The breast milk plays a crucial role in shaping the initial intestinal microbiota and mucosal immunity of the infant. Interestingly, breastfeeding has proven to be protective against the early onset ...of immune-mediated diseases including type 1 diabetes. Studies have shown that exosomes from human breast milk are enriched in immune-modulating miRNAs suggesting that exosomal miRNAs (exomiRs) transferred to the infant could play a critical role in the development of the infant's immune system. We extracted exomiRs from breast milk of 52 lactating mothers (26 mothers with type 1 diabetes and 26 healthy mothers), to identify any differences in the exomiR content between the two groups. Small RNA-sequencing was performed to identify known and novel miRNAs in both groups. A total of 631 exomiRs were detected by small RNA sequencing including immune-related miRNAs such as hsa-let-7c, hsa-miR-21, hsa-miR-34a, hsa-miR-146b, and hsa-miR-200b. In addition, ~200 novel miRNAs were identified in both type 1 diabetes and control samples. Among the known miRNAs, nine exomiR's were found differentially expressed in mothers with type 1 diabetes compared to healthy mothers. The highly up-regulated miRNAs, hsa-miR-4497, and hsa-miR-3178, increased lipopolysaccharide-induced expression and secretion of tumor necrosis factor α (TNFα) in human monocytes. The up-regulated miRNA target genes were significantly enriched for longevity-regulating pathways and FoxO signaling. Our findings suggest a role of breast milk-derived exomiRs in modulating the infant's immune system.
Type 2 diabetes increases the risk of nonalcoholic fatty liver disease (NAFLD), which is a potentially reversible condition but is also associated with progressive fibrosis and cirrhosis. Women with ...prior gestational diabetes mellitus (pGDM) have a higher risk for NAFLD.
One hundred women without diabetes who had pGDM (median interquartile range: age 38.6 6.4 years; BMI 31.0 6.2 kg/m
) and 11 healthy control subjects without NAFLD (age 37.9 7.8 years; BMI 28.1 0.8 kg/m
) underwent a 75-g oral glucose tolerance test (OGTT), DXA whole-body scan, and ultrasonic evaluation of hepatic steatosis.
Twenty-four (24%) women with pGDM had NAFLD on the basis of the ultrasound scan. None had cirrhosis. Women with NAFLD had a higher BMI (P = 0.0002) and waist circumference (P = 0.0003), increased insulin resistance (P = 0.0004), and delayed suppression of glucagon after the OGTT (P < 0.0001), but NAFLD was not associated with the degree of glucose intolerance (P = 0.2196). Visceral fat mass differed among the three groups, with the NAFLD group having the highest amount of fat and the control subjects the lowest (P = 0.0003). By logistic regression analysis, insulin resistance (P = 0.0057) and waist circumference (P = 0.0109) were independently associated with NAFLD.
NAFLD was prevalent in this cohort of relatively young and nonseverely obese women with pGDM who are considered healthy apart from their increased risk for diabetes. Insulin resistance and a larger waist circumference were independently associated with the presence of NAFLD, whereas glucose intolerance was not.
Introduction
The aim of the study was to examine the prevalence of anal incontinence (AI) during pregnancy and 1 year after delivery in primiparous women and to compare it with the prevalences in ...nulliparous women.
Material and methods
A validated questionnaire regarding AI was filled in by 1018 primiparous women after delivery and by 1836 nulliparous women (baseline). A similar questionnaire was filled in 1 year later by both groups.
Results
At baseline the prevalence of flatus incontinence was significantly higher in the primiparous than the nulliparous women (35 vs. 25%), while incontinence for liquid stools was significantly less frequent (8 vs. 20%). Prevalences of incontinence for solid stools were similar. One year later the prevalence of AI was similar in the two groups (flatus incontinence 24 vs. 25%, incontinence for liquid stools 18 vs. 19% and incontinence for solid stools 4 vs. 3%). AI 1 year after the delivery was not related to the mode of delivery. Women with grade 3 or 4 perineal lesions had a significantly higher prevalence of flatus incontinence 1 year after the delivery compared with women without such lesions (48 vs. 23%, p = 0.00).
Conclusions
This prospective cohort study showed remarkably high prevalences of AI during pregnancy and 1 year after delivery in primiparous women and likewise in nulliparous women at baseline and 1 year later. These results may indicate that factors other than pregnancy and delivery are of importance for AI in young women.
Aim
We investigated the effect of 52‐week treatment with liraglutide, a glucagon‐like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes ...mellitus (pGDM).
Materials and Methods
Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash‐out.
Results
In total, 104 women age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2 were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was −173 (95% confidence interval −250 to −97) mmol/L × min, p < .0001, but after wash‐out the difference disappeared ETD 58 (−30 to 146) mmol/L × min, p = .536. Liraglutide reduced FPG ETD −0.2 (−0.4 to −0.1) mmol/L, p = .018, HbA1c −2.2 (−3.5 to −0.8) mmol/mol, p = .018 and bodyweight −3.9 (−6.2 to −1.6) kg, p = .012. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo adjusted odds ratio 0.10 (0.03‐0.32), p = .002.
