Low estradiol-to-testosterone ratio is associated with oligo-anovulatory cycles and atherogenic lipidic pattern in women with polycystic ovary syndrome

The estradiol-to-testosterone (E2/T) ratio has been investigated in different diseases but few in vivo data are available with regard to its role in women with ovary syndrome (PCOS). The aim of this study was to evaluate the role of the E2/T ratio in the ovulatory function and metabolic pattern in such women.We retrospectively evaluated hyperandrogenemia, clinical hyperandrogenism, ovarian morphology, hypothalamo-hypophyseal axis and metabolic syndrome parameters in a cohort of 202 consecutive women affected by PCOS. An oral glucose tolerance test measured areas under the curve for insulin (AUC(2hIRI)), for glucose (AUC(2hglucose)), and the HOMA-IR and Matsuda index of insulin resistance we…

Difficoltà di identificazione della sindrome MEN2B ad esordio infantile: iter diagnostico.

Visual evoked potentials in insulin-dependent diabetics

The latency of pattern-reversal VEPs was studied in type I insulin-dependent diabetics without retinal and extraocular involvement. One hundred eyes of 50 diabetics (mean age 19.8 +/- 7.2 years) formed the study group; the duration of the disease ranged between 1 month and 15 years. The latencies of VEPs were progressively delayed in relation to the duration of the disease, becoming more and more evident and stabilizing after about 6 years from the onset of diabetes. The VEP alterations probably indicate alteration of membrane balance or demyelinization.

Adrenal incidentaloma: a new contributing factor in metabolic syndrome

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 238–247 Summary Background  Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Aims  To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. Methods  One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and H…

Analysis of T-Lymphocyte Subsets After Phytohemagglutinin Stimulation in Normal and Type 1 Diabetic Mothers and Their Infants

Our aim was to investigate the immunological status of diabetic pregnancy, which is an overlap of diabetic immunity abnormalities and the immunological modifications normally occurring during pregnancy. METHOD: We studied lymphocyte subpopulations and lymphokine production, after 96 h of phytohemagglutinin (PHA) stimulation, from normal and Type I diabetic pregnant women at delivery time and from the respective cord blood. RESULTS: Peripheral blood mononuclear cells (PBMC) from both normal and Type I diabetic mothers showed an increase in CD8+ and a decrease in CD4+ cells compared to the respective cord blood mononuclear cells (CBMC). Moreover, Type I PBMC showed a lower number of “activate…

Predictors of microvascular complications in type 1 diabetic patients at onset: The role of metabolic memory

Background Several epidemiological studies showed a close association between metabolic control and microvascular complications in type 1 Diabetes Mellitus (T1DM). The aim of our longitudinal observational study was to evaluate the predictive role of the main clinical and biochemical parameters in determining microvascular complications. Methods 376 T1DM patients, hospitalized in our division from 1991 to 2005 (mean follow-up = 10.93 ± 4.26 years) were studied. Stepwise Cox regression analysis was used to identify the influence of residual ß-cell function, ß-cell autoimmunity, HbA1c levels and other clinical and laboratory parameters in the development of microalbuminuria and retinopathy. R…

Th1 and Th2 cell phenotypes in AITD: role of allergy in Graves' disease

Thyrocytes--not innocent bystanders in autoimmune disease.

Distinct subsets of intrathyroidal regulatory CD4+CD25+ and CD8+CD25+ T cells in Hashimoto's thyroiditis: Potential role in the neoplastic cell growth.

The evaluation of metabolic parameters and insulin sensitivity for a more robust diagnosis of the polycystic ovary syndrome

BACKGROUND: Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy. OBJECTIVE: The aim of this study was to retrospectively evaluat…

Peak systolic velocity (PSV) in inferior thyroid arteries (ITA) at Graves'disease onset is predictive of the risk for ophtalmopathy development

Sviluppo di un sistema di supporto decisionale tipo Fuzzy per il controllo della glicemia post-prandiale nel diabete mellito tipo 1

Use of the Diabetes Risk Score for Opportunistic Screening of Undiagnosed Diabetes and Impaired Glucose Tolerance

