title: Mild Electrical Stimulation with Heat Shock Reduces Visceral Adiposity and Improves Metabolic Abnormalities in Subjects with Metabolic Syndrome or Type 2 Diabetes: Randomized Crossover Trials.
abstract: BACKGROUND
  The induction of heat shock protein (HSP) 72 by mild electrical stimulation with heat shock (MES + HS), which improves visceral adiposity and insulin resistance in mice, may be beneficial in treating metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Using open-label crossover trials, 40 subjects with MS or T2DM were randomly assigned using computer-generated random numbers to 12 weeks of therapeutic MES + HS followed by 12 weeks of no treatment, or vice versa. During the intervention period, physical and biochemical markers were measured.
  
  
  RESULTS
  Compared to no treatment, MES + HS treatment was associated with a significant decrease in visceral adiposity (- 7.54 cm(2) (- 8.61%), 95% CI - 8.55 to - 6.53 (p = 0.037) in MS, - 19.73 cm(2) (- 10.89%), 95% CI - 20.97 to - 18.49 (p = 0.003) in T2DM). Fasting plasma glucose levels were decreased by 3.74 mg/dL (- 5.28%: 95% CI - 4.37 to - 3.09 mg/dL, p = 0.029) in MS and by 14.97 mg/dL (10.40%: 95% CI - 15.79 to 14.15 mg/dL, p < 0.001) in T2DM, and insulin levels were also reduced by 10.39% and 25.93%, respectively. HbA1c levels showed a trend toward reduction (- 0.06%) in MS, and was significantly declined by - 0.43% (95% CI - 0.55 to - 0.31%, p = 0.009) in T2DM. HbA1c level of less than 7.0% was achieved in 52.5% of the MES + HS-treated T2DM patients in contrast to 15% of the non-treated period. Several insulin resistance indices, inflammatory cytokines or adipokines, including C-reactive protein, adiponectin, and tumor necrosis factor-α, were all improved in both groups. In isolated monocytes, HSP72 expression was increased and cytokine expression was reduced following MES + HS treatment. Glucose excursions on meal tolerance test were lower after using MES + HS in T2DM.
  
  
  CONCLUSIONS
  This combination therapy has beneficial impacts on body composition, metabolic abnormalities, and inflammation in subjects with MS or T2DM. Activation of the heat shock response by MES + HS may provide a novel approach for the treatment of lifestyle-related diseases.
  
  
  BACKGROUND
  Funding for this research was provided by MEXT KAKENHI (Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology, Japan).
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kitano
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Matsuyama
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Goto
authors.affiliation: Department of Molecular Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kawasaki
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Igata
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kawashima
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoshima
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Molecular Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
keywords: Chronic inflammation; Heat shock response; Insulin resistance; Metabolic syndrome; Type 2 diabetes