Adipokines as Possible New Predictors of Cardiovascular Diseases: A Case Control Study

Background and Aims. The secretion of several adipocytokines, such as adiponectin, retinol-binding protein 4 (RBP4), adipocyte fatty acid binding protein (aFABP), and visfatin, is altered in subjects with abdominal adiposity; these endocrine alterations could contribute to increased cardiovascular risk. The aim of the study was to assess the relationship among adiponectin, RBP4, aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A case-control study, nested within a prospective cohort, on 2945 subjects enrolled for a diabetes screening program was performed. We studied 18 patients with incident fatal or nonfatal IHD (Ischemic Heart Disease) or CVD (Cerebrovascular Disease), compared with 18 matched control subjects. Circulating adiponectin levels were significantly lower in cases of IHD with respect to controls. Circulating RBP4 levels were significantly increased in CVD and decreased in IHD with respect to controls. Circulating aFABP4 levels were significantly increased in CVD, while no difference was associated with IHD. Circulating visfatin levels were significantly lower in cases of both CVD and IHD with respect to controls, while no difference was associated with CVD. Conclusions. The present study confirms that low adiponectin is associated with increased incidents of IHD, but not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and RBP4 in the development of cardiovascular disease

Postnatal β2 adrenergic treatment improves insulin sensitivity in lambs with IUGR but not persistent defects in pancreatic islets or skeletal muscle

Placental insufficiency causes intrauterine growth restriction (IUGR) and disturbances in glucose homeostasis with associated β adrenergic receptor (ADRβ) desensitization. Our objectives were to measure insulin-sensitive glucose metabolism in neonatal lambs with IUGR and to determine whether daily treatment with ADRβ2 agonist and ADRβ1/β3 antagonists for 1 month normalizes their glucose metabolism. Growth, glucose-stimulated insulin secretion (GSIS) and glucose utilization rates (GURs) were measured in control lambs, IUGR lambs and IUGR lambs treated with adrenergic receptor modifiers: clenbuterol atenolol and SR59230A (IUGR-AR). In IUGR lambs, islet insulin content and GSIS were less than in controls; however, insulin sensitivity and whole-bodyGUR were not different from controls.Of importance, ADRβ2 stimulation with β1/β3 inhibition increases both insulin sensitivity and whole-body glucose utilization in IUGR lambs. In IUGR and IUGR-AR lambs, hindlimb GURs were greater but fractional glucose oxidation rates and ex vivo skeletal muscle glucose oxidation rates were lower than controls. Glucose transporter 4 (GLUT4) was lower in IUGR and IUGR-AR skeletal muscle than in controls but GLUT1 was greater in IUGR-AR. ADRβ2, insulin receptor, glycogen content and citrate synthase activity were similar among groups. In IUGR and IUGR-AR lambs heart rates were greater, which was independent of cardiac ADRβ1 activation. We conclude that targeted ADRβ2 stimulation improved whole-body insulin sensitivity but minimally affected defects in GSIS and skeletal muscle glucose oxidation. We show that risk factors for developing diabetes are independent of postnatal catch-up growth in IUGR lambs as early as 1 month of age and are inherent to the islets and myocytes

Assessment of Drug Therapy Problems Among Type 2 Diabetes Patients with Hypertension Comorbidity in Indonesia

Type 2 diabetes mellitus (T2DM) is a major chronic disease that affects a large number of people worldwide. Hypertension is a common disease comorbidity among T2DM patients, and often those patients received polypharmacy and complex treatment in long term duration. This condition may lead to an increased risk of drug therapy problems (DTPs). This study aimed to assess and determine potential drug therapy problems in type 2 diabetic patients with hypertension comorbidity. Retrospective cross-sectional design was conducted in a hospital setting, especially data sources from the prescription of ambulatory T2DM patients with hypertension. A total of 190 patients were studied. More than half of the participants were female (53.68%). The majority age range of participants was 50-59 years (46.84%). Almost all antidiabetic agents were prescribed as polypharmacy (73.16%). Metformin was the most antidiabetic agent prescribed as monotherapy and combination therapy (63.16%). Almost all antihypertensive agents were prescribed as polypharmacy (63.26%). Amlodipine was the most antihypertensive agent prescribed as monotherapy and combination therapy (34.74%). Among the study participants, 56.84% have at least one of DTPs. Adverse drug reaction was the most frequent (47.22%), followed by ineffective drug therapy (29.63%). Since the potential of DTPs in T2DM patients with hypertension comorbidity is relatively high, early identifying, resolving, and preventing drug therapy problems by the pharmacist is needed to achieve goals of treatment

