Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring

Panagiotopoulou, Olga; Syngelaki, Argyro; Georgiopoulos, Georgios; Simpson, John; Akolekar, Ranjit; Shehata, Hassan; Nicolaides, Kypros H.; Charakida, Marietta

doi:10.1016/j.ajog.2020.01.054

Cited by 18 publications

(24 citation statements)

References 36 publications

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“…Moreover, further follow-up of offspring born to metformin-treated PCOS women up to 10 years of age showed increased overweight and obesity [ 12 , 13 ], with an increased proportion of metabolically abnormal obese children in the metformin arm. In contrast, trials in obese glucose-tolerant women failed to show a relationship between metformin exposure and offspring adiposity at least up to 4 years of age [ 8 , 14 , 53 ], highlighting the importance of the longer-term follow-up of metformin-exposed offspring.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is plausible that metformin use in pregnancy might offer a suitable intervention to mitigate or negate the adverse effects of an obese diabetic intrauterine environment on offspring health globally. However, metformin readily crosses the placenta [ 9 ], and offspring follow-up in human randomised controlled trials investigating maternal metformin treatment remains sparse, with few studies reporting offspring outcomes beyond infancy [ 10 , 11 , 12 , 13 , 14 , 15 ]. However, the fact that several studies have reported an increased adiposity in children exposed to maternal metformin treatment in pregnancy warrants further investigation into the long-term effects [ 10 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner

Schoonejans

Blackmore

Ashmore

et al. 2021

IJMS

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Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR. Results: Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (p < 0.05), exaggerated adipocyte hyperplasia (p < 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (p < 0.05) and the mRNA expression of F4/80 (p < 0.05). These changes were not observed in female Ob-Met offspring. Conclusions: Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner

Schoonejans

Blackmore

Ashmore

et al. 2021

IJMS

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“…These studies have raised concerns that metformin, currently used by many women with GDM, does not adequately prevent adverse perinatal outcomes, and may have negative long-term effects on the metabolic health of the children (118). However, a recent study has provided more reassuring data: the 3-5 year old children of obese women randomised to take metformin in pregnancy had lower gluteal and tricep circumferences, lower systolic blood pressure and improved left ventricular diastolic function compared to the children of obese women randomised to placebo (119). Thus, more research is required to establish whether maternal metformin treatment improves long-term cardiometabolic outcomes for exposed fetuses.…”

Section: Gestational Diabetes Mellitusmentioning

confidence: 99%

ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation

Fan

Mitchell

Williamson

2021

European Journal of Endocrinology

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Bile acids are lipid-solubilising molecules that also regulate metabolic processes. Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) are two bile acid receptors with key metabolic roles. FXR regulates bile acid synthesis in the liver and influences bile acid uptake in the intestine. TGR5 is mainly involved in regulation of signalling pathways in response to bile acid uptake in the gut and therefore prandial response. Both FXR and TGR5 have potential as therapeutic targets for disorders of glucose and/or lipid homeostasis. Gestation is also known to cause small increases in bile acid concentrations, but physiological hypercholanaemia of pregnancy is usually not sufficient to cause any clinically relevant effects. This review focuses on how gestation alters bile acid homeostasis, which can become pathological if the elevation of maternal serum bile acids is more marked than physiological hypercholanaemia, and on the influence of FXR and TGR5 function in pregnancy on glucose and lipid metabolism. This will be discussed with reference to two gestational disorders: intrahepatic cholestasis of pregnancy (ICP), a disease where bile acids are pathologically elevated, and gestational diabetes mellitus (GDM), characterised by hyperglycaemia during pregnancy.

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“…The other two clinical conditions where metformin can be used during pregnancy are gestational obesity and PCOS. However, the data regarding the long-term outcome in such settings are very sparse[ 23 - 27 ]. A recently concluded obese pregnant woman off-spring follow-up study (77 metformin-exposed children aged 3.9 ± 1.0 years) noted similar peripheral arterial BP, arterial stiffness, and metabolic parameters (lipid profile, leptin and adiponectin) between the metformin and placebo groups[ 23 ].…”

Section: Long-term Effects Of Metformin On Offspring Of Mothers With Gestational Diabetesmentioning

confidence: 99%

“…However, the data regarding the long-term outcome in such settings are very sparse[ 23 - 27 ]. A recently concluded obese pregnant woman off-spring follow-up study (77 metformin-exposed children aged 3.9 ± 1.0 years) noted similar peripheral arterial BP, arterial stiffness, and metabolic parameters (lipid profile, leptin and adiponectin) between the metformin and placebo groups[ 23 ]. The body composition was similar between the two groups except for lower gluteal and triceps circumferences in the metformin group.…”

Section: Long-term Effects Of Metformin On Offspring Of Mothers With Gestational Diabetesmentioning

confidence: 99%

Long-term effects of metformin use in gestational diabetes mellitus on offspring health

Roy¹,

Sahoo²

2021

WJD

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Metformin is the first-line drug for the treatment of type 2 diabetes mellitus, but its role in gestational diabetes mellitus (GDM) management is not clear. Recent evidence suggests a certain beneficial effect of metformin in the treatment of GDM, but a high treatment failure rate leads to the initiation of additional medications, such as insulin. Moreover, since metformin crosses the placental barrier and reaches a significant level in the fetus, it is likely to influence the fetal metabolic milieu. The evidence indicates the long-term safety in children exposed to metformin in utero except for mild adverse anthropometric profiles. Diligent follow-up of metformin-exposed offspring is warranted from the clinician’s point of view.

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Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring

Cited by 18 publications

References 36 publications

Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner

Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner

ENDOCRINOLOGY IN PREGNANCY: Metabolic impact of bile acids in gestation

Long-term effects of metformin use in gestational diabetes mellitus on offspring health

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