OBJECTIVE—To evaluate an opportunistic screening strategy addressed to individuals with one or more cardiovascular risk factor, based on the Diabetes Risk Score (DRS) as the initial instrument, for the identification of individuals with type 2 diabetes or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—The DRS, a simple self-administered questionnaire, was completed by individuals identified by general practitioners and presenting with one or more cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance test (OGTT). The optimal DRS cutoff was calculated by applying the receiver-operating characteristic curve. RESULTS—Overall, 1,377 individuals aged betwe…

L’espressione di citochine TH1 e TH2 nei pazienti affetti da tireopatia autoimmune (AITD) e diabete di tipo 1

Early administration of an immunomodulator and induction of remission in insulin-dependent diabetes mellitus

A clinical trial was undertaken to determine whether intensive thymopentin administration enhances remission of insulin-dependent diabetes (IDDM) during the first year after diagnosis. Dosage with insulin was minimized with target control of blood glucose levels less than or equal to 7.8 mmol/l before meals. Remission was defined as a prolonged period after IDDM onset (not less than 3 months) characterized by a non-insulin-receiving (NIR) state in which target metabolic control was reached without administration of insulin and with a valid C-peptide response, evaluated after standard breakfast. Sixteen IDDM patients aged 12-31 years, recruited within 2 weeks of initiation of insulin therapy…

Effect of lercanidipine compared with ramipril on albumin excretion rate in hyprtensive Type 2 diabetic patients with microalbuminuria. DIAL Study (Ddiabete, Ipertensione, Albuminuria, Lercanidipina)

Metabolic parameters and adipokine profile during GH replacement therapy in children with GH deficiency

Objective: GH replacement therapy in children with GH deficiency (GHD) mainly promotes linear growth. Not only have very few studies fully analyzed the metabolic consequences of GH therapy, but also the question as to whether GH may affect adipokine secretion has been insufficiently investigated. Our aim was to study the effects of GH replacement therapy on auxological data, lipid and glycemic profiles, insulin homeostasis (HOMA-IR) and serum adipokines in children. Methods: This was a 1-year prospective study. Thirty-four GHD children (11.6 ± 2.6 years) and thirty healthy matched controls were enrolled. Children affected by GHD were studied both before beginning continuous GH replacement t…

Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.

Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus eryt…

Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1.

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirty-six consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. All biopsies were scored by on…

Soluble Interleukin-2 Receptor Secretion Defectin Vitroin HLA-B8, DR3 Positive Subjects

Several studies have shown that HLA-B8,DR3 positive subjects may display T cell dysfunctions. Recently, a soluble form of the receptor for IL-2 (sIL-2R) has been demonstrated in human sera and in vitro-stimulated culture supernatant from human T lymphocytes. In the present paper we report sIL-2R serum levels and sIL-2R production from peripheral blood mononuclear cells in HLA-B8,DR3 positive subjects. We found that HLA-B8,DR3 positive subjects have the highest values of serum sIL-2R, but comparing the values of these subjects with those of negative ones no significant difference was observed. As regards the in vitro production of sIL-2R, no difference exists for unstimulated cultures, where…

Insulin sensitivity and visceral adiposity index (VAI) in women with functional secondary amenorrhea.

High expression of peroxisome proliferator-activated receptor gamma (PPRgamma) in infiltrating lymphocytes from glands with Hashimoto's thyroiditis.

L’uso del hrTSH nel follow up del microcarcinoma tiroideo in pazienti sottoposti a tiroidectomia totale

Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients.

The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed (3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals an…

Valutazione morfologica e funzionale surrenalica nell’acromegalia

Valutazione dell'insulinoresistenza tramite un test pasto standard

Possible Pathogenetic Relevance of Interleukin-1beta in "Destructive" Organ-specific Autoimmune Disease (Hashimoto's Thyroiditis)

Thyroid follicular cells (TFC) abundantly express a variety of immunologically relevant surface molecules in Hashimoto's thyroiditis (HT), for example, MHC antigens and adhesion molecules such as ICAM-1. Cytokines produced by infiltrating type 1 helper and cytotoxic T cells are importantly involved in de novo expression or up-regulation of such molecules. We recently demonstrated that TFC from HT patients almost invariably bear on their surface two additive functional molecules: Fas/Apo1/CD95, an important participant in apoptosis, and B7.1, a member of a family of "co-stimulatory" molecules that are crucial for efficient antigen presentation. To date, 12 out of 14 surgical HT thyroid speci…

Changes in lipid profile and adipokine levels in GH deficient children during GH replacement therapy.

