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Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification by Smoking.
Diabetes Care 2018; 41(9):1878-1886DC

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.

Authors+Show Affiliations

School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. david.jenkins-5@manchester.ac.uk.MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, U.K.School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K.The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K. Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, U.K.School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, U.K.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29970414

Citation

Jenkins, David A., et al. "Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification By Smoking." Diabetes Care, vol. 41, no. 9, 2018, pp. 1878-1886.
Jenkins DA, Bowden J, Robinson HA, et al. Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification by Smoking. Diabetes Care. 2018;41(9):1878-1886.
Jenkins, D. A., Bowden, J., Robinson, H. A., Sattar, N., Loos, R. J. F., Rutter, M. K., & Sperrin, M. (2018). Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification by Smoking. Diabetes Care, 41(9), pp. 1878-1886. doi:10.2337/dc17-2508.
Jenkins DA, et al. Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification By Smoking. Diabetes Care. 2018;41(9):1878-1886. PubMed PMID: 29970414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification by Smoking. AU - Jenkins,David A, AU - Bowden,Jack, AU - Robinson,Heather A, AU - Sattar,Naveed, AU - Loos,Ruth J F, AU - Rutter,Martin K, AU - Sperrin,Matthew, Y1 - 2018/07/03/ PY - 2017/12/01/received PY - 2018/06/05/accepted PY - 2018/7/5/pubmed PY - 2018/10/12/medline PY - 2018/7/5/entrez SP - 1878 EP - 1886 JF - Diabetes care JO - Diabetes Care VL - 41 IS - 9 N2 - 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. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/29970414/Adiposity_Mortality_Relationships_in_Type_2_Diabetes_Coronary_Heart_Disease_and_Cancer_Subgroups_in_the_UK_Biobank_and_Their_Modification_by_Smoking_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=29970414 DB - PRIME DP - Unbound Medicine ER -