Natalie L Weir1, Sarah O Nomura1, Brian T Steffen1, Weihua Guan2, Amy B Karger1, Ronald Klein3, Barbara E K Klein3, Mary Frances Cotch4, Michael Y Tsai5. 1. University of Minnesota, Department of Laboratory Medicine & Pathology, Minneapolis, MN 55455, USA. 2. University of Minnesota, School of Public Health, Division of Biostatistics, Minneapolis, MN 55455, USA. 3. University of Wisconsin-Madison, Department of Ophthalmology & Visual Sciences, Madison, WI 53726, USA. 4. National Eye Institute (NEI), Division of Epidemiology and Clinical Applications, Bethesda, MD 20892, USA. 5. University of Minnesota, Department of Laboratory Medicine & Pathology, Minneapolis, MN 55455, USA. Electronic address: tsaix001@umn.edu.
Abstract
BACKGROUND & AIMS: Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin - fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. RESULTS: In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin -0.272 per SD, p < 0.001; HOMA-IR: -0.125 per SD, p = 0.03) and D5D activity (insulin: -0.530 per SD, p < 0.001; HOMA-IR: -0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). CONCLUSIONS: Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings.
BACKGROUND & AIMS: Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin - fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. RESULTS: In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin -0.272 per SD, p < 0.001; HOMA-IR: -0.125 per SD, p = 0.03) and D5D activity (insulin: -0.530 per SD, p < 0.001; HOMA-IR: -0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). CONCLUSIONS: Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings.
Authors: Annette M Chang; Marla J Smith; Cathie J Bloem; Andrzej T Galecki; Jeffrey B Halter; Mark A Supiano Journal: J Clin Endocrinol Metab Date: 2005-11-29 Impact factor: 5.958
Authors: Weihua Guan; Brian T Steffen; Rozenn N Lemaitre; Jason H Y Wu; Toshiko Tanaka; Ani Manichaikul; Millennia Foy; Luigi Ferrucci; Myriam Fornage; Dariush Mozafarrian; Michael Y Tsai; Lyn M Steffen; Stephen S Rich; Lu Wang; Jennifer A Nettleton; Weihong Tang; Xiangjun Gu; Stafania Bandinelli; Irena B King; Barbara McKnight; Bruce M Psaty; David Siscovick; Luc Djousse; Yii-Der Ida Chen Journal: Circ Cardiovasc Genet Date: 2014-05-13
Authors: Jason H Y Wu; Matti Marklund; Fumiaki Imamura; Nathan Tintle; Andres V Ardisson Korat; Janette de Goede; Xia Zhou; Wei-Sin Yang; Marcia C de Oliveira Otto; Janine Kröger; Waqas Qureshi; Jyrki K Virtanen; Julie K Bassett; Alexis C Frazier-Wood; Maria Lankinen; Rachel A Murphy; Kalina Rajaobelina; Liana C Del Gobbo; Nita G Forouhi; Robert Luben; Kay-Tee Khaw; Nick Wareham; Anya Kalsbeek; Jenna Veenstra; Juhua Luo; Frank B Hu; Hung-Ju Lin; David S Siscovick; Heiner Boeing; Tzu-An Chen; Brian Steffen; Lyn M Steffen; Allison Hodge; Gudny Eriksdottir; Albert V Smith; Vilmunder Gudnason; Tamara B Harris; Ingeborg A Brouwer; Claudine Berr; Catherine Helmer; Cecilia Samieri; Markku Laakso; Michael Y Tsai; Graham G Giles; Tarja Nurmi; Lynne Wagenknecht; Matthias B Schulze; Rozenn N Lemaitre; Kuo-Liong Chien; Sabita S Soedamah-Muthu; Johanna M Geleijnse; Qi Sun; William S Harris; Lars Lind; Johan Ärnlöv; Ulf Riserus; Renata Micha; Dariush Mozaffarian Journal: Lancet Diabetes Endocrinol Date: 2017-10-12 Impact factor: 32.069
Authors: Jonathan P Arm; Joshua A Boyce; Lin Wang; Heng Chhay; Muhammad Zahid; Vaishali Patil; Usha Govindarajulu; Priscilla Ivester; Kelly L Weaver; Susan Sergeant; Elliot Israel; Floyd H Chilton Journal: Lipids Health Dis Date: 2013-10-02 Impact factor: 3.876
Authors: Neil K Huang; Petra Bůžková; Nirupa R Matthan; Luc Djoussé; Calvin H Hirsch; Jorge R Kizer; W T Longstreth; Kenneth J Mukamal; Alice H Lichtenstein Journal: J Am Heart Assoc Date: 2021-03-08 Impact factor: 5.501
Authors: Carlos Jiménez-Cortegana; Pedro Iglesias; Josep Ribalta; Teresa Vilariño-García; Laura Montañez; Francisco Arrieta; Manuel Aguilar; Santiago Durán; Juan C Obaya; Antonio Becerra; Juan Pedro-Botet; Víctor Sánchez-Margalet Journal: Nutrients Date: 2021-11-19 Impact factor: 5.717
Authors: Tagreed A Mazi; Kamil Borkowski; Oliver Fiehn; Christopher L Bowlus; Souvik Sarkar; Karen Matsukuma; Mohamed R Ali; Dorothy A Kieffer; Yu-Jui Y Wan; Kimber L Stanhope; Peter J Havel; John W Newman; Valentina Medici Journal: Metabolites Date: 2022-02-19