Conclusions
Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1‐week drug wash‐out, the effect was lost.
Type 1 diabetes is an immune-driven disease, where the insulin-producing beta cells from the pancreatic islets of Langerhans becomes target of immune-mediated destruction. Several studies have ...highlighted the implication of circulating and exosomal microRNAs (miRNAs) in type 1 diabetes, underlining its biomarker value and novel therapeutic potential. Recently, we discovered that exosome-enriched extracellular vesicles carry altered levels of both known and novel miRNAs in breast milk from lactating mothers with type 1 diabetes. In this study, we aimed to characterize exosomal miRNAs in the circulation of lactating mothers with and without type 1 diabetes, hypothesizing that differences in type 1 diabetes risk in offspring from these groups are reflected in the circulating miRNA profile. We performed small RNA sequencing on exosome-enriched extracellular vesicles extracted from plasma of 52 lactating mothers around 5 weeks postpartum (26 with type 1 diabetes and 26 age-matched controls), and found a total of 2,289 miRNAs in vesicles from type 1 diabetes and control libraries. Of these, 176 were differentially expressed in plasma from mothers with type 1 diabetes (167 upregulated; 9 downregulated, using a cut-off of abs(log2FC) >1 and FDR adjusted p-value <0.05). Extracellular vesicles were verified by nanoparticle tracking analysis, transmission electron microscopy and immunoblotting. Five candidate miRNAs were selected based on their involvement in diabetes and immune modulation/beta-cell functions: hsa-miR-127-3p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p and hsa-miR-30d-5p. Real-time qPCR validation confirmed that hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p, and hsa-miR-30d-5p were significantly upregulated in lactating mothers with type 1 diabetes as compared to lactating healthy mothers. To determine possible target genes and affected pathways of the 5 miRNA candidates, computational network-based analyses were carried out with TargetScan, mirTarBase, QIAGEN Ingenuity Pathway Analysis and PantherDB database. The candidates showed significant association with inflammatory response and cytokine and chemokine mediated signaling pathways. With this study, we detect aberrant levels of miRNAs within plasma extracellular vesicles from lactating mothers with type 1 diabetes during the postpartum period, including miRNAs with associations to disease pathogenesis and inflammatory responses.
Introduction
Bacterial vaginosis (BV) is characterized by a dysbiosis of the vaginal microbiota with a depletion of Lactobacillus spp. In pregnancy, prevalence's between 7 and 30% have been reported ...depending on the study population and the definition. BV may be associated with an increased risk of spontaneous preterm delivery (sPTD). However, it is controversial whether or not BV‐positive pregnant women will benefit from treatment to reduce the risk of sPTD. We could not identify any good‐quality guideline addressing this issue. Consequently we aimed to produce this clinical recommendation based on GRADE.
Material and methods
Systematic literature searches were conducted in the following databases: Guidelines International Network: G‐I‐N, Medline, Embase, The Cochrane Database of Systematic Reviews, Web of Science and http://www.clinicaltrials.gov from 1999 to 3 October 2014. Hence, nine guidelines, 34 reviews, 18 randomized controlled trials and 12 observational studies were included.
Results
The GRADE quality of evidence was consistently low or very low, primarily because none of the risk ratios (RR) for the risk of sPTD at <37 weeks were statistically significant. Concerning treatment with metronidazole, RR was 1.11 (95% CI 0.93–1.34) in low‐risk pregnancies and 0.96 (95% CI 0.78–1.18) in high risk pregnancies. Concerning treatment with clindamycin at any gestational age, the RR was 0.87 (95% CI 0.73–1.05).
Conclusion
This systematic review gives a strong recommendation against treatment with metronidazole and a weak recommendation against treatment with clindamycin to reduce the sPTD rate in both high‐risk and low‐risk pregnancies with BV.
Introduction and hypothesis
The objective was to examine the relationship between maternal and perinatal factors and the occurrence of stress (SUI) or mixed (MUI) urinary incontinence (UI) 1 year ...after the first vaginal delivery in primiparous women.
Methods
Participants in this prospective cohort were recruited consecutively from June 2003 to July 2005 from all eligible women who delivered in the department. A validated questionnaire, the International Consultation of Incontinence Questionnaire Short Form (ICIQ-SF) was completed by all participants 2–3 days after delivery, and a similar second questionnaire was filled out 1 year later. Additional data were obtained from the medical records. The first questionnaire was completed by 1,018 women (63 %) and the second by 859 women (84 %). The study group comprised the 575 women without any UI before the pregnancy and who had a vaginal delivery. The primary analysis comprised 117 women with either SUI or MUI 1 year after the vaginal delivery and 403 women without any UI.
Results
In univariate analyses, the following factors were associated with SUI or MUI: prepregnancy body mass index (BMI) ≥ 30 (
p
< 0.05), UI during the pregnancy (
p
< 0.05), perineal lesions (
p
< 0.05), and anal sphincter tears (
p
= 0.05). Logistic regression analysis showed that SUI or MUI was strongly associated with UI during the pregnancy adjusted odds ratio (OR) 4.7, 95 % confidence interval (CI) 2.9–7.7) and inversely associated with oxytocin augmentation (adjusted OR 0.5, 95 % CI 0.3–0.9).
