energy and saturated fatty acid intake during the interventions. Energy intake was not reduced beyond the intervention period. Reduction in saturated fatty acid intake was maintained up to 7 to 8 years after the intervention in 2 trials (30, 34).

In light of the known benefit of pharmacologic treatment on surrogate markers, such as blood pressure, lipid levels, and hemoglobin A1c levels, and glucose control, we did a sensitivity analysis of the effect of comprehensive lifestyle interventions with and without medication (Appendix Table 5). There was no improvement in any metabolic outcomes for interventions that did not include pharmacotherapy. Improvement was noted in high-density lipid levels (mean difference, 0.04 [CI, 0.03 to 0.05]) and hemoglobin A1c levels (mean difference, −0.71 [CI, −1.31 to −0.12]) during the intervention in trials that included targeted pharmacotherapy (31, 33, 35).

We conducted a comprehensive systematic review of clinical trials that assessed the effect of a multifaceted lifestyle intervention on patient-centered outcomes, such as progression to type 2 diabetes for high-risk patients and microvascular and macrovascular outcomes, including CVD for patients with type 2 diabetes. Four trials that included high-risk patients and 2 trials that included patients with diabetes reported on patient-important outcomes. The remaining 15 studies reported on secondary or surrogate outcomes. The risk of bias was high or unclear for this body of evidence. The strength of evidence was often insufficient for all outcomes because of the small number of studies and sample sizes.

Moderate-strength evidence showed that participation in a comprehensive lifestyle intervention reduced the risk for type 2 diabetes in persons who are at increased risk (Diabetes Prevention Program [22, 46], Finnish Diabetes Prevention Study [23], European Diabetes Prevention Study–Newcastle [27], Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht [26], Da Qing Diabetes Prevention Trial [24], and Bo and colleagues [21]). Because diabetes is associated with comorbid conditions (4950), it is encouraging that lifestyle interventions seem to have a positive effect on prevention. Our findings are consistent with those of other reviews that have reported substantial benefit of lifestyle interventions in the prevention of type 2 diabetes (5152).

Two trials reported on cardiovascular outcomes in high-risk patients, but neither found benefit with lifestyle interventions. This is consistent with the Look AHEAD trial that involved patients with type 2 diabetes, although it contrasts with the smaller Steno-2 trial.

Recent observational studies have questioned whether high-risk patients are actually at increased risk for CVD compared with the general population. The Australian Diabetes, Obesity, and Lifestyle Study reported increased risk for CVD death in those with prediabetes (53). One systematic review of observational studies found a modest increased risk for stroke (54).

The Diabetes Prevention Program Outcomes Study (46), which involves long-term follow-up of patients in the Diabetes Prevention Program, has reported plans for further follow-up in 2014. This may shed light on whether prevention or delay of diabetes is associated with a delay in development of diabetic complications.

Similar to the results for patients with type 2 diabetes, lifestyle interventions resulted in an important decrease in body weight or BMI in high-risk patients. However, in contrast to the findings in patients with type 2 diabetes, this effect persisted for up to 4 years beyond the intervention period. This must be interpreted with caution because only 1 trial reported BMI at 4 years and only 2 trials assessed weight change. Whether the weight loss is easier to maintain in persons who have not yet progressed to diabetes is unclear. Previous research has found that patients with diabetes have poor weight-loss maintenance after an intervention compared with their counterparts without diabetes (55). If this were the case, it would underscore the importance of identifying persons at risk for diabetes and intervening early.

