David A Jenkins1, Jack Bowden2, Heather A Robinson3, Naveed Sattar4, Ruth J F Loos5,6, Martin K Rutter7,8, Matthew Sperrin3. 1. School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. david.jenkins-5@manchester.ac.uk. 2. MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, U.K. 3. School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. 4. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. 5. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 6. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY. 7. Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. 8. Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.
Abstract
OBJECTIVE: The obesity paradox in which overweight/obesity is associated with mortality benefits is believed to be explained by confounding and reverse causality rather than by a genuine clinical benefit of excess body weight. We aimed to gain deeper insights into the paradox through analyzing mortality relationships with several adiposity measures; assessing subgroups with type 2 diabetes, with coronary heart disease (CHD), with cancer, and by smoking status; and adjusting for several confounders. RESEARCH DESIGN AND METHODS: We studied the general UK Biobank population (N = 502,631) along with three subgroups of people with type 2 diabetes (n = 23,842), CHD (n = 24,268), and cancer (n = 45,790) at baseline. A range of adiposity exposures were considered, including BMI (continuous and categorical), waist circumference, body fat percentage, and waist-to-hip ratio, and the outcome was all-cause mortality. We used Cox regression models adjusted for age, smoking status, deprivation index, education, and disease history. RESULTS: For BMI, the obesity paradox was observed among people with type 2 diabetes (adjusted hazard ratio for obese vs. normal BMI 0.78 [95% CI 0.65, 0.95]) but not among those with CHD (1.00 [0.86, 1.17]). The obesity paradox was pronounced in current smokers, absent in never smokers, and more pronounced in men than in women. For other adiposity measures, there was less evidence for an obesity paradox, yet smoking status consistently modified the adiposity-mortality relationship. CONCLUSIONS: The obesity paradox was observed in people with type 2 diabetes and is heavily modified by smoking status. The results of subgroup analyses and statistical adjustments are consistent with reverse causality and confounding.
OBJECTIVE: The obesity paradox in which overweight/obesity is associated with mortality benefits is believed to be explained by confounding and reverse causality rather than by a genuine clinical benefit of excess body weight. We aimed to gain deeper insights into the paradox through analyzing mortality relationships with several adiposity measures; assessing subgroups with type 2 diabetes, with coronary heart disease (CHD), with cancer, and by smoking status; and adjusting for several confounders. RESEARCH DESIGN AND METHODS: We studied the general UK Biobank population (N = 502,631) along with three subgroups of people with type 2 diabetes (n = 23,842), CHD (n = 24,268), and cancer (n = 45,790) at baseline. A range of adiposity exposures were considered, including BMI (continuous and categorical), waist circumference, body fat percentage, and waist-to-hip ratio, and the outcome was all-cause mortality. We used Cox regression models adjusted for age, smoking status, deprivation index, education, and disease history. RESULTS: For BMI, the obesity paradox was observed among people with type 2 diabetes (adjusted hazard ratio for obese vs. normal BMI 0.78 [95% CI 0.65, 0.95]) but not among those with CHD (1.00 [0.86, 1.17]). The obesity paradox was pronounced in current smokers, absent in never smokers, and more pronounced in men than in women. For other adiposity measures, there was less evidence for an obesity paradox, yet smoking status consistently modified the adiposity-mortality relationship. CONCLUSIONS: The obesity paradox was observed in people with type 2 diabetes and is heavily modified by smoking status. The results of subgroup analyses and statistical adjustments are consistent with reverse causality and confounding.
Authors: Arshiya Mariam; Galen Miller-Atkins; Kevin M Pantalone; Neeraj Iyer; Anita D Misra-Hebert; Alex Milinovich; Janine Bauman; Michelle Mocarski; Abhilasha Ramasamy; B Gabriel Smolarz; Todd M Hobbs; Robert S Zimmerman; Bartolome Burguera; Michael W Kattan; Daniel M Rotroff Journal: Diabetes Obes Metab Date: 2021-09-28 Impact factor: 6.408
Authors: Fausto Petrelli; Alessio Cortellini; Alice Indini; Gianluca Tomasello; Michele Ghidini; Olga Nigro; Massimiliano Salati; Lorenzo Dottorini; Alessandro Iaculli; Antonio Varricchio; Valentina Rampulla; Sandro Barni; Mary Cabiddu; Antonio Bossi; Antonio Ghidini; Alberto Zaniboni Journal: JAMA Netw Open Date: 2021-03-01