Conclusions
SUI or MUI 1 year after the first vaginal delivery was strongly associated with UI during the pregnancy and inversely associated with oxytocin augmentation.
Aims/hypothesis
We investigated whether a reduced incretin effect, as observed in patients with type 2 diabetes, can be detected in high-risk individuals, such as women with prior gestational ...diabetes mellitus (pGDM).
Methods
In this cross-sectional study, 102 women without diabetes with pGDM and 15 control participants without pGDM and with normal glucose tolerance (NGT) underwent a 4 h 75 g OGTT and an isoglycaemic i.v. glucose infusion (IIGI). Women with pGDM were classified as having NGT or prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Insulin sensitivity was assessed using the Matsuda index and HOMA2-IR and the incretin effect was calculated from insulin responses during the study (100% × AUC
insulin,OGTT
− AUC
insulin,IIGI
/AUC
insulin,OGTT
).
Results
Sixty-three of the 102 women with pGDM (62%) had prediabetes (median interquartile range: age, 38.3 6.5 years; BMI, 32.1 5.8 kg/m
2
) and 39 women (38%) had NGT (age, 39.5 5.6 years; BMI, 31.0 6.7 kg/m
2
). Control participants (
n
= 15) were not significantly different from the pGDM group with regards to age (39.2 7.4 years) and BMI (28.8 9.2 kg/m
2
). Compared with women with NGT and control participants, women with prediabetes had lower insulin sensitivity, as measured by the Matsuda index (3.0 2.4 vs 5.0 2.6 vs 1.5 1.8, respectively;
p <
0.001). The incretin effect was 55.3% 27.8, 73.8% 19.0 and 76.7% 24.6 in women with prediabetes, women with normal glucose tolerance and control participants, respectively (
p <
0.01).
Conclusion/interpretation
Prediabetes was highly prevalent in women with pGDM, and alterations in the incretin effect were detected in this group before the development of type 2 diabetes.
Trial registration:
clinicaltrialsregister.eu 2012-001371-37-DK.
Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown ...beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features in women with pGDM. Eighty-two overweight/obese, nondiabetic women with pGDM were included. We performed abdominal ultrasound, transient elastography with controlled attenuation parameter (CAP), and blood sampling at baseline and after 1 year. Thirty-seven women were randomized to liraglutide (1.8 mg once-daily) and 45 to placebo. Based on the ultrasound scan, 18 women (22%) had ultrasound-verified NAFLD at baseline and of these, 10 (56%) received liraglutide treatment. After 1 year, eight participants no longer had steatosis, four in each treatment group. The number of participants who developed NAFLD was similar in the two treatment groups; five in the liraglutide group and six in the placebo group (p = 0.74). Compared to placebo, liraglutide reduced the CAP-assessed intrahepatic fat content (−28 (−44;−11) vs. 2 (−13;18) dB/m, p < 0.01) and body weight (−4.7 (−6.4;−2.9) vs. −1.4 (−3;0.3) kg, p < 0.01). One-year’s liraglutide treatment had no effect on the presence of ultrasound-diagnosed NAFLD in overweight/obese nondiabetic women with pGDM, but reduced body weight and steatosis assessed by transient elastography with CAP.
To examine the association of gestational weight gain (GWG) among women with pre-pregnancy overweight or obesity with infant weight and BMI z-score at birth.
This study is a secondary analysis of a ...randomized controlled trial including data from 208 infants at birth born by mothers with pre-pregnancy BMI between 28 and 45 kg/m
who completed the APPROACH study (randomized to a high-protein low-glycemic index diet or a moderate-protein moderate-glycemic index diet). This analysis pooled the two diet treatment groups together and data were analyzed using a linear mixed model.
Limiting GWG by 1 kg was associated with lower birthweight (-16 g,
= 0.003), BMI z-score (-0.03SD,
= 0.019), weight z-score (-0.03SD,
= 0.004), and infant abdominal circumference (-0.06 cm,
= 0.039). Infants born by mothers whose GWG was ≤9 kg weighed less (122 g, 95% CI: 6-249,
= 0.040), had similar BMI z-score (0.2SD, 95% CI: -0.06 to 0.55,
= 0.120), and lower incidence of emergency cesarean deliveries (11.5% vs. 23.1%,
= 0.044) compared to infants born by mothers whose GWG was >9 kg. When women were classified into GWG quartiles, women in Q1 (GWG range: -7.0 to 3.2 kg) gave birth to smaller infants (3,420 g,
= 0.015) with lower BMI z-score (-0.5SD,
= 0.041) than women in Q2 (3.3-7.1 kg), Q3 (7.2-10.9 kg) and Q4 (11.1-30.2 kg).
Limiting GWG among women with pre-pregnancy overweight or obesity was associated with lower infant weight, BMI z-score, weight z-score, and abdominal circumference at birth. Moreover, GWG below the Institute of Medicine guideline of a maximum of 9 kg was associated with lower birthweight and fewer emergency cesarean deliveries.
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