代谢组特征助力妊娠期糖尿病女性产后糖尿病患病风险预测
创作:Epi汪 审核:Epi汪 2020年06月05日
  • 纳入1010名患有妊娠期糖尿病(GDM),但之前无糖尿病病史的女性,产后及2年后,分别收集血样,并记录其产后8年内2型糖尿病(T2DM)发病情况,进行巢式病例对照研究;
  • 共鉴定出10种与T2DM发展有关的产后代谢产物变化,该变化可以预测未来T2DM风险,准确性达88.3%;
  • 具体代谢组特征表现为氨基酸、精氨酸/脯氨酸、支链氨基酸代谢上调,而鞘脂类、酰烷基甘油磷脂代谢水平下调;
  • GDM女性产后代谢组紊乱或可预测未来T2DM患病风险。
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Epi汪
诸多流行病学证据表明,妊娠期患有妊娠期糖尿病的女性未来得2型糖尿病的风险增高,但是其中的具体机制并不清楚。本研究通过巢式病例对照研究设计,发现产后女性血液中代谢水平的改变,或可预示未来2型糖尿病的患病风险。该研究具有重大的临床推广意义。
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PLoS Medicine [IF:10.5]

Amino acid and lipid metabolism in post-gestational diabetes and progression to type 2 diabetes: A metabolic profiling study

妊娠期糖尿病女性产后氨基酸和脂质代谢特征及其与未来2型糖尿病发展的关联:代谢组研究

10.1371/journal.pmed.1003112

2020-05-20, Article

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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) during midlife and an elevated risk of developing hypertension and cardiovascular disease. Glucose tolerance reclassification after delivery is recommended, but fewer than 40% of women with GDM are tested. Thus, improved risk stratification methods are needed, as is a deeper understanding of the pathology underlying the transition from GDM to T2D. We hypothesize that metabolites during the early postpartum period accurately distinguish risk of progression from GDM to T2D and that metabolite changes signify underlying pathophysiology for future disease development.
Methods and findings: The study utilized fasting plasma samples collected from a well-characterized prospective research study of 1,035 women diagnosed with GDM. The cohort included racially/ethnically diverse pregnant women (aged 20–45 years—33% primiparous, 37% biparous, 30% multiparous) who delivered at Kaiser Permanente Northern California hospitals from 2008 to 2011. Participants attended in-person research visits including 2-hour 75-g oral glucose tolerance tests (OGTTs) at study baseline (6–9 weeks postpartum) and annually thereafter for 2 years, and we retrieved diabetes diagnoses from electronic medical records for 8 years. In a nested case–control study design, we collected fasting plasma samples among women without diabetes at baseline (n = 1,010) to measure metabolites among those who later progressed to incident T2D or did not develop T2D (non-T2D). We studied 173 incident T2D cases and 485 controls (pair-matched on BMI, age, and race/ethnicity) to discover metabolites associated with new onset of T2D. Up to 2 years post-baseline, we analyzed samples from 98 T2D cases with 239 controls to reveal T2D-associated metabolic changes. The longitudinal analysis tracked metabolic changes within individuals from baseline to 2 years of follow-up as the trajectory of T2D progression. By building prediction models, we discovered a distinct metabolic signature in the early postpartum period that predicted future T2D with a median discriminating power area under the receiver operating characteristic curve of 0.883 (95% CI 0.820–0.945, p < 0.001). At baseline, the most striking finding was an overall increase in amino acids (AAs) as well as diacyl-glycerophospholipids and a decrease in sphingolipids and acyl-alkyl-glycerophospholipids among women with incident T2D. Pathway analysis revealed up-regulated AA metabolism, arginine/proline metabolism, and branched-chain AA (BCAA) metabolism at baseline. At follow-up after the onset of T2D, up-regulation of AAs and down-regulation of sphingolipids and acyl-alkyl-glycerophospholipids were sustained or strengthened. Notably, longitudinal analyses revealed only 10 metabolites associated with progression to T2D, implicating AA and phospholipid metabolism. A study limitation is that all of the analyses were performed with the same cohort. It would be ideal to validate our findings in an independent longitudinal cohort of women with GDM who had glucose tolerance tested during the early postpartum period.
Conclusions: In this study, we discovered a metabolic signature predicting the transition from GDM to T2D in the early postpartum period that was superior to clinical parameters (fasting plasma glucose, 2-hour plasma glucose). The findings suggest that metabolic dysregulation, particularly AA dysmetabolism, is present years prior to diabetes onset, and is revealed during the early postpartum period, preceding progression to T2D, among women with GDM.

First Authors:
Mi Lai

Correspondence Authors:
Feihan F Dai,Hannes L Ro¨st,Erica P Gunderson,Michael B Wheeler

All Authors:
Mi Lai,Ying Liu,Gabriele V Ronnett,Anne Wu,Brian J Cox,Feihan F Dai,Hannes L Ro¨st,Erica P Gunderson,Michael B Wheeler

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Medical Xpress新闻网站

Blood test could predict diabetes years before it strikes

2020-05-22

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