Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals

AIMS/HYPOTHESIS: We previously showed that type 2 diabetic patients are characterised by compromised intrinsic mitochondrial function. Here, we examined if exercise training could increase intrinsic mitochondrial function in diabetic patients compared with control individuals. METHODS: Fifteen male type 2 diabetic patients and 14 male control individuals matched for age, BMI and [Formula: see text] enrolled in a 12 week exercise intervention programme. Ex vivo mitochondrial function was assessed by high-resolution respirometry in permeabilised muscle fibres from vastus lateralis muscle. Before and after training, insulin-stimulated glucose disposal was examined during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Diabetic patients had intrinsically lower ADP-stimulated state 3 respiration and lower carbonyl cyanide 4-(trifluoro-methoxy)phenylhydrazone (FCCP)-induced maximal oxidative respiration, both on glutamate and on glutamate and succinate, and in the presence of palmitoyl-carnitine (p < 0.05). After training, diabetic patients and control individuals showed increased state 3 respiration on the previously mentioned substrates (p < 0.05); however, an increase in FCCP-induced maximal oxidative respiration was observed only in diabetic patients (p < 0.05). The increase in mitochondrial respiration was accompanied by a 30% increase in mitochondrial content upon training (p < 0.01). After adjustment for mitochondrial density, state 3 and FCCP-induced maximal oxidative respiration were similar between groups after training. Improvements in mitochondrial respiration were paralleled by improvements in insulin-stimulated glucose disposal in diabetic patients, with a tendency for this in control individuals. CONCLUSIONS/INTERPRETATION: We confirmed lower intrinsic mitochondrial function in diabetic patients compared with control individuals. Diabetic patients increased their mitochondrial content to the same extent as control individuals and had similar intrinsic mitochondrial function, which occurred parallel with improved insulin sensitivity

Evaluation of the efficacy and tolerability of miglitol in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylureas

The objective of this study is to examine the efficacy and tolerability of miglitol with respect to improving glycemic control in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment. This was a randomized, double-blinded, placebo-controlled, multicenter study. A total of 105 patients were randomized to receive 24 weeks of treatment with miglitol (n = 52; titrated from 50 mg to 100 mg 3 times daily) or placebo (n = 53). Concomitant sulfonylurea treatment and diet remained unchanged. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline at 24 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and postprandial serum insulin (PSI). The miglitol treatment group showed significantly greater reductions in HbA1c and PPG levels compared with the placebo group. With respect to adverse events, abdominal discomfort, diarrhea, and hypoglycemia occurred with similar frequency in both groups. Results of this study indicate that miglitol significantly improves metabolic control in Chinese patients with type 2 diabetes mellitus. Miglitol is safe and well tolerated, with the exception of abdominal discomfort. Therefore, miglitol may be a useful adjuvant therapy for Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Abdominal obesity and low physical activity are associated with insulin resistance in overweight adolescents: a cross-sectional study

ABSTRACT: Background: Previous studies have assessed the metabolic changes and lifestyles associated with overweight adolescents. However, these associations are unclear amongst overweight adolescents who have already developed insulin resistance. This study assessed the associations between insulin resistance and anthropometric, metabolic, inflammatory, food consumption, and physical activity variables amongst overweight adolescents. Methods: This cross-sectional study divided adolescents (n = 120) between 10 and 18 years old into 3 groups: an overweight group with insulin resistance (O + IR), an overweight group without insulin resistance (O-IR), and a normal-weight control group (NW). Adolescents were matched across groups based on age, sex, pubertal maturation, and socioeconomic strata. Anthropometric, biochemical, physical activity, and food consumption variables were assessed. Insulin resistance was assessed using homeostatic model assessment (HOMA Calculator Version 2.2.2 from ©Diabetes Trials Unit, University of Oxford), and overweight status was assessed using body mass index according to World Health Organization (2007) references. A chi-square test was used to compare categorical variables. ANOVAs or Kruskal-Wallis tests were used for continuous variables. Multiple linear regression models were used to calculate the probability of the occurrence of insulin resistance based on the independent variables. Results: The risk of insulin resistance amongst overweight adolescents increases significantly when they reach a waist circumference > p95 (OR = 1.9, CIs = 1.3-2.7, p = 0.013) and watch 3 or more hours/day of television (OR = 1.7, CIs = 0.98-2.8, p = 0.033). Overweight status and insulin resistance were associated with higher levels of inflammation (hsCRP ≥1 mg/L) and cardiovascular risk according to arterial indices. With each cm increase in waist circumference, the HOMA index increased by 0.082; with each metabolic equivalent (MET) unit increase in physical activity, the HOMA index decreased by 0.026. Conclusions: Sedentary behaviour and a waist circumference > p90 amongst overweight adolescents were associated with insulin resistance, lipid profile alterations, and higher inflammatory states. A screening that includes body mass index, in waist circumference, and physical activity evaluations of adolescents might enable the early detection of these alterations

