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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. 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. 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. ClinicalTrials.gov Identifier: NCT01967030.

Few projects adequately address design and evaluation Payments for Ecosystem Services (PES) mechanisms leverage economic and social incentives to shape how people influence natural processes and achieve conservation and sustainability goals. Beneficiaries of nature's goods and services pay owners or stewards of ecosystems that produce those services, with payments contingent on service provision ( 1 , 2 ). Integrating scientific knowledge and methods into PES is critical ( 3 , 4 ). Yet many projects are based on weak scientific foundations, and effectiveness is rarely evaluated with the rigor necessary for scaling up and understanding the importance of these approaches as policy instruments and conservation tools ( 2 , 5 , 6 ). Part of the problem is the lack of simple, yet rigorous, scientific principles and guidelines to accommodate PES design and guide research and analyses that foster evaluations of effectiveness ( 4 ). As scientists and practitioners from government, nongovernment, academic, and finance institutions, we propose a set of such guidelines and principles.

An ecological threshold is the point at which there is an abrupt change in an ecosystem quality, property or phenomenon, or where small changes in an environmental driver produce large responses in the ecosystem. Analysis of thresholds is complicated by nonlinear dynamics and by multiple factor controls that operate at diverse spatial and temporal scales. These complexities have challenged the use and utility of threshold concepts in environmental management despite great concern about preventing dramatic state changes in valued ecosystems, the need for determining critical pollutant loads and the ubiquity of other threshold-based environmental problems. In this paper we define the scope of the thresholds concept in ecological science and discuss methods for identifying and investigating thresholds using a variety of examples from terrestrial and aquatic environments, at ecosystem, landscape and regional scales. We end with a discussion of key research needs in this area.

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 .

Unsustainable fishing simplifies food chains and, as with aquaculture, can result in reliance on a few economically valuable species. This lack of diversity may increase risks of ecological and economic disruptions. Centuries of intense fishing have extirpated most apex predators in the Gulf of Maine (United States and Canada), effectively creating an American lobster (Homarus americanusj monoculture. Over the past 20 years, the economic diversity of marine resources harvested in Maine has declined by almost 70%. Today, over 80% of the value of Maine's fish and seafood landings is from highly abundant lobsters. Inflationcorrected income from lobsters in Maine has steadily increased by nearly 400% since 1985. Fisheries managers, policy makers, and fishers view this as a success. However, such lucrative monocultures increase the social and ecological consequences of future declines in lobsters. In southern New England, disease and stresses related to increases in ocean temperature resulted in more than a 70% decline in lobster abundance, prompting managers to propose closing that fishery. A similar collapse in Maine could fundamentally disrupt the social and economic foundation of its coast. We suggest the current success of Maine's lobster fishery is a gilded trap. Gilded traps are a type of social trap in which collective actions resulting from economically attractive opportunities outweigh concerns over associated social and ecological risks or consequences. Large financial gain creates a strong reinforcing feedback that deepens the trap. Avoiding or escaping gilded traps requires managing for increased biological and economic diversity. This is difficult to do prior to a crisis while financial incentives for maintaining the status quo are large. The long-term challenge is to shift fisheries management away from single species toward integrated social-ecological approaches that diversify local ecosystems, societies, and economies. La pesca no sustentable simplifica las cadenas alimenticias y, como la acuicultura, puede resultar en una dependencia en unas cuantas especies valiosas económicamente. Esta falta de biodiversidad puede incrementar los riesgos de disrupciones ecológicas y económicas. Siglos de pesca intensiva ban extirpado a la mayoría de los depredadores superiores en el Golfo de Maine (E.U.A. y Canadá), creando efectivamente un monocultivo de langosta americana Homarus americanus). Durante los últimos 20 años, la diversidad económica de los recursos marinos cosechados en Maine ha declinado en casi 70%. Ahora, más de 80% del valor de las capturas de peces y mariscos consiste en langostas que son muy abundantes. El ingreso, corregido para la inflación, por langostas ha incrementado consistentemente en casi 400% desde 1985. Manejadores de pesquerías, políticos y Pescadores ven esto como un éxito. Sin embargo, tales monocultivos lucrativos incrementan las consecuencias sociales y ecológicas de declinaciones de langostas en el futuro. En el sur de Nueva Inglaterra, las enfermedades y los estreses relacionados con incrementos en la temperatura del océano resultaron en una declinación de mas de 70% en la abundancia de langostas, lo que obligó a la propuesta del cierre de esa pesquería. Un colapso similar en Maine podría desestabilizar la base social y económica de su costa. Sugerimos que el éxito actual de la pesquería de langosta en Maine es una trampa dorada. Las trampas doradas son un tipo de trampa social en el que las acciones colectivas derivadas de oportunidades atractivas económicamente sobrepasan a las preocupaciones por los riesgos o consecuencias ecológicas y sociales asociadas. El gran ingreso financiero crea una fuerte retroalimentación reforzante que profundiza la trampa. Escapar de o evitar las trampas doradas requiere de manejo para el incremento de la diversidad biológica y ecológica. Esto es difícil de hacer antes de una crisis mientras los incentivos financieros para mantener el status quo son grandes. El reto a largo plazo es cambiar el manejo de pesquerías de una sola especie hacia enfoques sociales-ecológicos integrados que diversifiquen los ecosistemas, las sociedades y las economías locales.

Approximately, 35% of women with Gestational Diabetes (GDM) progress to Type 2 Diabetes (T2D) within 10 years. However, links between GDM and T2D are not well understood. We used a well-characterised GDM prospective cohort of 1035 women following up to 8 years postpartum. Lipidomics profiling covering >1000 lipids was performed on fasting plasma samples from participants 6–9 week postpartum (171 incident T2D vs. 179 controls). We discovered 311 lipids positively and 70 lipids negatively associated with T2D risk. The upregulation of glycerolipid metabolism involving triacylglycerol and diacylglycerol biosynthesis suggested activated lipid storage before diabetes onset. In contrast, decreased sphingomyelines, hexosylceramide and lactosylceramide indicated impaired sphingolipid metabolism. Additionally, a lipid signature was identified to effectively predict future diabetes risk. These findings demonstrate an underlying dyslipidemia during the early postpartum in those GDM women who progress to T2D and suggest endogenous lipogenesis may be a driving force for future diabetes onset.