There is low-strength evidence about the benefit of lifestyle intervention in prevention of all-cause mortality and insufficient-strength evidence about CVD and microvascular outcomes in adults with diabetes. Two studies reported on macrovascular outcomes. Look AHEAD, the largest included trial to date, with 5145 participants, was stopped early after a futility analysis (47). In contrast, Steno-2 reported long-term clinical benefit of lifestyle interventions. Both trials used pharmacotherapy as an adjunct to lifestyle interventions. Steno-2 used intensive targeted pharmacologic therapy, including many medications that have been previously shown to reduce overall mortality rates (such as statins [56], angiotensin-converting enzyme inhibitors for hypertension [57], and acetylsalicylic acid for secondary prevention [58]). Look AHEAD left management of medications to the patient's physician, although they used orlistat in some patients. Long-term trials assessing the effect of orlistat on death and illness are lacking (59). Event rates between the 2 trials differed greatly. At 13-year follow-up, there was a 50% mortality rate for patients in the control group of Steno-2 compared with an 8% mortality rate for those in the control group of Look AHEAD at 10 years. The choice of pharmacotherapy in Steno-2 or inclusion of patients who were inherently more ill may have contributed to the benefit seen on clinical outcomes.

Of interest, Steno-2 found that despite evidence of long-term clinical benefit, changes in behaviors or surrogate markers for CVD were not maintained over the long term. Trials in type 1 diabetes have shown that early intensive treatment results have an extended benefit in delaying the progression of diabetic outcomes beyond the intervention (6061). The mechanism by which benefit occurs despite normalization of behaviors and surrogate markers is unclear.

Limitations of this review include low- or insufficient-strength evidence for most outcomes across the various interventions. These low grades were driven by high or unclear risk of bias within individual studies (largely due to inability to blind patients in the treatment group), lack of direct evidence for patient-important outcomes, and lack of consistency and precision among studies.

There was considerable heterogeneity about dietary and lifestyle interventions. In particular, the third component of the intervention was quite variable, limiting our ability to comment on which additional interventions would be beneficial. Current literature has demonstrated that pharmacotherapy, exercise, and dietary changes have a positive effect on glycemic control and other diabetic indices (6263). Although growing evidence shows an additive effect when several risk factors are addressed together (64), we cannot conclusively say that comprehensive lifestyle interventions are better than diet and exercise alone.

Few trials provided data for clinically important outcomes, focusing on surrogate measures for which the clinical relevance is unclear. A further possible limitation includes the group of patients that we identified as being at increased risk for diabetes. This is a controversial area, with various definitions and diagnostic cut points having been proposed over the past few years (65).

Finally, we included only RCTs in this review. A systematic review of cohort studies may provide data on the effect of different lifestyle interventions over several years to assess the long-term sustainability and comparative effectiveness of these interventions.

Comprehensive lifestyle interventions that include exercise, dietary changes, and at least 1 other component are effective in decreasing the incidence of type 2 diabetes in high-risk patients, and the benefit extends beyond the active intervention phase. In patients who have already been diagnosed with type 2 diabetes, the evidence for benefit of comprehensive lifestyle interventions on patient-oriented outcomes is less clear. There is no evidence of benefit in all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes. Improvement was seen for some secondary outcomes, but it generally did not persist beyond the intervention phase, and the clinical significance is unclear.

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Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, 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.
PubMed
 
Eriksson J, Lindström J, Valle T, Aunola S, Hämäläinen H, Ilanne-Parikka P, et al. Prevention of type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme. Diabetologia. 1999; 42:793-801.
PubMed
CrossRef
 
Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997; 20:537-44.
PubMed
 
Oh EG, Bang SY, Hyun SS, Kim SH, Chu SH, Jeon JY, 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; 59:1035-43.
PubMed
CrossRef
 
Mensink M, Feskens EJ, Saris WH, De Bruin TW, Blaak EE. Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year. Int J Obes Relat Metab Disord. 2003; 27:377-84.
PubMed
CrossRef
 
Oldroyd JC, Unwin NC, White M, Imrie K, Mathers JC, Alberti KG. Randomised controlled trial evaluating the effectiveness of behavioural interventions to modify cardiovascular risk factors in men and women with impaired glucose tolerance: outcomes at 6 months. Diabetes Res Clin Pract. 2001; 52:29-43.
PubMed
CrossRef
 
Pinkston MM, Poston WS, Reeves RS, Haddock CK, Taylor JE, Foreyt JP. Does metabolic syndrome mitigate weight loss in overweight Mexican American women treated for 1-year with orlistat and lifestyle modification? Eat Weight Disord. 2006; 11:35-41.
PubMed
CrossRef
 
Lu YH, Lu JM, Wang SY, Li CL, Zheng RP, Tian H, et al. Outcome of intensive integrated intervention in participants with impaired glucose regulation in China. Adv Ther. 2011; 28:511-9.
PubMed
CrossRef
 
Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet. 1999; 353:617-22.
PubMed
CrossRef
 
Wing RR, Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010; 170:1566-75.
PubMed
 
Keyserling TC, Samuel-Hodge CD, Ammerman AS, Ainsworth BE, Henríquez-Roldán CF, Elasy TA, et al. A randomized trial of an intervention to improve self-care behaviors of African-American women with type 2 diabetes: impact on physical activity. Diabetes Care. 2002; 25:1576-83.
PubMed
CrossRef
 
Ménard J, Payette H, Baillargeon JP, Maheux P, Lepage S, Tessier D, et al. Efficacy of intensive multitherapy for patients with type 2 diabetes mellitus: a randomized controlled trial. CMAJ. 2005; 173:1457-66.
PubMed
CrossRef
 
Toobert DJ, Glasgow RE, Strycker LA, Barrera M Jr, Radcliffe JL, Wander RC, et al. Biologic and quality-of-life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial. Diabetes Care. 2003; 26:2288-93.
PubMed
CrossRef
 
Aubert RE, Herman WH, Waters J, Moore W, Sutton D, Peterson BL, et al. Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial. Ann Intern Med. 1998; 129:605-12.
PubMed
CrossRef
 
Christian JG, Bessesen DH, Byers TE, Christian KK, Goldstein MG, Bock BC. Clinic-based support to help overweight patients with type 2 diabetes increase physical activity and lose weight. Arch Intern Med. 2008; 168:141-6.
PubMed
CrossRef
 
Mayer-Davis EJ, D'Antonio AM, Smith SM, Kirkner G, Levin Martin S, Parra-Medina D, et al. Pounds off with empowerment (POWER): a clinical trial of weight management strategies for black and white adults with diabetes who live in medically underserved rural communities. Am J Public Health. 2004; 94:1736-42.
PubMed
CrossRef
 
Samuel-Hodge CD, Keyserling TC, Park S, Johnston LF, Gizlice Z, Bangdiwala SI. A randomized trial of a church-based diabetes self-management program for African Americans with type 2 diabetes. Diabetes Educ. 2009; 35:439-54.
PubMed
CrossRef
 
Vanninen E, Uusitupa M, Siitonen O, Laitinen J, Länsimies E. Habitual physical activity, aerobic capacity and metabolic control in patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus: effect of 1-year diet and exercise intervention. Diabetologia. 1992; 35:340-6.
PubMed
CrossRef
 
Toobert DJ, Strycker LA, Barrera M Jr, Osuna D, King DK, Glasgow RE. Outcomes from a multiple risk factor diabetes self-management trial for Latinas: Viva Bien!. Ann Behav Med. 2011; 41:310-23.
PubMed
CrossRef
 
Uusitupa M, Peltonen M, Lindström J, Aunola S, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, et al, Finnish Diabetes Prevention Study Group. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study—secondary analysis of the randomized trial. PLoS One. 2009; 4:5656.
PubMed
CrossRef
 
Gong Q, Gregg EW, Wang J, An Y, Zhang P, Yang W, et al. Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study. Diabetologia. 2011; 54:300-7.
PubMed
CrossRef
 
Bo S, Gambino R, Ciccone G, Rosato R, Milanesio N, Villois P, et al. Effects of TCF7L2 polymorphisms on glucose values after a lifestyle intervention. Am J Clin Nutr. 2009; 90:1502-8.
PubMed
CrossRef
 
Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, et al, Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001; 344:1343-50.
PubMed
CrossRef
 
Oldroyd JC, Unwin NC, White M, Mathers JC, Alberti KG. Randomised controlled trial evaluating lifestyle interventions in people with impaired glucose tolerance. Diabetes Res Clin Pract. 2006; 72:117-27.
PubMed
CrossRef
 
Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, et al, Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009; 374:1677-86.
PubMed
 
Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al, Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013; 369:145-54.
PubMed
 
Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008; 358:580-91.
PubMed
CrossRef
 
Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999; 22:233-40.
PubMed
CrossRef
 
Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, et al, Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010; 375:2215-22.
PubMed
 
Horton ES. Effects of lifestyle changes to reduce risks of diabetes and associated cardiovascular risks: results from large scale efficacy trials. Obesity (Silver Spring). 2009; 17:Suppl 3S43-8.
PubMed
CrossRef
 
Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007; 334:299.
PubMed
CrossRef
 
Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007; 116:151-7.
PubMed
CrossRef
 
Lee M, Saver JL, Hong KS, Song S, Chang KH, Ovbiagele B. Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ. 2012; 344:3564.
PubMed
CrossRef
 
Guare JC, Wing RR, Grant A. Comparison of obese NIDDM and nondiabetic women: short- and long-term weight loss. Obes Res. 1995; 3:329-35.
PubMed
 
Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013; 1:CD004816.
PubMed
 
van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012; 33:2088-97.
PubMed
CrossRef
 
Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002; 324:71-86.
PubMed
 
Siebenhofer A, Jeitler K, Horvath K, Berghold A, Siering U, Semlitsch T. Long-term effects of weight-reducing drugs in hypertensive patients. Cochrane Database Syst Rev. 2013; 3:CD007654.
PubMed
 
Writing Team for the Diabetes Control and Complications Trial, Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA. 2003; 290:2159-67.
PubMed
 
White NH, Sun W, Cleary PA, Danis RP, Davis MD, Hainsworth DP, et al. Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the Diabetes Control and Complications Trial. Arch Ophthalmol. 2008; 126:1707-15.
PubMed
 
Franz MJ, Monk A, Barry B, McClain K, Weaver T, Cooper N, et al. Effectiveness of medical nutrition therapy provided by dietitians in the management of non-insulin-dependent diabetes mellitus: a randomized, controlled clinical trial. J Am Diet Assoc. 1995; 95:1009-17.
PubMed
 
Thomas DE, Elliott EJ, Naughton GA. Exercise for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2006; CD002968.
PubMed
 
Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman RR. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006; 49:1761-9.
PubMed
CrossRef
 
Ratner RE, Sathasivam A. Treatment recommendations for prediabetes. Med Clin North Am. 2011; 95:385-95, viii-ix.
PubMed
CrossRef
 
Toobert DJ, Strycker LA, King DK, Barrera M Jr, Osuna D, Glasgow RE. Long-term outcomes from a multiple-risk-factor diabetes trial for Latinas: Viva Bien!. Transl Behav Med. 2011; 1:416-426.
PubMed
CrossRef
 
Toobert DJ, Strycker LA, Barrera M, Glasgow RE. Seven-year follow-up of a multiple-health-behavior diabetes intervention. Am J Health Behav. 2010; 34:680-94.
PubMed
 

Figures

Grahic Jump Location
Figure 1.

Summary of evidence search and selection.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Effect of lifestyle interventions versus usual care on development of diabetes for high-risk patients.

M–H = Mantel–Haenszel.

Grahic Jump Location
Grahic Jump Location
Figure 3.

Effect of lifestyle interventions versus usual care on all-cause mortality for patients with type 2 diabetes.

M–H = Mantel–Haenszel.

Grahic Jump Location

Tables

Table Jump PlaceholderAppendix Table 1. Search Strategy 
Table Jump PlaceholderAppendix Table 2. Descriptions of Lifestyle Interventions for Patients at Risk for Diabetes 
Table Jump PlaceholderAppendix Table 3. Descriptions of Lifestyle Interventions for Patients With Type 2 Diabetes 
Table Jump PlaceholderAppendix Table 4. Summary of Results for Patients at Risk for Diabetes 
Table Jump PlaceholderAppendix Table 5. Summary of Results for Patients With Type 2 Diabetes 

References

Centers for Disease Control and Prevention.  Diabetes: Successes and Opportunities for Population-Based Prevention and Control—At a Glance 2011. Atlanta: Centers for Disease Control and Prevention; 2011. Accessed at www.cdc.gov/chronicdisease/resources/publications/AAG/ddt.htm on 25 January 2013.
 
