OBJECTIVEObservational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers, but intervention studies are required to investigate causality. We examined the acute effects on postprandial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking.RESEARCH DESIGN AND METHODSOverweight/obese adults (n = 19), aged 45–65 years, were recruited for a randomized three-period, three-treatment acute crossover trial: 1) uninterrupted sitting; 2) seated with 2-min bouts of light-intensity walking every 20 min; and 3) seated with 2-min bouts of moderate-intensity walking every 20 min. A standardized test drink was provided after an initial 2-h period of uninterrupted sitting. The positive incremental area under curves (iAUC) for glucose and insulin (mean [95% CI]) for the 5 h after the test drink (75 g glucose, 50 g fat) were calculated for the respective treatments.RESULTSThe glucose iAUC (mmol/L) ⋅ h after both activity-break conditions was reduced (light: 5.2 [4.1–6.6]; moderate: 4.9 [3.8–6.1]; both P < 0.01) compared with uninterrupted sitting (6.9 [5.5–8.7]). Insulin iAUC (pmol/L) ⋅ h was also reduced with both activity-break conditions (light: 633.6 [552.4–727.1]; moderate: 637.6 [555.5–731.9], P < 0.0001) compared with uninterrupted sitting (828.6 [722.0–950.9]).CONCLUSIONSInterrupting sitting time with short bouts of light- or moderate-intensity walking lowers postprandial glucose and insulin levels in overweight/obese adults. This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk.

Patients with type 2 diabetes have reduced gene expression of heat shock protein (HSP) 72, which correlates with reduced insulin sensitivity. Heat therapy, which activates HSP72, improves clinical parameters in these patients. Activation of several inflammatory signaling proteins such as c-jun amino terminal kinase (JNK), inhibitor of B kinase, and tumor necrosis factor-␣, can induce insulin resistance, but HSP 72 can block the induction of these molecules in vitro. Accordingly, we examined whether activation of HSP72 can protect against the development of insulin resistance. First, we show that obese, insulin resistant humans have reduced HSP72 protein expression and increased JNK phosphorylation in skeletal muscle. We next used heat shock therapy, transgenic overexpression, and pharmacologic means to overexpress HSP72 either specifically in skeletal muscle or globally in mice. Herein, we show that regardless of the means used to achieve an elevation in HSP72 protein, protection against diet-or obesityinduced hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance was observed. This protection was tightly associated with the prevention of JNK phosphorylation. These findings identify an essential role for HSP72 in blocking inflammation and preventing insulin resistance in the context of genetic obesity or high-fat feeding.inflammation ͉ stress proteins ͉ metabolic disorders ͉ JNK ͉ type 2 diabetes

The goal of this study was to review the origin, clinical relevance and treatment of pulse pressure (PP). Elevated PP is increasingly being recognized as a risk factor for cardiovascular, particularly coronary, disease. Pulse pressure is discussed in terms of both Windkessel and distributive models of the arterial circulation. Pulse pressure arises from the interaction of cardiac ejection (stroke volume) and the properties of the arterial circulation. An increased stiffness of the aorta and large arteries leads to an increase in PP through a reduction in arterial compliance and effects on wave reflection. A number of factors are known to influence arterial wall behavior and, therefore, PP. In addition to the effects of aging and blood pressure on arterial wall elasticity, there is some evidence that atherosclerosis, per se, amplifies these effects. Thus, the relationship between PP and coronary disease may be bidirectional. A number of dietary and lifestyle interventions have been shown to modify large artery behavior. These include aerobic exercise training and consumption of n-3 fatty acids. Conversely, strength training is associated with an increase in arterial stiffness and a higher PP. The effects of antihypertensive medication have been extensively studied, but many studies are difficult to interpret because of concomitant change in blood pressure, and to a lesser degree, heart rate. However a number of studies do suggest direct arterial wall effects, particularly for angiotensin-converting enzyme inhibitors. A distributed compliance model of the arterial circulation provides a framework for understanding the causes, effects and potential treatment of elevations in PP.

