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Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes.

ABSTRACT: OBJECTIVES:Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring. METHODS:We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42.4% of invited) and 27 (52.9% of invited) boys whose mothers had been treated with metformin or insulin, respectively, participated in the study. Testicular size was measured by a ruler, an orchidometer, and by ultrasonography at the age of 33 to 85 months. RESULTS:The mean age of the boys was 60 months at the time of examination, and did not differ between the metformin and insulin group (p = 0.88). There was no difference in testicular size between the boys in the two groups (p always ? 0.40), and there were no significant differences in height, weight, BMI, BMI z-score, or waist-to-hip ratio (WHR) between the boys in the groups. CONCLUSIONS:Prepubertal testicular size did not differ between offspring born to metformin-treated mothers and those born to insulin-treated mothers.

SUBMITTER: Tertti K

PROVIDER: S-EPMC5291182 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes.

Tertti Kristiina K Toppari Jorma J Virtanen Helena E HE Sadov Sergey S Rönnemaa Tapani T

The review of diabetic studies : RDS 20160128 1

<h4>Objectives</h4>Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring.<h4>Methods</h4>We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42 ...[more]

PMID: 26859658

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Project description:BACKGROUND:Gestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention. OBJECTIVE:We examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures. METHODS:We analyzed 604 Faroese pregnant women and their offsprings born in 1997-2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM. RESULTS:Serum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: -169g; 95% CI: -359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures. CONCLUSIONS:We found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.

Project description:AIMS/HYPOTHESIS:This study aimed to explore the infancy growth trajectories of 'recent' and 'earlier' offspring of mothers with gestational diabetes mellitus (OGDM), each compared with the same control infants, and investigate whether 'recent' OGDM still exhibit a classical phenotype, with macrosomia and increased adiposity. METHODS:Within a prospective observational birth cohort, 98 'earlier' OGDM born between 2001 and 2009 were identified using 75 g oral glucose tolerance testing at 28 weeks gestation, 122 recent OGDM born between 2011 and 2013 were recruited postnatally through antenatal diabetes clinics, and 876 normal birthweight infants of mothers with no history of diabetes were recruited across the full study period as the control group. All infants followed the same study protocol (measurements at birth, 3, 12 and 24 months, including weight, length and skinfold thickness indicating adiposity, and detailed demographic data). In all cases, GDM was defined using the International Association of Diabetes and Pregnancy Study Group criteria. RESULTS:Earlier OGDM had higher birthweight SD scores (SDS) than control infants. Conversely, recent OGDM had similar birthweight- and length SDS to control infants (mean?±?SD, 0.1?±?1.0 and-?0.1?±?0.9, respectively), but lower mean skinfold thickness SDS (-0.4?±?0.6 vs 0.0?±?0.9; p?<?0.001). After birth, earlier OGDM showed reduced gains in weight and length between 3 and 12 months. In contrast, recent OGDM had increased weight and skinfold thickness gains until 3 months, followed by reduced gains in those variables from 3 to 12 months, compared with control infants. At 24 months, recent OGDM had lower adiposity than control infants (mean skinfold thickness SDS -0.3?±?0.7 vs 0.0?±?0.8; p?<?0.001). At all time points recent OGDM had lower growth measurements than earlier OGDM. CONCLUSIONS/INTERPRETATION:Recent OGDM showed different growth trajectories to the earlier group, namely normalisation of birthweight and reduced adiposity at birth, followed by initial rapid weight gain but subsequent reduced adiposity postnatally. While avoidance of macrosomia at birth may be advantageous, the longer-term health implications of these changing growth trajectories are uncertain.

Project description:Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childhood and adulthood. In a convenience sample, we examined whether the intestinal tract of children born to mothers with GDM is differentially colonized in early life compared to offspring of mothers with normal gestational glucose regulation. Secondly, we examined whether any such difference persists during infancy, thus potentially conferring increased risk of developing metabolic disease later in life. Methods: Fecal samples were collected from children of mothers with (n = 43) and without GDM (n = 82) during the first week of life and again at an average age of 9 months. The gut microbiota was characterized by 16S rRNA gene amplicon sequencing (V1-V2). Differences in diversity and composition according to maternal GDM status were assessed, addressing potential confounding by mode of delivery, perinatal antibiotics treatment, feeding and infant sex. Results: Children of mothers with GDM were featured by a differential composition of the gut microbiota, both during the first week of life and at 9 months, at higher taxonomic and OTU levels. Sixteen and 15 OTUs were differentially abundant after correction for multiple testing during the first week of life and at 9 months, respectively. Two OTUs remained differentially abundant after adjustment for potential confounders both during the first week of life and at 9 months. Richness (OTU) was decreased in neonates born to mothers with GDM; however, at 9 months no difference in richness was observed. There was no difference in Shannon's diversity or Pielou's evenness at any timepoint. Longitudinally, we detected differential changes in the gut microbiota composition from birth to infancy according to GDM status. Conclusion: Differences in glycaemic regulation in late pregnancy is linked with relatively modest variation in the gut microbiota composition of the offspring during the first week of life and 9 months after birth.

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Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes.

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Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes.

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