scholarly journals Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: the SWIFT study

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziyi Zhang ◽  
Mi Lai ◽  
Anthony L. Piro ◽  
Stacey E. Alexeeff ◽  
Amina Allalou ◽  
...  

Abstract Background Women with a history of gestational diabetes mellitus (GDM) have a 7-fold higher risk of developing type 2 diabetes (T2D). It is estimated that 20-50% of women with GDM history will progress to T2D within 10 years after delivery. Intensive lactation could be negatively associated with this risk, but the mechanisms behind a protective effect remain unknown. Methods In this study, we utilized a prospective GDM cohort of 1010 women without T2D at 6-9 weeks postpartum (study baseline) and tested for T2D onset up to 8 years post-baseline (n=980). Targeted metabolic profiling was performed on fasting plasma samples collected at both baseline and follow-up (1-2 years post-baseline) during research exams in a subset of 350 women (216 intensive breastfeeding, IBF vs. 134 intensive formula feeding or mixed feeding, IFF/Mixed). The relationship between lactation intensity and circulating metabolites at both baseline and follow-up were evaluated to discover underlying metabolic responses of lactation and to explore the link between these metabolites and T2D risk. Results We observed that lactation intensity was strongly associated with decreased glycerolipids (TAGs/DAGs) and increased phospholipids/sphingolipids at baseline. This lipid profile suggested decreased lipogenesis caused by a shift away from the glycerolipid metabolism pathway towards the phospholipid/sphingolipid metabolism pathway as a component of the mechanism underlying the benefits of lactation. Longitudinal analysis demonstrated that this favorable lipid profile was transient and diminished at 1-2 years postpartum, coinciding with the cessation of lactation. Importantly, when stratifying these 350 women by future T2D status during the follow-up (171 future T2D vs. 179 no T2D), we discovered that lactation induced robust lipid changes only in women who did not develop incident T2D. Subsequently, we identified a cluster of metabolites that strongly associated with future T2D risk from which we developed a predictive metabolic signature with a discriminating power (AUC) of 0.78, superior to common clinical variables (i.e., fasting glucose, AUC 0.56 or 2-h glucose, AUC 0.62). Conclusions In this study, we show that intensive lactation significantly alters the circulating lipid profile at early postpartum and that women who do not respond metabolically to lactation are more likely to develop T2D. We also discovered a 10-analyte metabolic signature capable of predicting future onset of T2D in IBF women. Our findings provide novel insight into how lactation affects maternal metabolism and its link to future diabetes onset. Trial registration ClinicalTrials.gov NCT01967030.

2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X697469
Author(s):  
Rebecca Ward ◽  
Fahmy W Hanna ◽  
Ann Shelley-Hitchen ◽  
Ellen Hodgson ◽  
Adrian Heald ◽  
...  

BackgroundWomen with gestational diabetes (GDM) have an elevated risk of developing type 2 diabetes (T2DM). NICE Guidance recommends women who develop GDM are screened 6 weeks post-partum and annually thereafter.AimTo evaluate conformity to guidance of screening in women with GDM by 6-week post-partum fasting plasma glucose (FPG) and annual FPG and determine time between delivery and development of T2DM.MethodRecords at a tertiary referral centre were used to identify women (n = 54) diagnosed with GDM by antenatal oral glucose tolerance test between July 1999 and January 2007. Data from laboratory records were used to collect investigations of glycaemic status during the follow-up period (median follow-up 12.4 years, range 9.5–17.1 years).ResultsOf 252 women, 102 (40.2%) did not have a FPG at 6 weeks (+/−2 weeks). Of these, median time to first test was 1.2 years (range 0.04–10.8 years), with only 43.1% followed-up within 1 year. In those who had a 6-week FPG, 17 (11.3%) women had no further tests. A total of 84 (33% of those with gestational diabetes in the index pregnancy) women were diagnosed with T2DM; median time from delivery to diagnosis was 5.2 years (range 0.35–15.95). We found the only significant factor for a follow-up test at 1-year post-partum was the use of insulin.ConclusionOur data suggest an alternative approach is needed for monitoring women with a history of GDM. This needs to be appropriate for a generally healthy group in which traditional screening mechanisms may not be adequate or sufficient.


