Abstract
BackgroundGestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.MethodsThis is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined.ResultsIn the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p < 0.0001) and all IGFBP-1 phosphoisoforms (p < 0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain.ConclusionsMetformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.Trial registrationThe trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov (NCT01240785) November 3, 2010. Retrospectively registered.
Highlights
Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation
Metformin and insulin groups were similar in terms of oral glucose tolerance test (OGTT) values, glycated hemoglobin (HbA1c) at both time points, C-peptide, age, pre-pregnancy Body mass index (BMI) and gestational weight gain (GWG)
There were no differences between the metformin and insulin groups regarding pregnancy outcomes, except for higher labor induction rates in the insulin group compared to the metformin group (54.2% vs. 37.6%, p = 0.014)
Summary
Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. Gestational diabetes mellitus (GDM) is a growing health concern. It is associated with obesity and low-grade inflammation and increases the risk for pregnancy complications, such as macrosomia, preeclampsia, neonatal hypoglycemia and hyperbilirubinemia and the need for neonatal intensive care [1, 2]. Metformin treatment of GDM reduces gestational weight gain (GWG), gestational hypertension, the incidence of neonatal hypoglycemia and the need for neonatal intensive care compared to insulin treatment [5]. The benefits of metformin treatment during the pregnancy have been well characterized, there are concerns regarding the long term effects specially on the offspring [6]. We do not know whether metformin has beneficial effects on low-grade inflammation compared to insulin
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