Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study.
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.



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.



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.



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.
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.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Christian
C
Herder
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Julia M
JM
Kannenberg
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Cornelia
C
Huth
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Maren
M
Carstensen-Kirberg
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Wolfgang
W
Rathmann
Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany.
Wolfgang
W
Koenig
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Margit
M
Heier
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Sonja
S
Püttgen
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Barbara
B
Thorand
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Annette
A
Peters
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Michael
M
Roden
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Christa
C
Meisinger
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Dan
D
Ziegler
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein