Lactation is associated with altered metabolomic signatures in women with gestational diabetes.

AIMS/HYPOTHESIS: Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures postpartum. METHODS: We enrolled 197 women with gestational diabetes at a median of 3.6 years (interquartile range 0.7-6.5 years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3 months and women who lactated for ≤3 months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks. RESULTS: Lactation for >3 months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branched-chain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3 months and have been linked to the pathophysiology of type 2 diabetes in previous studies. CONCLUSIONS/INTERPRETATION: Lactation for >3 months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes.

Beneficial effects of breastfeeding in women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) increases the future risk of developing type 2 diabetes mellitus (T2DM). There is now a growing evidence that breastfeeding has short- and long-term health benefits for mothers with GDM. Mothers with GDM who breastfeed have improved lipid and glucose metabolic profiles for the first 3 months after birth. However, women with GDM are less likely to breastfeed and, if they do, breastfeeding is usually continued for a shorter duration compared with women without GDM. One long-term prospective study followed women with GDM from delivery for up to 19 years postpartum, and found that breastfeeding for ≥3 months reduced the risk of T2DM and delayed the development of T2DM by a further 10 years compared with breastfeeding for <3 months. However, the physiological mechanisms underlying the protective effects of breastfeeding are still unknown, even though it is important to gain a full understanding of the pathways involved in these effects. Therefore, the purpose of this review is to provide a comprehensive analysis of the recent developments in the field of GDM and breastfeeding. We reviewed data from animal experiments and human studies. We also provide insight into the molecular pathways and describe promising topics for future research.

Postpartum outcomes in women with gestational diabetes and their offspring: POGO study design and first-year results.

BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for mothers to develop type 2 diabetes (T2D) postpartum, and for their children to develop obesity. The aim of the ongoing POGO study is to identify long-lasting changes in the maternal and fetal metabolism and microbiome, after GDM, which contribute to subsequent development of T2D and obesity. METHODS: Women screened for GDM are asked to attend a postpartum study visit together with their offspring. At the visit, demographic, nutritional, and anthropometric data are recorded. Additionally, data about physical activity, metabolism, and genetic susceptibility are collected using accelerometers, breath gas analyses, 75g oral glucose tolerance tests (OGTT), and bio-samples such as blood and stool. RESULTS: To date, 121 women (median follow-up time postpartum: 5.5 years) have been enrolled together with 133 index children. GDM has been diagnosed using OGTT in 105 women (and 117 children). It showed that 47 mothers had abnormal glucose tolerance, including 19 cases of impaired glucose tolerance, 19 of impaired fasting glucose, eight with T2D, and one with type 1 diabetes (T1D). The prevalence of obesity in the offspring of GDM mothers was 5.1%. Of 61 children tested by OGTT, three were diagnosed with impaired glucose tolerance, another three with impaired fasting glucose, and none with T1D or T2D. CONCLUSIONS: The POGO study will contribute to the understanding of the pathogenesis of T2D and obesity after GDM, and will thus help to develop appropriate prevention and intervention strategies. This article presents the first results of the ongoing study, which are looking promising.

Long-term protective effect of lactation on the development of type 2 diabetes in women with recent gestational diabetes mellitus.

Women with gestational diabetes mellitus (GDM) have a high risk of developing postpartum type 2 diabetes. Strategies to prevent postpartum type 2 diabetes are important to reduce the epidemic of diabetes and its societal impact. Breastfeeding was reported to improve early postpartum glucose tolerance and reduce the subsequent risk of type 2 diabetes. To investigate whether breastfeeding influences short- and long-term postpartum diabetes outcomes, women with GDM (n = 304) participating in the prospective German GDM study were followed from delivery for up to 19 years postpartum for diabetes development. All participants were recruited between 1989 and 1999. Postpartum diabetes developed in 147 women and was dependent on the treatment received during pregnancy (insulin vs. diet), BMI, and presence/absence of islet autoantibodies. Among islet autoantibody-negative women, breastfeeding was associated with median time to diabetes of 12.3 years compared with 2.3 years in women who did not breastfeed. The lowest postpartum diabetes risk was observed in women who breastfed for >3 months. On the basis of these results, we recommend that breastfeeding should be encouraged among these women because it offers a safe and feasible low-cost intervention to reduce the risk of subsequent diabetes in this high-risk population.