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Altered triglyceride and phospholipid metabolism predates the diagnosis of gestational diabetes in obese pregnancy.

ABSTRACT: Gestational diabetes (GDM), a common pregnancy complication associated with obesity and long-term health risks, is usually diagnosed at approximately 28 weeks of gestation. An understanding of lipid metabolism in women at risk of GDM could contribute to earlier diagnosis and treatment. We tested the hypothesis that altered lipid metabolism at the beginning of the second trimester in obese pregnant women is associated with a diagnosis of GDM. Plasma samples from 831 participants (16-45 years, 15-18 weeks gestation, BMI ? 30) from the UPBEAT study of obese pregnant women were used. The lipid, sterol and glyceride fraction was isolated and analysed in a semi-quantitative fashion using direct infusion mass spectrometry. A combination of uni-, multi-variate and multi-variable statistical analyses was used to identify candidate biomarkers in plasma associated with a diagnosis of GDM (early third trimester; IADPSG criteria). Multivariable adjusted analyses showed that participants who later developed GDM had a greater abundance of several triglycerides (48:0, 50:1, 50:2, 51:5, 53:4) and phosphatidylcholine (38:5). In contrast sphingomyelins (32:1, 41:2, 42:3), lyso-phosphatidylcholine (16:0, 18:1), phosphatidylcholines (35:2, 40:7, 40:10), two polyunsaturated triglycerides (46:5, 48:6) and several oxidised triglycerides (48:6, 54:4, 56:4, 58:6) were less abundant. We concluded that both lipid and triglyceride metabolism were altered at least 10 weeks before diagnosis of GDM. Further investigation is required to determine the functional consequences of these differences and the mechanisms by which they arise.

SUBMITTER: Furse S

PROVIDER: S-EPMC7100894 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Altered triglyceride and phospholipid metabolism predates the diagnosis of gestational diabetes in obese pregnancy.

Furse Samuel S White Sara L SL Meek Claire L CL Jenkins Benjamin B Petry Clive J CJ Vieira Matias C MC Ozanne Susan E SE Dunger David B DB Poston Lucilla L Koulman Albert A

Molecular omics 20191201 6

Gestational diabetes (GDM), a common pregnancy complication associated with obesity and long-term health risks, is usually diagnosed at approximately 28 weeks of gestation. An understanding of lipid metabolism in women at risk of GDM could contribute to earlier diagnosis and treatment. We tested the hypothesis that altered lipid metabolism at the beginning of the second trimester in obese pregnant women is associated with a diagnosis of GDM. Plasma samples from 831 participants (16-45 years, 15- ...[more]

PMID: 31599289

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Project description:Aims/hypothesisThis study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; ISOGTT), insulin response and disposition index (DI) from late pregnancy (34-37 weeks gestation, T1), to early postpartum (1-5 days, T2) and late postpartum (6-12 weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in ISOGTT, insulin response and DI.MethodsISOGTT, insulin response and DI were calculated at the three time points (T1, T2 and T3) using the results of a 75 g OGTT. Adipokines, cytokines and lipids were measured prior to each OGTT. Linear mixed-effects models were used to compare changes across each time point. Changes in ISOGTT, insulin response and DI were correlated with changes in maternal adipokines, cytokines and lipids at each time point.ResultsA total of 27 women completed all assessments. Compared with T1, ISOGTT was 11.20 (95% CI 8.09, 14.31) units higher at 1-5 days postpartum (p < 0.001) and was 5.49 (95% CI 2.38, 8.60) units higher at 6-12 weeks postpartum (p < 0.001). Compared with T1, insulin response values were 699.6 (95% CI 957.5, 441.6) units lower at T2 (p < 0.001) and were 356.3 (95% CI 614.3, 98.3) units lower at T3 (p = 0.004). Compared with T1, the DI was 6434.1 (95% CI 2486.2, 10,381.0) units higher at T2 (p = 0.001) and was 4262.0 (95% CI 314.6, 8209.3) units higher at T3 (p = 0.03). There was a decrease in mean cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol from T1 to T2 (all p < 0.001), and an increase in mean C-reactive protein, IL-6 and IL-8 from T1 to T2 (all p < 0.001). Mean leptin decreased from T1 to T2 (p = 0.001). There was no significant change in mean adiponectin (p = 0.99) or TNF-α (p = 0.81) from T1 to T2. The mean maternal BMI decreased from T1 to T2 (p = 0.001) and T3 (p < 0.001). There were no significant correlations between any measure of change in ISOGTT, insulin response and DI and change in maternal cytokines, adipokines, lipids or weight from T1 to T2.Conclusions/interpretationIn women with GDM, delivery was associated with improvement in both insulin sensitivity and insulin production within the first few days. Improvement in insulin production persisted for 6-12 weeks, but insulin sensitivity deteriorated slightly. These changes in glucose metabolism were not associated to changes in lipids, leptin, inflammation markers or body weight.Trial registrationClinicalTrials.gov NCT02082301.

