Hybrid Training System Improves Insulin Resistance in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

Hybrid Training System Improves Insulin Resistance in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

SOHEI IWANAGA,^1,2 RYUKI HASHIDA,^1,2 YOSHIO TAKANO,³ MASAFUMI BEKKI,^1,2 DAN NAKANO,⁴ MASAYUKI OMOTO,^1,2 TAKESHI NAGO,^1,2 TAKUMI KAWAGUCHI,⁴ HIROO MATSUSE,^1,2 TAKUJI TORIMURA⁴ and NAOTO SHIBA^1,2

¹Division of Rehabilitation, Kurume University Hospital, Kurume, Fukuoka, Japan
²Department of Orthopedics, Kurume University School of Medicine, Kurume, Fukuoka, Japan
³Department of Physical Therapy School of Health Sciences at Fukuoka, International University Health and Welfare, Okawa, Fukuoka, Japan
⁴Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan

Insulin resistance is associated with the progression of nonalcoholic fatty liver disease (NAFLD). Insulin resistance is regulated by various cytokines, including interleukin-6 (IL-6), a proinflammatory myokine, and selenoprotein P (SeP), a liver-derived secretory hepatokine. High levels of IL-6 and/or SeP have been shown to contribute to insulin resistance, and exercise is a first-line therapy for NAFLD. We have developed a hybrid training system (HTS): a neuromuscular electrical stimulation device to enhance exercise results. We aimed to investigate the effects of HTS on insulin resistance as well as serum IL-6 and SeP in patients with NAFLD. This is a randomized, single-blind (assessor), controlled trial. Subjects with NAFLD walked on a treadmill with or without HTS (9 subjects each) for 30 minutes three times a week for six weeks (HTS vs. control group; median age 45 vs. 45; male/female 5/4 vs. 6/3). We examined subjects before the first session and at the end of the final session. Serum SeP levels were measured by ELISA which measures the fragment of SeP. In the HTS group, HOMA-IR values were significantly reduced compared to the control group (Δ−0.71 vs. Δ0.05; P < 0.05). IL-6 and SeP levels in serum were also significantly reduced compared to that of the control group (IL-6; Δ−0.6 vs. Δ0.29 pg/mL; P < 0.05, SeP; Δ−1288.5 vs. Δ−435.4 ng/mL; P < 0.05, respectively). In conclusion, we propose that HTS improves insulin resistance by reducing serum IL-6 and SeP levels in patients with NAFLD.

Keywords —— electrical stimulation; exercise; hepatokine; interleukin-6; myokine

===============================

Tohoku J. Exp. Med., 2020 , 252, 23-32.

Correspondence: Ryuki Hashida, M.D., Ph.D., Department of Orthopedics, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.

e-mail: hashida_ryuuki@med.kurume-u.ac.jp