Ki-Su Kim1, Yu-Mi Lee1, In-Kyu Lee2, Dae-Jung Kim3, David R Jacobs4, Duk-Hee Lee5. 1. Department of Preventive Medicine and. 2. Department of Endocrinology, School of Medicine, Kyungpook National University, Daegu, Korea. 3. Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea. 4. Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis. 5. Department of Preventive Medicine and BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea. lee_dh@knu.ac.kr.
Abstract
BACKGROUND: Insulin resistance is linked to many human chronic diseases. Paradoxically, however, impaired insulin signaling contributes to longevity in various organisms and is suggested as an adaptive mechanism against external stressors, including obesity. We formulated a novel hypothesis that insulin resistance can be beneficial in obese humans, insofar as it does not cause glucose dysmetabolism. METHODS: N = 5,241 participants aged ≥40 with normal fasting glucose were combined across the 1988-1994 and 1999-2004 National Health and Nutrition Examination Survey datasets. Mean follow-up period was 6.6 years. Insulin resistance was measured with homeostasis model assessment (HOMA-IR). Outcomes were all causes (n = 724), cardiovascular diseases (CVD, n = 316), and cancer mortality (n = 190). RESULTS: Supporting the hypothesis, obese persons with high HOMA-IR showed a decreased risk of total and CVD mortality compared to those with the lowest HOMA-IR. Adjusted hazard ratios were 1.0, 0.8, 0.4, and 0.4 (p(trend) = .02) for all death and 1.0, 0.6, 0.2, and 0.2 (p(trend) < .01) for CVD death. On the other hand, lean persons with high HOMA-IR showed about twice the total and CVD mortality compared to persons with the lowest HOMA-IR (p(trend) < .01, respectively). CONCLUSIONS: Insulin resistance in obese individuals may begin as an adaptive mechanism and can be beneficial if it is not associated with glucose dysmetabolism. In contrast, insulin resistance in lean individuals associated with higher risk of total and CVD mortality. Insulin resistance may be multifaceted and conventional approaches to regard insulin resistance itself as a pathological condition may be reconsidered in this light.
BACKGROUND:Insulin resistance is linked to many humanchronic diseases. Paradoxically, however, impaired insulin signaling contributes to longevity in various organisms and is suggested as an adaptive mechanism against external stressors, including obesity. We formulated a novel hypothesis that insulin resistance can be beneficial in obesehumans, insofar as it does not cause glucose dysmetabolism. METHODS: N = 5,241 participants aged ≥40 with normal fasting glucose were combined across the 1988-1994 and 1999-2004 National Health and Nutrition Examination Survey datasets. Mean follow-up period was 6.6 years. Insulin resistance was measured with homeostasis model assessment (HOMA-IR). Outcomes were all causes (n = 724), cardiovascular diseases (CVD, n = 316), and cancer mortality (n = 190). RESULTS: Supporting the hypothesis, obesepersons with high HOMA-IR showed a decreased risk of total and CVD mortality compared to those with the lowest HOMA-IR. Adjusted hazard ratios were 1.0, 0.8, 0.4, and 0.4 (p(trend) = .02) for all death and 1.0, 0.6, 0.2, and 0.2 (p(trend) < .01) for CVD death. On the other hand, lean persons with high HOMA-IR showed about twice the total and CVD mortality compared to persons with the lowest HOMA-IR (p(trend) < .01, respectively). CONCLUSIONS:Insulin resistance in obese individuals may begin as an adaptive mechanism and can be beneficial if it is not associated with glucose dysmetabolism. In contrast, insulin resistance in lean individuals associated with higher risk of total and CVD mortality. Insulin resistance may be multifaceted and conventional approaches to regard insulin resistance itself as a pathological condition may be reconsidered in this light.
Authors: Leocadio Rodríguez-Mañas; Javier Angulo; José A Carnicero; Mariam El Assar; Francisco J García-García; Alan J Sinclair Journal: Geroscience Date: 2021-06-01 Impact factor: 7.581