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EBioMedicine. 2014 Nov 11;1(1):80-9. doi: 10.1016/j.ebiom.2014.11.001. eCollection 2014 Nov.

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.

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Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Molecular Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.



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).


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.


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.


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.


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).


Chronic inflammation; Heat shock response; Insulin resistance; Metabolic syndrome; Type 2 diabetes

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