LETTER
The importance of lifestyle-based efforts in reducing mortality in overweight and obese individuals with type-2 diabetes To the Editor: Diabetes is considered a 21st century epidemic. Nearly 90% of patients with type-2 diabetes are overweight or obese at the time of incident diabetes (1), and it is well known that a sedentary lifestyle and unhealthy habits contribute to both obesity and diabetes. Mounting evidence has revealed a benefit with exercise and dietary interventions in diabetes prevention (2,3). However, the beneficial effects of multifaceted lifestyle interventions on clinically oriented outcomes in diabetic patients have not been clearly shown. A recent meta-analysis (4) concluded that there is no evidence of reduced all-cause mortality (in spite of a trend in that direction: risk ratio 0.75; 95% CI, 0.53–1.06): In particular, the Look AHEAD (Action for Health in Diabetes) research group (5) randomly assigned 5145 overweight or obese patients with type-2 diabetes to participate in an intensive multicomponent lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group), or to receive diabetes support and education (control group). Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). However, although the need for medications was reduced, and several measures of well-being were improved, at a median follow-up of 9.6 years, when the trial was prematurely stopped ‘for futility’, there was no significant difference between the two groups in the rate of cardiovascular events. This conclusion could push physicians and patients to reduce lifestyle-based efforts, relying only on drugs. We think that the trial (5) should not have been interrupted. Cardiovascular events were the main outcome, but a more patient-oriented outcome – any cause
deaths – showed a promising HR = 0.85 (95% CI 0.69–1.04). With the planned 13.5year follow-up and under the conservative hypothesis of constant mortality trend and HR, the number of deaths would increase from 376 to 529, with 95% CI 0.71–1.01 and 90% CI 0.73–0.98. The latter may be more appropriate because a priori one would not have expected any detrimental effect of moderate physical activity/weight loss in patients with a mean BMI of 36.0 6.0 (5). Because of the increasing age (nearly 59 years at baseline) and comorbidity, most likely the number of deaths, and, therefore, the power would have been higher. More so if considering the general population instead of the healthy volunteers of a trial (6). Indeed, in a longitudinal study of 1810 older participants followed up for 18 years (7), several lifestyle behaviours were associated with longevity, even after age 75 and independently of health status. Furthermore, healthy behaviours remained predictive of survival also among the very elderly and those with multiple morbidities. Of note, a metaepidemiological study (8) of 16 meta-analyses including 305 randomised controlled trials with 339,274 participants found a comparable effectiveness of exercise and drug interventions on mortality outcomes in the secondary prevention of cardiovascular diseases, and in prediabetes. Therefore, we suggest that physicians should not mainly focus on drugs to treat conditions brought on by unhealthy behaviours. A. Donzelli,1 L. Mascitelli,2 M. R. Goldstein,3 F. Berrino4 1 ASL di Milano, Milano, Italy 2 Medical Service, Comando Brigata alpina “Julia”/Multinational Land Force, Udine, Italy
4
3 NCH Physician Goup, Naples, FL, USA Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy E-mail: [email protected]
References 1 Carnethon MR, De Chavez PJ, Biggs ML et al. Association of weight status with mortality in adults with incident diabetes. JAMA 2012; 308: 581–90. 2 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. 3 Orozco LJ, Buchleitner AM, Gimenez-Perez G, Roque I Figuls M, Richter B, Mauricio D. Exercise or exercise and diet for preventing type 2 diabetes mellitus. Cochrane Database Syst Rev 2008; 3: CD003054. 4 Sumamo Schellenberg E, Dryden DM, Vandermeer B et al. Lifestyle interventions for patients with and at risk for type 2 diabetes. A systematic review and meta-analysis. Ann Intern Med 2013; 159: 543–51. 5 The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369: 145–54. 6 Pinsky PF, Miller A, Kramer BS et al. Evidence of a Healthy Volunteer Effect in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Epidemiol 2007; 165: 874–81. 7 Rizzuto D, Orsini N, Qiu C, Wang HX, Fratiglioni L. Lifestyle, social factors, and survival after age 75: population based study. BMJ 2012; 345: e5568. 8 Naci H, Ioannidis JP. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ 2013; 347: f5577.
Disclosure None. doi: 10.1111/ijcp.12383
LETTER
Do randomised studies of traditional Asian therapies generate different results than non-randomised trials? To the Editor: In clinical trials, randomisation is employed to minimise bias. When treatment groups are allocated through an adequate random procedure, they are likely to be similar in all ª 2014 John Wiley & Sons Ltd Int J Clin Pract, May 2014, 68, 5, 655–658
quantifiable and unquantifiable aspects. Based on this rationale, the randomised clinical trial (RCT) has become the gold standard for testing the efficacy of therapeutic interventions.
