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Evaluating the Obesity Paradox in the Henry Ford Exercise Testing Project

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Evaluating the Obesity Paradox in the Henry Ford Exercise Testing Project Diabetes Care Volume 43, March 2020 677 Seamus P. Whelton,1 Paul A. McAuley,2 Association of BMI, Fitness, and Zeina Dardari,1 Olusola A. Orimoloye,1 Clinton A. Brawner,3 Jonathan K. Ehrman,3 Mortality in Patients With Steven J. Keteyian,3 Mouaz Al-Mallah,4 and Diabetes: Evaluating the Obesity Michael J. Blaha1 Paradox in the Henry Ford Exercise Testing Project (FIT Project) Cohort Diabetes Care 2020;43:677–682 | https://doi.org/10.2337/dc19-1673 OBJECTIVE To determine the effect of fitness on the association between BMI and mortality among patients with diabetes. RESEARCH DESIGN AND METHODS We identified 8,528 patients with diabetes (self-report, medication use, or electronic medical record diagnosis) from the Henry Ford Exercise Testing Project (FIT Project). Patients with a BMI <18.5 kg/m2 or cancer were excluded. Fitness was measuredas theMETs achieved during a physician-referred treadmill stress test and categorized as low (<6), moderate (6–9.9), or high (‡10). Adjusted hazard ratios for mortality were calculated using standard BMI (kilograms per meter squared) cutoffs 1 of normal (18.5–24.9), overweight (25–29.9), and obese (‡30). Adjusted splines Johns Hopkins Ciccarone Center for the Pre- CARDIOVASCULAR AND METABOLIC RISK 2 vention of Cardiovascular Disease, Johns Hopkins centered at 22.5 kg/m were used to examine BMI as a continuous variable. School of Medicine, Baltimore, MD 2Department of Health, Physical Education and RESULTS Sport Studies, Winston-Salem State University, Patients had a mean age of 58 6 11 years (49% women) with 1,319 deaths over a Winston-Salem, NC 3 mean follow-up of 10.0 6 4.1 years. Overall, obese patients had a 30% lower Division of Cardiovascular Medicine, Henry Ford P < Hospital, Detroit, MI mortality hazard ( 0.001) compared with normal-weight patients. In adjusted 4Houston Methodist DeBakey Heart & Vascular spline modeling, higher BMI as a continuous variable was predominantly associated Center, Houston, TX with a lower mortality risk in the lowest fitness group and among patients with Corresponding author: Seamus P. Whelton, moderate fitness and BMI ‡30 kg/m2. Compared with the lowest fitness group, [email protected] patients with higher fitness had an ∼50% (6–9.9 METs) and 70% (‡10 METs) lower Received 20 August 2019 and accepted 21 De- mortality hazard regardless of BMI (P < 0.001). cember 2019 This article contains Supplementary Data online CONCLUSIONS at https://care.diabetesjournals.org/lookup/suppl/ Among patients with diabetes, the obesity paradox was less pronounced for doi:10.2337/dc19-1673/-/DC1. patients with the highest fitness level, and these patients also had the lowest risk of This article is featured in a podcast available at https://www.diabetesjournals.org/content/ mortality. diabetes-core-update-podcasts. © 2020 by the American Diabetes Association. There is conflicting evidence on whether BMI is associated with adverse cardiovas- Readers may use this article as long as the work is properly cited, the use is educational and not for cular outcomes and mortality in patients with diabetes. A number of studies have profit, and the work is not altered. More infor- demonstrated a lower mortality risk among individuals with diabetes who are mation is available at https://www.diabetesjournals overweight or obese compared with normal-weight individuals, a finding that has .org/content/license. 678 Diabetes, BMI, Fitness, and Mortality Diabetes Care Volume 43, March 2020 been termed the “obesity paradox” (1,2). or based on electronic medical record A trained nurse and/or clinical exercise Conversely, other studies among individ- (EMR) diagnosis. We required that an physiologist recorded the patients’ de- uals with diabetes have not demonstrated EMR diagnosis of diabetes or any other mographics and CVD risk factors along alowermortalityriskorhavedemonstrated medical condition (e.g., hypertension or with current medication use and past a higher risk of mortality for overweight or hyperlipidemia) be coded on at least medical history immediately preceding obese individuals (3,4). three separate encounters in the EMR in the treadmill stress test. Patients re- Understanding whether the obesity order to be included as a diagnosis in our ported their race, height, and current paradox exists among patients with type database. Among patients diagnosed smoking status. Weight was measured 2 diabetes is of particular importance, withdiabetes,85%hadanHbA1c $6.5% at the time of the treadmill stress test, because a higher BMI is one of the and/or were taking a glucose-lowering and the EMR recorded weight was used strongest risk factors for the develop- medication, 11% had an HbA1c $5.7– for any missing values. BMI was cate- ment of type 2 diabetes, which is in- 6.4% (39–46 mmol/mol), and 4% had an gorized as normal (18.5–24.9 kg/m2), 2 dependently associated with an higher HbA1c ,5.7% (39 mmol/mol). We ex- overweight (25–29.9 kg/m ), or obese risk for cardiovascular disease (CVD) cludedpersonswithaBMI,18.5kg/m2 ($30 