Visceral adiposity index is associated with insulin sensitivity and adipocytokine levels in newly diagnosed acromegalic patients.

Complete biochemical control and pituitary adenoma disappearance in a child with gigantism: Efficacy of octreotide therapy

Detection of BRAFv600E mutation in papillary thyroid carcinoma using real time allele-specific amplification on fine needle aspiration biopsy specimens.

Genetic Pattern and Haemorheological Determinants in Type 1 Diabetics

Janus kinase (JAK) 2 V617F mutation as the cause of primary thrombocythemia in acromegaly with severe visceromegaly and divergence between growth hormone and insulin-like growth factor-1 concentrations during the follow-up: causal or casual association?

OBJECTIVE: An increased prevalence of hematological abnormalities is reported in acromegaly, but to date no reports about the presence of the Janus Kinase (JAK) 2 mutation in acromegalic patients have been described. DESIGN: We report the complex clinical presentation of the unique case, never described, of acromegaly due to GH-secreting pituitary adenoma associated with JAK2 V617F mutation. RESULTS: The patient shows primary thrombocythemia and myelofibrosis, due to JAK2 V617F mutation, severe visceromegaly and a peculiar clinical course of the disease characterized by discrepant values of GH and IGF-1 during somatostatin analog (SA) treatment despite a significant reduction in pituitary a…

Adrenal morphology and function in acromegalic patients in relation to disease activity.

Visceromegaly is a common consequence of acromegaly. However, few studies investigated the chronic effects of growth hormone on adrenal glands. Our aim was to evaluate adrenal morphology and function in a cohort of acromegalic patients in relation to disease activity. Twenty-six acromegalics (10 males and 16 females) and 21 healthy subjects were investigated. Gland morphology was evaluated by computerized axial tomography, measuring central, lateral, and medial adrenal segments. Uncontrolled acromegalics showed increased volume of all adrenal segments, higher urinary free cortisol (UFC), and lower morning adrenocorticotropic hormone in comparison with healthy subjects. However, normal corti…

Identification and enrichment of thyroid stem cells in anaplastic cell lines

Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials

Background Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of retinopathy in type 1 diabetes. Methods Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent 1 trial and those with existing retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or…

Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1.

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirtysix consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and highdensity lipoprotein cholesterol. All biopsies were scored by one …

Osmocellular Fas and Fas ligand interactions mediate thyrocyte destruction in Hashimoto's thyroiditis

In Vitro Generation of Pancreatic Endocrine Cells from Human Adult Fibroblast-Like Limbal Stem Cells

Stem cells might provide unlimited supply of transplantable cells for β-cell replacement therapy in diabetes. The human limbus is a highly specialized region hosting a well-recognized population of epithelial stem cells, which sustain the continuous renewal of the cornea, and the recently identified stromal fibroblast-like stem cells (f-LSCs), with apparent broader plasticity. However, the lack of specific molecular markers for the identification of the multipotent limbal subpopulation has so far limited the investigation of their differentiation potential. In this study we show that the human limbus contains uncommitted cells that could be potentially harnessed for the treatment of diabete…

Phenotipic characteristics of GAD Antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe

BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy.

BRAFV600E is the most common mutation found in papillary thyroid carcinoma (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and nuclear factor (NF)-κB have been shown to play an important role in thyroid cancer. In particular, TIMP-1 binds its receptor CD63 on cell surface membrane and activates Akt signaling pathway, which is eventually responsible for its anti-apoptotic activity. The aim of our study was to evaluate whether interplay among these three factors exists and exerts a functional role in PTCs. To this purpose, 56 PTC specimens were analyzed for BRAFV600E mutation, TIMP-1 expression, and NF-κB activation. We found that BRAFV600E mutation occurs selectively in PTC nodules an…

Study of T-cell activation in Type I diabetic patients and pre-Type I diabetic subjects by cytometric analysis: Antigen expression defectin vitro