Characteristics of Slow Progression to Type 1 Diabetes in Children With Increased HLA-Conferred Disease Risk

Context: Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for prevention of T1D. Slow progressors might carry natural immunomodulators that delay beta-cell destruction and mediate preservation of beta-cell function. Objective: To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D. Design: H LA-susceptible children (n = 7410) were observed from birth for islet cell antibody (ICA), insulin autoantibody (IAA), glutamic acid decarboxylase (GADA), and islet antigen-2 autoantibodies (IA-2A), and for clinical T1D. Disease progression that lasted >= 7.26 years (slowest) quartile from initial seroconversion to diagnosis was considered slow. Autoantibody and genetic characteristics including 45 non-HLA single nucleotide polymorphisms (SNPs) predisposing to T1D were analyzed. Results: By the end of 2015, 1528 children (21 %) had tested autoantibody positive and 247 (16%) had progressed to T1D. The median delay from seroconversion to diagnosis was 8.7 years in slow (n = 62, 25%) and 3.0 years in other progressors. Compared with other progressors, slow progressors were less often multipositive, had lower ICA and IAA titers, and lower frequency of IA-2A at seroconversion. Slow progressors were born more frequently in the fall, whereas other progressors were born more often in the spring. Compared with multipositive nonprogressors, slow progressors were younger, had higher ICA titers, and higher frequency of IAA and multiple autoantibodies at seroconversion. We found no differences in the distributions of non-HLA SNPs between progressors. Conclusions: We observed differences in autoantibody characteristics and the season of birth among progressors, but no characteristics present at seroconversion that were specifically predictive for slow progression.Peer reviewe

The pituitary TGFb1 system as a novel target for the treatment of resistant prolactinomas

Prolactinomas are the most frequently observed pituitary adenomas and most of themrespond well to conventional treatment with dopamine agonists (DAs). However, a subsetof prolactinomas fails to respond to such therapies and is considered as DA-resistantprolactinomas (DARPs). New therapeutic approaches are necessary for these tumors.Transforming growth factor b1 (TGFb1) is a known inhibitor of lactotroph cell proliferationand prolactin secretion, and it partly mediates dopamine inhibitory action. TGFb1 is secretedto the extracellular matrix as an inactive latent complex, and its bioavailability is tightlyregulated by different components of the TGFb1 system including latent binding proteins,local activators (thrombospondin-1, matrix metalloproteases, integrins, among others), andTGFb receptors. Pituitary TGFb1 activity and the expression of different components of theTGFb1 system are regulated by dopamine and estradiol. Prolactinomas (animal models andhumans) present reduced TGFb1 activity as well as reduced expression of several componentsof the TGFb1 system. Therefore, restoration of TGFb1 inhibitory activity represents a noveltherapeutic approach to bypass dopamine action in DARPs. The aim of this review is tosummarize the large literature supporting TGFb1 important role as a local modulator ofpituitary lactotroph function and to provide recent evidence of the restoration of TGFb1activity as an effective treatment in experimental prolactinomasFil: Recouvreux, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Cedars Sinai Medical Center; Estados UnidosFil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rifkin, Daniel B.. University of New York; Estados UnidosFil: Diaz, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Incretin System: New Pharmacological Target in Obese Women with Polycystic Ovary Syndrome

Introduction: Obesity is highly prevalent in polycystic ovary syndrome (PCOS). It aggravates adverse features of the syndrome. Weight management by lifestyle intervention is often insufficient. We reviewed studies addressing the use of agents mediating through incretin system in obese PCOS

Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years

Context: We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design: HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results: By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A- and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01). Conclusions: In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.Peer reviewe