Abstract

Background

The Diabetes Prevention Program (DPP) study showed that weight loss in high-risk adults lowered diabetes incidence and cardiovascular disease risk. No prior analyses have aggregated weight and cardiometabolic risk factor changes observed in studies implementing DPP interventions in nonresearch settings in the United States.

Methods and Findings

In this systematic review and meta-analysis, we pooled data from studies in the United States implementing DPP lifestyle modification programs (focused on modest [5%–7%] weight loss through ≥150 min of moderate physical activity per week and restriction of fat intake) in clinical, community, and online settings. We reported aggregated pre- and post-intervention weight and cardiometabolic risk factor changes (fasting blood glucose [FBG], glycosylated hemoglobin [HbA1c], systolic or diastolic blood pressure [SBP/DBP], total [TC] or HDL-cholesterol). We searched the MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov databases from January 1, 2003, to May 1, 2016. Two reviewers independently evaluated article eligibility and extracted data on study designs, populations enrolled, intervention program characteristics (duration, number of core and maintenance sessions), and outcomes. We used a random effects model to calculate summary estimates for each outcome and associated 95% confidence intervals (CI). To examine sources of heterogeneity, results were stratified according to the presence of maintenance sessions, risk level of participants (prediabetes or other), and intervention delivery personnel (lay or professional).

Forty-four studies that enrolled 8,995 participants met eligibility criteria. Participants had an average age of 50.8 years and body mass index (BMI) of 34.8 kg/m², and 25.2% were male. On average, study follow-up was 9.3 mo (median 12.0) with a range of 1.5 to 36 months; programs offered a mean of 12.6 sessions, with mean participant attendance of 11.0 core sessions. Sixty percent of programs offered some form of post-core maintenance (either email or in person). Mean absolute changes observed were: weight -3.77 kg (95% CI: -4.55; -2.99), HbA1c -0.21% (-0.29; -0.13), FBG -2.40 mg/dL (-3.59; -1.21), SBP -4.29 mmHg (-5.73, -2.84), DBP -2.56 mmHg (-3.40, 1.71), HDL +0.85 mg/dL (-0.10, 1.60), and TC -5.34 mg/dL (-9.72, -0.97). Programs with a maintenance component achieved greater reductions in weight (additional -1.66kg) and FBG (additional -3.14 mg/dl).

Findings are subject to incomplete reporting and heterogeneity of studies included, and confounding because most included studies used pre-post study designs.

Conclusions

DPP lifestyle modification programs achieved clinically meaningful weight and cardiometabolic health improvements. Together, these data suggest that additional value is gained from these programs, reinforcing that they are likely very cost-effective.

 

Discussion

This is the first meta-analysis to aggregate both weight and cardiovascular risk factor changes from US community-based studies of DPP-based lifestyle interventions. Characteristics of participants in these studies of DPP lifestyle programs were very similar to those of the original trial participants, but translation study participants had a slightly higher mean starting weight and higher proportion of females [13]. The original DPP participants had a greater mean weight loss at 1 y than the participants in this meta-analysis (6.8 kg versus 3.8 kg), which was likely due to the more resource intensive intervention and individualized support in the trial [13]. However, this weight change was closer to the 4.2 kg weight loss reported in the Finnish Diabetes Prevention Study (DPS) [11]. Studies with adequate control groups showed an additional 1.9 kg weight lost across intervention arms when compared with their respective control arms (3.3 versus 0.6 kg). Indeed, the control groups in these effectiveness studies achieved some benefit from participation, even if only exposed to minimal intervention. Compared to the original DPP, HbA1c, and SBP reductions observed in translation studies were similar; FBG and DBP reductions were somewhat lower than the reductions achieved in the efficacy trial; and comparisons for HDL and TC were not possible.

We noted no difference in cardiometabolic risk factor changes in people with biochemically confirmed prediabetes versus those with diabetes risk factors. That said, progression to diabetes and its complications varies by type of prediabetes. The DPP enrolled patients with both IGT and IFG, who are at approximately three times higher risk of progression to diabetes compared to those with IFG alone [7]. The Finnish DPS, Malmo, and Da Qing studies also included participants with IGT or combined IGT and IFG, who are at higher risk than those with IFG alone [7,9,14]. Meanwhile, the US-based DPP-translation studies primarily used IFG criteria, and none used oral glucose tolerance tests to determine high-risk status. This suggests that participants in these studies had a lower risk profile, which was also reflected in their lower baseline FBG and HbA1c levels. Assuming the participants in this analysis were at a lower baseline risk, the changes in cardiometabolic risks observed were commensurate with the starting risk level, and are therefore still noteworthy. It remains unclear whether the DPP intervention is effective in preventing diabetes among participants with impaired fasting glucoses but normal post-load glucose levels. Also, given ease of testing, HbA1c is now commonly used to diagnose prediabetes, and it is unclear whether DPP results can be extended to this prediabetes population defined by HbA1c.