kg/m2). A diagnosis of hyperten- and all-cause mortality (5–7). Overweight (n 5 252) and those with prevalent sion and hyperlipidemia was based on or obese individuals with a high fitness cancer (n 5 604). patient self-report, the use of a disease- level have been termed “fat but fit,” and Total mortality was the primary out- specific medication, or a database-verified it has been suggested that individuals come and was ascertained through a diagnosis. Patients were classified as with a higher BMI who are metabolically search of the Social Security Death Index having a family history of coronary artery healthy may partly account for the ob- with follow-up through the year 2013. A disease if they reported a first-degree served obesity paradox (8,9). While there previously described algorithm using a relative with a history of a clinical cor- is significant heterogeneity in CVD risk for combination of first name, last name, onary artery disease event. Labora- patients with diabetes, they are often dateofbirth,andSocial Securitynumber tory values for tests performed within consideredas a CVDriskequivalentgroup, wasusedtoperformmatching(14). 90 days of the stress test were obtained and diabetes is one of the four groups Follow-up was calculated from date of through a retrospective search of the identified by the 2018 American Heart the exercise test to the date of death EMR and associated laboratory data- Association/American College of Cardiol- or through April 2013. bases. Hemoglobin A1c values were only ogyCholesterolGuidelinestobenefitfrom Bruce protocol treadmill stress testing available for 5,786 individuals (68%), statin therapy (10,11). However, fitness was performed using standard method- and fasting glucose values were not modifies the relationship between BMI ology, and the test was stopped if the available. For patients who participated and mortality among patients with CVD, patient experienced chest pain, dyspnea, in the Henry Ford Health System in- and we therefore hypothesized that 1) or other exercise-limiting symptoms (e.g., tegrated health plan, a retrospective among individuals with diabetes, those chest pain, dyspnea, or dizziness) as de- search of the EMR, administrative da- with a higher fitness level would not termined by the supervising clinician or if tabases, and/or pharmacy claims files haveaparadoxicalrelationshipbetween the patient requested that the test be was performed to obtain additional data BMI and mortality; and 2) individuals stopped. The test could also have been on medication use and past medical with a higher fitness level would have a stopped if the patient had an abnormal history. lower risk of mortality regardless of BMI blood pressure response, significant ST We calculated age-adjusted mortality category (12,13). Accordingly, we inves- segment changes, or a clinically significant rates per 1,000 person-years’ follow-up tigated the association between obesity arrhythmia as defined by the American stratified by BMI and fitness group. We and mortality among individuals with Heart Association/American College of also performed progressively adjusted diabetes in the Henry Ford Exercise Test- Cardiology guidelines (15,16). Each pa- Cox proportional hazards modeling to ing Project (FIT Project) and whether tient’s maximal exercise capacity (e.g., examine the association of BMI and total fitness modified this relationship. fitness) was estimated by calculating their mortality within each fitness group. Us- METs, which were calculated by the Quin- ing Cox proportional hazards modeling, ton treadmill controller (Q-Stress; Quin- we also examined the association of fit- RESEARCH DESIGN AND METHODS ton Instrument Company, Bothell, WA) ness and total mortality within each BMI This analysis includes 8,528 individuals using their peak exercise workload (tread- group. Model 1 included age, sex, and with diabetes from the Henry Ford Ex- mill speed and grade) achieved during ethnicity. Model 2 additionally adjusted ercise Testing Project (FIT Project) who the stress test based on equations pub- for hypertension, current smoking, hyper- performedaclinicallyindicated,physician- lished by the American College of Sports tension medication use, lipid-lowering referred Bruce protocol exercise tread- Medicine (17). We categorized fitness as medication use, oral glucose-lowering mill stress test between 1991 and 2009 at low (,6 METs), moderate (6–9.9 METs), medication use, and a history of CVD. the Henry Ford Health System medical and high ($10 METs), as consistent with Model 3additionally included insulinuse. centersinmetropolitan Detroit, MI, ashas our prior work (18). The stress test in- We also used Cox proportional hazards previously been described in detail else- dication was categorized into common modeling within each fitness group to where(14). Patientswere at least18years indications basedonthe physicianreferral examine whether there were differences old and had a diagnosis of diabetes, which information, which primarily included in the relationship between BMI and was defined by patient self-report, use chest pain, dyspnea, and preoperative mortality for prespecified subgroups of of a blood glucose–lowering medication, evaluation.
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