Can maternal treatment with metformin during gestation and lactation cause metabolic and cardiovascular disorders in rat offspring?

Novi, Daniella R B S; Vidigal, Camila Borecki; Marques, Bruno V D; Forcato, Simone; Raquel, Hiviny Ataides; Zaia, Dimas Augusto Morozin; Zaia, Cássia Thaïs Bussamra Vieira; Martins‐Pinge, Marli Cardoso; Gerardin, Daniela Cristina Ceccatto; Ceravolo, Graziela Scalianti

doi:10.1080/13813455.2018.1517804

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…None of the outcomes of glucose homeostasis differed between the two groups, Figure 6. Eleven studies presented glucose concentration ( n = 556 offspring, n = 172 dams, SMD 0.07 [95% CI −0.61; 0.75] I 2 = 92% for all offspring and SMD −0.14 [95% CI −0.48; 0.20] I 2 = 31% per litter) 36,37,39,43,49,51,53–57 . Eight presented glucose concentration 60 min after a glucose load injection ( n = 520 offspring, n = 92 dams, SMD −0.10 [95% CI −0.54; 0.34] I 2 = 80% for all offspring, SMD −0.93 [95% CI −1.99; 0.13] I 2 = 83% per litter) 36,37,49,51–53,58,59 .…”

Section: Resultsmentioning

confidence: 99%

“…Eleven studies presented glucose concentration (n = 556 offspring, n = 172 dams, SMD 0.07 [95% CI −0.61; 0.75] I 2 = 92% for all offspring and SMD −0.14 [95% CI −0.48; 0.20] I 2 = 31% per litter). 36,37,39,43,49,51,[53][54][55][56][57] Eight presented glucose concentration 60 min after a glucose load injection (n = 520 offspring, n = 92 dams, SMD −0.10 [95% CI −0.54; 0.34] I 2 = 80% for all offspring, SMD −0.93 [95% CI −1.99; 0.13] I 2 = 83% per litter). 36,37,49,[51][52][53]58,59 The same eight studies that presented glucose concentration at 60 min were used to obtain the largest difference between groups in glucose concentration during a glucose tolerance test (SMD −0.…”

Section: Perinatal Anthropometric Outcomesmentioning

confidence: 99%

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Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments

van Hoorn,

Rademaker,

van der Wel

et al. 2023

Diabet Med

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BackgroundThe impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development and health remains unclear.ObjectivesOur objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes.MethodsA systematic search was conducted in Pubmed and Embase from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta‐analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in case of 10 comparisons or more per subgroup.ResultsWe included 37 articles (n= 3133 offspring from n=716 litters, containing n= 51 comparisons) in this review, mostly (95%) on rodent models and 6% pig models. Follow‐up of offspring ranged from birth to two years of age. Thirty four of the included articles could be included in the meta‐analysis. No significant effects in the overall meta‐analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details.ConclusionThis systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non‐human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.

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Section: Resultsmentioning

confidence: 99%

Section: Perinatal Anthropometric Outcomesmentioning

confidence: 99%

Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments

van Hoorn,

Rademaker,

van der Wel

et al. 2023

Diabet Med

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“…Body weight measurements were performed on the first day of each week for 8 weeks. Body length was defined as the distance from the nose to the anus of rats (Lee index: LI = body weight (g) 1/3×1000/body length (cm)) [37]. Standard rat-chow (CD) was transformed into high-fat rat chow (HFD) as previously described [38].…”

Section: Animalsmentioning

confidence: 99%

High-fat diet induced cardiac hemodynamic changes: effects of exercise and obestatin

MEMI¹,

Öztürk²,

Palabıyık³

2023

jrp

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The obese population has been rapidly increasing because of high-fat consumption and a sedentary lifestyle. Large amounts of dietary fat intake increase the risk of cardiovascular disease. We aimed to investigate the effects of exercise and obestatin on a high-fat diet (HFD) induced cardiac hemodynamic changes. Seventy-nine Sprague-Dawley rats (200 to 250 g) were fed either control diet or HFD for 8 weeks. In the 5th week, each diet group was subgrouped as follows; control, exercise, obestatin (25μg/kg, i.p), exercise+obestatin (25μg/kg, i.p). After the end of 4 weeks of exercise (swimming exercise, 5 days a week/ 20 min day) and obestatin administration period, all animals were sacrificed. Hearts were removed for hemodynamic measurements with the Langendorff apparatus. Blood samples were collected for biochemical measurements. Data were analyzed by Graphpad Prism 6.0. and p<0.05 was accepted as statistically significant. Cardiac contractility and hemodynamic parameters in the HFD model have been evaluated. And the effects of chronic obestatin treatment and exercise were studied together. Obestatin ameliorated derangements in LVDP, heart rate, and blood lipid levels induced by an HFD. Also, obestatin prevents decreasing BNP levels with highfat consumption. Obestatin treatment potentiated the beneficial effects of exercise evidenced by LVDP, heart rate, blood lipids, BNP, and AT2R1 measurements. We believe that obestatin has the potential for the maintenance of cardiac function in HFD.

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“…abundance was elevated in MT-treated male offspring, whereas female offspring were characterized by elevated levels of Clostridium spp. However, it has been shown that maternal MT treatment leads to adipocytosis in male offspring [78] without altering the metabolic effects [79].…”

Section: Metforminmentioning

confidence: 99%

The Role of Gut Microbiota in Gestational Diabetes Mellitus Affecting Intergenerational Glucose Metabolism: Possible Mechanisms and Interventions

Ren,

Zeng,

et al. 2023

Nutrients

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The incidence of type 2 diabetes is increasing every year and has become a serious public health problem. In addition to genetic factors, environmental factors in early life development are risk factors for diabetes. There is growing evidence that the gut microbiota plays an important role in glucose metabolism, and the gut microbiota of pregnant women with gestational diabetes mellitus (GDM) differs significantly from that of healthy pregnant women. This article reviews the role of maternal gut microbiota in offspring glucose metabolism. To explore the potential mechanisms by which the gut microbiota affects glucose metabolism in offspring, we summarize clinical studies and experimental animal models that support the hypothesis that the gut microbiota affects glucose metabolism in offspring from dams with GDM and discuss interventions that could improve glucose metabolism in offspring. Given that adverse pregnancy outcomes severely impact the quality of survival, reversing the deleterious effects of abnormal glucose metabolism in offspring through early intervention is important for both mothers and their offspring.

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Can maternal treatment with metformin during gestation and lactation cause metabolic and cardiovascular disorders in rat offspring?

Cited by 8 publications

References 38 publications

Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments

Fetal and post‐natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta‐analysis of animal experiments

High-fat diet induced cardiac hemodynamic changes: effects of exercise and obestatin

The Role of Gut Microbiota in Gestational Diabetes Mellitus Affecting Intergenerational Glucose Metabolism: Possible Mechanisms and Interventions

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