Body fat percentage is associated with cardiometabolic dysregulation in BMI-defined normal weight subjects

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Abstract

Background and aims

Nearly 25% of normal weight individuals display abnormal metabolic profiles associated with obesity. As a wide range in body fat percentage (%BF) exists for BMI-defined normal weight individuals, we investigated whether elevated %BF (determined using DXA) was associated with cardiometabolic dysregulation among 977 normal weight subjects (192 men, 785 women) from the Canadian province of Newfoundland and Labrador.

Methods and results

BMI and %BF were measured after a 12-h fasting period. Cardiometabolic abnormalities considered included elevated triglyceride, glucose and hsCRP levels, decreased HDL cholesterol, insulin resistance, and hypertension. Subjects were classified as metabolically healthy (0 or 1 cardiometabolic abnormality) or abnormal (≥2 cardiometabolic abnormalities) and divided into sex-specific %BF tertiles as follows: low (≤15.2% men, ≤29.7% women), medium (15.3–20.7%% men, 29.8–34.9%% women) and high (≥20.8% men, ≥35.0% women). The prevalence of the metabolically abnormal phenotype was higher among medium and high %BF subjects (12.0% and 19.5%, respectively) compared to the low group (7.4%; p < 0.05). Furthermore, the odds of being metabolically abnormal were 1.61 (95% CI 0.94–2.77) for medium %BF subjects compared to the low group and nearly tripled for high %BF subjects (OR 2.73, 95% CI 1.63–4.86). ORs remained significant after further adjustment for waist circumference.

Conclusion

Our findings indicate that those with elevated %BF are at increased risk of developing cardiometabolic disease despite having a normal BMI. Future development of adequate screening tools to identify these individuals is crucial to the prevention of obesity-associated disease.

Introduction

The global prevalence of obesity has increased substantially in the past three decades and is now estimated to affect over 400 million [1]. Obesity is closely associated with a number of comorbidities such as type 2 diabetes, hypertension, coronary artery disease, and many types of cancer [2]. Recently, recognition of different subtypes of obesity has been reported in the literature including metabolically healthy but obese (elevated body fat but normal metabolic profiles) and metabolically obese, normal weight (MONW) [3]. Although lean, MONW individuals present with clustering of metabolic and cardiovascular risk factors similar to what is often associated with being overweight or obese including elevated fasting glucose, insulin resistance, increased triglyceride and decreased HDL cholesterol levels, and systemic inflammation [4], [5], [6]. In addition, MONW women demonstrate an increased risk for cardiovascular mortality [7]. The prevalence of this phenotype is substantial; it has been estimated that approximately 25% of normal weight individuals have abnormal metabolic profiles and are at increased risk of developing obesity-associated diseases [4], [5].

Although obesity is characterized by an excessive amount of body fat, it is commonly measured using body mass index (BMI) which is unable to differentiate between elevated body fat content and preserved or increased lean mass [8], [9], [10]. This is especially true in normal weight individuals (BMI ≤ 24.9 kg m−2) [9], [11]. Specifically, we recently demonstrated that a wide range in body fat percentage (%BF) measured using dual energy x-ray absorptiometry (DXA) exists for BMI-defined normal weight men (5.6–31.2%) and women (4.6–51.1%) [9]. Similarly, a recent study involving a large multiethnic sample from the US population found significant inter-subject variability in %BF for individuals with a BMI of 25.0 kg m−2 [8]. Taken together, these data suggest that some individuals with a normal BMI are in fact obese and as such, may display the MONW phenotype. Indeed, it was recently demonstrated that individuals with a normal BMI and high body fat content had a higher prevalence of cardiometabolic dysregulation, metabolic syndrome, and cardiovascular disease risk factors [7], [12]. In these studies, however, body fat was estimated using bioelectrical impedance analysis (BIA), a less accurate method of estimating %BF. We have shown that BIA tends to overestimate %BF in lean adults and underestimate %BF in obese adults compared to DXA, a more accurate reference method [13]. At the present time, there is no data available regarding the prevalence of cardiometabolic disease in a large cohort of BMI-defined normal weight individuals with high %BF determined using more reliable DXA measurements. Therefore, the objectives of the current study were as follows: 1) to determine if %BF measured using DXA is associated with a number of cardiometabolic abnormalities in a large Newfoundland cohort of BMI-defined normal weight individuals; 2) to determine the prevalence of MONW individuals (defined using BMI) according to gender-specific %BF tertiles; 3) to estimate the risk of cardiometabolic disease associated with higher %BF if normal weight.

Section snippets

Study population

A total of 977 subjects (192 men, 785 women) from the Canadian province of Newfoundland and Labrador were recruited from an ongoing large scale nutrigenomics study (CODING Study) to take part in the current study [5], [9], [14], [15], [16], [17]. Inclusion criteria were as follows: 1) subjects with a normal BMI (18.5–24.9 kg m−2); 2) between the ages of 20 and 79 years old; 3) at least third generation Newfoundlander; 4) healthy, without any serious metabolic, cardiovascular or endocrine

Physical characteristics and cardiometabolic biomarkers in subjects

Physical and biochemical characteristics of all subjects according to gender-specific %BF tertiles are shown in Table 2. As those in the low %BF group were significantly younger, analyses of all variables were adjusted for age as well as gender. As expected, weight, waist circumference, BMI, and %BF were significantly higher in the medium and high %BF groups compared to the low group. In terms of cardiometabolic biomarkers, both medium and high %BF subjects had abnormal metabolic profiles

Discussion

Recent evidence suggests that some individuals cannot be classified as obese based solely on their BMI. Indeed, a substantial proportion of BMI-defined normal weight subjects display clustering of cardiometabolic abnormalities that puts them at an increased risk for future development of cardiovascular and other obesity-related disease. Although these people tend to have higher %BF, work to date has measured adiposity using less accurate methods. In the present study, we investigated the

Acknowledgments

We would like to thank all of the volunteers who participated in the present study. We would also like to thank the following people for their contributions to the collection of data: Hongwei Zhang, Farrell Cahill, Kristina Sheridan, Kristian Green, and Aaron Kennedy. GS holds the position of chair of pediatric genetics, which is supported by Novartis Pharmaceuticals. This study is supported in part by the Canadian Foundation for Innovation (CFI) and the Canadian Institute for Health Research

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