Keming Yang1,2, Michele R Forman3, Patrick O Monahan4, Brett H Graham5, Andrew T Chan6,7, Xuehong Zhang1,7, Immaculata De Vivo7,8, Edward L Giovannucci1,7,8, Fred K Tabung1,9, Hongmei Nan2,10,11. 1. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 2. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. 3. Department of Nutrition Science, College of Health and Human Science, Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, USA. 4. Department of Biostatistics, School of Medicine and Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. 5. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. 6. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 7. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 9. Department of Internal Medicine, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH, USA. 10. Department of Global Health, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. 11. IU Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
Abstract
BACKGROUND: Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. OBJECTIVES: Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. METHODS: This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. RESULTS: We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows: Q1: 0.14 ± 0.05; Q2: 0.04 ± 0.06; Q3: 0.008 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows: Q1: 0.25 ± 0.09; Q2: 0.23 ± 0.09; Q3: 0.07 ± 0.09; Q4: 0.02 ± 0.09; and Q5: -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows: Q1: 0.16 ± 0.05; Q2: 0.07 ± 0.05; Q3: 0.01 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.05 ± 0.05 (P-trend = 0.0004). CONCLUSIONS: Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.
BACKGROUND: Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. OBJECTIVES: Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. METHODS: This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. RESULTS: We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows: Q1: 0.14 ± 0.05; Q2: 0.04 ± 0.06; Q3: 0.008 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows: Q1: 0.25 ± 0.09; Q2: 0.23 ± 0.09; Q3: 0.07 ± 0.09; Q4: 0.02 ± 0.09; and Q5: -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows: Q1: 0.16 ± 0.05; Q2: 0.07 ± 0.05; Q3: 0.01 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.05 ± 0.05 (P-trend = 0.0004). CONCLUSIONS:Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.
Authors: Shaowei Wu; Xin Li; Shasha Meng; Teresa Fung; Andrew T Chan; Geyu Liang; Edward Giovannucci; Immaculata De Vivo; Jin Hyup Lee; Hongmei Nan Journal: Am J Clin Nutr Date: 2019-02-01 Impact factor: 7.045
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Authors: Anna L Guyatt; Kimberley Burrows; Philip A I Guthrie; Sue Ring; Wendy McArdle; Ian N M Day; Raimondo Ascione; Debbie A Lawlor; Tom R Gaunt; Santiago Rodriguez Journal: Mitochondrion Date: 2017-08-15 Impact factor: 4.160
Authors: Keming Yang; Michele R Forman; Brett H Graham; Patrick O Monahan; Edward L Giovannucci; Immaculata De Vivo; Andrew T Chan; Hongmei Nan Journal: Cancer Epidemiol Date: 2020-07-14 Impact factor: 2.890