Some experts have, however, suggested that randomisation may be misguided as non-randomised studies (NRS) tend to generate similar results as RCTs (1). This may be true in certain, but not in all circumstances;
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The importance of lifestyle-based efforts in reducing mortality in overweight and obese individuals with type-2 diabetes To the Editor: Diabetes is considered a 21st century epidemic. Nearly 90% of patients with type-2 diabetes are overweight or obese at the time of incident diabetes (1), and it is well known that a sedentary lifestyle and unhealthy habits contribute to both obesity and diabetes. Mounting evidence has revealed a benefit with exercise and dietary interventions in diabetes prevention (2,3). However, the beneficial effects of multifaceted lifestyle interventions on clinically oriented outcomes in diabetic patients have not been clearly shown. A recent meta-analysis (4) concluded that there is no evidence of reduced all-cause mortality (in spite of a trend in that direction: risk ratio 0.75; 95% CI, 0.53–1.06): In particular, the Look AHEAD (Action for Health in Diabetes) research group (5) randomly assigned 5145 overweight or obese patients with type-2 diabetes to participate in an intensive multicomponent lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group), or to receive diabetes support and education (control group). Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). However, although the need for medications was reduced, and several measures of well-being were improved, at a median follow-up of 9.6 years, when the trial was prematurely stopped ‘for futility’, there was no significant difference between the two groups in the rate of cardiovascular events. This conclusion could push physicians and patients to reduce lifestyle-based efforts, relying only on drugs. We think that the trial (5) should not have been interrupted. Cardiovascular events were the main outcome, but a more patient-oriented outcome – any cause
deaths – showed a promising HR = 0.85 (95% CI 0.69–1.04). With the planned 13.5year follow-up and under the conservative hypothesis of constant mortality trend and HR, the number of deaths would increase from 376 to 529, with 95% CI 0.71–1.01 and 90% CI 0.73–0.98. The latter may be more appropriate because a priori one would not have expected any detrimental effect of moderate physical activity/weight loss in patients with a mean BMI of 36.0 6.0 (5). Because of the increasing age (nearly 59 years at baseline) and comorbidity, most likely the number of deaths, and, therefore, the power would have been higher. More so if considering the general population instead of the healthy volunteers of a trial (6). Indeed, in a longitudinal study of 1810 older participants followed up for 18 years (7), several lifestyle behaviours were associated with longevity, even after age 75 and independently of health status. Furthermore, healthy behaviours remained predictive of survival also among the very elderly and those with multiple morbidities. Of note, a metaepidemiological study (8) of 16 meta-analyses including 305 randomised controlled trials with 339,274 participants found a comparable effectiveness of exercise and drug interventions on mortality outcomes in the secondary prevention of cardiovascular diseases, and in prediabetes. Therefore, we suggest that physicians should not mainly focus on drugs to treat conditions brought on by unhealthy behaviours. A. Donzelli,1 L. Mascitelli,2 M. R. Goldstein,3 F. Berrino4 1 ASL di Milano, Milano, Italy 2 Medical Service, Comando Brigata alpina “Julia”/Multinational Land Force, Udine, Italy
4
3 NCH Physician Goup, Naples, FL, USA Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy E-mail: [email protected]
References 1 Carnethon MR, De Chavez PJ, Biggs ML et al. Association of weight status with mortality in adults with incident diabetes. JAMA 2012; 308: 581–90. 2 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. 3 Orozco LJ, Buchleitner AM, Gimenez-Perez G, Roque I Figuls M, Richter B, Mauricio D. Exercise or exercise and diet for preventing type 2 diabetes mellitus. Cochrane Database Syst Rev 2008; 3: CD003054. 4 Sumamo Schellenberg E, Dryden DM, Vandermeer B et al. Lifestyle interventions for patients with and at risk for type 2 diabetes. A systematic review and meta-analysis. Ann Intern Med 2013; 159: 543–51. 5 The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369: 145–54. 6 Pinsky PF, Miller A, Kramer BS et al. Evidence of a Healthy Volunteer Effect in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Epidemiol 2007; 165: 874–81. 7 Rizzuto D, Orsini N, Qiu C, Wang HX, Fratiglioni L. Lifestyle, social factors, and survival after age 75: population based study. BMJ 2012; 345: e5568. 8 Naci H, Ioannidis JP. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ 2013; 347: f5577.
Disclosure None. doi: 10.1111/ijcp.12383
LETTER
Do randomised studies of traditional Asian therapies generate different results than non-randomised trials? To the Editor: In clinical trials, randomisation is employed to minimise bias. When treatment groups are allocated through an adequate random procedure, they are likely to be similar in all ª 2014 John Wiley & Sons Ltd Int J Clin Pract, May 2014, 68, 5, 655–658
quantifiable and unquantifiable aspects. Based on this rationale, the randomised clinical trial (RCT) has become the gold standard for testing the efficacy of therapeutic interventions.
Some experts have, however, suggested that randomisation may be misguided as non-randomised studies (NRS) tend to generate similar results as RCTs (1). This may be true in certain, but not in all circumstances;
655
