Melanie Cree-Green1, Abhinav Gupta2, Gregory V Coe2, Amy D Baumgartner2, Laura Pyle3, Jane E B Reusch4, Mark S Brown5, Bradley R Newcomer6, Kristen J Nadeau7. 1. Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045; Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045. Electronic address: Melanie.green@childrenscolorado.org. 2. Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045. 3. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, 80045. 4. Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045; Division of Endocrinology, Metabolism and Diabetes, University to Colorado Anschutz Medical Campus, Aurora, CO, 80045; Veterans Affairs Medical Center, Aurora, CO, 80012. 5. Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045. 6. Honors Program, James Madison University, Harrisonburg, VA, 22807. 7. Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045; Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045.
Abstract
AIMS: Insulin resistance (IR) correlates with mitochondrial dysfunction, free fatty acids (FFAs), and intramyocellular lipid (IMCL) in adults with type 2 diabetes (T2D). We hypothesized that muscle IR would relate to similar factors in T2D youth. METHODS: Participants included 17 youth with T2D, 23 normal weight controls (LCs), and 26 obese controls (OBs) of similar pubertal stage and activity level. RESULTS: T2D and OB groups were of similar BMI. T2D youth were significantly more IR and had higher calf IMCL and serum FFA concentrations during hyperinsulinemia. ADP time constant (ADPTC), a blood-flow dependent mitochondrial function measure, was slowed and oxidative phosphorylation rates lower in T2D. In multiple linear regression of the entire cohort, lack of FFA suppression and longer ADPTC, but not IMCL or HbA1c, were independently associated with IR. CONCLUSION: We found that elevated FFAs and mitochondrial dysfunction are early abnormalities in relatively well-controlled youth with T2D. Further, post-exercise oxidative metabolism appears affected by reduced blood flow, and is not solely an inherent mitochondrial defect. Thus, lowering FFAs and improving mitochondrial function and blood flow may be potential treatment targets in youth with T2D.
AIMS: Insulin resistance (IR) correlates with mitochondrial dysfunction, free fatty acids (FFAs), and intramyocellular lipid (IMCL) in adults with type 2 diabetes (T2D). We hypothesized that muscle IR would relate to similar factors in T2D youth. METHODS:Participants included 17 youth with T2D, 23 normal weight controls (LCs), and 26 obese controls (OBs) of similar pubertal stage and activity level. RESULTS: T2D and OB groups were of similar BMI. T2D youth were significantly more IR and had higher calfIMCL and serum FFA concentrations during hyperinsulinemia. ADP time constant (ADPTC), a blood-flow dependent mitochondrial function measure, was slowed and oxidative phosphorylation rates lower in T2D. In multiple linear regression of the entire cohort, lack of FFA suppression and longer ADPTC, but not IMCL or HbA1c, were independently associated with IR. CONCLUSION: We found that elevated FFAs and mitochondrial dysfunction are early abnormalities in relatively well-controlled youth with T2D. Further, post-exercise oxidative metabolism appears affected by reduced blood flow, and is not solely an inherent mitochondrial defect. Thus, lowering FFAs and improving mitochondrial function and blood flow may be potential treatment targets in youth with T2D.
Authors: Mandeep Bajaj; Swangjit Suraamornkul; Anthony Romanelli; Gary W Cline; Lawrence J Mandarino; Gerald I Shulman; Ralph A DeFronzo Journal: Diabetes Date: 2005-11 Impact factor: 9.461
Authors: Melanie Cree-Green; Bradley R Newcomer; Gregory Coe; Lindsey Newnes; Amy Baumgartner; Mark S Brown; Laura Pyle; Jane E Reusch; Kristen J Nadeau Journal: Am J Physiol Endocrinol Metab Date: 2015-02-24 Impact factor: 4.310
Authors: Melanie Cree-Green; Bradley R Newcomer; Mark Brown; Amber Hull; Amy D West; Debra Singel; Jane E B Reusch; Kim McFann; Judith G Regensteiner; Kristen J Nadeau Journal: Med Sci Sports Exerc Date: 2014-10 Impact factor: 5.411
Authors: Dana Dabelea; Ronny A Bell; Ralph B D'Agostino; Giuseppina Imperatore; Judith M Johansen; Barbara Linder; Lenna L Liu; Beth Loots; Santica Marcovina; Elizabeth J Mayer-Davis; David J Pettitt; Beth Waitzfelder Journal: JAMA Date: 2007-06-27 Impact factor: 56.272
Authors: James P DeLany; John J Dubé; Robert A Standley; Giovanna Distefano; Bret H Goodpaster; Maja Stefanovic-Racic; Paul M Coen; Frederico G S Toledo Journal: J Clin Endocrinol Metab Date: 2014-08-08 Impact factor: 5.958
Authors: Petter Bjornstad; David M Maahs; David Z Cherney; Melanie Cree-Green; Amy West; Laura Pyle; Kristen J Nadeau Journal: Diabetes Care Date: 2014-07-28 Impact factor: 19.112
Authors: Rebecca L Scalzo; Deirdre Rafferty; Irene Schauer; Amy G Huebschmann; Melanie Cree-Green; Jane E B Reusch; Judith G Regensteiner Journal: J Diabetes Complications Date: 2019-05-10 Impact factor: 2.852
Authors: Melanie Cree-Green; Ninghe Cai; Laura Pyle; Brandy Ringham; Mark S Brown; Bradley R Newcomer; Kristen J Nadeau; Dana Dabelea Journal: J Clin Endocrinol Metab Date: 2017-05-01 Impact factor: 5.958
Authors: Melissa L Erickson; Jacob M Allen; Daniel P Beavers; Linda M Collins; Karina W Davidson; Kirk I Erickson; Karyn A Esser; Matthijs K C Hesselink; Kerrie L Moreau; Eric B Laber; Charlotte A Peterson; Courtney M Peterson; Jane E Reusch; John P Thyfault; Shawn D Youngstedt; Juleen R Zierath; Bret H Goodpaster; Nathan K LeBrasseur; Thomas W Buford; Lauren M Sparks Journal: Geroscience Date: 2022-10-15 Impact factor: 7.581
Authors: Rebecca L Scalzo; Irene E Schauer; Deirdre Rafferty; Leslie A Knaub; Nina Kvaratskhelia; Taro Kaelix Johnson; Gregory B Pott; Layla A Abushamat; Mary O Whipple; Amy G Huebschmann; Melanie Cree-Green; Jane E B Reusch; Judith G Regensteiner Journal: J Physiol Date: 2021-03-05 Impact factor: 5.182