Metformin and insulin treatment of gestational diabetes: effects on inflammatory markers and IGF-binding protein-1 – secondary analysis of a randomized controlled trial

Abstract Background Gestational 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. Methods This 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. Results In 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. Conclusions Metformin 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 registration The trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov ( NCT01240785 ) November 3, 2010. Retrospectively registered

Metformin and insulin treatment of gestational diabetes : effects on inflammatory markers and IGF-binding protein-1-secondary analysis of a randomized controlled trial

Background: Gestational 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. Methods: This 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. Results: In 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. Conclusions: Metformin 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.Peer reviewe

Serum lipids and their association with birth weight in metformin and insulin treated patients with gestational diabetes

AimsTo compare the effects of metformin and insulin treatment on maternal serum lipids in patients with gestational diabetes (GDM), and to analyse the associations between individual lipids and birth weight (BW).MethodsThis is a secondary analysis of a randomized trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum lipidome was measured at baseline (the time of diagnosis, mean 30 gestational weeks, gw) and at 36 gw using nuclear magnetic resonance spectroscopy.ResultsTotal and VLDL triglycerides, and VLDL cholesterol increased from baseline to 36 gw in both treatment groups. The rise in triglycerides was greater in the metformin treated patients (p ConclusionCompared to insulin, metformin treatment of GDM led to higher maternal serum concentrations of triglyceride-rich lipoproteins. Especially triglycerides and cholesterol in VLDL were positively associated with BW. Women with high VLDL cholesterol or high apoB/apoA-1 may benefit from insulin treatment over metformin with respect to offspring BW.</p

Amino acid profile in women with gestational diabetes mellitus treated with metformin or insulin

Aims: We compared the effects of metformin and insulin treatments of gestational diabetes mellitus (GDM) on amino acid metabolism.Methods: 217 pregnant women diagnosed with GDM were randomized to receive either metformin or insulin. 1H nuclear magnetic spectroscopy was used to determine serum concentrations of alanine, glutamine, glycine, isoleucine, leucine, valine, histidine, phenylalanine, tyrosine, glucose and lactate at the time of diagnosis and at 36 gestational weeks (gw).Results: Majority of the amino acid concentrations increased from 30 to 36 gw. The rise in alanine (16% vs. 8%, p Conclusions: Compared to insulin metformin caused a greater increase in serum alanine, isoleucine and lactate concentrations. Although the observed differences in the metabolic variables were relatively small and not outright concerning, additional studies and follow-up data are required to ensure the safety of metformin use in pregnancy.</p

Cord serum metabolome and birth weight in patients with gestational diabetes treated with metformin, insulin, or diet alone

AbstractIntroductionRecent research has demonstrated the benefits of metformin treatment in gestational diabetes (GDM) on short-term pregnancy outcomes (including excessive fetal growth and pre-eclampsia), but its effects on fetal metabolism remain mostly unknown. Our aim was to study the effects of metformin treatment compared with insulin or diet on the cord serum metabolome and also to assess how these metabolites are related to birth weight (BW) in pregnancies complicated by GDM.Research design and methodsCord serum samples were available from 113, 97, and 98 patients with GDM treated with diet, insulin, and metformin, respectively. A targeted metabolome was measured using nuclear magnetic resonance spectroscopy. The patients in the metformin and insulin groups had participated in a previous randomized trial (NCT01240785).ResultsCord serum alanine was elevated in the metformin group (0.53 mmol/L) compared with the insulin (0.45 mmol/L, pConclusionsMetformin treatment in GDM leads to an increase in cord serum alanine. The possible long-term implications of elevated neonatal alanine in this context need to be evaluated in future studies. Although previous studies have shown that metformin increased maternal TG levels, the cord serum TG levels were not affected. Cord serum HDL cholesterol and several FA variables are related to the regulation of fetal growth in GDM. Moreover, these associations seem to be independent of maternal confounding factors.Trial registration number NCT01240785.</p

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland

Aim The aim was to determine temporal changes in increased risk of epilepsy among children with type 1 diabetes.Methods The incidence of epilepsy up to age 15 in children with prior type 1 diabetes was analysed regarding the general Finnish child population using data from the Finnish nationwide hospital register. Type 1 diabetes and epilepsy were identified by the International Classification of Diseases 9th and 10th revision codes. Epilepsy was defined according to ILAE guidelines. The analyses were done using negative binomial regression models. Results Preceding type 1 diabetes was diagnosed in 6162 (0.91%) of the 679 375 general children population. Incidence rate of new-onset epilepsy among children with type 1 diabetes was higher than in controls (140 vs 82 per 100 000 person-years at risk, respectively). The excess incidence diminished with time (P = 0.033 for diabetes to birth cohort interaction), from over twofold in birth cohort 1990-1993 [incidence rate ratio 2.2 (95% CI 1.7-2.9)] to 40% in birth cohort 1998-2000 [1.4 (95% CI 1.001-1.9)]. Conclusion In a population study setting, children with type 1 diabetes had an increased, but slowly declining risk of developing epilepsy. Future research may elucidate the underlying mechanisms.</p

Metformin and insulin treatment of gestational diabetes: effects on inflammatory markers and IGF-binding protein-1-secondary analysis of a randomized controlled trial

Background: Gestational 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.Methods: This 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.Results: In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p Conclusions: Metformin 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.</div

Dietary quality influences body composition in overweight and obese pregnant women

BACKGROUND & AIMS: Excessive adiposity and gestational weight gain (GWG) have been linked with maternal and offspring morbidity. We investigated the relation of maternal diet, physical activity and GWG on body composition in overweight and obese pregnant women.METHODS: Fat mass (FM) and fat free mass (FFM) of 110 overweight and obese pregnant women were measured by air displacement plethysmography in early and late pregnancy (mean 13.5 and 35.3 gestational weeks). At the same time points, the quality of overall diet was assessed by validated index of diet quality (IDQ) questionnaire (score < 10/15 denotes poor dietary quality and score ≥ 10/15 denotes good dietary quality), nutrient intakes by 3-day food diaries, and physical activity by questionnaire. Weight gain between early and late pregnancy was compared to the gestational weight gain guidelines issued by Institute of Medicine.RESULTS: Of the women, 77% gained more weight than recommended; this was related to greater dietary fat consumption (80 ± 21 g/day vs. 67 ± 11 g/day, p = 0.010) and greater increase in FM (2.7 ± 3.0 kg vs. -1.0 ± 2.4 kg, p < 0.001) compared to women with ideal GWG. Dietary protein intake (g) correlated positively with FFM at both time points (early pregnancy: r = 0.31, p < 0.002, late pregnancy: r = 0.39, p < 0.001). Women with higher dietary quality index score had more FFM, compared to women with lower dietary quality (early pregnancy FFM: 48.8 ± 5.8 kg vs. 45.8 ± 4.7 kg, p = 0.004, late pregnancy FFM: 56.1 ± 6.4 kg vs. 53.4 ± 5.6 kg, p = 0.025). No correlations were detected between total energy intake or physical activity and FM or FFM at early or late pregnancy.CONCLUSIONS: Body composition changes from early to late pregnancy were related to the amount of weight gained and overall dietary quality during pregnancy. Higher dietary quality and protein intake were associated with greater FFM, while dietary fat intake was related to excess weight gain. Identification of these dietary determinants of body composition and weight offers new targets for dietary counseling of pregnant women and thus potential for ensuing health benefits through reduced adiposity.</p