The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized that a 12-week controlled aerobic exercise program without weight loss reduces visceral, hepatic, and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents. Twenty-nine postpubertal (Tanner stage IV and V), Hispanic adolescents, 15 obese (7 boys, 8 girls; 15.6 +/- 0.4 years; 33.7 +/- 1.1 kg/m(2); 38.3 +/- 1.5% body fat) and 14 lean (10 boys, 4 girls; 15.1 +/- 0.3 years; 20.6 +/- 0.8 kg/m(2); 18.9 +/- 1.5% body fat), completed a 12-week aerobic exercise program (4 x 30 min/week at>or =70% of peak oxygen consumption (VO(2)peak)). Measurements of cardiovascular fitness, visceral, hepatic, and intramyocellular fat content (magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS)), and insulin resistance were obtained at baseline and postexercise. In both groups, fitness increased (obese: 13 +/- 2%, lean: 16 +/- 4%; both P<0.01). In obese participants, intramyocellular fat remained unchanged, whereas hepatic fat content decreased from 8.9 +/- 3.2 to 5.6 +/- 1.8%; P<0.05 and visceral fat content from 54.7 +/- 6.0 to 49.6 +/- 5.5 cm(2); P<0.05. Insulin resistance decreased indicated by decreased fasting insulin (21.8 +/- 2.7 to 18.2 +/- 2.4 microU/ml; P<0.01) and homeostasis model assessment of insulin resistance (HOMA(IR)) (4.9 +/- 0.7 to 4.1 +/- 0.6; P<0.01). The decrease in visceral fat correlated with the decrease in fasting insulin (R(2) = 0.40; P<0.05). No significant changes were observed in any parameter in lean participants except a small increase in lean body mass (LBM). Thus, a controlled aerobic exercise program, without weight loss, reduced hepatic and visceral fat accumulation, and decreased insulin resistance in obese adolescents.

CONTEXT:Data are limited on the effects of controlled aerobic exercise programs (without weight loss) on insulin sensitivity and glucose metabolism in children and adolescents.

OBJECTIVE:To determine whether a controlled aerobic exercise program (without weight loss) improves peripheral and hepatic insulin sensitivity and affects glucose production (GPR), gluconeogenesis and glycogenolysis in sedentary lean and obese Hispanic adolescents.

PATIENTS AND DESIGN:Twenty-nine post-pubertal adolescents (14 lean: 15.1 +/- 0.3 y; 20.6 +/- 0.8 kg/m(2); 18.9+/-1.5% body fat and 15 obese: 15.6 +/- 0.4 y; 33.2 +/- 0.9 kg/m(2); 38.4 +/- 1.4% body fat) (mean +/- SE), completed a 12 wk aerobic exercise program (4 x 30 min/week at>or=70% of VO(2) peak). Peripheral and hepatic insulin sensitivity and glucose kinetics were quantified using GCMS pre- and post-exercise.

RESULTS:No weight loss occurred. Lean and obese participants complied well with the program ( approximately 90% of the exercise sessions attended, resulting in approximately 15% increase in fitness in both groups). Peripheral and hepatic insulin sensitivity were higher in lean than obese adolescents but increased in both groups; peripheral insulin sensitivity by 35 +/- 14% (lean) (p<0.05) and 59 +/- 19% (obese) (p<0.01) and hepatic insulin sensitivity by 19 +/- 7% (lean) (p<0.05) and 23 +/- 4% (obese) (p<0.01). GPR, gluconeogenesis and glycogenolysis did not differ between the groups. GPR decreased slightly, 3 +/- 1% (lean) (p<0.05) and 4 +/- 1% (obese) (p<0.01). Gluconeogenesis remained unchanged, while glycogenolysis decreased slightly in the obese group (p<0.01).

CONCLUSION:This well accepted aerobic exercise program, without weight loss, is a promising strategy to improve peripheral and hepatic insulin sensitivity in lean and obese sedentary adolescents. The small decrease in GPR is probably of limited clinical relevance.

