#23 Diabetes in Pregnancy Exposure, Mitochondrial Markers, and Diastolic Function in Adolescents with Type 2 Diabetes
Laetitia Guillemette, University of Manitoba; Allison Dart, Children’s Hospital Research Institute of Manitoba; Brandy Wicklow, Children’s Hospital Research Institute of Manitoba; Vernon W Dolinsky, Children’s Hospital Research Institute of Manitoba; Davinder Jassal, St. Boniface Hospital Research Centre; Elizabeth Sellers, Children’s Hospital Research Institute of Manitoba; Todd A Duhamel, St. Boniface Hospital Research Centre; Jonathan M McGavock, Children’s Hospital Research Institute of Manitoba
Mitochondrial dysfunction is intimately linked to type 2 diabetes (T2D) and cardiovascular disease (CVD). We hypothesized that exposure to diabetes in pregnancy (DiP) would adversely affect mitochondrial function and CVD risk in youth with T2D.
We analysed serum metabolomic markers of mitochondrial function/oxidative stress (ultra-performance liquid chromatography-tandem mass spectroscopy) as well as cardiac diastolic function (echocardiography-measured left ventricular early-to-late [E/A] blood flow velocity) in youth with T2D. DiP exposure was classified as T2D (n=34), gestational diabetes (n=16), and normoglycemia (NG; n=38). Significance was set at q (p-value adjusted for false discovery rate)<0.05.
Groups were similar for sex (62 vs 43 vs 71% female), age (14.8±2.7 vs 15.4±2.8 vs 15.4±2.6 years), duration of diabetes (3.0, [interquartile range]: [2.0-5.0] vs 2.0 [1.0-3.5] vs 3.0 [2.0-5.0]years), fat percentage (30±10 vs 31±10 vs 33±13%) and systolic blood pressure load (45 [22-74] vs 42 [24-53] vs 33 [19-61]%). DiP exposure was not associated with metabolomic markers of mitochondrial function but worsened oxidative stress (hydroxyoctadecadienoic acids [13-/9-HODE]; T2D/NG ratio=2.20, q=0.02; methionine sulfoxide T2D/NG ratio=2.06, q=0.01). Mitochondrial metabolomic markers were not associated with diastolic function (leucine: r= −0.23, q=0.08; isoleucine: r= −0.25, q=0.06; valine: r= −0.22, q=0.09; carnitine: r=0.19, q=0.13). Oxidative stress was inversely associated with diastolic function (13-/9-HODE: r= −0.23, q=0.08; methionine sulfoxide: r= −0.23, q=0.08).
Oxidative stress, but not mitochondrial dysfunction, is associated with DiP exposure and impaired diastolic function in adolescents with T2D.