title: Plasma Levels of the Interleukin-1-Receptor Antagonist Are Lower in Women with Gestational Diabetes Mellitus and Are Particularly Associated with Postpartum Development of Type 2 Diabetes.
abstract: Diabetes mellitus is a group of diseases characterized by chronic hyperglycemia. Women who develops hyperglycemia for the first time during pregnancy receive the diagnosis gestational diabetes mellitus (GDM). Presently, there is no consensus about the diagnostic criteria for GDM. A majority of these women subsequently develop postpartum overt diabetes making it important to identify these patients as early as possible. In this study we investigated if plasma levels of the interleukin-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1 signaling, can be used as a complementary biomarker for diagnosing GDM and predicting postpartum development of overt diabetes mellitus. Patients participating in this study (n = 227) were diagnosed with their first GDM 2004-2013 at Lund University Hospital, Lund, Sweden. Healthy pregnant volunteers (n = 156) were recruited from women's welfare centers in the same region 2014-2015. Levels of IL-1Ra and C-peptide were analyzed in ethylenediaminetetraacetic acid (EDTA)-plasma or serum using enzyme linked immunosorbent assay (ELISA). GDM patients had significantly lower levels of IL-1Ra than the control group (p = 0.012). In addition, GDM patients that had developed impaired glucose tolerance (IGT) or type 2 diabetes mellitus postpartum had significantly lower levels of IL-1Ra, and significantly higher levels of C-peptide than GDM patients that had not developed diabetes mellitus postpartum (p = 0.023) and (p = 0.0011) respectively. An inverse correlation was found between IL-1Ra and serum C-peptide levels in the control group (rs = -0.31 p = 0.0001). Our results show that IL-1Ra might be included in a future panel of biomarkers, both for diagnosing GDM to complement blood glucose, and also identifying GDM patients that are at risk of developing type 2 diabetes mellitus postpartum. However, the ROC curve analysis provided a sensitivity of 52.2% and specificity of 67.1%, which nonetheless may not be sufficient enough to use IL-1Ra as a sole biomarker.
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, Lund, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Katra
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, Lund, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Dereke
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, Lund, Sweden.|Department of Pediatrics, Helsingborg Hospital, Helsingborg, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, Lund, Sweden.
authors.forename: Magnus
authors.identifier: 0000-0001-6749-2829
authors.initials: M
authors.lastname: Hillman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D008297:Male; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood*; D011644:Puerperal Disorders / Q000097:blood*
chemical_list: D015415:Biomarkers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein