Decreased Mitochondrial Respiration in Peripheral Mononuclear Blood Cells in Chil-dren and Adolescents with Obesity and Type 2 Diabetes Mellitus

BackgroundThe prevalence of childhood obesity continues to rise worldwide. Obesity leads to major health risks already early in life, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The pathogenesis of these conditions includes mitochondrial alterations, however, data on mitochondrial health in pediatric populations are scarce to date. MethodsThe study evaluated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) from children and adolescents (6-18 years) with obesity with different stages of IR or T2DM, respectively. Participants were stratified according to pubertal stage and metabolic status. Mitochondrial health was determined by key parameters of mitochondrial respiration (ATP production, coupling efficiency, proton leak), and the Bioenergetic Health Index (BHI) served as an integrative marker of mitochondrial performance. ResultsA total of 162 participants were included. The Bioenergetic Health Index (BHI) was significantly lower in postpubertal T2DM adolescents compared to postpubertal IR participants, despite of equal pubertal stage and BMI (p=0,0126). The mitochondrial respiration rates and BHI between prepubertal and peripubertal children with obesity and IR showed no statistical differences. However, GlycoATP was correlated to higher insulin and HbA1c levels in children with obesity and IR. In line, the T2DM group demonstrated significantly reduced coupling efficiency (p = 0.003), reduced mitoATP and elevated glycoATP production, indicating impaired mitochondrial efficiency. ConclusionThese data suggest for the first time, that progression of IR towards manifest T2DM in children with obesity leads to impaired mitochondrial function. Thus, mitochondrial alterations in PBMCs may detect early metabolic impairment in young people with obesity and altered glucose metabolism. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/25336982v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@a70e3aorg.highwire.dtl.DTLVardef@1970646org.highwire.dtl.DTLVardef@1ce5a9org.highwire.dtl.DTLVardef@129bc5b_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- GlycoATP is correlated to higher insulin and HbA1c levels in children with obesity and - Insulin resistance (IR) - Adolescents with T2DM have significantly reduced coupling efficiency, reduced mito- - ATP and elevated glycoATP production, indicating impaired mitochondrial efficiency - Data suggest for the first time, that progression of IR towards manifest T2DM in children with obesity leads to impaired mitochondrial function - Mitochondrial alterations in PBMCs may detect early metabolic impairment in young - people with obesity and altered glucose metabolism.