Abstract
BackgroundThe 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). MethodsUsing open-label crossover trials, 40 subjects with MS or T2DM were randomly assigned using computer-generated random numbers to 12weeks of therapeutic MES+HS followed by 12weeks of no treatment, or vice versa. During the intervention period, physical and biochemical markers were measured. FindingsCompared to no treatment, MES+HS treatment was associated with a significant decrease in visceral adiposity (−7.54cm2 (−8.61%), 95% CI −8.55 to −6.53 (p=0.037) in MS, −19.73cm2 (−10.89%), 95% CI −20.97 to −18.49 (p=0.003) in T2DM). Fasting plasma glucose levels were decreased by 3.74mg/dL (−5.28%: 95% CI −4.37 to −3.09mg/dL, p=0.029) in MS and by 14.97mg/dL (10.40%: 95% CI −15.79 to 14.15mg/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. InterpretationThis 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. FundingFunding for this research was provided by MEXT KAKENHI (Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology, Japan).
Highlights
DCCT, UKPDS and our Kumamoto Study (Shichiri et al, 2000) have shown that strict glycemic control could prevent microvascular complications, the increase of diabetes is still an important issue worldwide
Visceral fat has been demonstrated to express more pro-inflammatory cytokines than subcutaneous fat in obese states (Ohman et al, 2009). Inflammatory markers such as C-reactive protein (CRP) (Tamakoshi et al, 2003) and tumor necrosis factor (TNF)-α have been linked to metabolic syndrome (MS)
We investigated the effects of mild electrical stimulation (MES) + heat shock (HS) on glucose homeostasis, insulin resistance, visceral adiposity and inflammatory cytokine levels in male subjects with MS or type 2 diabetes mellitus (T2DM)
Summary
DCCT, UKPDS and our Kumamoto Study (Shichiri et al, 2000) have shown that strict glycemic control could prevent microvascular complications, the increase of diabetes is still an important issue worldwide. Visceral fat has been demonstrated to express more pro-inflammatory cytokines than subcutaneous fat in obese states (Ohman et al, 2009). Inflammatory markers such as C-reactive protein (CRP) (Tamakoshi et al, 2003) and tumor necrosis factor (TNF)-α have been linked to MS. 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). HSP72 expression was increased and cytokine expression was reduced following MES + HS treatment.
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