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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adolescent, Diabetes Mellitus, Type 2, Exercise, Fatty Acids, Nonesterified, Female, Glucose Clamp Technique, Humans, Insulin Resistance, Lipid Metabolism, Magnetic Resonance Spectroscopy, Male, Mitochondria, Muscle, Muscle, Skeletal, Obesity, Oxygen Consumption, Regional Blood Flow.
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Does insulin resistance in type 2 diabetes youth relate to serum free fatty acids and muscle mitochondrial dysfunction? Context: 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. Participants included 17 youth with T2D, 23 normal weight controls (LCs), and 26 obese controls (OBs) of similar pubertal stage and activity level. 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.
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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. Final Decision: yes