• Shoa L Clarke, Gerald M Reaven, David Leonard, Carolyn E Barlow, William L Haskell, Benjamin L Willis, Laura DeFina, Joshua W Knowles, and David J Maron.
• Division of Cardiovascular Medicine, Stanford University School of Medicine, Calif. Electronic address: shoa@stanford.edu.
• Am. J. Med. 2020 Jul 1; 133 (7): 825830.e2825-830.e2.

BackgroundInsulin resistance may be present in healthy adults and is associated with poor health outcomes. Obesity is a risk factor for insulin resistance, but most obese adults do not have insulin resistance. Fitness may be protective, but the association between fitness, weight, and insulin resistance has not been studied in a large population of healthy adults.MethodsA cross-sectional analysis of cardiorespiratory fitness, body mass index, and markers of insulin resistance was performed. Study participants were enrolled at the Cooper Clinic in Dallas, Texas. The analysis included 19,263 women and 48,433 men with no history of diabetes or cardiovascular disease. Cardiorespiratory fitness was measured using exercise treadmill testing. Impaired fasting glucose (100-125 mg/dL) and elevated fasting triglycerides (≥150 mg/dL) were used as a markers of insulin resistance.ResultsAmong individuals with normal weight, poor fitness was associated with 2.2-fold higher odds of insulin resistance in women (1.4-3.6; P = .001) and 2.8-fold higher odds in men (2.1-3.6; P <.001). The impact of fitness remained significant for overweight and obese individuals, with the highest risk group being the unfit obese. Among obese women, the odds ratio for insulin resistance was 11.0 for fit women (8.7-13.9; P <.001) and 20.3 for unfit women (15.5-26.5; P <.001). Among obese men, the odds ratio for insulin resistance was 7.4 for fit men (6.7-8.2; P < .001) and 12.9 for unfit men (11.4-14.6; P < .001).ConclusionsIndependent of weight, poor fitness is associated with risk of insulin resistance. Obese individuals, particularly women, may benefit from the greatest absolute risk reduction by achieving moderate fitness.Copyright © 2020 Elsevier Inc. All rights reserved.

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