A recent movement has emerged in nutrition and health, under the auspice, ‘Health at Every Size’. Its central tenet is advocating a move toward a “weight-normative” or “weight-inclusive” approach in healthcare, given much recent evidence shows that weight per se is not directly tied to risk for chronic lifestyle disease . These arguments have provoked some thought in nutrition and health research, and in healthcare. We have developed a presumption that weight alone is a determinant of health, but “weight” is not how risk is assessed in healthcare or subjects classified for research purposes: Body Mass Index [BMI] is. At the root of this issue is classification of risk and health status by reference to BMI alone, and researchers arguing for a weight-inclusive paradigm have called for an end to BMI-based decisions in healthcare .
Body Mass Index is Redundant
There is merit to this argument. As a clinical tool, BMI lacks strong predictability for health outcomes. Type-2 Diabetes [T2DM] serves as a good example of this issue. While there is an association between BMI and risk for the disease, and increased adiposity does increase risk, the association is not exclusively linear . Defined by BMI alone, adiposity in T2DM varies significantly at time of diagnosis, which indicates that the risk for T2DM is more associated with the underlying metabolic complications that are hallmarks for the disease . Adiposity is a factor in those underlying metabolic complications – impaired fasting blood glucose, insulin resistance, impaired pancreatic beta-cell function – but in analysis of initially healthy subjects with the same baseline BMI, subjects who progressed to diagnoses at 13-years follow-up were those who had greater impairment of those factors when assessed at baseline . Of particular note was the fact that increasing BMI did not increase risk in subjects in this cohort: those who maintained BMI with the ‘overweight’ classification [25-29.9kg/m2] had a higher prevalence of progression to diagnosis and greater declines in pancreatic beta-cell function and insulin sensitivity 5-years prior to diagnosis, compared to persistently obese or progressive weight gaining subjects . Collectively, the data in diabetes shows that underlying metabolic dysfunction is the real driver of disease risk, not BMI.
In addition, BMI does not account for cardiorespiratory fitness, and a phenotype of “fat but fit” has emerged in the literature. There is a continuum of factors influencing degrees of fatness vs. degree of fitness, which interplay to influence the health status of an individual irrespective of the degree of visible adiposity . Assessing health by reference to adiposity alone can thus mislead healthcare practitioners toward incorrect assumptions regarding the health status of the individual based on observed adiposity only, then quantified according to BMI .
Illustration from: 1, JE. Journal of Diabetes & Metabolic Disorders, 2012; 11:19.
Physical activity and fitness may improve a wide range of physiological factors associated with adiposity, including increasing insulin sensitivity, reducing inflammation, and improving body composition [reduction in fat mass, increased fat-free mass] . In this respect, low levels of cardiorespiratory fitness [CRF], an objective and reliable measure of habitual physical activity levels, are associated with significant increases in risk for cardiometabolic disease . An early analysis of cardiometabolic disease risk associated with fitness compared to BMI found an almost equal relative risk increase from being unfit in both ‘normal’ BMI subjects [19-25kg/m2], and subjects with BMI >27.8kg/m2 .
How might fitness attenuate the negative effects of increased adiposity? Within the continuum of “fat-fit”, there are contributing factors to each: cardiorespiratory fitness, musculoskeletal fitness, metabolic flexibility contributing to overall fitness, total fat mass, fat-free mass, and visceral fat contributing to overall adiposity . Counteracting the negative effects of increased adiposity through increased fitness is very much a function of where body composition changes occur.
Waist Circumference: More Predictive of Risk than BMI
I emphasised visible in relation to adiposity above for a particular reason. More recent evidence has emphasised the importance of regional distribution of adipose tissue. An interesting observation in relation to risk for disease and anthropometric risk factors has been that abdominal adiposity, defined by waist-to-hip ratio and waist-to-thigh ratio, is more predictive of cardiometabolic disease than BMI .
The relationship between increased CRF and reduced risk for cardiometabolic disease, even at higher levels of adiposity, may be due to positive effects on abdominal adiposity. In analysis of the association between physical activity and cardiometabolic risk, increased physical activity was associated with reduced disease risk over 5.6 years independent of changes in adiposity (8). However, after adjusting for changes in physical activity, energy expenditure, and aerobic fitness, the strongest factor associated with reduced metabolic risk was reductions in waist circumference .
This may be more indicative of the beneficial effects of reducing central, abdominal – i.e., visceral – adiposity. While associations between BMI and adverse health outcomes are typically consistent at higher obesity classifications [>30kg/m2], waist-hip ratio has been shown to be predictive of risk amongst both persons with obesity [BMI >30kg/m2] and persons defined as ‘normal’ weight [BMI 19-25kg/m2]. This association has been confirmed by meta-analysis of recent studies utilizing imaging techniques to assess visceral fat accumulation: visceral fat is strongly predictive of adverse cardiometabolic health outcomes, yet reductions in visceral and total abdominal fat may occur without any change in BMI .
Thus, while CRF is important, it is arguable that the benefit of increased fitness is a result of body composition changes in specific tissues: in particular a reduction in visceral abdominal fat, and increased metabolic flexibility in skeletal muscle . Thus, a simple assessment of weight status like BMI fails to give any true assessment of individual health status, which is influenced by this interaction between body composition and adipose tissue distribution.
All Fat is Not Created Equally
The phenomenon of “fat but fit” or “healthy obese” implies a dichotomy: that ‘metabolic obesity,’ i.e. the negative effects of increased adiposity, is a consequence of adipose tissue function. The dated view of adipose tissue was as a benign, storage depot. Adipose tissue is now recognized as an endocrine and immunoregulatory organ, responsible for the synthesis and secretion of signaling compounds involved in energy balance, substrate metabolism, inflammation, and immunity . Obese but metabolically healthy subjects are defined by low hepatic triglyceride [TG] levels and normal insulin sensitivity, and demonstrate resistance to adverse cardiometabolic effects from increases in adiposity, compared to obese but metabolically unhealthy subjects .
What underlies these differences is the variance in metabolic effects of adipose tissues. In metabolically unhealthy obesity, the function of adipocytes is compromised, resulting in an overspill of triglycerides to other tissues, in particular the liver . The accumulation of triglycerides in the liver upregulates VLDL [very-low density lipoprotein] synthesis and contributes to remodelling of LDL-C and HDL-C . The resulting “atherogenic lipoprotein phenotype,” defined by high LDL, low HDL, and high triglycerides, is the most significant risk factor for cardiovascular disease . The increase in liver fat deposition also drives hepatic insulin resistance, causing increased concentrations of circulating free fatty acids in the postprandial period, contributing to new TG synthesis and impairing postprandial TG clearance . The increase in flow of fats to other tissues, known as ‘lipotoxicity,’ in turn drives increased adipose tissue inflammatory signalling, immune responses, and oxidative stress .JOIN NOW to continue reading...
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