2020 ◽  
Vol 8 (2) ◽  
pp. e001229
Author(s):  
Sylvia H Ley ◽  
Jorge E Chavarro ◽  
Stefanie N Hinkle ◽  
Mengying Li ◽  
Michael Y Tsai ◽  
...  

IntroductionLonger duration of lactation is associated with lower cardiometabolic disease risk, but pathogenic pathways involved in the disease progression are unclear, especially among high-risk women. We aimed to examine the associations of lifetime lactation duration with cardiometabolic biomarkers among middle-aged women with a history of gestational diabetes (GDM).Research design and methodsWomen with a history of GDM participating in the Nurses’ Health Study II, a prospective cohort study, were identified and followed through biennial questionnaires beginning in 1991. Lactation history was asked in three follow-up questionnaires to calculate lifetime duration. In 2012–2014, fasting blood samples were collected through the Diabetes & Women’s Health Study to measure inflammatory (C-reactive protein (CRP), interleukin (IL) 6), liver enzyme (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase), and lipid biomarkers (total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol).ResultsAt follow-up blood collection, women were at median age 58.2 (95% CI 51 to 65) years and 26.3 (95% CI 15.7 to 34.1) years since GDM index pregnancy. After multiple adjustment including prepregnancy body mass index (BMI), longer duration of lactation was significantly associated with lower CRP (least squares (LS) mean 1.90 mg/L (95% CI 1.47 to 2.45) for 0-month lactation, 1.98 mg/L (95% CI 1.68 to 2.32) for up to 12-month lactation, 1.67 mg/L (95% CI 1.42 to 1.97) for 12–24 month lactation, and 1.39 mg/L (95% CI 1.19 to 1.62) for >24-month lactation; p trend=0.003) and IL-6 (1.25 pg/L (95% CI 0.94 to 1.68), 1.19 pg/L (95% CI 0.99 to 1.42), 1.04 pg/L (95% CI 0.87 to 1.25), and 0.93 pg/L (95% CI 0.78 to 1.11); p trend=0.04). Longer duration of lactation was associated with lower risk for chronic inflammation using CRP 3 mg/L cut-off in middle-aged women (OR 0.81 (95% CI 0.69 to 0.940 per 1-year increase) with multiple adjustment.ConclusionsLonger lifetime duration of lactation was associated with favorable inflammatory biomarker concentrations in middle-aged women with a history of GDM. Chronic inflammatory pathways may be responsible for previously reported associations between lactation and long-term risk for cardiometabolic diseases.


2020 ◽  
Author(s):  
Ling Pei ◽  
Huangmeng Xiao ◽  
Fenghua Lai ◽  
Zeting Li ◽  
Zhuyu Li ◽  
...  

Abstract Background: This study aimed to analyze the incidence of early postpartum dyslipidemia and its potential predictors in women with a history of gestational diabetes mellitus (GDM).Methods: This was a retrospective study. 589 women diagnosed with GDM were enrolled and followed up at 6–12 weeks after delivery. A 75g oral glucose tolerance test (OGTT) and lipid levels were performed during mid-trimester and the early postpartum period. Participants were divided into the normal lipid group and dyslipidemia group according to postpartum lipid levels. Demographic and metabolic parameters were analyzed. Multiple logistic regression was performed to analyze the potential predictors for early postpartum dyslipidemia. A receiver operating characteristic curve (ROC) was calculated to determine the cut-off values.Results: A total of 38.5% of the 589 women developed dyslipidemia in early postpartum and 60% of them had normal glucose metabolism. Delivery age, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of early postpartum dyslipidemia in women with a history of GDM. The cut-offs of maternal age, SBP, HbA1c values, and LDL-C levels were 35 years, 123mmHg, 5.1%, and 3.56 mmol/L, respectively. LDL-C achieved a balanced mix of high sensitivity (63.9%) and specificity (69.2%), with the highest area under the receiver operating characteristic curve (AUC) (0.696). When LDL-C was combined with age, SBP, and HbA1c, the AUC reached to 0.733.Conclusions: A lipid metabolism evaluation should be recommended in women with a history of GDM after delivery, particularly those with a maternal age > 35 years, SBP > 123 mmHg before labor, HbA1c value > 5.1%, or LDL-C levels > 3.56 mmol/L in the second trimester of pregnancy.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 556
Author(s):  
Franziska Schleger ◽  
Katarzyna Linder ◽  
Louise Fritsche ◽  
Jan Pauluschke-Fröhlich ◽  
Martin Heni ◽  
...  

