Multimorbidity in people with type 2 diabetes in the Basque Country (Spain): Prevalence, comorbidity clusters and comparison with other chronic patients.

Background: Multimorbidity is a common problem in ageing societies and has a wide range of individual and social consequences. The objective of this study was to compare multimorbidity in a population with type 2 diabetes (T2DM) with that in other chronic patients, and identify disease clusters in patients with T2DM.

Methods: We included all citizens in the Basque Health Service aged ≥ 35 years, and identified the population with chronic conditions (from a list of 51 diseases) and those with T2DM.

SIRT1 enhances glucose tolerance by potentiating brown adipose tissue function.

Objective: SIRT1 has been proposed to be a key signaling node linking changes in energy metabolism to transcriptional adaptations. Although SIRT1 overexpression is protective against diverse metabolic complications, especially in response to high-fat diets, studies aiming to understand the etiology of such benefits are scarce. Here, we aimed to identify the key tissues and mechanisms implicated in the beneficial effects of SIRT1 on glucose homeostasis.

Consumption of orange fermented beverage reduces cardiovascular risk factors in healthy mice.

The consumption of fruits prevents the risk of cardiovascular diseases. Alcoholic fermentation has been carried out in fruits resulting in products which provide high concentration of bioactive compounds and variable alcohol content. The aim of this study was to assess the potential beneficial effect of an orange beverage obtained by alcoholic fermentation and pasteurization of orange juice on cardiovascular risk biomarkers.

Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy.

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered (1)H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers.

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients.

HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted.

Inhibition of BACE2 counteracts hIAPP-induced insulin secretory defects in pancreatic β-cells.

BACE2 (β-site APP-cleaving enzyme 2) is a protease localized in the brain, where it appears to play a role in the development of Alzheimer disease (AD). It is also found in the pancreas, although its biologic function is not fully known. Amyloidogenic diseases, including AD and type 2 diabetes mellitus (T2D), share the accumulation of abnormally folded and insoluble proteins that interfere with cell function.

Longitudinal changes of blood pressure after weight loss: factors involved.

Background: The combination of obesity and hypertension (HT) places patients at a higher risk for adverse cardiovascular outcomes and raises the need to establish the pathogenic mechanisms of this relationship. The aim of this study was to assess the effects of important weight loss on longitudinal changes in blood pressure (BP) and investigate the pathogenic factors associated with these changes.

Methods: We performed a prospective, open-label study including 37 obese hypertensive patients (28 females, mean age 52±8 yr) undergoing BS.

Night-time sleep duration and the incidence of obesity and type 2 diabetes. Findings from the prospective Pizarra study.

Background: Several recent studies have related short sleep duration with different health problems, though the results related with the risk of obesity and type 2 diabetes (T2D) are far from conclusive. The aim of this study was to investigate the association between night-time sleep duration and the incidence of obesity and T2D in a prospective study with a follow-up of 11 years.

Material And Methods: The study comprised 1145 people evaluated in 1997-1998 and re-evaluated after 6 years and 11 years.

Profile of individuals who are metabolically healthy obese using different definition criteria. A population-based analysis in the Spanish population.

Background: Obesity is associated with numerous metabolic complications such as diabetes mellitus type 2, dyslipidemia, hypertension, cardiovascular diseases and several forms of cancer. Our goal was to compare different criteria to define the metabolically healthy obese (MHO) with metabolically unhealthy obese (MUHO) subjects. We applied Wildman (W), Wildman modified (WM) with insulin resistance (IR) with cut-off point ≥ 3.

Suppressor of cytokine signaling 1-derived peptide inhibits Janus kinase/signal transducers and activators of transcription pathway and improves inflammation and atherosclerosis in diabetic mice.

Objective: Activation of Janus kinase/signal transducers and activators of transcription (STAT) pathway by hyperglycemia and dislypidemia contributes to the progression of diabetic complications, including atherosclerosis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate Janus kinase/STAT and have emerged as promising target for anti-inflammatory therapies. We investigated whether a cell-permeable lipopeptide corresponding to the kinase inhibitory region of SOCS1 could reduce atherosclerosis in diabetic mice and identified the mechanisms involved.

New splice site acceptor mutation in AIRE gene in autoimmune polyendocrine syndrome type 1.

Autoimmune polyglandular syndrome type 1 (APS-1, OMIM 240300) is a rare autosomal recessive disorder, characterized by the presence of at least two of three major diseases: hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. We aim to identify the molecular defects and investigate the clinical and mutational characteristics in an index case and other members of a consanguineous family. We identified a novel homozygous mutation in the splice site acceptor (SSA) of intron 5 (c.

Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the Di@bet.es study.

Background And Aim: Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations.

Therapeutic approaches to diabetic nephropathy--beyond the RAS.

