Letter by Stefan et al Regarding Article, “Impact of Body Mass Index and the Metabolic Syndrome on the Risk of Cardiovascular Disease and Death in Middle-Aged Men”
To the Editor:
In the recent article by Arnlov et al,1 middle-aged men with the metabolic syndrome had an increased risk of cardiovascular events. An increased risk was also found for overweight and obese men without the metabolic syndrome, as defined by Arnlov et al.1 Therefore, it was concluded that being overweight and obese without metabolic derangements is not benign.
The question of whether some overweight or obese subjects are protected from cardiovascular disease and death is important particularly because the resources used to prevent these events often involve lifelong lifestyle and/or pharmacological intervention, which are expensive and often have considerable side effects. The authors are commended for the concise presentation of the data in men with a relatively long follow-up. However, we do not agree with the main conclusion of Arnlov et al that a metabolically benign condition does not exist in overweight and obese individuals. First, the problem is that waist circumference, a simple estimate of visceral adiposity, which is a stronger determinant of mortality than body mass index, could not be used to estimate the metabolic syndrome in all subjects. Thus, in our opinion, it is not clear that the authors succeeded in categorizing individuals as having a metabolically benign versus malign phenotype. In the article by Meigs et al from the Framingham Offspring Study,2 where subjects who were metabolically and healthfully overweight or obese were found to be protected from cardiovascular disease, waist circumference was used to define the metabolic syndrome; in contrast to the study by Arnlov et al, type 2 diabetes mellitus was also excluded by a 2-hour oral glucose tolerance test, allowing the researchers to more precisely characterize subjects at baseline.
Second, because body mass is more closely related to the amount of visceral fat in men than in women,3 it is plausible that in women, if a similar analytic approach as was done in the study by Arnlov et al was used, results would be different than in men.
Third, in the study by Arnlov et al, insulin sensitivity was estimated from the homeostasis model assessment using fasting glucose and insulin levels, which is not a precise measurement of insulin sensitivity. Thus, it is possible that in the overweight and obese insulin-sensitive groups, insulin-resistant subjects were included. In our recent study, where we described the phenotype of metabolically benign obesity, insulin sensitivity was measured during a dynamic test (oral glucose tolerance test), allowing us to more precisely define the metabolically benign phenotype.4 Finally, using the high-sensitivity C-reactive protein level as an estimate of subclinical inflammation, as was done in the report from the National Health and Nutrition Examination Surveys 1999 to 2004,5 may help to achieve this goal.
In conclusion, caution is warranted when describing the metabolically healthy phenotype. In the future, efforts should be made to come to a consensus for defining this interesting and important condition.
Sources of Funding
N.S. is supported by a Heisenberg-Grant from the Deutsche Forschungsgemeinschaft (STE 1096/1-1).
Arnlöv J, Ingelsson E, Sundström J, Lind L. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2010; 121: 230–236.
Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, Sowers MR. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med. 2008; 168: 1617–1124.