Project description:BACKGROUND: It is generally appreciated that gestational diabetes is a risk factor for type 2 diabetes. However, the precise relation between these 2 conditions remains unknown. We sought to determine the incidence of diabetes mellitus after diagnosis of gestational diabetes. METHODS: We used a population-based database to identify all deliveries in the province of Ontario over the 7-year period from Apr. 1, 1995, to Mar. 31, 2002. We linked these births to mothers who had been given a diagnosis of gestational diabetes through another administrative database that records people with diabetes on the basis of either physician service claims or hospital admission records. We examined database records for these women from the time of delivery until Mar. 31, 2004, a total of 9 years. We determined the presence of diabetes mellitus according to a validated administrative database definition for this condition. RESULTS: We identified 659 164 pregnant women who had no pre-existing diabetes. Of these, 21 823 women (3.3%) had a diagnosis of gestational diabetes. The incidence of gestational diabetes rose significantly over the 9-year study period, from 3.2% in 1995 to 3.6% in 2001 (p < 0.001). The probability of diabetes developing after gestational diabetes was 3.7% at 9 months after delivery and 18.9% at 9 years after delivery. After adjustment for age, urban or rural residence, neighbourhood income quintile, whether the woman had a previous pregnancy, whether the woman had hypertension after the index delivery, and primary care level before the index delivery, the most significant risk factor for diabetes was having had gestational diabetes during the index pregnancy (hazard ratio 37.28, 95% confidence interval 34.99-40.88; p < 0.001). Age, urban residence and lower income were also important factors. When analyzed by year of delivery, the rate of development of diabetes was higher among the latest subcohort of women with gestational diabetes (delivery during 1999-2001) than among the earliest subcohort (delivery during 1995 or 1996) (16% by 4.7 years after delivery v. 16% by 9.0 years). INTERPRETATION: In this large population-based study, the rate of development of diabetes after gestational diabetes increased over time and was almost 20% by 9 years. This estimate should be used by clinicians to assist in their counselling of pregnant women and by policy-makers to target these women for screening and prevention.

Project description:Gestational diabetes mellitus (GDM) is a unique form of glucose intolerance, in that it is transient and solely occurs in pregnancy. Pregnancies with GDM are at high risk of developing preeclampsia (PE), a leading cause of fetal and maternal morbidity or mortality. Since PE is associated with excessive activation of circulatory neutrophils and occurrence of neutrophil extracellular traps (NETs) in affected placentae, we examined these features in cases with GDM, as this could be a feature linking the two conditions. Our data indicate that neutrophil activity is indeed altered in GDM, exhibiting pronounced activation and spontaneous generation of NETs by isolated neutrophils in in vitro culture. In this manner, GDM may similarly affect neutrophil behavior and NET formation as witnessed in other forms of diabetes, with the addition of the physiological changes mediated by pregnancy. Since circulatory TNF-α levels are elevated in cases with GDM, a feature also observed in this study, we examined whether this pro-inflammatory cytokine contributed to neutrophil activation. By using infliximab, a clinically utilized TNF-α antagonist, we observed that the pro-NETotic effect of GDM sera was significantly reduced. We also detected pronounced neutrophil infiltrates in placentae from GDM cases. The occurrence of NETs in these tissues is suggested by the extracellular co-localization of citrullinated histones and myeloperoxidase. In addition, elevated neutrophil elastase (NE) mRNA and active enzymatic protein were also detected in such placentae. This latter finding could be important in the context of previous studies in cancer or diabetes model systems, which indicated that NE liberated from infiltrating neutrophils enters surrounding cells, altering cell signaling by the degradation of IRS1. These findings could potentiate the underlying inflammatory response process in GDM and possibly open an avenue for the therapeutic interventions in gestational hyperglycemia.

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Altered triglyceride and phospholipid metabolism predates the diagnosis of gestational diabetes in obese pregnancy.

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Altered triglyceride and phospholipid metabolism predates the diagnosis of gestational diabetes in obese pregnancy.

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