Immunodiagnosis of endemic mycoses and bronchopulmonary aspergilosis: A multicenter study in Argentina

Fil: Canteros, C. E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Rivas, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Soria, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Lee, W. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Perrotta, Diego. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Rodero, L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Davel, Graciela Odelsia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología; Argentina.Fil: Berducci, O. Grupo EMMB; Argentina.Fil: Bonardello, N. Grupo EMMB; Argentina.Fil: Castro, H. Grupo EMMB; Argentina.Fil: Chacón, Y. Grupo EMMB; Argentina.Fil: Cendán Colombo, L. Grupo EMMB; Argentina.Fil: De Vechi, M. Grupo EMMB; Argentina.Fil: Errecalde, G. Grupo EMMB; Argentina.Fil: Fernández, N. Grupo EMMB; Argentina.FIl: Gorostiaga, J. L. Grupo EMMB; Argentina.Fil: López, C. Grupo EMMB; Argentina.Fil: Mackay, P. Grupo EMMB; Argentina.Fil: Gonzalez, R. Grupo EMMB; Argentina.Fil: Cacace, María Luisa. Grupo EMMB; Argentina.Fil: Mestron, S. Grupo EMMB; Argentina.Fil: Mónaco, L. Grupo EMMB; Argentina.Fil: Nardin, M. E. Grupo EMMB; Argentina.Fil: Ramos, L. Grupo EMMB; Argentina.Fil: Pagella, H. Grupo EMMB; Argentina.Fil: Petrussi, N. Grupo EMMB; Argentina.Fil: Pizarro, M. R. Grupo EMMB; Argentina.Fil: Sánchez, R. Grupo EMMB; Argentina.Fil: Saporiti, A. M. Grupo EMMB; Argentina.Fil: Tichellio, A. G. Grupo EMMB; Argentina.Fil: Tiraboschi, N. Grupo EMMB; Argentina.Fil: Tonelli, L. Grupo EMMB; Argentina.Fil: Zanuso, A. Grupo EMMB; Argentina.Se realizó entre 01-04-2000 y 30-03-2001, un estudio de corte transversal, para conocer la frecuencia relativa de las enfermedades por hongos dimorfos y Aspergillus spp. en la República Argentina y evaluar la certeza en el diagnóstico de los laboratorios de diferentes áreas geográficas. Participaron 25 centros de salud provenientes de 12 provincias y de la Ciudad Autónoma de Buenos Aires. Fueron analizados en el laboratorio de origen 965 sueros de pacientes con sospecha clínica de histoplasmosis (HP), paracoccidioidomicosis (PCM), coccidioidomicosis (CM) y aspergilosis. Todos los sueros positivos y el 35% de los negativos fueron reevaluados en el laboratorio de referencia por inmunodifusión doble en agar. La concordancia entre los resultados obtenidos en los centros de origen y el de referencia fue de 98,8%. Se detectaron anticuerpos específicos en 120 sueros correspondientes a 98 pacientes. El 71,4% (70 casos) de los diagnósticos correspondió a micosis endémicas (HP, PCM y CM) y el resto a aspergilosis. PCM fue diagnosticada en 47,9% (47 casos), aspergilosis en 28,6% (28 casos), HP en13,3% (13 casos) y CM en 10,2% (10 casos). La participación en este estudio fue voluntaria y no todos los centros del país estaban representados, sin embargo, las frecuencias de enfermedades fúngicas fueron las esperadas y coincidentes con estudios previos realizados a nivel nacional. (EN) In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01- 2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM) or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done locally. All positive and 35% of negative sera were retested in the reference center. Results of laboratories of origin showed 98.8% concordance with those of reference center. Antibodies against any of the etiological agents were detected in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies of the different mycoses in decreasing order w ere PCM 47 patients (47.9%), aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients (10.2%). The study was carried out on a voluntary basis and some areas of the country were not represented. However, the frequencies were in range with the expected rates in the population under study