Melanie Cree-Green1, Ninghe Cai1, Laura Pyle2,3, Brandy Ringham4, Mark S Brown5, Bradley R Newcomer6, Kristen J Nadeau1, Dana Dabelea2,4. 1. Pediatric Endocrinology, University of Colorado Anschutz and Children's Hospital Colorado, Aurora, Colorado 80045. 2. Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado 80045. 3. Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado 80045. 4. Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado 80045. 5. Radiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado 80045. 6. Department of Physics, James Madison University, Harrisonburg, Virginia 22807.
Abstract
Context: Obesity, insulin resistance (IR), and diabetes are increasing in youth, especially in girls. IR is associated with muscle mitochondrial dysfunction in youth and adults with diabetes. However, it is unknown whether this relationship is present in youth prior to development of diabetes. Objective: Assess IR and mitochondrial function, including sex differences, in nondiabetic youth. Design: Cross-sectional study of youth in the Exploring Perinatal Outcomes among Children, Resistance to InSulin in Type 1 And Type 2 diabetes, and Androgens and Insulin Resistance Study cohorts. Setting: Academic medical university. Participants: Two hundred seventy-five youth, 13 to 19 years old [43% males: 17.1 (16.52, 17.63) years, body mass index z-score (BMI-Z) 0.36, 64.7% Tanner 5; 57% females: 17.2 (16.43, 17.67) years, BMI-Z 0.72, 78.9% Tanner 5]. Interventions: Fasting laboratories, oral glucose tolerance test, and 31P magnetic resonance spectroscopy. Main Outcome Measures: IR [triglyceride:high-density lipoprotein (HDL) ratio, Matsuda index, and homeostasis model for insulin resistance (HOMA-IR)] and muscle mitochondrial function (adenosine 5'-diphosphate time constant and oxidative phosphorylation rate). Results: Compared with males, females were more insulin resistant, with higher triglyceride:HDL ratio [1.95 (1.30, 2.79) vs 1.69 (1.21, 2.23), P = 0.042], HOMA-IR [3.18 (2.42, 4.39) vs 2.76 (2.02, 4.08), P = 0.035], and fasting free fatty acids (FFAs) and lower Matsuda score [3.98 (2.71, 5.96) vs 5.39 (3.43, 7.57), P < 0.001]. After adjustment for the higher BMI and Tanner stage and lower physical activity levels seen in females, there were no sex differences in mitochondrial function nor in any IR measure except FFAs. We did not find an association between measures of IR and mitochondrial function. Conclusions: The greater IR seen in adolescent girls vs boys is mostly explained by differences in BMI and physical activity. Mitochondrial function does not appear to be related to IR in a large cohort of nondiabetic youth.
Context: Obesity, insulin resistance (IR), and diabetes are increasing in youth, especially in girls. IR is associated with muscle mitochondrial dysfunction in youth and adults with diabetes. However, it is unknown whether this relationship is present in youth prior to development of diabetes. Objective: Assess IR and mitochondrial function, including sex differences, in nondiabetic youth. Design: Cross-sectional study of youth in the Exploring Perinatal Outcomes among Children, Resistance to InSulin in Type 1 And Type 2 diabetes, and Androgens and Insulin Resistance Study cohorts. Setting: Academic medical university. Participants: Two hundred seventy-five youth, 13 to 19 years old [43% males: 17.1 (16.52, 17.63) years, body mass index z-score (BMI-Z) 0.36, 64.7% Tanner 5; 57% females: 17.2 (16.43, 17.67) years, BMI-Z 0.72, 78.9% Tanner 5]. Interventions: Fasting laboratories, oral glucose tolerance test, and 31P magnetic resonance spectroscopy. Main Outcome Measures: IR [triglyceride:high-density lipoprotein (HDL) ratio, Matsuda index, and homeostasis model for insulin resistance (HOMA-IR)] and muscle mitochondrial function (adenosine 5'-diphosphate time constant and oxidative phosphorylation rate). Results: Compared with males, females were more insulin resistant, with higher triglyceride:HDL ratio [1.95 (1.30, 2.79) vs 1.69 (1.21, 2.23), P = 0.042], HOMA-IR [3.18 (2.42, 4.39) vs 2.76 (2.02, 4.08), P = 0.035], and fasting free fatty acids (FFAs) and lower Matsuda score [3.98 (2.71, 5.96) vs 5.39 (3.43, 7.57), P < 0.001]. After adjustment for the higher BMI and Tanner stage and lower physical activity levels seen in females, there were no sex differences in mitochondrial function nor in any IR measure except FFAs. We did not find an association between measures of IR and mitochondrial function. Conclusions: The greater IR seen in adolescent girls vs boys is mostly explained by differences in BMI and physical activity. Mitochondrial function does not appear to be related to IR in a large cohort of nondiabetic youth.
Authors: Brian A Irving; Ian R Lanza; Gregory C Henderson; Rajesh R Rao; Bruce M Spiegelman; K Sreekumaran Nair Journal: J Clin Endocrinol Metab Date: 2015-01-19 Impact factor: 5.958
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: Petter Bjornstad; Uyen Truong; Laura Pyle; Jennifer L Dorosz; Melanie Cree-Green; Amy Baumgartner; Gregory Coe; Judith G Regensteiner; Jane E B Reusch; Kristen J Nadeau Journal: J Diabetes Complications Date: 2016-04-13 Impact factor: 2.852
Authors: Stephanie Cung; Laura Pyle; Kristin Nadeau; Dana Dabelea; Melanie Cree-Green; Shanlee M Davis Journal: J Investig Med Date: 2021-09-07 Impact factor: 2.895
Authors: Kalie L Tommerdahl; Karl Baumgartner; Michal Schäfer; Petter Bjornstad; Isabella Melena; Shannon Hegemann; Amy D Baumgartner; Laura Pyle; Melanie Cree-Green; Uyen Truong; Lorna Browne; Judith G Regensteiner; Jane E B Reusch; Kristen J Nadeau Journal: Diabetes Care Date: 2021-01-05 Impact factor: 19.112
Authors: Melanie Cree-Green; Haseeb Rahat; Bradley R Newcomer; Bryan C Bergman; Mark S Brown; Gregory V Coe; Lindsey Newnes; Yesenia Garcia-Reyes; Samantha Bacon; Jessica E Thurston; Laura Pyle; Ann Scherzinger; Kristen J Nadeau Journal: J Endocr Soc Date: 2017-06-01