title: Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance.
abstract: Insulin resistance (IR) increases cardiovascular morbidity and is associated with mitochondrial dysfunction. IR is now recognized to be present in type 1 diabetes; however, its relationship with mitochondrial function is unknown. We determined the relationship between IR and muscle mitochondrial function in type 1 diabetes using the hyperinsulinemic-euglycemic clamp and (31)P-MRS before, during, and after near-maximal isometric calf exercise. Volunteers included 21 nonobese adolescents with type 1 diabetes and 17 nondiabetic control subjects with similar age, sex, BMI, Tanner stage, and activity levels. We found that youths with type 1 diabetes were more insulin resistant (median glucose infusion rate 10.1 vs. 18.9 mg/kglean/min; P < 0.0001) and had a longer time constant of the curve of ADP conversion to ATP (23.4 ± 5.3 vs. 18.8 ± 3.9 s, P < 0.001) and a lower rate of oxidative phosphorylation (median 0.09 vs. 0.21 mmol/L/s, P < 0.001). The ADP time constant (β = -0.36, P = 0.026) and oxidative phosphorylation (β = 0.02, P < 0.038) were related to IR but not HbA1c. Normal-weight youths with type 1 diabetes demonstrated slowed postexercise ATP resynthesis and were more insulin resistant than control subjects. The correlation between skeletal muscle mitochondrial dysfunction in type 1 diabetes and IR suggests a relationship between mitochondrial dysfunction and IR in type 1 diabetes.
authors.affiliation: Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO melanie.green@childrenscolorado.org.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cree-Green
authors.affiliation: Department of Clinical and Diagnostic Sciences, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Newcomer
authors.affiliation: Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brown
authors.affiliation: Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Baumgartner
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO Division of Endocrinology and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Bryan
authors.initials: B
authors.lastname: Bergman
authors.affiliation: Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Brendan
authors.initials: B
authors.lastname: Drew
authors.affiliation: Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO Divisions of General Internal Medicine and Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Judith G
authors.initials: JG
authors.lastname: Regensteiner
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO Division of Endocrinology and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO Veterans Affairs Medical Center, Denver, CO.
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
authors.affiliation: Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nadeau
mesh_terms: D000293:Adolescent; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*