Maternal metabolism and intrauterine conditions influence development of health and disease in offspring, leading to metabolic, physiologic, and/or epigenetic adaptation of the fetus. Maternal gestational diabetes (GDM) leads to higher incidence of obesity and type 2 diabetes in offspring. We have previously shown that fetuses of insulin-resistant mothers with GDM have a delayed reaction to auditory stimuli in the postprandial state, indicating a fetal central insulin resistance. We tested whether this effect could be influenced by a lifestyle intervention in mothers with GDM, including diet counselling and regular blood glucose measurements. We measured fetal brain activity over the course of a maternal glucose challenge, at two measurement time points (baseline at an average of 29 weeks of gestation and follow-up after 4 weeks) in mothers with GDM and mothers with normal glucose tolerance (NGT). Data from eight mothers were able to be included. Fetuses of GDM mothers showed longer latencies than those of NGT mothers postprandially at both measurement time points during the third trimester and did not show a difference in response patterns between baseline and after 4 weeks. Maternal postprandial blood glucose and insulin values did not change from baseline to follow-up either. While the overall intervention seems to have been effective, it does not appear to have influenced the fetal postprandial brain responses. This might have been because interventions for GDM take place relatively late in pregnancy. Future research should focus on maternal lifestyle interventions as early as possible during gestation, or even prenatally.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karsten Kaiser ◽  
Michael Festersen Nielsen ◽  
Ervin Kallfa ◽  
Greta Dubietyte ◽  
Finn Friis Lauszus

AbstractTo evaluate the incidence and timing of the diagnosis of metabolic syndrome in a cohort of Danish women after a pregnancy with gestational diabetes (GDM) to estimate the optimum time for preventative actions in relation to metabolic syndrome (MetS). In this follow-up study, 435 women were included from a consecutive cohort with prior history of GDM. Data on dyslipidemia, hypertension and other cardiovascular disorders (CVD) were extracted from the electronic patient journal. Any antidiabetic, cardiovascular and cholesterol-lowering medicine was ascertained in the national prescription database. Similarly, any blood test taken was evaluated. We defined a patient having MetS if the criteria of the WHO based definition of diabetes or impaired glucose regulation were met. Further, we added as alternative for glucose intolerance, a glycosylated hemoglobin (HbA1c) > 44 mmol/mol or the former level ≥ 6.5%. Further, dyslipidemia, lipid lowering medications, BMI > 30 kg/m2 or antihypertensive treatment were used. For MetS outcome, diagnosis or medication for CVD was registered. All women were followed for median 5.7 years (range 0; 9). The incidence of MetS was 28%. Thirteen percent of these qualified already within one year after pregnancy for the diagnosis of MetS. Postpartum MetS was detected after a median of 3 years (range 0; 7 years); further, 36 (8%) had been diagnosed with manifest diabetes after pregnancy. The diagnosis of postpartum MetS was strongly associated with the prevalence of manifest diabetes. Six years after pregnancy the rate of metabolic syndrome was more than tripled (25 vs. 89%, no DM vs manifest DM, RR: 6.7; 95% CI 2.7–17, p < 0.001). At 40 years the MetS rate nearly tripled if manifest DM was diagnosed (26 vs. 78%, no DM vs. manifest DM, RR: 3.3, 95% CI 1.8–6, p < 0.001). We found that GDM and later on manifest DM in women increase the risk of metabolic syndrome. There seems to be a window of opportunity before the early thirties where it would be especially beneficial to begin preventive efforts in women with GDM.


