Induction of Heat Shock Proteins in the Therapy of Type 2 Diabetes and Metabolic Syndrome

Exercise is one of the best therapies, if not the best, for the prevention and treatment of type 2 diabetes. Kondo, Araki, Kai and colleagues, in this issue of EBioMedicine, introduce a device that mimics exercise (1). When applied to subjects with metabolic syndrome (MS) or type 2 diabetes (t2DM) the therapy improves the diverse parameters inherit to metabolic syndrome (MS) and type 2 diabetes (t2DM)—inflammation, hypertension, glycemia, dyslipidemia, abdominal obesity, body weight, and insulin signaling. The results are a quantum leap toward understanding type 2 diabetes and treating it. The researchers are to be congratulated in their single-minded quest to move from the bench to the bedside. As they sought methods to duplicate the beneficial effects of exercise, their research moved from heat, to heat shock proteins (Hsps, also known as stress proteins), to a tailored electrical-heat stimulation that maximizes Hsp induction. Specifically, Kondo and colleagues studied 40 patients with MS or t2DM in a randomized crossover trial of 12 weeks of therapy with mild electric stimulation and heat shock (MES + HS) versus no intervention for 12 weeks. The device transmits direct electric current and heat through the upper abdomen, fitting like a cumberbund. MES + HS was applied for 1 h four times per week. Improvements in glycemic, lipid, and fat deposition measurements were more pronounced in t2DM thanMS. Of particular note was a .72% reduction in A1c in t2DM subjects with higher baseline levels (7.6–10.0%) (Kondo et al., 2014). This level of reduction is similar to that seen by recently introduced drugs like sitagliptin (a dipeptidyl peptidase 4 (DPP-4) inhibitor) that drops A1c .6% when used in monotherapy (Zerilli and Pyon, 2007). A remarkable 55% drop in albuminuria was observed in t2DMwith a drop in serum creatinine. The fall in albuminuria is in the same order of magnitude as observedwith ACE inhibitor therapy (Yilmaz et al., 2010). The same research group has demonstrated MES + HS reduced renal function loss in an animal model of renal failure (Koga et al., 2012). Regarding its efficacy in reducing inflammation in MS, MES + HS dropped hs-CRP by 54%. hs-CRP in t2DM improves prediction of cardiovascular disease and has been suggested that itsmeasurement be added to the definition of metabolic syndrome. The reduction in inflammation cannot be understated, as cardiovascular disease is indeed the major cause of mortality in these disease states (Haffner, 2006). The 54% drop in hs-CRP compares favorablywith the drop observedwith atorvastatin (35%) in t2DM patients (Sindhu et al., 2011).