title: Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy.
abstract: This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis. We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices. SBMA patients had lower body mass index, blood glucose, and Hemoglobin A1c, but higher blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR, a marker of insulin resistance), total cholesterol, and adiponectin levels than the control subjects. There were no differences in visceral fat areas, high-density lipoprotein-cholesterol (HDL-C), or triglyceride levels in two groups. Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-β, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.|Department of Neurology, Kasugai Municipal Hospital, Kasugai, Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Araki
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashizume
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hijikata
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.|Department of Clinical Research, Innovation Center for Clinical Research, National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.|Department of Neurology, Sarashina Rehabilitation Clinic, Ichihara, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Suga
authors.affiliation: Department of Neurology, Aichi Medical University School of Medicine, Aichi, Japan.|Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohyama
authors.affiliation: Hitachi, Ltd. Hitachi Health Care Center, Hitachi, Ibaraki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.|Kishida Clinic, Osaka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.|Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. ka2no@med.nagoya-u.ac.jp.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. sobueg@med.nagoya-u.ac.jp.|Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. sobueg@med.nagoya-u.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000328:Adult; D001786:Blood Glucose; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology*; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009069:Movement Disorders / Q000209:etiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D020966:Muscular Disorders, Atrophic / Q000150:complications* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011972:Receptor, Insulin / Q000378:metabolism; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008075:Lipoproteins, HDL; D011972:Receptor, Insulin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human
keywords: Insulin receptor; Insulin resistance; SBMA; Spinal and bulbar muscular atrophy