Background-Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activated protein kinase, in skeletal muscle. Methods and Results-Thirteen patients with type 2 diabetes mellitus received both intravenous reconstituted HDL (rHDL: 80 mg/kg over 4 hours) and placebo on separate days in a double-blind, placebo-controlled crossover study. A greater fall in plasma glucose from baseline occurred during rHDL than during placebo (at 4 hours rHDLϭϪ2.6Ϯ0.4; placeboϭϪ2.1Ϯ0.3mmol/L; Pϭ0.018). rHDL increased plasma insulin (at 4 hours rHDLϭ3.4Ϯ10.0; placeboϭ Ϫ19.2Ϯ7.4 pmol/L; Pϭ0.034) and also the homeostasis model assessment ␤-cell function index (at 4 hours rHDLϭ18.9Ϯ5.9; placeboϭ8.6Ϯ4.4%; Pϭ0.025). Acetyl-CoA carboxylase ␤ phosphorylation in skeletal muscle biopsies was increased by 1.7Ϯ0.3-fold after rHDL, indicating activation of the AMP-activated protein kinase pathway. Both HDL and apolipoprotein AI increased glucose uptake (by 177Ϯ12% and 144Ϯ18%, respectively; PϽ0.05 for both) in primary human skeletal muscle cell cultures established from patients with type 2 diabetes mellitus (nϭ5). The mechanism is demonstrated to include stimulation of the ATP-binding cassette transporter A1 with subsequent activation of the calcium/calmodulin-dependent protein kinase kinase and the AMP-activated protein kinase pathway. Conclusions-rHDL reduced plasma glucose in patients with type 2 diabetes mellitus by increasing plasma insulin and activating AMP-activated protein kinase in skeletal muscle. These findings suggest a role for HDL-raising therapies beyond atherosclerosis to address type 2 diabetes mellitus. Key Words: glucose Ⅲ insulin Ⅲ lipoproteins Ⅲ metabolism Ⅲ muscles H igh-density lipoprotein (HDL) is associated with protection from adverse cardiovascular outcomes in large epidemiological trials. 1 Type 2 diabetes mellitus and the cluster of pathologies including glucose intolerance/insulin resistance, obesity, and high plasma triglycerides that constitute the metabolic syndrome are associated with low and dysfunctional HDL. 2,3 In contrast, aerobically trained individuals have high HDL and display enhanced glucose tolerance. 4 Although the mechanisms linking low HDL to atherosclerosis are well characterized, the links between low HDL and disordered energy metabolism remain relatively unexplored. Given the high and escalating prevalence of type 2 diabetes mellitus, obesity, and the metabolic syndrome and the associated marked elevation in cardiovascular morbidity and mortality, this is an important area of investigation. Clinical Perspective p 2111Recent cell-based studies suggest that HDL may modulate plasma glucose through both insulin-dependent 5,6 and -independent mechanisms. 7 The ATP-binding cassette transporter A1 (ABCA1) has been shown to modulate insulin secretion, 6 and HDL can reverse ...

OBJECTIVETo determine whether interrupting prolonged sitting with brief bouts of lightintensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODSIn a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 6 6 years old) underwent the following 8-h conditions on three separate days (with 6-14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h 21 ) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions. RESULTS Compared with SIT CONCLUSIONSInterrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postprandial glucose, insulin, C-peptide, and triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical.Lifestyle interventions, including exercise, are the recommended front-line therapy in the management of type 2 diabetes (T2D), even after the commencement of hypoglycemic agents. Current guidelines stipulate that, in addition to 150 min/week of moderate-vigorous aerobic exercise, individuals with T2D should engage in resistance exercises at least 2-3 days/week (1). However, despite the known benefits, particularly for glucose metabolism and insulin sensitivity, meeting prescribed