In Type I diabetes the observation of a decreased release of interleukin-2 (IL-2) and soluble IL-2 receptors by means of stimulated lymphocytes in vitro indicates that a primary immunoregulatory defect may be involved. To confirm this hypothesis we investigated the T-cell activation trend, evaluating the surface expression of IL-2 receptor (CD25), transferrin (CD71), HLA class II (DR), and CD69 phenotypes after in vitro stimulation with phytohemagglutinin (PHA; 1 and 10 micrograms/ml) and concanavalin A (12.5 micrograms/ml) in six newly diagnosed Type I diabetics and six islet cell- and insulin autoantibody-positive first-degree relatives. As controls were studied six long-standing Type I d…

In Vitro Phenotypic, Genomic and Proteomic Characterization of a Cytokine-Resistant Murine β-TC3 Cell Line

Type 1 diabetes mellitus (T1DM) is caused by the selective destruction of insulin-producing β-cells. This process is mediated by cells of the immune system through release of nitric oxide, free radicals and pro-inflammatory cytokines, which induce a complex network of intracellular signalling cascades, eventually affecting the expression of genes involved in β-cell survival. The aim of our study was to investigate possible mechanisms of resistance to cytokine-induced β-cell death. To this purpose, we created a cytokine-resistant β-cell line (β-TC3R) by chronically treating the β-TC3 murine insulinoma cell line with IL-1β + IFN-γ. β-TC3R cells exhibited higher proliferation rate and resistan…

Lower insulin sensitivity differentiates hirsute from non-hirsute Sicilian women with polycystic ovary syndrome

Objective: It is well known that hyperandrogenism and insulin-resistance with or without compensatory hyperinsulinism are closely associated, but the Rotterdam Consensus has concluded that principally obese women with polycystic ovary syndrome (PCOS) should be evaluated for the metabolic syndrome. Our aim was to study insulin sensitivity in PCOS women with hirsutism regardless of obesity. Methods: Clinical characteristics, sex hormones and fasting- and after OGTT-glycemia and insulinemia, homeostatic model of insulin resistance (HOMA IR), and Matsuda index of insulin sensitivity were analyzed in 130 women with PCOS. Hirsutism has been evaluated through the Ferriman–Gallwey (FG) map scoring …

In Vitro Identification and Characterization of CD133pos Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines

BackgroundRecent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown.Methodology/principal findingsATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos) cells only in ARO and KAT-4 (64+/-9% and 57+/-12%, respectively). These …

No association between BRAFV660E and metalloproteinase activity in anaplastic thyroid cell lines

Systolic flow peak of inferior thyroid arteries in Graves’disease: A predictive parameter for the ophalmopathy development.

Leptina e adiponectina nella valutazione del compenso glicometabolico in corso di diabete mellito di tipo 1 normopeso.

Transient chylomicronemia preceding the onset of insulin-dependent diabetes in a young girl with no humoral markers of islet autoimmunity

OBJECTIVE: We investigated the possible causes of diabetes in a young child who presented with hyperglycemia associated with severe hypertriglyceridemia (>166 mmol/l), hypercholesterolemia (>38 mmol/l) and fasting chilomicrons. RESULTS: The patient did not have any of the HLA and autoantibody markers typically associated with type 1 diabetes. A glucose clamp failed to demonstrate insulin resistance (peripheral glucose utilization rate (M)=4.3 mg/kg per min) and there was no family history of type 2 diabetes or maturity onset diabetes in youth. Both fasting and stimulated C-peptide levels, including those in response to i.v. glucagon, were below the limit of detection. This is consiste…

Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial.

Summary Background Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of retinopathy in type 1 diabetes. Methods Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent 1 trial and those with existing retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once …

Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study.

To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC(INS), visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS…

Increated central corneal thickness in acromegalic patients

OCT is not useful for detection of minimal diabetic retinopathy in type 1 diabetes.

