Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin

Balani, Jyoti; Hyer, Steve; Syngelaki, Argyro; Akolekar, Ranjit; Nicolaides, Kypros H.; Johnson, Antoinette; Shehata, Hassan

doi:10.1177/1753495x17725465

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…And although in our data there were no differences in GWG between the treatment groups, non-pIGFBP-1 and low-pIGFBP-1 were inversely associated with GWG. This effect however was unlikely mediated by reduction of insulin resistance in obese patients [47]. In line with these findings, neither IGFBP-1's nor the inflammatory markers were associated with the risk of hypertensive disorders in our data.…”

supporting

confidence: 81%

“…Metformin has been found to reduce the risk of gestational hypertension in comparison to insulin [ 5 ] and the risk of preeclampsia when compared to placebo [ 45 ]. This effect however was unlikely mediated by reduction of insulin resistance in obese patients [ 47 ]. In line with these findings, neither IGFBP-1’s nor the inflammatory markers were associated with the risk of hypertensive disorders in our data.…”

Section: Discussionmentioning

confidence: 99%

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

Huhtala

Tertti

Juhila

et al. 2020

BMC Pregnancy Childbirth

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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.

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supporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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

Huhtala

Tertti

Juhila

et al. 2020

BMC Pregnancy Childbirth

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“…However this finding needs to be confirmed in a larger study. On the other hand the women who are hyperlipidemic, tend also to be more obese and insulin resistant, and could therefore benefit from metformin treatment, as metformin reduces insulin resistance [35] and GWG [8].…”

Section: Discussionmentioning

confidence: 99%

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

Huhtala

Tertti

Rönnemaa

2020

Diabetes Research and Clinical Practice

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To 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).Methods: This 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.Results: Total 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 < 0.01). Baseline total and VLDL triglycerides, VLDL cholesterol, and apolipoprotein B to A-1 ratio (apoB/apoA-1) associated positively with BW, more strongly in the metformin group. Among patients in the highest baseline VLDL cholesterol or apoB/apoA-1 quartile, those treated with insulin had lower BWs than those treated with metformin (p < 0.03). Conclusion:Compared 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.

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“…A parallel situation occurs with the use of metformin for the prevention of GDM. While metformin prevents type 2 diabetes over time [ 17 ], no reduction in the development of GDM was seen in either the Effect of Metformin on Maternal and Fetal Outcomes in Obese Pregnant Women (EMPOWaR) or in the Metformin in Obese Non-Diabetic Pregnant Women (MOP) RCTs of metformin for the prevention of GDM [ 18 , 19 ], although MOP did show a reduction in insulin resistance [ 20 ]. However, one would expect that the intervention would have been effective in reducing GDM in a proportion of women, but this was not seen.…”

Section: Discussionmentioning

confidence: 99%

Association between Gestational Weight Gain, Gestational Diabetes Risk, and Obstetric Outcomes: A Randomized Controlled Trial Post Hoc Analysis

et al. 2018

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Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m2 <20 weeks gestation without GDM (n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24–28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p < 0.01), and a higher rate of caesarean section (38% vs. 27% p < 0.05). The GWG over the median at 35–37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p < 0.05). A post hoc comparison among women from the five sites with a GWG difference >3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester.

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Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin

Abstract: Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

Cited by 8 publications

References 35 publications

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

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

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

Association between Gestational Weight Gain, Gestational Diabetes Risk, and Obstetric Outcomes: A Randomized Controlled Trial Post Hoc Analysis

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