Background and aim Gestational diabetes mellitus (GDM) poses a threat to the mother and child. The aim of this study was to examine the effect of acupressure on the glycemic control and insulin requirement of GDM females. Materials and methods Thirty GDM female patients were randomized to either the study group (SG; n=15), which was treated with acupressure and the standard antenatal care, or the control group (CG; n=15), which was treated with the standard antenatal care. Fasting and 2-h post-prandial blood glucose levels, requirement for insulin and insulin resistance were measured at 24 and 36 weeks' gestation (WG). Also, neonatal outcomes were registered at delivery. Results The pre intervention showed no statistically significant differences between SG and CG for baseline characteristics of participants (p>0.05). Within group analyses, after 12 weeks intervention had shown that 75 g oral glucose tolerance test (OGTT), insulin resistance, number of required insulin and measure of utilized insulin were significantly reduced (p<0.05), with significant increase in body mass index (BMI) (p<0.05) in both groups. All outcome measures were not significantly changed (p>0.05) between both groups at 24 and 36 WG. No significant differences (p>0.05) in pregnancy and neonatal outcomes between both groups at labor. Conclusions Acupressure may help to reduce gestational diabetes or insulin treatment for overweight female patients with GDM.

AIM/HYPOTHESIS:Skeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes. Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation. We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid (AA) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with type 2 diabetes.

METHODS:Participants with stable glucose control commenced a randomized cross-over study involving four months of AA (2×500mg/day) or placebo supplementation. Insulin sensitivity was assessed using a hyperinsulinaemic, euglycaemic clamp coupled with infusion of 6,6-D2 glucose. Muscle biopsies were measured for AA concentration and oxidative stress markers that included basal measures (2',7'-dichlorofluorescin [DCFH] oxidation, ratio of reduced-to-oxidized glutathione [GSH/GSSG] and F2-Isoprostanes) and insulin-stimulated measures (DCFH oxidation). Antioxidant concentrations, citrate synthase activity and protein abundances of sodium-dependent vitamin C transporter 2 (SVCT2), total Akt and phosphorylated Akt (ser473) were also measured in muscle samples.

RESULTS:AA supplementation significantly increased insulin-mediated glucose disposal (delta rate of glucose disappearance;∆Rd) (p=0.009), peripheral insulin-sensitivity index (p=0.046), skeletal muscle AA concentration (p=0.017) and muscle SVCT2 protein expression (p=0.008); but significantly decreased skeletal muscle DCFH oxidation during hyperinsulinaemia (p=0.007) when compared with placebo. Total superoxide dismutase activity was also lower following AA supplementation when compared with placebo (p=0.006). Basal oxidative stress markers, citrate synthase activity, endogenous glucose production, HbA1C and muscle Akt expression were not significantly altered by AA supplementation.

CONCLUSIONS/INTERPRETATION:In summary, oral AA supplementation ameliorates skeletal muscle oxidative stress during hyperinsulinaemia and improves insulin-mediated glucose disposal in people with type 2 diabetes. Findings implicate AA supplementation as a potentially inexpensive, convenient, and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes.

BACKGROUND:Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments.

METHODS:Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined.

RESULTS:The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells.

CONCLUSIONS:Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.

AIM:- To determine whether exercise training improves insulin actions through concomitant body weight loss (BWL).

METHODS:- Subjects (aged 55± 8 years) with metabolic syndrome (MetS), prediabetes (fasting blood glucose: 111 ± 2 mg·dL, HbA1c: 5.85± 0.05%) and abdominal obesity (waist circumference: 104 ± 7.9 cm) were randomly allocated to either a group performing aerobic interval training (EXER; n = 76) or a sedentary group receiving lifestyle counselling (CONT; n = 20) for 16 weeks. Results - At baseline, insulin sensitivity (according to HOMA2 and intravenous glucose tolerance test; CS), body composition and VOwere similar between the groups. After the intervention, both groups had similar BWL (1-2%), but only the EXER group showed decreased [mean (95% CI)] trunk fat mass [from 18.2 (17.4-18.9) to 17.3 kg (16.6-17.9); P<0.001] and HOMA2 scores [from 1.6 (1.5-1.7) to 1.4 (1.3-1.5); P = 0.001], and increased VO[from 2.07 (1.92-2.21) to 2.28 (2.11-2.45) LO·min; P<0.001]. However, CSdid not improve in any group. Within-group subdivision by BWL (≤ 0%, 0-3%, ≥ 3%) revealed higher CSin those with BWL≥ 3% in both groups. Trunk fat mass reductions were closely associated with CSand HOMA-IR improvement (r = -0.452-0.349; P<0.001).

