10-YEAR FOLLOW-UP OF DIABETES INCIDENCE AND WEIGHT LOSS IN THE DIABETES PREVENTION PROGRAM OUTCOMES STUDY
Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al
Lancet. 2009;374:1677-1686.
Study Summary: The Diabetes Prevention Program (DPP), a randomized clinical trial, demonstrated that intensive lifestyle intervention or metformin prevented or delayed development of type 2 diabetes in high-risk adults compared with placebo. The current article is the first report of the Diabetes Prevention Program Outcomes Study (DPPOS), a long-term follow-up of the DPP designed to determine whether the delay in diabetes seen during the DPP can be sustained.
After being informed of the main DPP results, patients in the metformin and placebo groups entered a 1-to 2-week drug washout phase. All participants were offered a group-administered version of the 16-session lifestyle curriculum as a bridge protocol. Once the DPPOS follow-up began, all participants were offered a lifestyle session every 3 months. The DPP lifestyle group participants were also offered 4 group sessions per year. Those in the metformin group continued to receive metformin (850 mg twice daily). As in the DPP, the primary outcome was development of diabetes. Median follow-up from original DPP randomization was 10 years.
In the original DPP, diabetes incidence was reduced by 58% with intensive lifestyle and by 31% with metformin compared with placebo. During DPPOS, diabetes incidence rates were not significantly different between groups. Incidence rates were stable in the lifestyle group, but decreased in the placebo and metformin groups during the DPPOS. During the combined DPP, bridge, and DPPOS periods, the incidence was decreased by 34% (95% confidence interval [CI], 24%-42%) in the lifestyle group and by 18% (95% CI, 7%-28%) in the metformin group compared with placebo. The delay in median time to diabetes diagnosis was previously estimated from DPP results to be 11 years for the lifestyle group and 3 years for the metformin group. However, the current study estimated the delay to be about 4 years by lifestyle intervention and 2 years by metformin. Attendance at the quarterly lifestyle session averaged 18% for the original lifestyle group, 15% for the metformin group, and 14% for the placebo group.
ASSOCIATION OF DIET, EXERCISE, AND SMOKING MODIFICATION WITH RISK OF EARLY CARDIOVASCULAR EVENTS AFTER ACUTE CORONARY SYNDROMES
Chow CK, Jolly S, Rao-Melacini P, Fox KAA, Anand SS, Yusuf S
Circulation. 2010;121:750-758.
Background: Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events.
Methods and Results: The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise.
Conclusions: Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome.
Editor's Comment. I have selected two articles with similar aims to review for this issue. The first article is a long-term follow-up of the Diabetes Prevention Study. That study demonstrated that lifestyle intervention was better at preventing the onset of type 2 diabetes than metformin (58% vs. 31%). The second article is an international epidemiological study of acute coronary syndrome (ACS) patients. Both articles reach similar conclusions-not only is lifestyle modification effective for secondary prevention, it may be the most effective treatment. The authors for the Diabetes Prevention Program (DPP) continued their study after discontinuing the blinded use of metformin and re-randomizing in 1999. Over the subsequent 10-year period, they did not further intervene other than to simply follow the patients. From the original 3800 patients in the DPP, approximately 3100 remained in this outcomes study. The authors reported that lifestyle modification helped delay the onset of diabetes by 4 years (vs. 2 years for metformin), and it resulted in lower blood pressure and improved lipid profiles.
In their epidemiological study, Chow et al. (N > 18 000) report that adherence to multiple lifestyle interventions (regular exercise, healthy diet, and not smoking compared to no diet or exercise changes with continued smoking) is associated with a 4-fold decrease in mortality at only 6 months after ACS. Chow et al. concluded by suggesting that even after controlling for confounding variables and finding little difference in adherence rates to drug interventions, "the benefits of adherence to lifestyle modification are additional to the benefits conferred by drugs and interventions." Unfortunately, this study also demonstrated what we know about adherence to these lifestyle modifications-it is poor. Over 34% of the smokers continued smoking, and worse, less than 30% of these patients were adherent to both diet and exercise recommendations at 30 days after ACS. The overriding and really remarkable conclusion is that lifestyle modification is effective not only at reducing mortality but also in the short term!! Cardiac rehabilitation and secondary prevention programs need to spread the word, especially in light of the acknowledged "dose response" effect of participation (see Hammill et al.1). -JLR
Reference
1. Hammill BG, Curtis LH, Schulman KA, Whellan DJ. Relationship between cardiac rehabilitation and long-term risks of death and myocardial infraction among elderly Medicare beneficiaries. Circ. 2010;121(1):63-70. [Context Link]
CRITICAL COMPARISONS OF THE CLINICAL PERFORMANCE OF OXYGEN CONSERVING DEVICES
Palwai A, Skowronski M, Coreno A, Drummond C, McFadden ER, Jr
Am J Respir Crit Care Med. Published online first February 4, 2010; doi:10.1164/rccm.200910-1638OC
Rationale: Clinical testing of oxygen conserving devices is not mandated before marketing. Consequently, little is known about individual or comparative therapeutic effectiveness.
Objective: To relate oxygen delivery from prototypical instruments to physiological performance.
