Are Metabolically Normal but Obese Individuals at Lower Risk for All-Cause Mortality?

Abstract

OBJECTIVEThe clinical relevance of the metabolically normal but obese phenotype for mortality risk is unclear. This study examines the risk for all-cause mortality in metabolically normal and abnormal obese (MNOB and MAOB, respectively) individuals.RESEARCH DESIGN AND METHODSThe sample included 6,011 men and women from the Third National Health and Nutrition Examination Survey (NHANES III) with public-access mortality data linkage (follow-up = 8.7 ± 0.2 years; 292 deaths). Metabolically abnormal was defined as insulin resistance (IR) or two or more metabolic syndrome (MetSyn) criteria (excluding waist).RESULTSA total of 30% of obese subjects had IR, and 38.4% had two or more MetSyn factors, whereas only 6.0% (or 1.6% of the whole population) were free from both IR and all MetSyn factors. By MetSyn factors or IR alone, MNOB subjects (hazard ratio [HR]MetSyn 2.80 [1.18–6.65]; HRIR 2.58 [1.00–6.65]) and MAOB subjects (HRMetSyn 2.74 [1.46–5.15]; HRIR 3.09 [1.55–6.15]) had similar elevations in mortality risk compared with metabolically normal, normal weight subjects.CONCLUSIONSAlthough a rare phenotype, obesity, even in the absence of overt metabolic aberrations, is associated with increased all-cause mortality risk.

Does metabolic health in overweight and obesity persist? – Individual variation and cardiovascular mortality over two decades

“…In accord with our findings, despite inconsistencies in the definitions of MH, the majority have found CVD risk to not be increased in MH OB compared with MH NW individuals (18,26,29,32,33,34,35), or have found CVD risk to be lower in MH OB compared with MUH OB (36), but not all studies agree (10). Moreover, several studies have found evidence for increased risk in MH OB compared with MH NW individuals in studies with >15 years follow-up (17,19,37).…”

“…The question then arises, how many, if any, of the criteria may be allowed to be present before MH can be excluded? Previous studies of MHO employing similar criteria have allowed none (4,12,15), ≤1 (10,11,16,17) or ≤2 (18,19,20,21). In the present analysis, in the full dataset before exclusions (see below), each of the five risk factors was confirmed as a predictor of CVD and total mortality in univariate Cox proportional hazards models, unadjusted for any factors that might influence variation in risk factor levels.…”

“…Clearly, increased BMI cannot be included as a criterion for MH in an analysis of MH OW or OB, and this extends to increased waist circumference which displays marked co-linearity with BMI (4) and has been excluded from the majority of definitions of MH OW or OB (7,10,11,12). Other readily available criteria then include plasma lipid, lipoprotein and glucose concentrations and blood pressure.…”

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

“…Three prospective studies observed that metabolically healthy obese persons have a risk of cardiovascular disease, mortality, and all‐cause mortality similar to that of metabolically healthy nonobese persons 18, 41, 42. In contrast, 2 other studies suggested that, compared with metabolically healthy nonobese persons, metabolically healthy obese persons have a higher risk of cardiovascular mortality and all‐cause mortality 16, 17. More recently, Ortega et al showed that when accounting for fitness, cardiovascular risk was lower for metabolically healthy obese persons compared with metabolically unhealthy obese persons 19.…”

“…Metabolically healthy obese persons are characterized by having excessive body fat while displaying a favorable metabolic profile characterized by high levels of insulin sensitivity; no hypertension; and a favorable lipid, inflammation, hormonal, liver enzyme, and immune profile 15. Recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality,16, 17 whereas other studies suggested that this population might have cardiovascular risk comparable to metabolically healthy nonobese persons 18, 19. To the best of our knowledge, the role of CRP in the assessment of CHD risk has not been described previously in metabolically healthy obese persons.…”