Christian Herder1,2, Julia M Kannenberg3,2, Cornelia Huth2,4, Maren Carstensen-Kirberg3,2, Wolfgang Rathmann2,5, Wolfgang Koenig6,7, Margit Heier4, Sonja Püttgen3,2, Barbara Thorand2,4, Annette Peters2,4, Michael Roden3,2,8, Christa Meisinger2,4, Dan Ziegler3,2,8. 1. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany christian.herder@ddz.uni-duesseldorf.de. 2. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. 3. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 4. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 5. Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 6. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. 7. German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany. 8. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Abstract
OBJECTIVE: Experimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort. RESEARCH DESIGN AND METHODS: This study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6.5 years. The predictive value of systemic levels of eight biomarkers of inflammation was assessed for incident DSPN in 133 incident case subjects and 397 individuals without incident DSPN, and for DSPN progression in 57 patients with prevalent DSPN at both time points. RESULTS: Higher hs-CRP, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (IL-1RA), and soluble intercellular adhesion molecule (sICAM-1) and lower adiponectin levels were associated with incident DSPN in age- and sex-adjusted analysis; IL-18 and omentin were not. IL-6 (odds ratio 1.31 [95% CI 1.00-1.71]) and TNF-α (odds ratio 1.31 [95% CI 1.03-1.67]) remained associated with incident DSPN after adjusting for known DSPN risk factors. The addition of both cytokines to a clinical risk model improved model fit and reclassification. sICAM-1 and IL-1RA were positively associated with progression of DSPN. CONCLUSIONS: Systemic subclinical and vascular inflammation predicted both the onset and progression of DSPN over 6.5 years in an older general population. Thus modulation of inflammatory processes may be relevant to prevent and/or treat diabetic neuropathy.
OBJECTIVE: Experimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort. RESEARCH DESIGN AND METHODS: This study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6.5 years. The predictive value of systemic levels of eight biomarkers of inflammation was assessed for incident DSPN in 133 incident case subjects and 397 individuals without incident DSPN, and for DSPN progression in 57 patients with prevalent DSPN at both time points. RESULTS: Higher hs-CRP, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (IL-1RA), and soluble intercellular adhesion molecule (sICAM-1) and lower adiponectin levels were associated with incident DSPN in age- and sex-adjusted analysis; IL-18 and omentin were not. IL-6 (odds ratio 1.31 [95% CI 1.00-1.71]) and TNF-α (odds ratio 1.31 [95% CI 1.03-1.67]) remained associated with incident DSPN after adjusting for known DSPN risk factors. The addition of both cytokines to a clinical risk model improved model fit and reclassification. sICAM-1 and IL-1RA were positively associated with progression of DSPN. CONCLUSIONS: Systemic subclinical and vascular inflammation predicted both the onset and progression of DSPN over 6.5 years in an older general population. Thus modulation of inflammatory processes may be relevant to prevent and/or treat diabetic neuropathy.
Authors: Christian Stevns Hansen; Dorte Vistisen; Marit Eika Jørgensen; Daniel R Witte; Eric J Brunner; Adam G Tabák; Mika Kivimäki; Michael Roden; Marek Malik; Christian Herder Journal: Cardiovasc Diabetol Date: 2017-12-01 Impact factor: 9.951