CONCLUSION:- In obese MetS subjects with prediabetes, 3% BWL is required for consistent improvement in insulin sensitivity. Thus, exercise-training programmes should be combined with calorie restriction to achieve BWL levels that prevent the development of diabetes.

The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes.

The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissue. Adipose tissue macrophages play a critical role in the establishment of chronic inflammatory states and metabolic dysfunctions.(.)andextract polyphenols exhibit anti-carcinogenesis, anti-inflammatory, and anti-oxidant activities. However, the action ofpolyphenols in obesity-related inflammation has not been reported. The aim of this study was to explore the anti-inflammatory action of polyphenols fromextract (ISE) in macrophages and the interaction between macrophages and adipocytes.RAW264.7 macrophages were stimulated with LPS or conditioned medium of hypertrophied 3T3-L1 adipocytes or cocultured with differentiated adipocytes in the presence of different doses of ISE. The inflammatory cytokines were evaluated by ELISA, the MAPK, NF-κB, and IL-6/STAT3 signals were determined by immunoblotting, and the migrated function of macrophages was determined by migration assay.ISE suppressed the inflammatory mediators including NO, TNF-α, IL-6, and MCP-1 induced by either LPS or conditioned medium derived from 3T3-L1 adipocytes. ISE also decreased the production of these inflammatory mediators in cocultures of 3T3-L1 adipocytes and RAW264.7 macrophages. Furthermore, ISE blocked RAW264.7 macrophages migration toward 3T3-L1 adipocytes in cocultures. Finally, this effect of ISE might be mediated via inhibiting ERK, p38, and STAT3 activation.Our findings indicate the possibility that ISE suppresses the interaction between macrophages and adipocytes, attenuates chronic inflammation in adipose tissue and improves obesity-related insulin resistance and complication, suggesting that ISE might be a valuable medicinal food effective in improving insulin resistance and metabolic syndrome.

AIM:The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT.

METHODS:Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m(-2) min(-1)) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated.

RESULTS:In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05).

CONCLUSION:Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment.

Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postprandial energy storage. We conducted a study to examine this hypothesis by reversing muscle insulin resistance with a single bout of exercise and measuring hepatic de novo lipogenesis and hepatic triglyceride synthesis after a carbohydrate-rich meal. We studied 12 healthy, young, lean, insulin resistant individuals in an interventional, randomized cross-over trial. The response to the ingestion of a carbohydrate-rich meal was studied at rest and after one 45-min bout of exercise on an elliptical trainer. Hepatic de novo lipogenesis was assessed by using (2)H(2)O, and changes in glycogen and fat content in liver and muscle were measured by (13)C and (1)H magnetic resonance spectroscopy, respectively. Exercise resulted in a greater than threefold increase in postprandial net muscle glycogen synthesis (P<0.001), reflecting improved muscle insulin responsiveness, and a≈40% reduction (P<0.05) in net hepatic triglyceride synthesis. These changes in whole body energy storage were accompanied by a≈30% decrease in hepatic de novo lipogenesis (P<0.01) and were independent of changes in fasting or postprandial plasma glucose and insulin concentrations. These data demonstrate that skeletal muscle insulin resistance is an early therapeutic target for the treatment and prevention of atherogenic dyslipidemia and NAFLD in young insulin resistant individuals who are prone to develop the metabolic syndrome and type 2 diabetes.

BACKGROUND:and purpose Acupuncture has gained increasing attention in the treatment of insulin resistance (IR). This study systematically reviews the efficacy of acupuncture on clinical IR outcomes.

METHODS:Cochrane Central Register of Controlled Trials, Embase, Medline (via OVID), China National Knowledge Infrastructure (CNKI), Wan Fang and China Science and Technology Journal Database (VIP) were searched to collect randomized controlled trials (RCTs) of patients with IR treated by acupuncture. Meta-analysis was performed by RevMan 5.3.

RESULTS:With acupuncture, the homeostasis model assessment of insulin resistance (homa-IR) significantly decreased (mean difference (MD) = -1.04, 95% confidence interval (CI) -1.37 to -0.71; P < 0.00001), as did fasting blood glucose (FBG) (MD = -0.56, 95% CI -0.88 to -0.25; P = 0.0005), 2 h postprandial blood glucose (2hPG) (MD = -0.91, 95% CI -1.62 to -0.20; P = 0.01), and fasting insulin (FINS) (MD = -3.23, 95% CI -4.14 to -2; P < 0.00001). Meanwhile, the insulin sensitivity index (ISI) (MD = 0.36, 95% CI 0.18 to 0.53; P < 0.0001) increased, and fewer adverse events occurred.