Optical coherence tomography (OCT) has been proven useful in measuring retinal thickness (RT) in patients with diabetes, although with discordant results in different studies. We examined RT in patients with type 1 diabetes (T1D) with or without minimal diabetic retinopathy (MDR) to test whether OCT is able to identify early retinal changes and potential correlations with metabolic parameters. RT of 102 patients with T1D (53 females, 49 males, aged 27.03 +/- 7.4 years) and of 42 healthy controls was examined, with analysis of nine different sectors (fovea, four pericentral and four peripheral sectors). According to the results of basal fundus photography, patients were divided into two grou…

Complete biochemical control and oituitary adenoma disappearance in a child with gigantism: efficay of octreotide therapy

Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus

Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset less than 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 +/- 8.5% versus 70.7 +/- 8.0%), helper/inducer cells (OKT4+: 33.8 +/- 7.0% versus 47.1 +/- 8.3%), suppressor/cytotoxic cells (OKT8+: 18.5 +/- 7.3% versus 32 +/- 6.8%) and monocytes (OKM1+: 11.5 +/- 3.8% versus 19.9 +/- 5.2%) (p less than 0.…

Iter diagnostico "rapido" per un caso di MEN IIb in un giovane adolescente

Congenital anomaly rate in offspring of Italian mothers with type 1 diabetes treated with insulin lyspro during pregnancy

Identification of Tyrosine Phosphatase 2(256-760) Construct as a New, Sensitive Marker for the Detection of Islet Autoimmunity in Type 2 Diabetic Patients: The Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study 2

Abstract OBJECTIVE: The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasian LADA patients, identifying the most sensitive construct to evaluate IA-2 immunoreactivity and comparing LADA IA-2 epitope specificities to those found in type 1 diabetes. RESEARCH DESIGN AND METHODS: We analyzed 177 LADA and 978 type 2 diabetic patients with different disease duration, collected in a nationwide Italian survey, the Non-Insulin Requiring Autoimmune D…

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Cut-off points of the visceral adiposity index (VAI) identifying a visceral adipose dysfunction associated with cardiometabolic risk in a Caucasian Sicilian population

Abstract Background The Visceral Adiposity Index (VAI) is a sex-specific mathematical index, based on Waist Circumference (WC), Body Mass Index (BMI), triglycerides (TG) and HDL cholesterol (HDL) levels, indirectly expressing visceral adipose function and insulin sensitivity. Our aim was to find the optimal cut-off points of VAI identifying a visceral adipose dysfunction (VAD) associated with cardiometabolic risk in a Caucasian Sicilian population. Methods Medical check-up data of 1,764 Primary Care patients (PC patients) were retrospectively and cross-sectionally examined using a receiver-operating characteristic (ROC) curve to determine appropriate stratified-for-age cut-off of VAI, for t…

Fine-Needle Aspiration (FNAB) Molecular Analysis for the Diagnosis of Papillary Thyroid Carcinoma through BRAFv600E mutation and RET/PTC rearrangement

Objective: To evaluate BRAFV600E mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB’s usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET=PTC1 and RET=PTC3 rearrangements obtained from ex vivo thyroid nodules. Design: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET=PTC rearrangements. The results were compared with the cytological diagnosis and histopathol…

Rotterdam consensus, NIH and EAS: comparison among the three different diagnostic criteria for the diagnosis of PCOS.

Potential involvement of fas and its ligand in the pathogenesis of Hashimoto's thyroiditis

The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1β (IL-1β), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1β induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1β-induced Fas expression serves as a limiting factor for thyrocyte destruction. Th…

Alterazioni del metabolismo glucidico determinate da eccesso di ormoni contro regolatori.

Visceral Adiposity Index

OBJECTIVE To individuate a novel sex-specific index, based on waist circumference, BMI, triglycerides, and HDL cholesterol, indirectly expressing visceral fat function. RESEARCH DESIGN AND METHODS Visceral adiposity index (VAI) was first modeled on 315 nonobese healthy subjects. Using two multiple logistic regression models, VAI was retrospectively validated in 1,498 primary care patients in comparison to classical cardio- and cerebrovascular risk factors. RESULTS All components of metabolic syndrome increased significantly across VAI quintiles. VAI was independently associated with both cardiovascular (odd ratio [OR] 2.45; 95% CI 1.52–3.95; P < 0.001) and cerebrovascular (1.63; 1.0…

Different Th1/Th2 cytokine expression in Type 1 diabetes mellitus patients (T1DM) alone or associated with autoimmune thyroid disease (AITD)

Visceral Adiposity Index (VAI): A Reliable Indicator Of Visceral Fat Function Associated With Cardiometabolic Risk.

