Christian Herder1, Kristine Færch2, Maren Carstensen-Kirberg3, Gordon D Lowe4, Rita Haapakoski5, Daniel R Witte6, Eric J Brunner5, Michael Roden7, Adam G Tabák8, Mika Kivimäki5, Dorte Vistisen2. 1. Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes ResearchMünchen-Neuherberg, Germany christian.herder@ddz.uni-duesseldorf.de. 2. Steno Diabetes CenterGentofte, Denmark. 3. Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes ResearchMünchen-Neuherberg, Germany. 4. Institute of Cardiovascular and Medical SciencesUniversity of Glasgow, Glasgow, UK. 5. Department of Epidemiology and Public HealthUniversity College London, London, UK. 6. Department of Public HealthAarhus University, Aarhus, Denmark Danish Diabetes AcademyOdense, Denmark. 7. Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes ResearchMünchen-Neuherberg, Germany Department of Endocrinology and DiabetologyMedical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 8. Department of Epidemiology and Public HealthUniversity College London, London, UK First Department of MedicineFaculty of Medicine, Semmelweis University, Budapest, Hungary.
Abstract
OBJECTIVE: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. DESIGN AND METHODS: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. RESULTS: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. CONCLUSIONS: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.
OBJECTIVE: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. DESIGN AND METHODS: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. RESULTS: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. CONCLUSIONS: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.
Authors: Christian Stevns Hansen; Kristine Færch; Marit Eika Jørgensen; Marek Malik; Daniel R Witte; Eric J Brunner; Adam G Tabák; Mika Kivimäki; Dorte Vistisen Journal: Diabetes Care Date: 2019-04-02 Impact factor: 19.112
Authors: Dorte Vistisen; Daniel R Witte; Eric J Brunner; Mika Kivimäki; Adam Tabák; Marit E Jørgensen; Kristine Færch Journal: Diabetes Care Date: 2018-02-16 Impact factor: 19.112
Authors: Kirstine J Belongie; Ele Ferrannini; Kjell Johnson; Patricia Andrade-Gordon; Michael K Hansen; John R Petrie Journal: PLoS One Date: 2017-08-28 Impact factor: 3.240
Authors: Cornelia Then; Christian Herder; Holger Then; Barbara Thorand; Cornelia Huth; Margit Heier; Christa Meisinger; Annette Peters; Wolfgang Koenig; Wolfgang Rathmann; Michael Roden; Michael Stumvoll; Haifa Maalmi; Thomas Meitinger; Andreas Lechner; Jürgen Scherberich; Jochen Seissler Journal: Clin Kidney J Date: 2020-09-06