Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop type 2 diabetes

Lai, Mi; Rijjal, Dana Al; Röst, Hannes L.; Dai, Feihan F.; Gunderson, Erica P.; Wheeler, Michael B.

doi:10.7554/elife.59153

Cited by 25 publications

(30 citation statements)

References 44 publications

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“…We identified downregulated sphingolipid metabolism as the major molecular pathway eclipsing upregulated fatty acid biosynthesis in the Hispanic cohort ( Figure 2 A). Our findings support a previously identified association between sphingolipids with T2D development ( Buschard et al., 2005 ; Khan et al., 2019b ; Lai et al., 2020 ). Experimentally, we show that downregulated sphingolipid metabolism in mice affected insulin sensitivity ( Figure 3 C) and caused pancreatic β cell dysfunction in both isolated islets and pancreatic β cells ( Figure 4 ).…”

Section: Discussionsupporting

confidence: 92%

“…This study intended to gain a better understanding of the early-stage T2D pathophysiology, excluding major confounding factors (i.e., race, age, BMI, sex, and blood glucose). To this end, we designed a 1:1 pair-matched (i.e., race, age, BMI, sex, and glucose tolerance) case-control study that mined metabolomic ( Allalou et al., 2016 ) and lipidomic ( Khan et al., 2019b ; Lai et al., 2020 ) datasets of the SWIFT cohort. We identified downregulated sphingolipid metabolism as the major molecular pathway eclipsing upregulated fatty acid biosynthesis in the Hispanic cohort ( Figure 2 A).…”

Section: Discussionmentioning

confidence: 99%

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Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction

et al. 2020

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Summary Gestational diabetes mellitus (GDM) is the top risk factor for future type 2 diabetes (T2D) development. Ethnicity profoundly influences who will transition from GDM to T2D, with high risk observed in Hispanic women. To better understand this risk, a nested 1:1 pair-matched, Hispanic-specific, case-control design was applied to a prospective cohort with GDM history. Women who were non-diabetic 6–9 weeks postpartum (baseline) were monitored for the development of T2D. Metabolomics were performed on baseline plasma to identify metabolic pathways associated with T2D risk. Notably, diminished sphingolipid metabolism was highly associated with future T2D. Defects in sphingolipid metabolism were further implicated by integrating metabolomics and genome-wide association data, which identified two significantly enriched T2D-linked genes, CERS2 and CERS4 . Follow-up experiments in mice and cells demonstrated that inhibiting sphingolipid metabolism impaired pancreatic β cell function. These data suggest early postpartum alterations in sphingolipid biosynthesis contribute to β cell dysfunction and T2D risk.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction

et al. 2020

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“…Risk factors for GDM are known to be affected by hormonal changes and genetic factors as well as environmental factors such as obesity, diet, and lack of exercise [1][2][3]5]. Among environmental factors, food has been reported as an important factor, and it has been suggested that the frequent consumption of carbohydrates composed of simple sugars or animal fats is closely related to diabetes [8,9].…”

Section: Discussionmentioning

confidence: 99%

“…With its prevalence clearly growing worldwide-specifically in South Korea, it is also rising-the trend has been suggested to be due to an inflation in the average maternal age at childbirth and a problem resulting from a lack of exercise [4]. Although the risk factors for GDM are similar to those for type 2 diabetes, its onset is known to be affected by overweightness, lack of exercise, and environmental factors and eating habits [5]. In addition, GDM has been reported to cause various physiological negative effects in pregnancy and on the fetus such as prematurity and fetal macrosomia [3].…”

Section: Introductionmentioning

confidence: 99%

Experiences of Changes in Eating Habits and Eating Behaviors of Women First Diagnosed with Gestational Diabetes

Kim

Cho

Shin

2021

IJERPH

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As gestational diabetes, which is increasing steadily around the world, can cause complications in the mother and fetus, it is essential to change eating habits and eating behavior to prevent this. According to the 2020 American Diabetes Association recommendations, the food plan should be designed for the adequate calorie intake to achieve glycemic goals and consequently promote maternal and fetal health. Thus, the following study has used the qualitative theme analysis method to assess what it means for 28 South Korean women, who were diagnosed with gestational diabetes for the first time, to change their eating habits and behaviors. As a result, themes were derived related to reflection on daily life, formation of new relationships in the same group, efforts that must be made, rediscovery of couples, and lifestyles reborn as new roles. Based on the results of the study, it is shown that the study participants recovered the peace in their mental state after the crisis of gestational diabetes to pursue relaxation and ultimately higher quality of life by following the plan to fulfill healthy achievements, such as changing their eating habits and behaviors. Therefore, future research and support measures to help the healthy behaviors should be sought by comprehensively exploring the effects of women’s experiences in changing their eating habits and behaviors.

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“…The lipidomics data was obtained from our recently published paper where the details of lipidomics analysis were described [36]…”

Section: Targeted Lipidomic Profiling and Data Pre-processingmentioning

confidence: 99%

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

Zhang

Lai

Piro

et al. 2021

BMC Med

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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.

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Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop type 2 diabetes

Cited by 25 publications

References 44 publications

Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction

Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction

Experiences of Changes in Eating Habits and Eating Behaviors of Women First Diagnosed with Gestational Diabetes

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

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