Methods and Results: Thirteen subjects with obstructive lung disease performed progressive treadmill exercise while inhaling either room air, 2 L of oxygen/minute, or bolus oxygen from 4 commercially available conserving devices at regulator settings of 2, 5, and continuous. The devices were studied blindly in random order after first being tested to determine performance characteristics. Pulse oximetry, oxygen delivery, and nasal and oral ventilations were monitored at rest and with exertion. At a setting of 2 at rest, all conservers maintained saturation > 90% but there were significant differences in oxygenation between systems. Only one equaled 2 L of oxygen/minute. With exertion, saturation fell with all conservers but not with 2 L O2/min. One device did not perform any better than room air. Two systems provided less oxygen than predicted, one more, and in one the expected and actual amounts were equal only at rest. Breath by breath performance was highly variable with irregular activation and inconsistent oxygen bolus size delivery. Increasing oxygen pulse volume to the point of eradicating conservation with the continuous setting did not eliminate all disparities.
Conclusions: The mechanical and clinical performances of current oxygen conservers are highly variable and in some instances actually contribute to limitations in exercise ability. Seemingly equivalent technical features do not guarantee equivalent therapeutic functionality.
Editor's Comment. Medical equipment has to pass more safety than efficacy testing to be licensed and approved for clinical use. This study highlights the misplaced trust that can result from such an approach in a system conditioned to higher standards applied to all of its other prescribables. The data presented here emphasize the gap between reality ("clinical efficacy") and expectation ("engineering design and equivalency") in the area of oxygen conserving devices. All but 1 of 4 failed to meet even the basic requirement of providing the set flow rate at rest, and all fell short of requirements with exercise. Various reasons for these failures are possible; the authors offer the following: O2 bolus sizes may not be large enough during exertion to meet metabolic demands, the completeness of reservoir filling could be frequency limited, or there may be poor synchronization between triggering and respiratory activity. The real problem is the lack of a requirement that these devices be shown to do what is claimed for them before they can be marketed as such. Until then, if you must trust, try also to verify. -SK
THE 6 MINUTE WALK IN IDIOPATHIC PULMONARY FIBROSIS: LONGITUDINAL CHANGES AND MINIMUM IMPORTANT DIFFERENCE
Swigris JJ, Wamboldt FS, Behr J, du Bois RM, King TE, Raghu G, Brown KK
Thorax. 2010;65:173-177.
Rationale: The response characteristics of the 6 minute walk test (6MWT) in studies of idiopathic pulmonary fibrosis (IPF) are only poorly understood, and the change in walk distance that constitutes the minimum important difference (MID) over time is unknown.
Objectives: To examine changes over time in distance walked (ie, 6MWD) during the 6MWT and to estimate the change in distance that constitutes the MID in patients with IPF.
Methods: Data from a recently completed trial that included subjects with IPF who completed the 6MWT, Saint George's Respiratory Questionnaire (SGRQ) and forced vital capacity (FVC) at 6 and 12 months were used to examine longitudinal changes in 6MWD. Both anchor- and distribution-based approaches as well as linear regression analyses were used to determine the MID for 6MWD. The SGRQ Total score and FVC were used as clinical anchors.
Main Results: Among 123 subjects alive and able to complete the 6MWT at both follow-up time points, 6MWD did not change significantly over time (378.1 m at baseline vs 376.8 m at 6 months vs 361.3 m at 12 months, p=0.5). The point estimate for the 6MWD MID was 28 m with a range of 10.8-58.5 m.
Conclusion: In a group of patients with IPF with moderate physiological impairment, for those alive and able to complete a 6MWT, 6MWD does not change over 12 months. At the population level, the MID for 6MWD appears to be ~28 m. Further investigation using other anchors and derivation methods is required to refine estimates of the MID for 6MWD in this patient population.
Editor's Comment. The 6-minute walk test (6MWT) has been progressively elevated from a reasonably reproducible, low-tech, low-cost test to its present pre-eminence as the defining endpoint in many studies, and an almost equivalent surrogate for life and death!! That has to be one reason for the presence of 5 of the world's leading luminaries in the field of interstitial lung diseases being authors of this article. (Conflict of interest: I was one of the additional investigators recognized in the Acknowledgements section of this report as having participated in the BUILD 1 study from which the data used here are derived.)
Regardless of its antecedents, the question being asked does have clinical relevance-what is the minimum important difference (MID) in the 6-minute walk distance (6MWD) in patients with moderately severe idiopathic pulmonary fibrosis (IPF)? The answer arrived at is limited by the fact that these patients had to be alive and able to complete three 6MWTs over a 12-month period. The statistical techniques used-and this report is based entirely on statistical analysis-combine a distribution and anchor-based model. The results (point estimate ~28 m, range 10.8-58.5 m) are similar to earlier estimates of MID in IPF, arrived at by different methods, but only half of similar estimates in chronic obstructive pulmonary disease. In the end, although the 6MWT remains easy, inexpensive, and reproducible, the MID remains only approximately defined so far. I would suggest, for a clinical test such as this, approximate is not only good enough but also as good as it is likely to get. -SK