2018 ◽  
Vol 57 (23) ◽  
pp. 3413-3418
Author(s):  
Toshiyuki Ikeoka ◽  
Ayaka Sako ◽  
Genpei Kuriya ◽  
Hiroshi Yamashita ◽  
Ichiro Yasuhi ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Marica Franzago ◽  
Federica Fraticelli ◽  
Marta Di Nicola ◽  
Francesco Bianco ◽  
Daniela Marchetti ◽  
...  

Gestational diabetes mellitus (GDM) can be considered a silent risk for out-of-pregnancy diabetes mellitus (DM) and cardiovascular disease (CVD) later in life. We aimed to assess the predictive role of 3rd trimester lipid profile during pregnancy for the susceptibility to markers of subclinical atherosclerosis (CVD susceptibility) at 3 years in a cohort of women with history of GDM. A secondary aim is to evaluate the usefulness of novel nutrigenetic markers, in addition to traditional parameters, for predicting early subclinical atherosclerosis in such women in order to plan adequate early prevention interventions. We assessed 28 consecutive GDM women in whom we collected socio-demographic characteristics and clinical and anthropometric parameters at the 3rd trimester of pregnancy. In a single blood sample, from each patient, we assessed 9 single nucleotide polymorphisms (SNPs) from 9 genes related to nutrients and metabolism, which were genotyped by High Resolution Melting analysis. All women then attended a 3-year-postpartum follow-up and on that occasion performed an oral glucose tolerance test (OGTT, with 75 g oral glucose), the measurement of carotid artery intima-media thickness (cIMT), and analyses of metabolic parameters. In addition, we evaluated the physical activity level and the adherence to Mediterranean diet (MedDiet) using the International Physical Activity Questionnaire (IPAQ-short version) and PREDIMED questionnaires. We found an association between 3rd trimester triglycerides and cIMT (p=0.014). We also found significant associations between the APOA5 CC genotype and cIMT after adjustments for age and body mass index (p=0.045) and between the interaction CC APOA5/CC LDLR and cIMT (p=0.010). At the follow-up, the cohort also featured a mean BMI in the overweight range and a high mean waist circumference. We found no difference in the MedDiet adherence, physical activity, and smoking but an inverse correlation between the PREDIMED and the IPAQ scores with the IMT. In conclusion, this preliminary study provides insight into the predictive role of lipid profile during pregnancy and of some genetic variants on cIMT taken as a parameter of subclinical CVD susceptibility in GDM.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Pei ◽  
Huangmeng Xiao ◽  
Fenghua Lai ◽  
Zeting Li ◽  
Zhuyu Li ◽  
...  

Abstract Background This study aimed to analyze the incidence of early postpartum dyslipidemia and its potential predictors in women with a history of gestational diabetes mellitus (GDM). Methods This was a retrospective study. Five hundred eighty-nine women diagnosed with GDM were enrolled and followed up at 6–12 weeks after delivery. A 75 g oral glucose tolerance test (OGTT) and lipid levels were performed during mid-trimester and the early postpartum period. Participants were divided into the normal lipid group and dyslipidemia group according to postpartum lipid levels. Demographic and metabolic parameters were analyzed. Multiple logistic regression was performed to analyze the potential predictors for early postpartum dyslipidemia. A receiver operating characteristic curve (ROC) was calculated to determine the cut-off values. Results A total of 38.5% of the 589 women developed dyslipidemia in early postpartum and 60% of them had normal glucose metabolism. Delivery age, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of early postpartum dyslipidemia in women with a history of GDM. The cut-offs of maternal age, SBP, HbA1c values, and LDL-C levels were 35 years, 123 mmHg, 5.1%, and 3.56 mmol/L, respectively. LDL-C achieved a balanced mix of high sensitivity (63.9%) and specificity (69.2%), with the highest area under the receiver operating characteristic curve (AUC) (0.696). When LDL-C was combined with age, SBP, and HbA1c, the AUC reached to 0.733. Conclusions A lipid metabolism evaluation should be recommended in women with a history of GDM after delivery, particularly those with a maternal age > 35 years, SBP > 123 mmHg before labor, HbA1c value > 5.1%, or LDL-C levels > 3.56 mmol/L in the second trimester of pregnancy.


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