Insulin resistance in type 2 diabetes youth relates to serum free fatty acids and muscle mitochondrial dysfunction

• Published in: Journal of diabetes and its complications Vol. 31; no. 1; pp. 141 - 148
• Main Authors: Cree-Green, Melanie, Gupta, Abhinav, Coe, Gregory V, Baumgartner, Amy D, Pyle, Laura, Reusch, Jane E.B, Brown, Mark S, Newcomer, Bradley R, Nadeau, Kristen J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017; Elsevier Limited
• Subjects: Adolescent; Adolescents; Adults; Body mass index; Children & youth; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Endocrinology & Metabolism; Exercise; Exercise - physiology; Fatty Acids, Nonesterified - blood; Female; Free fatty acids; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin resistance; Insulin Resistance - physiology; Lipid Metabolism - physiology; Lipids; Magnetic Resonance Spectroscopy; Male; Metabolism; Metabolites; Mitochondria, Muscle - metabolism; Mitochondria, Muscle - physiology; Mitochondrial function; Morbidity; Mortality; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Obesity - complications; Obesity - metabolism; Obesity - physiopathology; Oxygen Consumption - physiology; Pediatrics; Phosphorylation; Physical fitness; Regional Blood Flow - physiology; Type 2 diabetes; Variance analysis; Adolescents; Free Fatty Acids; Type 2 Diabetes; Insulin Resistance; Mitochondrial Function; Type 2 diabetes; Insulin resistance; Mitochondrial function; Free fatty acids
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2016.10.014

Abstract Aims Insulin resistance (IR) correlates with mitochondrial dysfunction, free fatty acids (FFA), 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 (LC), and 26 obese controls (OB) 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 FFA's 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 FFA and improving mitochondrial function and blood flow may be potential treatment targets in youth with T2D.