Explore the vast range of titles available.

The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity.

Background Cardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years. Methods This observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods. Results Subclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81–108, p  < 0.001) for MACE and an odds ratio (OR) of 7.57 (95% CI 1.97–53.9, p  = 0.004) for death. Conclusion Subclinical atherosclerosis is independently associated with increased overall mortality and MACE in patients with type 1 diabetes. Identifying clinical predictors can improve risk stratification and personalised therapeutic strategies to prevent MACEs in this high-risk population. Graphical Abstract

Serum Visfatin Increases With Progressive β-Cell Deterioration Abel López-Bermejo 1 2 , Berta Chico-Julià 1 2 , Mercè Fernàndez-Balsells 1 2 , Mònica Recasens 1 2 , Eduardo Esteve 1 2 , Roser Casamitjana 3 , Wifredo Ricart 1 2 and José-Manuel Fernández-Real 1 2 1 Diabetes, Endocrinology and Nutrition Unit, Dr. Josep Trueta Hospital, Girona, Spain 2 Girona Institute for Biomedical Research, Girona, Spain 3 Endocrine Laboratory, University Clinical Hospital, Barcelona, Spain Address correspondence and reprint requests to Abel López-Bermejo, MD, Unit of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Av. Francia s/n, 17007 Girona, Spain. E-mail: uden.alopez{at}htrueta.scs.es Abstract Visfatin has shown to be increased in type 2 diabetes but to be unrelated to insulin sensitivity. We hypothesized that visfatin is associated with insulin secretion in humans. To this aim, a cross-sectional study was conducted in 118 nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1 diabetic patients with long-standing disease ( n = 58; 31 men and 27 women) were also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity ( S i ) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (β = −0.29, P = 0.001). Circulating visfatin was increased in type 2 diabetes (mean 18 [95% CI 16–21] vs. 15 ng/ml [13–17] for type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for sex, age, and BMI), although this association was largely attenuated after accounting for HbA 1c (A1C). Finally, circulating visfatin was found to be increased in patients with long-standing type 1 diabetes, even after adjusting for A1C values (37 ng/ml [34–40]; P < 0.0001, adjusted for sex, age, BMI, and A1C compared with either type 2 diabetic or nondiabetic subjects). In summary, circulating visfatin is increased with progressive β-cell deterioration. The study of the regulation and role of visfatin in diabetes merits further consideration. AIRg, acute insulin response to glucose FSIGT, frequently sampled intravenous glucose tolerance test OGTT, oral glucose tolerance test Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted July 19, 2006. Received February 23, 2006. DIABETES

Serum Interleukin-6 Correlates With Endothelial Dysfunction in Healthy Men Independently of Insulin Sensitivity Eduardo Esteve , MD, PHD 1 2 , Antoni Castro , MD, PHD 1 2 , Abel López-Bermejo , MD, PHD 1 2 , Joan Vendrell , MD, PHD 3 , Wifredo Ricart , MD 1 2 and Jose-Manuel Fernández-Real , MD, PHD 1 2 1 Unit of Diabetes, Endocrinology, and Nutrition, Department of Internal Medicine, Hospital of Girona Dr. Josep Trueta, Girona, Spain 2 CIBER Pathophysiology of Obesity (CB/06), Girona, Spain 3 Unit of Diabetes, Endocrinology and Nutrition, Hospital of Tarragona “Joan XXIII,” Tarragona, Spain Address correspondence and reprint requests to J.M. Fernández-Real, MD, PhD, Unit of Diabetes, EndocrinologyNutrition, Hospital de Girona “Dr Josep Trueta,” Ctra. França s/n, 17007 Girona, Spain. E-mail: uden.jmfernandezreal{at}htrueta.scs.es Abstract OBJECTIVE —Interleukin (IL)-6 is a proinflammatory cytokine that is implicated in the pathogenesis of atherosclerosis and insulin resistance. Both endothelial dysfunction and insulin resistance are among the earliest abnormalities that can be detected in people at risk for cardiovascular events. We aimed to evaluate whether increased serum IL-6 concentrations associated with endothelial dysfunction are independent of insulin sensitivity in apparently healthy men. RESEARCH DESIGN AND METHODS —Association studies were performed in well-characterized nondiabetic Caucasian men ( n = 99) recruited for energy balance studies. Insulin sensitivity (minimal model) and brachial vascular reactivity (high-resolution external ultrasound) were assessed. Circulating IL-6 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS —Serum IL-6 was an independent contributor to the variance of endothelium-dependent vasodilatation after adjusting for age, BMI, smoking status, LDL cholesterol, systolic blood pressure, diastolic blood pressure, and insulin sensitivity ( P = 0.001). In fact, circulating IL-6 was negatively associated with endothelium-dependent vasodilatation ( r = −0.247, P = 0.014) and insulin sensitivity ( r = −0.262, P = 0.011) and correlated positively with age ( r = 0.241, P = 0.016), BMI ( r = 0.240, P = 0.017), systolic blood pressure ( r = 0.299, P = 0.003), diastolic blood pressure ( r = 0.295, P = 0.003), and triglycerides ( r = 0.212, P = 0.035). No significant associations were observed between endothelium-independent vasodilatation and serum IL-6 concentrations. CONCLUSIONS —Circulating IL-6 is linked to endothelial dysfunction independently of insulin sensitivity in apparently healthy men. IL, interleukin TNF, tumor necrosis factor Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact. Accepted December 28, 2006. Received August 24, 2006. DIABETES CARE

