Luke W Johnston1, Stewart B Harris2, Ravi Retnakaran3,4, Adria Giacca5, Zhen Liu1, Richard P Bazinet1, Anthony J Hanley6,7,8. 1. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College Street, Toronto, ON, M5S 3E2, Canada. 2. Centre for Studies in Family Medicine, University of Western Ontario, London, ON, Canada. 3. Division of Endocrinology, University of Toronto, Toronto, ON, Canada. 4. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. 5. Department of Physiology, University of Toronto, Toronto, ON, Canada. 6. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College Street, Toronto, ON, M5S 3E2, Canada. anthony.hanley@utoronto.ca. 7. Division of Endocrinology, University of Toronto, Toronto, ON, Canada. anthony.hanley@utoronto.ca. 8. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. anthony.hanley@utoronto.ca.
Abstract
AIMS/HYPOTHESIS: Our aim was to determine the longitudinal associations of individual NEFA with the pathogenesis of diabetes, specifically with differences in insulin sensitivity and beta cell function over 6 years in a cohort of individuals who are at risk for diabetes. METHODS: In the Prospective Metabolism and Islet Cell Evaluation (PROMISE) longitudinal cohort, 477 participants had serum NEFA measured at the baseline visit and completed an OGTT at three time points over 6 years. Outcome variables were calculated using the OGTT values. At each visit, insulin sensitivity was assessed using the HOMA2 of insulin sensitivity (HOMA2-%S) and the Matsuda index, while beta cell function was assessed using the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion-sensitivity index-2 (ISSI-2). Generalised estimating equations were used, adjusting for time, waist, sex, ethnicity, baseline age, alanine aminotransferase (ALT) and physical activity. NEFA were analysed as both concentrations (nmol/ml) and proportions (mol%) of the total fraction. RESULTS: Participants' (73% female, 70% with European ancestry) insulin sensitivity and beta cell function declined by 14-21% over 6 years of follow-up. In unadjusted models, several NEFA (e.g. 18:1 n-7, 22:4 n-6) were associated with lower insulin sensitivity, however, nearly all of these associations were attenuated in fully adjusted models. In adjusted models, total NEFA, 16:0, 18:1 n-9 and 18:2 n-6 (as concentrations) were associated with 3.7-8.0% lower IGI/IR and ISSI-2, while only 20:5 n-3 (as mol%) was associated with 7.7% higher HOMA2-%S. CONCLUSIONS/ INTERPRETATION: Total NEFA concentration was a strong predictor of lower beta cell function over 6 years. Our results suggest that the association with beta cell function is due to the absolute size of the serum NEFA fraction, rather than the specific fatty acid composition.
AIMS/HYPOTHESIS: Our aim was to determine the longitudinal associations of individual NEFA with the pathogenesis of diabetes, specifically with differences in insulin sensitivity and beta cell function over 6 years in a cohort of individuals who are at risk for diabetes. METHODS: In the Prospective Metabolism and Islet Cell Evaluation (PROMISE) longitudinal cohort, 477 participants had serum NEFA measured at the baseline visit and completed an OGTT at three time points over 6 years. Outcome variables were calculated using the OGTT values. At each visit, insulin sensitivity was assessed using the HOMA2 of insulin sensitivity (HOMA2-%S) and the Matsuda index, while beta cell function was assessed using the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion-sensitivity index-2 (ISSI-2). Generalised estimating equations were used, adjusting for time, waist, sex, ethnicity, baseline age, alanine aminotransferase (ALT) and physical activity. NEFA were analysed as both concentrations (nmol/ml) and proportions (mol%) of the total fraction. RESULTS:Participants' (73% female, 70% with European ancestry) insulin sensitivity and beta cell function declined by 14-21% over 6 years of follow-up. In unadjusted models, several NEFA (e.g. 18:1 n-7, 22:4 n-6) were associated with lower insulin sensitivity, however, nearly all of these associations were attenuated in fully adjusted models. In adjusted models, total NEFA, 16:0, 18:1 n-9 and 18:2 n-6 (as concentrations) were associated with 3.7-8.0% lower IGI/IR and ISSI-2, while only 20:5 n-3 (as mol%) was associated with 7.7% higher HOMA2-%S. CONCLUSIONS/ INTERPRETATION: Total NEFA concentration was a strong predictor of lower beta cell function over 6 years. Our results suggest that the association with beta cell function is due to the absolute size of the serum NEFA fraction, rather than the specific fatty acid composition.
Authors: James S Pankow; Bruce B Duncan; Maria Inês Schmidt; Christie M Ballantyne; David J Couper; Ron C Hoogeveen; Sherita H Golden Journal: Diabetes Care Date: 2004-01 Impact factor: 19.112
Authors: Jan P Vandenbroucke; Erik von Elm; Douglas G Altman; Peter C Gøtzsche; Cynthia D Mulrow; Stuart J Pocock; Charles Poole; James J Schlesselman; Matthias Egger Journal: PLoS Med Date: 2007-10-16 Impact factor: 11.069
Authors: Rachel E Walker; Jennifer L Ford; Raymond C Boston; Olga V Savinova; William S Harris; Michael H Green; Gregory C Shearer Journal: Am J Physiol Endocrinol Metab Date: 2020-01-07 Impact factor: 4.310
Authors: Luke W Johnston; Zhen Liu; Ravi Retnakaran; Bernard Zinman; Adria Giacca; Stewart B Harris; Richard P Bazinet; Anthony J Hanley Journal: J Lipid Res Date: 2018-07-09 Impact factor: 5.922
Authors: Domenico Tricò; Alessandro Mengozzi; Lorenzo Nesti; Mensud Hatunic; Rafael Gabriel Sanchez; Thomas Konrad; Katarina Lalić; Nebojša M Lalić; Andrea Mari; Andrea Natali Journal: Diabetologia Date: 2019-11-01 Impact factor: 10.122