Our findings are also similar to other recent studies. A Community Guide Review, which evaluated interventions across diverse countries and settings, had similar decreases in FPG with a nonsignificant trend towards decreased blood pressure and cholesterol [22]. The MOVE! program evaluated a ten-module program among 238,000 veterans; high intensity intervention participants achieved 2.7% weight loss at 6 mo compared to a 0.6% weight loss in the low intensity group [13,74]. Our findings were also similar to a systematic review and meta-analysis that pooled 22 studies published before July 2012 that translated diabetes prevention for real-life settings in multiple countries (US, Australia, Europe, and Japan) and had ≥12 mo of follow-up [75]. Since multiple countries were involved, heterogeneous study interventions were benchmarked to Europe-wide diabetes prevention implementation guidelines and showed overall pre-post changes in weight (-2.32 kg), HbA1c (-0.13 mmol/mol), FPG (-0.10 mmol/L [-1.8 mg/dl]), SBP and DBP (-4.30/-4.28 mmHg), HDL (+0.01 mmol/L [+0.39 mg/dl]), and TC (-0.18 mmol/L [-6.96 mg/dl]); importantly, greater adherence to recommendations was associated with larger weight reduction. Our study expands on this work with a larger number of pooled studies and participants, all using a similar core set of intervention principles and comparison to the original DPP Study.

Effective translation of a program depends on multiple components, including referral, uptake, engagement, completion, and post-program sustainability of outcomes in the whole population. In our review, after eligibility criteria was applied, 25.5% of all eligible participants did not enroll; of those who enrolled, there was an additional 23.8% attrition. Rates of attrition also inherently select for those who are the most motivated participants, which biases the results towards effectiveness. This limits the generalizability of our findings, which more accurately apply to those who complete the program.

Implementation of DPP lifestyle programs have been limited by both cost and sustainability of ongoing program participation and risk factor reductions [76]. Most of the programs studied in this analysis provided free testing and intervention supplies but offered few additional incentives to encourage participation. The most common methods used to decrease cost were modifications to the intervention, such as offering the intervention in accessible locations, delivering the intervention through lay providers, and taking advantage of group classes and electronic delivery options. Over 80% of studies tested group interventions, most had fewer mean core sessions compared to DPP, and only 60% offered a maintenance component. Importantly, we noted similar risk factor benefits were achievable in interventions delivered by different providers in both group and individual formats. The similarities in weight loss and secondary outcomes compared to the DPP is encouraging for the ability to make the intervention cost-effective without sacrificing the effectiveness. With options that include group sessions, community-based programs with social support, cultural tailoring, and remote low-cost maintenance such as text messages or phone calls, the interventions allow for scaling to a wider audience.

Reach and sustainability of behavior change interventions remain, as do other challenges of implementing diabetes prevention. The advantages of community-based interventions that were pooled in this study include familiar context, peer support, and convenience to facilitate continued participation. The success of electronic and remote interventions is also encouraging, as these could be distributed nationally with ease. The option of pre-recorded workouts on in-home cable TV illustrates a low-cost method of delivery that does not necessitate travel and is available on demand, in contrast to on-site workout regimens for which participants pay to participate [77]. This preliminary analysis also suggests that programs that implemented a maintenance component after the completion of the core sessions had greater reductions in weight and fasting glucose. The duration and intensity of maintenance that is most effective and the utility after the 1 y mark is largely unknown. Further evaluation of types of maintenance programs following a year-long program would be helpful to understand long-term benefit and sustainability.

Limitations

A key limitation of our analysis was the heterogeneity of the studies included, which is inherent in all meta-analyses. Differences in duration of follow-up (from 1.5 to 36 mo), location of delivery, and other delivery format adaptations of the original DPP program were the most likely sources of heterogeneity. However, as the intervention (DPP-lifestyle program principles) and outcomes were similar, this study adds to the literature by providing external validity and noteworthy pre-post and between group cardiometabolic risk factor changes.

The lack of statistical significance found in most of the stratified analyses is likely due to lack of statistical power, which resulted in large, overlapping confidence intervals, as well as our conservative definition of statistical significance based only on non-overlapping CI’s. As most meta-analyses, our study is confined to the use of previously reported results. We used a more conservative definition of statistical significance by comparing stratum specific results, though this did not allow a more consistent adjustment for confounders. However, a less conservative analytical approach may have found other program characteristics that had “statistically significant” associations with cardiometabolic changes.

Additionally, studies varied significantly in quality. We conducted a sensitivity analysis to evaluate change in weight stratified by study quality (high versus average quality), which showed no significant difference. However, this alone is not expected to account for variation that arises during recruitment, enrollment, and study conduct. The majority of studies in our review used pre-post single group study designs and may be subject to confounding. To address this, we separately examined studies that had control groups and demonstrated that intervention groups achieved larger benefits than control groups.

Conclusion

Delivery of lifestyle programs adhering to DPP principles tested in community and clinical settings achieved similar 1 y decreases in weight, FBG, and HbA1c as the original DPP study, despite the modifications made to lower cost and improve acceptability across various settings. Though unclear if these changes truly translate into reductions in diabetes incidence, prior studies have found decreased incidence to be most closely related to weight loss [13]. Methods to increase uptake and decrease attrition are both needed to enable long-lasting, sustainable lifestyle change in patients with the highest risk of progression to diabetes and its associated complications.