Body composition and effect of insulin treatment during pregnancy in Socs2(-/-) mice with gestational diabetes and macrosomia

Abstract

Background and aims: The Suppressor of Cytokine Signaling 2 (SOCS2) protein modulates cytokine response, growth, inflammatory processes, and cytokine-mediated metabolism of lipids and carbohydrates. Thus, its ablation in mice (Socs2-/-) generates gigantism and insulin- resistance aswell as gestational diabetes (GDM) andmacrosomia with high mortality rates (>88%). Our aim is to evaluate the body composition variations in pregnant Socs2-/- as a potential early diagnostic tool for macrosomia. Additionally, we assess the potential use of insulin to prevent foetal macrosomia. Materials and methods: BodyWeight (BW) and composition (lean, fat and fluid) were evaluated in 7 Socs2-/- and 4 C57BI/6J pregnant females (age: 196.3±28 days,) using an NMR-TD spectrometer (Minispec+ LF90II). Basal glucose was measured at days 7 and 14 of pregnancy (first and second gestational thirds) using a glucometer (Glucomen Areo Menarini). Besides, Socs2-/- mothers and offspring were retrospectively analyzed and compared for the presence of macrosomia, based on whether the mother was insulin-treated (0.5U/kg, Glargine) or not during pregnancy (3 females with 22 neonates vs 21 females with 137 neonates, respectively). Macrosomia in this strain was previously defined as >1.43 g birth weight. Mann-Whitneys’s U, Student’s test and Chi2 test were used for comparisons. Results: Basal blood glucose did not differ between groups for the whole evaluation (Socs2-/-: 151±2.19 mg/dL; control: 144±13.63 mg/dL) (p=0.46). BW of Socs2-/- tended to be greater at day 7 compared to controls (29.5±2.2 vs 25.7±2.1g, respectively; p=0.063) and was significantly higher at day 14 of pregnancy (36±3.2 vs 28.2±2.3g, respectively; p=0.006). Fat percentage was higher in controls (7d: 26.2±3.1%; 14d: 21.3±2.8%) than in Socs2-/- (7d: 10.6±2.1%; 14d: 11±2.9%) (p=0.016; p=0.012). Fluid content was reduced in Socs2-/- compared to controls at 7d (6.06±1.16 vs 9.3±0.7%, p=0.016), but not at 14d (10.3±1.0 vs 11.7 ±1.5%; p=0.16). Finally, differences were no significantly (p>0.05) in lean percentage on days 7 and 14 between control (7d: 79.9±2.9%; 14d: 80.5±3.0%) and Socs2-/- (7d: 63.3±16.3%; 14d: 71.9±6.9%). Neonates from untreated mothers were heavier than offspring of mice receiving insulin (1.5±0.2g vs 0.8±0.4g, respectively; p<0.001) and the prevalence of macrosomia was higher, too (65.9 ±24.01% vs 20 ±34.6%, respectively; p=0.007). Conclusion: Although it is necessary to extend the analysis of body composition to more animals and later pregnancy periods to assesses if these variables indeed predictmacrosomia, actual results showweight, fat and fluid as parameters with potential noninvasive pre-diagnostic interest for macrosomia. Insulinization of pregnant Socs2-/- resulted in almost 50% decreased occurrence of macrosomia, reinforcing a novel in vivo model for GDM. New specific insulin evaluations will be conducted to define its potential to ameliorate the severity of macrosomia. Further studies should be performed to fully elucidate the potential role of SOCS2 in the development of GDM.