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Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation

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Title: Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation
Authors: Rachel J. Fenske, Alicia M. Weeks, Michael Daniels, Randall Nall, Samantha Pabich, Allison L. Brill, Darby C. Peter, Margaret Punt, Elizabeth D. Cox, Dawn Belt Davis, Michelle E. Kimple
Source: Metabolites, Vol 12, Iss 12, p 1234 (2022)
Publisher Information: MDPI AG, 2022.
Publication Year: 2022
Collection: LCC:Microbiology
Subject Terms: type 2 diabetes, prostaglandin E2, inflammation, diabetes control, biomarker, HbA1c, Microbiology, QR1-502
More Details: Over half of patients with type 2 diabetes (T2D) are unable to achieve blood glucose targets despite therapeutic compliance, significantly increasing their risk of long-term complications. Discovering ways to identify and properly treat these individuals is a critical problem in the field. The arachidonic acid metabolite, prostaglandin E2 (PGE2), has shown great promise as a biomarker of β-cell dysfunction in T2D. PGE2 synthesis, secretion, and downstream signaling are all upregulated in pancreatic islets isolated from T2D mice and human organ donors. In these islets, preventing β-cell PGE2 signaling via a prostaglandin EP3 receptor antagonist significantly improves their glucose-stimulated and hormone-potentiated insulin secretion response. In this clinical cohort study, 167 participants, 35 non-diabetic, and 132 with T2D, were recruited from the University of Wisconsin Hospital and Clinics. At enrollment, a standard set of demographic, biometric, and clinical measurements were performed to quantify obesity status and glucose control. C reactive protein was measured to exclude acute inflammation/illness, and white cell count (WBC), erythrocyte sedimentation rate (ESR), and fasting triglycerides were used as markers of systemic inflammation. Finally, a plasma sample for research was used to determine circulating PGE2 metabolite (PGEM) levels. At baseline, PGEM levels were not correlated with WBC and triglycerides, only weakly correlated with ESR, and were the strongest predictor of T2D disease status. One year after enrollment, blood glucose management was assessed by chart review, with a clinically-relevant change in hemoglobin A1c (HbA1c) defined as ≥0.5%. PGEM levels were strongly predictive of therapeutic response, independent of age, obesity, glucose control, and systemic inflammation at enrollment. Our results provide strong support for future research in this area.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2218-1989
Relation: https://www.mdpi.com/2218-1989/12/12/1234; https://doaj.org/toc/2218-1989
DOI: 10.3390/metabo12121234
Access URL: https://doaj.org/article/08a0b32c202b471e9122aef220854e8f
Accession Number: edsdoj.08a0b32c202b471e9122aef220854e8f
Database: Directory of Open Access Journals
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  Data: Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation
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  Data: Metabolites, Vol 12, Iss 12, p 1234 (2022)
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  Data: MDPI AG, 2022.
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  Data: <searchLink fieldCode="DE" term="%22type+2+diabetes%22">type 2 diabetes</searchLink><br /><searchLink fieldCode="DE" term="%22prostaglandin+E2%22">prostaglandin E2</searchLink><br /><searchLink fieldCode="DE" term="%22inflammation%22">inflammation</searchLink><br /><searchLink fieldCode="DE" term="%22diabetes+control%22">diabetes control</searchLink><br /><searchLink fieldCode="DE" term="%22biomarker%22">biomarker</searchLink><br /><searchLink fieldCode="DE" term="%22HbA1c%22">HbA1c</searchLink><br /><searchLink fieldCode="DE" term="%22Microbiology%22">Microbiology</searchLink><br /><searchLink fieldCode="DE" term="%22QR1-502%22">QR1-502</searchLink>
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  Data: Over half of patients with type 2 diabetes (T2D) are unable to achieve blood glucose targets despite therapeutic compliance, significantly increasing their risk of long-term complications. Discovering ways to identify and properly treat these individuals is a critical problem in the field. The arachidonic acid metabolite, prostaglandin E2 (PGE2), has shown great promise as a biomarker of β-cell dysfunction in T2D. PGE2 synthesis, secretion, and downstream signaling are all upregulated in pancreatic islets isolated from T2D mice and human organ donors. In these islets, preventing β-cell PGE2 signaling via a prostaglandin EP3 receptor antagonist significantly improves their glucose-stimulated and hormone-potentiated insulin secretion response. In this clinical cohort study, 167 participants, 35 non-diabetic, and 132 with T2D, were recruited from the University of Wisconsin Hospital and Clinics. At enrollment, a standard set of demographic, biometric, and clinical measurements were performed to quantify obesity status and glucose control. C reactive protein was measured to exclude acute inflammation/illness, and white cell count (WBC), erythrocyte sedimentation rate (ESR), and fasting triglycerides were used as markers of systemic inflammation. Finally, a plasma sample for research was used to determine circulating PGE2 metabolite (PGEM) levels. At baseline, PGEM levels were not correlated with WBC and triglycerides, only weakly correlated with ESR, and were the strongest predictor of T2D disease status. One year after enrollment, blood glucose management was assessed by chart review, with a clinically-relevant change in hemoglobin A1c (HbA1c) defined as ≥0.5%. PGEM levels were strongly predictive of therapeutic response, independent of age, obesity, glucose control, and systemic inflammation at enrollment. Our results provide strong support for future research in this area.
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        Value: 10.3390/metabo12121234
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        StartPage: 1234
    Subjects:
      – SubjectFull: type 2 diabetes
        Type: general
      – SubjectFull: prostaglandin E2
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      – SubjectFull: inflammation
        Type: general
      – SubjectFull: diabetes control
        Type: general
      – SubjectFull: biomarker
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      – SubjectFull: HbA1c
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      – TitleFull: Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation
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