A randomized clinical trial reveals that the antidiabetic effects of metformin are at least partially due to beneficial changes in the microbiota. Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin–microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.

Adipocytokines and Insulin Resistance The possible role of lipocalin-2, retinol binding protein-4, and adiponectin Eduardo Esteve , MD, PHD , Wifredo Ricart , MD and José Manuel Fernández-Real , MD, PHD From the Unit of Diabetes, Endocrinology and Nutrition, Biomedical Research Institute of Girona, and CIBEROBN Fisiopatología de la Obesidad y Nutrición, Girona, Spain. Corresponding author: J.M. Fernández-Real, jmfernandezreal.girona.ics{at}gencat.cat . It is well known that adipocytes and resident macrophages that have migrated to adipose tissue produce and secrete a variety of biologically active mediators (adipocytokines), which are thought to contribute to the development of insulin resistance, type 2 diabetes, and cardiovascular disease ( 1 ). The abnormal function of adipocytes may play an important role in the development of a chronic low-grade proinflammatory state associated with obesity ( 2 ). For example, adipocyte hypertrophy appears to lead to an imbalance between pro- and anti-inflammatory adipokines. The secretion of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and granulocyte colony–stimulating factor have been positively correlated with adipocyte size. Adipose tissue is an important inflammatory source in obesity and type 2 diabetes, not only because of cytokines produced from the adipocyte itself, but also because of infiltration by proinflammatory macrophages ( 3 ). Not only do adipocytes, but also adipose tissue macrophage numbers, increase with obesity and participate in inflammatory pathways of obese individuals. Macrophages from adipose tissue are responsible for almost all adipose tissue tumor necrosis factor (TNF)-α and significant amounts of IL-6 production. Macrophages migrating to adipose tissue in response to high-fat feeding overexpress proinflammatory cytokines. Different cytokines synthesized by adipocytes or by macrophages from adipose tissue may induce insulin resistance, such as IL-6, TNF-α, leptin, resistin, adiponectin, retinol binding protein-4 (RBP4), or lipocalin-2 (LCN2). This review focuses on the latter adipocytokines, hinting at their role in obesity-associated insulin resistance. LCN2 LCN2 (or neutrophil gelatinase-associated lipocalin) is a recently identified adipokine that belongs to the superfamily of lipocalins (such as RBP4), which seems to affect glucose metabolism and insulin sensitivity ( 4 ). LCN2 protein has been implicated in diverse actions, such as apoptosis and innate immunity, and is expressed in several tissues, including neutrophils, liver, kidney, adipocytes, and macrophages ( 5 ). Lipocalins comprise a class of proteins that are … [Full Text of this Article]

Conversely, LCN2 has recently been claimed to display anti-inflammatory effects, so that increased LCN2 levels in obesity and insulin resistance may constitute a protective mechanism against inflammation (10). [...] LCN2 upregulated peroxisome proliferatoractivated receptor (PPAR)-γ and its target genes, adiponectin, leptin, fatty acid synthase, and lipoprotein lipase in adipocytes.

Scientific Reports 5: Article number: 14600; published online: 12 October 2015; updated: 24 February 2016. In this Article, Figure 4g is a duplication of Figure 5a. The correct Figure 4g appears below as Fig. 1.