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Property "Has-20abstract" (as page type) with input value "Insulin-20resistance,-20a-20key-20feature-20of-20type-202-20diabetes-20(T2D),-20has-20been-20associated-20with-20inherited-20and-20acquired-20abnormalities-20of-20skeletal-20muscle-20mitochondrial-20function.-20Increased-20availability-20of-20free-20fatty-20acids-20(FFA)-20is-20involved-20in-20insulin-20resistance,-20impairment-20of-20mitochondrial-20function-20and-20non-2Dalcoholic-20fatty-20liver-20disease-20(NAFLD).-20However,-20it-20remains-20unclear,-20which-20factors-20influence-20the-20associations-20of-20insulin-20sensitivity-20with-20mitochondrial-20function-20in-20patients-20with-20recent-2Donset,-20well-2Dcontrolled-20T2D-20and-20whether-20specific-20lipid-20metabolites-20contribute-20to-20insulin-20resistance-20and-20abnormal-20mitochondrial-20function-20and-20thereby-20promote-20NAFLD.-0A-0AThese-20questions-20were-20addressed-20by-20one-20study-20in-20136-20patients-20with-20metabolically-20well-2Dcontrolled,-20recent-2Donset-20T2D,-20enrolled-20in-20the-20German-20Diabetes-20Study-20(GDS),-20and-20another-20study-20in-2021-20participants-20(7-20lean-20controls-20and-2014-20obese-20with-20or-20without-20NAFLD)-20of-20the-20Bariatrix-20study.-20All-20volunteers-20underwent-20thorough-20metabolic-20phenotyping-20using-20gold-20standard-20methodology,-20including-20hyperinsulinemic-2Deuglycemic-20clamps-20for-20measuring-20insulin-20sensitivity-20(M-2Dvalue).-20GDS-20participants-20also-20underwent-20indirect-20calorimetry-20and-20spiroergometry-20to-20assess-20metabolic-20flexibility-20(ΔRQ)-20and-20maximal-20oxygen-20uptake-20(VO-3Csub-3E2-3C-2Fsub-3Emax),-20respectively,-20as-20measures-20of-20whole-20body-20energy-20metabolism.-20In-20the-20Bariatrix-20study,-20direct-20measurement-20of-20hepatic-20oxidative-20capacity-20and-20inflammation-20was-20combined-20with-20targeted-20lipidomics-20to-20quantify-20sphingolipid-20concentrations-20in-20various-20tissues.-0A-0AThe-20first-20study-20revealed-20that-20in-20recent-2Donset-20T2D,-20ΔRQ-20and-20VO-3Csub-3E2-3C-2Fsub-3Emax-20independently-20associate-20with-20the-20M-2Dvalue,-20even-20upon-20various-20adjustments-20and-20that-20only-20fasting-20FFA-20could-20abolish-20these-20relationships.-20ΔRQ-20associated-20positively-20with-20FFA,-20whereas-20VO-3Csub-3E2-3C-2Fsub-3Emax-20was-20lower-20in-20the-20carriers-20of-20a-20polymorphism-20in-20the-20fat-20and-20obesity-2Drelated-20(FTO)-20gene-20and-20related-20negatively-20with-20C-2Dreactive-20protein.-20The-20second-20study-20found-20that-20NAFLD-20patients-20feature-20higher-20total-20hepatic-20ceramide-20levels.-20Specific-20serum-20ceramide-20species-20correlated-20with-20peripheral-20insulin-20resistance.-20Particularly,-20hepatic-20ceramide-2016:0-20and-20lactosylceramides-20also-20correlated-20with-20increased-20oxidative-20stress-20and-20inflammation-20in-20the-20liver.-0A-0AIn-20conclusion,-20circulating-20FFA-20play-20a-20central-20role-20even-20in-20the-20early-20course-20of-20T2D,-20affecting-20muscle-20mitochondrial-20function-20and-20peripheral-20insulin-20sensitivity.-20In-20particular,-20increased-20serum-20and-20hepatic-20sphingolipid-20species-20seem-20to-20be-20important-20for-20the-20development-20of-20insulin-20resistance-20and-20hepatic-20inflammation-20and-20the-20progression-20of-20NAFLD." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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