Despite improvements in glycaemic and blood pressure control, and the efficacy of renin-angiotensin system (RAS) blockade for proteinuria reduction, diabetic nephropathy is the most frequent cause of end-stage renal disease in developed countries. This finding is consistent with the hypothesis that key pathogenetic mechanisms leading to progression of renal disease are not modified or inactivated by current therapeutic approaches. Although extensive research has elucidated molecular signalling mechanisms that are involved in progression of diabetic kidney disease, a number of high-profile clinical trials of potentially nephroprotective agents have failed, highlighting an insufficient understanding of pathogenic pathways.

Activation of toll-like receptors and inflammasome complexes in the diabetic cardiomyopathy-associated inflammation.

Diabetic cardiomyopathy is defined as a ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and hypertension. Hyperglycemia, hyperlipidemia, and insulin resistance are major inducers of the chronic low-grade inflammatory state that characterizes the diabetic heart. Cardiac Toll-like receptors and inflammasome complexes may be key inducers for inflammation probably through NF-κB activation and ROS overproduction.

Modifications of the homeostasis model assessment of insulin resistance index with age.

The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study.

BACH2, a candidate risk gene for type 1 diabetes, regulates apoptosis in pancreatic β-cells via JNK1 modulation and crosstalk with the candidate gene PTPN2.

Type 1 diabetes is a chronic autoimmune disease characterized by specific destruction of pancreatic β-cells by the immune system. Linkage and genome-wide association studies have identified more than 50 loci across the human genome associated with risk of type 1 diabetes. Recently, basic leucine zipper transcription factor 2 (BACH2) has been associated with genetic risk to develop type 1 diabetes, in an effect ascribed to the immune system.

Balanced duo of anti-inflammatory SFRP5 and proinflammatory WNT5A in children.

Background: Secreted frizzled-related protein 5 (SFRP5) is an adipokine protecting against obesity-related insulin resistance and diabetes. SFRP5 binds to wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (WNT5A) to improve insulin sensitivity. We performed the first study of SFRP5 and WNT5A simultaneously in children.

Clinical decisions in patients with diabetes and other cardiovascular risk factors. A statement of the Spanish Society of Internal Medicine.

Although the mortality associated to cardiovascular diseases (CVD) has been reduced in the last decades, CVD remains the main cause of mortality in Spain and they are associated with an important morbidity and a huge economic burden. The increasing prevalence of obesity and diabetes could be slowing down the mortality reduction in Spain. Clinicians have often difficulty making clinical decisions due to the multiple clinical guidelines available.

Reduced sTWEAK and increased sCD163 levels in HIV-infected patients: modulation by antiretroviral treatment, HIV replication and HCV co-infection.

Background: Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily.

Hypertension remission 1 year after bariatric surgery: predictive factors.

Background: There is scarce information about predictive factors of hypertension (HT) remission after bariatric surgery (BS). The aims of this study were to determine the clinical characteristics differentiating obese patients with and without HT and to evaluate the predictive factors associated with the risk of persistence of HT after BS.

Patients And Methods: From January 2007 to December 2009, a review of patients who had undergone BS was performed.

Undercarboxylated osteocalcin relates to cardiovascular risk markers in offspring of families with metabolic syndrome.

Background: The undercarboxylated form of osteocalcin (ucOC) is an emerging marker of cardiovascular disease. It is unknown if ucOC in related to common cardiovascular risk markers in children. In offspring of families with and without metabolic syndrome (MetS+ and MetS- families), we assessed whether ucOC was related to a continuous metabolic syndrome score (MetS score) and to carotid intima-media thickness (cIMT).

Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice.

Background: Klotho is a renal protein with anti-aging properties that is downregulated in conditions related to kidney injury. Hyperlipidemia accelerates the progression of renal damage, but the mechanisms of the deleterious effects of hyperlipidemia remain unclear.

Methods: We evaluated whether hyperlipidemia modulates Klotho expression in kidneys from C57BL/6 and hyperlipidemic apolipoprotein E knockout (ApoE KO) mice fed with a normal chow diet (ND) or a Western-type high cholesterol-fat diet (HC) for 5 to 10 weeks, respectively.

FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway.

Purpose: The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs).

Methods And Results: A DNA 5-bromo-2'-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs.

Alteration of energy substrates and ROS production in diabetic cardiomyopathy.

Diabetic cardiomyopathy is initiated by alterations in energy substrates. Despite excess of plasma glucose and lipids, the diabetic heart almost exclusively depends on fatty acid degradation. Glycolytic enzymes and transporters are impaired by fatty acid metabolism, leading to accumulation of glucose derivatives.

Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers.

Background And Aim: MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes, including complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Some particular microRNAs have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. The aim of this profiling study was to characterize the expression of miRNA in serum samples of obese, nonobese diabetic and obese diabetic individuals to determine whether miRNA expression was deregulated in these serum samples and to identify whether any observed deregulation was specific to either obesity or diabetes or obesity with diabetes.