OBJECTIVEDiabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed.RESEARCH DESIGN AND METHODSMitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition– and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed.RESULTSWaist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA1c, high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O2 consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist.CONCLUSIONSOxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.

Objective: Increased C3 has been related to body mass index (BMI) and insulin resistance, although there are not sufficient studies in subjects with morbid obesity. The purpose of this study was to evaluate the levels of C3 as a function of the BMI in subjects of both sexes, with severe, morbid and extreme obesity, and their possible relationship to insulin resistance or associated diseases such as diabetes, hypertension and dyslipidemia. Subjects: The study included a total of 316 patients (110 men and 206 women) with severe obesity (17.1%), morbid obesity (54.4%) and extreme obesity (28.4%), with an average BMI of 46.7077.37 kg/m 2 . Measurements: The glucose and insulin levels were determined baseline, and 2 h after a 75 g of oral glucose load. The homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated. A lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B100) was obtained and C3 levels determined by nephelometry. Results: When distributing the patients by quartiles of BMI, we found a progressive increase in the levels of C3, and no significant differences in the rest of analytical variables studied were found; the mean values of C3 were 127.78729.7 mg/dl. A significant correlation was found between C3 and the BMI (r ¼ 0.263, Po0.001), baseline insulin (r ¼ 0.237, P ¼ 0.001) and HOMA-IR (r ¼ 0.237, P ¼ 0.001). High blood pressure was found in 111 patients, type 2 diabetes in 74 patients and dyslipidemia in 139 cases. When distributing the levels of C3 according to the number of associated risk factors (hypertension, diabetes and dyslipidemia), we found significant differences between these patients and those who presented no associated diseases (Po0.01). Conclusion: A relationship between C3 and the progressive increase of BMI in subjects with severe, morbid or extreme obesity was established. This increase in C3 was closely related to insulin levels and the values for HOMA-IR. Furthermore, we also found an increase in C3 as more diseases related to insulin resistance, such as diabetes, hypertension and dyslipidemia, were associated with the obesity.

Introduction One of the factors involved in type 2 diabetes in males is a reduction in levels of testosterone, which has been shown to predict resistance to insulin and the development of cardiovascular diseases. Aim To assess the levels of testosterone in patients with type 2 diabetes and to evaluate their relationship with cardiovascular risk factors, peripheral arterial disease (PAD) and silent myocardial ischemia (SMI). Methods Total testosterone and sex hormone binding globulin were measured and free and bioavailable testosterones were calculated using Vermeulen’s formula. Levels of total testosterone ≥12 nmol/L or free testosterone >225 pmol/L were considered normal. PAD was evaluated using the ankle-brachial index. SMI was assessed using a baseline ECG, Doppler echocardiogram, 24-hour electrocardiogram (ECG) Holter, exercise stress testing (EST), nuclear stress (if EST inconclusive), and if the result was positive, a coronary angiography. Main Outcome Measures PAD, SMI, testosterone, erectile dysfunction, 24-hour blood pressure Holter, body mass index (BMI), waist circumference, lipid profile, insulin resistance, chronic inflammation, United Kingdom Prospective Diabetes Study cardiovascular risk score, nephropathy, retinopathy, and neuropathy. Results The study population was composed of 192 diabetic males with a mean age of 56.1 ± 7.8 years and without a history of vascular disease. Twenty-three percent presented total testosterone below normal and 21.8% presented low free testosterone. BMI, waist circumference, neuropathy, triglycerides, C-reactive protein (CRP), glucose, insulin, and HOMA-IR were found to be significantly incremented with respect to subjects with normal testosterone. There was a negative correlation of HOMA-IR with total testosterone. PAD was detected in 12% and SMI in 10.9% of subjects, and differences were not related to testosterone levels. Conclusions We have verified the prevalence of low testosterone levels in male patients with type 2 diabetes and have related them to variations in BMI, waist circumference, neuropathy, triglycerides, CRP, glucose, insulin and HOMA-IR, but not with an increase of SMI or PAD.