Letter to the Editor From Stumpf et al: “Cancer Outcomes Among Prediabetes and Type 2 Diabetes Populations With Dietary and Physical Activity–based Lifestyle Interventions” Free

Dear Editor, we read with great interest the article published by Zhang et al in JCEM (1). The meta-analysis evaluated cancer outcomes in prediabetes and type 2 diabetes patients with dietary and physical activity programs. The review concluded that the intervention is not superior to usual care concerning cancer mortality. However, some comments should be made.

The only method to prove cardiovascular or cancer mortality reduction, lower cancer incidence, and other key outcomes is to examine lifestyle changes in patients who truly continued the intervention, with high adherence (ie, sustained weight loss >10% during long-term follow-up). As demonstrated in classic trials (2), patients regained weight when the intervention became less rigid and intensive, resulting in noncompliance. Nevertheless, highly motivated participants, who lost more than 10% of body weight, had a decrease in cardiovascular mortality in a subgroup analysis of Look AHEAD (3).

The length of the studies evaluated by the review is an important limitation. Most actions of primary prevention for cancer are expected to reduce its incidence (and consequently, mortality) many years after the intervention. A typical example is the use of oral contraceptives as primary prevention for ovarian cancer (4). Modest short-term weight loss may not be sufficient to fully overcome the deleterious effects of long-term obesity in cancer pathogenesis.

The meta-analysis also stated that no drugs or interventions have been found to reduce cancer risk in this population (1), which is not accurate. Bariatric surgery is a proven method that reduced cancer incidence in some cohort trials. The SOS study showed a reduction of 37% in cancer incidence (5), as properly commented (1). The main reason is that this type of intervention does not require a high level of patient compliance for weight loss. Moreover, it is a lifetime procedure, ensuring long-term benefits.

Interestingly, another review including observational studies revealed lower cancer incidence and mortality rates (6). In some cases, randomized clinical trials may be not suitable for evaluating large-scale and public health interventions (7) because of the Hawthorne effect (8). For instance, the control group in Look AHEAD had a consistent and persistent weight loss of 3.5% at the end of the trial (2). Oddly, contrasting with the intervention group, no weight regain was observed.

Real data about lifestyle modification are often limited, with bias and controversial results between trials. The diversity in protocol interventions, control population, and length of the study sometimes justify some different outcomes. Cautious is always needed for a correct interpretation of a meta-analysis result. Based on this review, physicians could think that advising dietary changes and exercises is irrelevant, which is unreasonable.

Disclosures

The authors have nothing to disclose.

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