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No increased risk for death in ‘metabolically healthy’ adults with obesity
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Adults with abdominal obesity considered to be metabolically healthy have no greater risk for all-cause death vs. adults who are metabolically healthy and do not have abdominal obesity, according to a long-term, prospective study.
“The natural course of ‘healthy obesity’ is an intriguing and important factor in assessing the long-term health risk of these individuals,” Soraya Doustmohamadian, of the School of Medical Sciences at Semnan University of Medical Sciences in Iran, and colleagues wrote. “Recent data show that a considerable percentage of those categorized as [having metabolically healthy obesity/metabolically healthy abdominal obesity] at baseline lose their metabolic health in short-term follow-ups (< 10 years), and this number reaches as high as 50% during longer follow-ups ... so it would be likely that a proportion of [adults with metabolically healthy abdominal obesity] developed additional metabolic derangements over time, losing their ‘healthy obesity’ status.”
Doustmohamadian and colleagues analyzed data from 8,804 adults aged at least 30 years participating in the Tehran Lipid and Glucose Study (54.8% women; mean age, 48 years; mean BMI, 27.6 kg/m²; mean follow-up time, 12.3 years). Researchers measured weight, height and waist circumference (abdominal obesity defied as 89 cm for men and 91 cm for women), as well as physical activity, blood pressure, fasting blood glucose, lipid profile and insulin resistance via homeostatic model of insulin resistance (HOMA-IR). Metabolic health was defined as fewer than one component of metabolic syndrome, excluding waist circumference. The cohort was stratified into four phenotypes: Metabolically healthy with abdominal obesity (abdominal obesity with less than one risk factor for metabolic syndrome); metabolically unhealthy with abdominal obesity (at least two risk factors for metabolic syndrome); metabolically healthy without abdominal obesity, and metabolically unhealthy with abdominal obesity. Risk for all-cause mortality was defined as death due to any cause as a primary outcome.
Within the cohort, 54.6% had abdominal obesity at baseline; 36.5% were metabolically healthy; among those with abdominal obesity, 23.4% were metabolically healthy. During follow-up, 540 participants died (278 cardiovascular-related; 82 cancer-related; 162 from other causes).
Compared with adults without abdominal obesity who were metabolically healthy, researchers found that adults with (HR = 1.46; 95% CI, 1.05-2.02) and without (HR = 1.39; 95% CI, 1-2) abdominal obesity who were metabolically unhealthy had an increased risk for death from any cause in models adjusted for age, sex, smoking status, education level and physical activity. However, results were not statistically significant for adults with abdominal obesity considered metabolically healthy (HR = 1.35; 95% CI, 0.89-2.03).
The researchers noted that the study was not powered for fully adjusted models or sex-specific analyses, and insulin levels were measured in only 3,920 participants.
“According to our results, [the metabolically healthy abdominal obesity] phenotype was not at increased risk of all-cause mortality in a 12-year follow-up when compared to healthy non-abdominally obese individuals,” the researchers wrote. “However, considering inadequate power for fully adjusted models, these findings do not provide conclusive data in favor of [the] benign nature of [metabolically healthy abdominal obesity]. Therefore, larger studies with longer follow-ups are needed to shed more lights in this field.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Due to limitations of statistical nature, it was unclear in this study whether or not metabolically healthy abdominal obesity presented an increased risk for comorbidity. This paper is flawed for two reasons: BMI average was low, and follow-up was not long enough to see higher mortality. The mean BMI was 27 kg/m2, which is considerably lower than the cutoff point for obesity (30 kg/m2). It has been shown that BMI and increased mortality may not be seen in BMI lower than 35 kg/m2.
Long-term studies have shown that more than half of individuals with obesity and no comorbidities develop obesity-related disease during their lifetime (Kramer CK, et al. Ann Intern Med. 2013;doi:10.7326/0003-4819-159-11-201312030-00008). There is an effect of time on the expression of risk factors in those with obesity, and this has been seen in the Framingham data set where mortality was followed for 30 years. For the first 12 years, the higher-BMI group had a lower mortality than those with low BMI. However, a curvilinear relationship was seen at 18 years, which became stronger over time (Batsis JA, et al. Eur J Intern Med. 2014;doi:10.1016/j.ejim.2014.05.008). At 26 years, it was clear that obesity was an independent risk factor for heart disease (Hubert HB, et al. Circulation. 1983;67:968-977).
Daniel H. Bessesen
This study of 8,804 adults categorized people as metabolically healthy or unhealthy based on the presence or absence of two or more features of the metabolic syndrome. The researchers further identified those who had abdominal obesity or not based on waist circumference. Risk for mortality was measured over 12 years. Metabolically healthy adults without abdominal obesity had the lowest mortality (31/100,000 person-years) with increasing mortality in metabolically healthy adults with abdominal obesity (51/100,000 person-years), metabolically unhealthy adults without abdominal obesity (68/100,000 person-years) and metabolically unhealthy adults with abdominal obesity (83/100,000 person-years). Mortality was not significantly higher in the unhealthy participants with obesity compared to those without, and in fact, the absolute mortality rate was higher in the metabolically unhealthy subjects without abdominal obesity compared with metabolically healthy subjects with abdominal obesity.
The study did not have sufficient power to identify small differences between groups. However, it adds to increasing evidence that BMI and waist circumference are not sufficient for assessing risk for metabolic disease. Clinicians should incorporate other risk factors, such as blood pressure, glucose and triglyceride levels, to more comprehensively assess risk in those with obesity as well as those of normal weight. Metabolically healthy people with abdominal obesity may not be completely healthy, but they do not appear to be at greater risk than metabolically unhealthy people without abdominal obesity. Habitual levels of physical activity may have an important moderating role.
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