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Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population
INTRODUCTION: Small fiber neuropathy (SFN) is an early manifestation in diabetic polyneuropathy (DPN); however, the mechanisms are not fully understood. In diabetes, SFN is presumed to be common in individuals with overt DPN, enhancing activation of polyol pathway, oxidative stress, advanced glycati...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590358/ https://www.ncbi.nlm.nih.gov/pubmed/33099510 http://dx.doi.org/10.1136/bmjdrc-2020-001739 |
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author | Kudoh, Kazuhiro Mizukami, Hiroki Itabashi, Chieko Fuke, Nobuo Osonoi, Sho Takeuchi, Yuki Wada, Kanichiro Igawa, Akiko Ogasawara, Saori Ishibashi, Yasuyuki Hakamada, Kenichi Yagihashi, Soroku Nakaji, Shigeyuki |
author_facet | Kudoh, Kazuhiro Mizukami, Hiroki Itabashi, Chieko Fuke, Nobuo Osonoi, Sho Takeuchi, Yuki Wada, Kanichiro Igawa, Akiko Ogasawara, Saori Ishibashi, Yasuyuki Hakamada, Kenichi Yagihashi, Soroku Nakaji, Shigeyuki |
author_sort | Kudoh, Kazuhiro |
collection | PubMed |
description | INTRODUCTION: Small fiber neuropathy (SFN) is an early manifestation in diabetic polyneuropathy (DPN); however, the mechanisms are not fully understood. In diabetes, SFN is presumed to be common in individuals with overt DPN, enhancing activation of polyol pathway, oxidative stress, advanced glycation end products (AGEs), and inflammation. We explored the relationship between clinicohematological factors related to DPN and pain sensation in the Japanese population. RESEARCH DESIGN AND METHODS: We conducted a population-based study, recruiting 1030 individuals (average age 54.4±0.5 years), in 2017, to participate in our Iwaki project. After initial screening by fasting blood glucose and glycohemoglobin A1c (HbA1c) measurements, the subjects were categorized into control (n=894), type 2 diabetes (n=81), and impaired fasting glucose (n=55) groups. Clinical data were gathered, and relationships between pain threshold from intraepidermal electrical stimulation (PINT) and DPN were examined by analysis of variance, post hoc test, and χ(2) tests to study correlations among and between groups of the clinical data and DPN. RESULTS: Univariate linear regression analyses showed significant correlations between PINT and serum lipopolysaccharide-binding protein (LBP) level (ß=0.1025, p=0.001). Adjustments for the clinical measurements confirmed a positive correlation (ß=0.070, p=0.034). Logistic regression analysis revealed high LBP value (>6.7 mg/dL) as a significant risk factor toward abnormal PINT (≥0.35 mA). LBP significantly correlated with the high-sensitivity C reactive protein, inflammation marker, elevated similarly in both pre-diabetic and overt-diabetic groups, compared with controls, but it did not correlate with a decreased Achilles tendon reflex. In contrast, urine 8-hydroxy-2'-deoxyguanosine, oxidative stress marker, and pentosidine, AGEs, markedly increased in individuals with type 2 diabetes with high HbA1c. CONCLUSIONS: Individuals with high LBP exhibited an elevated PINT in the Japanese population. Low level of inflammation evoked by metabolic endotoxemia is possibly implicated in the pathophysiology of SFN from pre-diabetic stage. |
format | Online Article Text |
id | pubmed-7590358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-75903582020-11-03 Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population Kudoh, Kazuhiro Mizukami, Hiroki Itabashi, Chieko Fuke, Nobuo Osonoi, Sho Takeuchi, Yuki Wada, Kanichiro Igawa, Akiko Ogasawara, Saori Ishibashi, Yasuyuki Hakamada, Kenichi Yagihashi, Soroku Nakaji, Shigeyuki BMJ Open Diabetes Res Care Pathophysiology/Complications INTRODUCTION: Small fiber neuropathy (SFN) is an early manifestation in diabetic polyneuropathy (DPN); however, the mechanisms are not fully understood. In diabetes, SFN is presumed to be common in individuals with overt DPN, enhancing activation of polyol pathway, oxidative stress, advanced glycation end products (AGEs), and inflammation. We explored the relationship between clinicohematological factors related to DPN and pain sensation in the Japanese population. RESEARCH DESIGN AND METHODS: We conducted a population-based study, recruiting 1030 individuals (average age 54.4±0.5 years), in 2017, to participate in our Iwaki project. After initial screening by fasting blood glucose and glycohemoglobin A1c (HbA1c) measurements, the subjects were categorized into control (n=894), type 2 diabetes (n=81), and impaired fasting glucose (n=55) groups. Clinical data were gathered, and relationships between pain threshold from intraepidermal electrical stimulation (PINT) and DPN were examined by analysis of variance, post hoc test, and χ(2) tests to study correlations among and between groups of the clinical data and DPN. RESULTS: Univariate linear regression analyses showed significant correlations between PINT and serum lipopolysaccharide-binding protein (LBP) level (ß=0.1025, p=0.001). Adjustments for the clinical measurements confirmed a positive correlation (ß=0.070, p=0.034). Logistic regression analysis revealed high LBP value (>6.7 mg/dL) as a significant risk factor toward abnormal PINT (≥0.35 mA). LBP significantly correlated with the high-sensitivity C reactive protein, inflammation marker, elevated similarly in both pre-diabetic and overt-diabetic groups, compared with controls, but it did not correlate with a decreased Achilles tendon reflex. In contrast, urine 8-hydroxy-2'-deoxyguanosine, oxidative stress marker, and pentosidine, AGEs, markedly increased in individuals with type 2 diabetes with high HbA1c. CONCLUSIONS: Individuals with high LBP exhibited an elevated PINT in the Japanese population. Low level of inflammation evoked by metabolic endotoxemia is possibly implicated in the pathophysiology of SFN from pre-diabetic stage. BMJ Publishing Group 2020-10-23 /pmc/articles/PMC7590358/ /pubmed/33099510 http://dx.doi.org/10.1136/bmjdrc-2020-001739 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Pathophysiology/Complications Kudoh, Kazuhiro Mizukami, Hiroki Itabashi, Chieko Fuke, Nobuo Osonoi, Sho Takeuchi, Yuki Wada, Kanichiro Igawa, Akiko Ogasawara, Saori Ishibashi, Yasuyuki Hakamada, Kenichi Yagihashi, Soroku Nakaji, Shigeyuki Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population |
title | Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population |
title_full | Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population |
title_fullStr | Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population |
title_full_unstemmed | Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population |
title_short | Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population |
title_sort | lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general japanese population |
topic | Pathophysiology/Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590358/ https://www.ncbi.nlm.nih.gov/pubmed/33099510 http://dx.doi.org/10.1136/bmjdrc-2020-001739 |
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