Interventions Pre-conception and During Pregnancy to Improve Glucose Tolerance and Prevent Gestational Diabetes: Investigation in Mouse Models

Abstract

Background: Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycaemia during gestation. This hyperglycaemia usually manifests itself through impaired glucose tolerance due to insulin resistance. Gestational diabetes affects approximately 10% of New Zealand pregnancies, and the number of women diagnosed is set to further increase with the obesity epidemic. For this reason, an easily adhered to, effective intervention that could be taken both before and during pregnancy, could be beneficial. Aim: This thesis aimed to investigate a combination of insulin sensitising agents, vitamins and a probiotic in the prevention of GDM in mice. The potential for a treatment that targets inflammation in cases of GDM was also investigated, using interleukin-1-receptor-1 knock-out mice (IL1R1-/-). Method: The work detailed in this thesis covers four studies: (1) The impact of supplementation of myo-inositol (MI) and vitamins B2, B6, B12 and D were investigated in a genetic mouse model of GDM (pregnant db/+ dams). (2) Upon discovering that the db/+ mice in the aforementioned study did not demonstrate GDM as expected, the cause of the loss of phenotype was investigated. (3) The effects of supplementation with MI and probiotics was examined in a high fat diet (HFD)-induced GDM mouse model. (4) The impact of IL1R1-/- was explored in a HFD-induced GDM mouse model. Results: In contrast to previous studies, db/+ mice did not display glucose intolerance compared with control mice during pregnancy. However, C57BL/6J fed HFD for one week prior to and throughout pregnancy were an effective model of GDM. MI generally improved glucose intolerance and insulin resistance. Vitamins B2, B6, B12, and D reduced markers of adipose tissue inflammation. Probiotic supplementation reduced gestational weight gain and ectopic fat deposition in the liver. IL1R1-/- did not improve maternal glucose tolerance and surprisingly worsened some indicators of GDM. Conclusion: These studies provide novel contributions to the field of GDM prevention and treatment, especially with respect to the effects of vitamin B2, the mechanisms underlying MI and probiotic supplementation, and the counterintuitive impact of modified inflammatory signalling.