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PubMed
 
Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Education Program-Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care. 2007; 30:8-13.
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Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: a high-risk state for diabetes development. Lancet. 2012; 379:2279-90.
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Ford ES, Zhao G, Li C. Pre-diabetes and the risk for cardiovascular disease: a systematic review of the evidence. J Am Coll Cardiol. 2010; 55:1310-7.
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Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010; 56:1113-32.
PubMed
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Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994; 17:961-9.
PubMed
 
Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003; 163:427-36.
PubMed
 
American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013; 36:Suppl 1S11-66.
PubMed
 
Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007; 334:299.
PubMed
CrossRef
 
Orozco LJ, Buchleitner AM, Gimenez-Perez G, Roqué I, Figuls M, Richter B, Mauricio D. Exercise or exercise and diet for preventing type 2 diabetes mellitus. Cochrane Database Syst Rev. 2008; CD003054.
PubMed
 
Yamaoka K, Tango T. Efficacy of lifestyle education to prevent type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetes Care. 2005; 28:2780-6.
PubMed
CrossRef
 
Yoon U, Kwok LL, Magkidis A. Efficacy of lifestyle interventions in reducing diabetes incidence in patients with impaired glucose tolerance: a systematic review of randomized controlled trials. Metabolism. 2013; 62:303-14.
PubMed
CrossRef
 
Hopper I, Billah B, Skiba M, Krum H. Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled clinical trials. Eur J Cardiovasc Prev Rehabil. 2011; 18:813-23.
PubMed
 
Higgins JPT, Altman DG. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, UK: J Wiley; 2008; 187-241.
 
Sismondo S. Pharmaceutical company funding and its consequences: a qualitative systematic review. Contemp Clin Trials. 2008; 29:109-13.
PubMed
CrossRef
 
Owens DK, Lohr KN, Atkins D, Treadwell JR, Reston JT, Bass EB, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol. 2010; 63:513-23.
PubMed
CrossRef
 
Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to Meta-analysis. Chichester, UK: J Wiley; 2009.
 
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21:1539-58.
PubMed
CrossRef
 
Bo S, Ciccone G, Baldi C, Benini L, Dusio F, Forastiere G, et al. Effectiveness of a lifestyle intervention on metabolic syndrome. A randomized controlled trial. J Gen Intern Med. 2007; 22:1695-703.
PubMed
CrossRef
 
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, 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.
PubMed
 
Eriksson J, Lindström J, Valle T, Aunola S, Hämäläinen H, Ilanne-Parikka P, et al. Prevention of type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme. Diabetologia. 1999; 42:793-801.
PubMed
CrossRef
 
Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997; 20:537-44.
PubMed
 
Oh EG, Bang SY, Hyun SS, Kim SH, Chu SH, Jeon JY, 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; 59:1035-43.
PubMed
CrossRef
 
Mensink M, Feskens EJ, Saris WH, De Bruin TW, Blaak EE. Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year. Int J Obes Relat Metab Disord. 2003; 27:377-84.
PubMed
CrossRef
 
Oldroyd JC, Unwin NC, White M, Imrie K, Mathers JC, Alberti KG. Randomised controlled trial evaluating the effectiveness of behavioural interventions to modify cardiovascular risk factors in men and women with impaired glucose tolerance: outcomes at 6 months. Diabetes Res Clin Pract. 2001; 52:29-43.
PubMed
CrossRef
 
Pinkston MM, Poston WS, Reeves RS, Haddock CK, Taylor JE, Foreyt JP. Does metabolic syndrome mitigate weight loss in overweight Mexican American women treated for 1-year with orlistat and lifestyle modification? Eat Weight Disord. 2006; 11:35-41.
PubMed
CrossRef
 
Lu YH, Lu JM, Wang SY, Li CL, Zheng RP, Tian H, et al. Outcome of intensive integrated intervention in participants with impaired glucose regulation in China. Adv Ther. 2011; 28:511-9.
PubMed
CrossRef
 
Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet. 1999; 353:617-22.
PubMed
CrossRef
 
Wing RR, Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010; 170:1566-75.
PubMed
 
Keyserling TC, Samuel-Hodge CD, Ammerman AS, Ainsworth BE, Henríquez-Roldán CF, Elasy TA, et al. A randomized trial of an intervention to improve self-care behaviors of African-American women with type 2 diabetes: impact on physical activity. Diabetes Care. 2002; 25:1576-83.
PubMed
CrossRef
 
Ménard J, Payette H, Baillargeon JP, Maheux P, Lepage S, Tessier D, et al. Efficacy of intensive multitherapy for patients with type 2 diabetes mellitus: a randomized controlled trial. CMAJ. 2005; 173:1457-66.
PubMed
CrossRef
 
Toobert DJ, Glasgow RE, Strycker LA, Barrera M Jr, Radcliffe JL, Wander RC, et al. Biologic and quality-of-life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial. Diabetes Care. 2003; 26:2288-93.
PubMed
CrossRef
 
Aubert RE, Herman WH, Waters J, Moore W, Sutton D, Peterson BL, et al. Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization. A randomized, controlled trial. Ann Intern Med. 1998; 129:605-12.
PubMed
CrossRef
 
Christian JG, Bessesen DH, Byers TE, Christian KK, Goldstein MG, Bock BC. Clinic-based support to help overweight patients with type 2 diabetes increase physical activity and lose weight. Arch Intern Med. 2008; 168:141-6.
PubMed
CrossRef
 
Mayer-Davis EJ, D'Antonio AM, Smith SM, Kirkner G, Levin Martin S, Parra-Medina D, et al. Pounds off with empowerment (POWER): a clinical trial of weight management strategies for black and white adults with diabetes who live in medically underserved rural communities. Am J Public Health. 2004; 94:1736-42.
PubMed
CrossRef
 
Samuel-Hodge CD, Keyserling TC, Park S, Johnston LF, Gizlice Z, Bangdiwala SI. A randomized trial of a church-based diabetes self-management program for African Americans with type 2 diabetes. Diabetes Educ. 2009; 35:439-54.
PubMed
CrossRef
 
Vanninen E, Uusitupa M, Siitonen O, Laitinen J, Länsimies E. Habitual physical activity, aerobic capacity and metabolic control in patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus: effect of 1-year diet and exercise intervention. Diabetologia. 1992; 35:340-6.
PubMed
CrossRef
 
Toobert DJ, Strycker LA, Barrera M Jr, Osuna D, King DK, Glasgow RE. Outcomes from a multiple risk factor diabetes self-management trial for Latinas: Viva Bien!. Ann Behav Med. 2011; 41:310-23.
PubMed
CrossRef
 
Uusitupa M, Peltonen M, Lindström J, Aunola S, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, et al, Finnish Diabetes Prevention Study Group. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study—secondary analysis of the randomized trial. PLoS One. 2009; 4:5656.
PubMed
CrossRef
 
Gong Q, Gregg EW, Wang J, An Y, Zhang P, Yang W, et al. Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study. Diabetologia. 2011; 54:300-7.
PubMed
CrossRef
 
Bo S, Gambino R, Ciccone G, Rosato R, Milanesio N, Villois P, et al. Effects of TCF7L2 polymorphisms on glucose values after a lifestyle intervention. Am J Clin Nutr. 2009; 90:1502-8.
PubMed
CrossRef
 
Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, et al, Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001; 344:1343-50.
PubMed
CrossRef
 
Oldroyd JC, Unwin NC, White M, Mathers JC, Alberti KG. Randomised controlled trial evaluating lifestyle interventions in people with impaired glucose tolerance. Diabetes Res Clin Pract. 2006; 72:117-27.
PubMed
CrossRef
 
Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, et al, Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009; 374:1677-86.
PubMed
 
Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al, Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013; 369:145-54.
PubMed
 
Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008; 358:580-91.
PubMed
CrossRef
 
Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999; 22:233-40.
PubMed
CrossRef
 
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