CONCLUSION:Acupuncture may improve homa-IR, ISI, FBG, 2hPG and FINS with fewer adverse events than other treatments, making it a viable treatment for IR.

Exercise could afford multiple beneficial effects on obesity-related metabolic disorders. To address this issue, C57BL/6J mice were used to investigate the effects of 13 weeks of swim training on HFD-induced obesity and related insulin resistance and inflammation. Our results show that swim training can significantly prevent HFD-induced weight gain and increase resting energy expenditure without affecting food intake. The insulin sensitivity was enhanced in the HFD + swim group than in the HFD + sedentary group. Moreover, swim training considerably decreased serum LPS content and downregulates epididymis white adipose tissue (eWAT) expression of the inflammatory mediator Tnf-α, Il-6, and Mcp-1. In summary, 13 weeks of swim training could reverse HFD-induced metabolic disorders including insulin resistance and inflammation.

A growing interest has emerged in the beneficial effects of plant-based diets for the prevention of cardiovascular disease, diabetes and obesity. The Mediterranean diet, one of the most widely evaluated dietary patterns in scientific literature, includes in its nutrients two fluid foods: olive oil, as the main source of fats, and a low-to-moderate consumption of wine, mainly red, particularly during meals. Current mechanisms underlying the beneficial effects of the Mediterranean diet include a reduction in inflammatory and oxidative stress markers, improvement in lipid profile, insulin sensitivity and endothelial function, as well as antithrombotic properties. Most of these effects are attributable to bioactive ingredients including polyphenols, mono- and poly-unsaturated fatty acids. Polyphenols are a heterogeneous group of phytochemicals containing phenol rings. The principal classes of red wine polyphenols include flavonols (quercetin and myricetin), flavanols (catechin and epicatechin), anthocyanin and stilbenes (resveratrol). Olive oil has at least 30 phenolic compounds. Among them, the main are simple phenols (tyrosol and hydroxytyrosol), secoroids and lignans. The present narrative review focuses on phenols, part of red wine and virgin olive oil, discussing the evidence of their effects on lipids, blood pressure, atheromatous plaque and glucose metabolism.

AIMS:We investigated whether sprint interval training (SIT) was a time-efficient exercise strategy to improve insulin sensitivity and other indices of cardiometabolic health to the same extent as traditional moderate-intensity continuous training (MICT). SIT involved 1 minute of intense exercise within a 10-minute time commitment, whereas MICT involved 50 minutes of continuous exercise per session.

METHODS:Sedentary men (27±8y; BMI = 26±6kg/m2) performed three weekly sessions of SIT (n = 9) or MICT (n = 10) for 12 weeks or served as non-training controls (n = 6). SIT involved 3x20-second 'all-out' cycle sprints (~500W) interspersed with 2 minutes of cycling at 50W, whereas MICT involved 45 minutes of continuous cycling at ~70% maximal heart rate (~110W). Both protocols involved a 2-minute warm-up and 3-minute cool-down at 50W.

RESULTS:Peak oxygen uptake increased after training by 19% in both groups (SIT: 32±7 to 38±8; MICT: 34±6 to 40±8ml/kg/min; p<0.001 for both). Insulin sensitivity index (CSI), determined by intravenous glucose tolerance tests performed before and 72 hours after training, increased similarly after SIT (4.9±2.5 to 7.5±4.7, p = 0.002) and MICT (5.0±3.3 to 6.7±5.0 x 10-4 min-1 [μU/mL]-1, p = 0.013) (p<0.05). Skeletal muscle mitochondrial content also increased similarly after SIT and MICT, as primarily reflected by the maximal activity of citrate synthase (CS; P<0.001). The corresponding changes in the control group were small for VO2peak (p = 0.99), CSI (p = 0.63) and CS (p = 0.97).

CONCLUSIONS:Twelve weeks of brief intense interval exercise improved indices of cardiometabolic health to the same extent as traditional endurance training in sedentary men, despite a five-fold lower exercise volume and time commitment.