Objective: To individuate a novel sex-specific index, based on Waist Circumference (WC), Body Mass Index (BMI), Triglycerides (TG) and HDL cholesterol (HDL), indirectly expressing visceral fat function. Research design and Methods: Visceral Adiposity Index (VAI) was first modelled on 315 non-obese healthy subjects. Using two multiple logistic regression models, VAI was retrospectively validated in 1,498 primary care patients in comparison to classical cardio and cerebrovascular risk factors. Results: All components of metabolic syndrome increased significantly across VAI quintiles. VAI was independently associated with both cardiovascular (OR:2.45; 95%CI: 1.52-3.95; p<0.001) and cerebrov…

The oligomenorrhoic phenotypes of polycystic ovary syndrome are characterized by a high visceral adiposity index: a likely condition of cardiometabolic risk.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dys- lipidemia and hypertension, which are characteristic features of a condition of cardiometabolic risk. Our objective was to investigate the relationship between visceral adiposity index (VAI) and phenotypic characteristics in women with PCOS. METHODS: We conducted a cross-sectional case-control study in our Endocrinology Outpatients Clinic. A total of 220 women with PCOS (Rotterdam definition) and I44 age- and BMI-matched healthy women were studied. We evaluated hyperandrogenemia and clinical hyperandrogenism, ovarian morphology, hypothalamic-hypophyseal axis and …

Leukocyte migration test (LMT) in patients with thyroid disease: the response to human thyroid subcellular fractions.

The response of circulating leukocytes to thyroid subcellular fractions was investigated in 19 patients with Graves' disease, 15 patients with Hashimoto's thyroiditis, 7 patients with toxic adenoma, 19 patients with nontoxic goiter and in 10 healthy students as control subjects. For this purpose, the leukocyte migration test of Soborg and Bendixen was performed against human crude thyroid extract (CTE), cell plasma membranes, nuclei, ribosomes, mitochondria and microsomes. Our results show positive LMT against: 1) CTE in patients with Graves' disease (61 +/- 13, p less than 0.001) and Hashimoto's thyroiditis (65 +/- 11, p less than 0.001) compared to controls (90 +/- 11); 2) cell plasma mem…

The influence of high dose intravenous immunoglobulins on immunological and metabolic pattern in newly diagnosed type I diabetic patients

In autoimmune disease the functional deficiency of T suppressor cells, also described in Type I diabetes, may be restored through immunoglobulin (Ig) infusion, which increases antigen phagocytosis, NK activity, cell clones and antibody anti-idiotype responses. Sixteen Type I diabetic patients were studied: eight were treated soon after the initial correction of disease-onset glycemic deterioration with intensive intravenous (i.v.) 7S Ig treatment (0.4 g/kg/BW) for 1 week and once per week for 6 months, whilst the remaining patients constituted the control group. All patients were evaluated during the study for metabolic and immunological parameters. A reduction in insulin requirement compar…

40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode …

Interleukin 2 and soluble interleukin 2-receptor secretion defect in vitro in newly diagnosed type I diabetic patients

In this study, we investigated whether an interleukin 2 (IL-2) secretion defect by peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with phytohemagglutinin (PHA-M) occurs in either newly diagnosed or long-standing type I (insulin-dependent) diabetic patients and whether it is accompanied by a dysregulation of soluble IL-2— receptor (IL-2RS) production. PBMC cultures (2.5 × 106 cells), unstimulated or stimulated with PHA-M (25 μg/ml), from 20 type I diabetic patients (10 with time since onset <3 mo and 10 with long-term diabetes of <3 yr) and 10 control subjects were studied for the production of IL-2 and IL-2RS in their respective supernatants. No differen…

Il c-peptide come marker principale nella storia naturale del Diabete tipo 1: ruolo della funzione b-cellulare pancreatica nelle complicanze

Prevalence of residual B-cell function related to age at onset and genetic profile in newly diagnosed type I diabetics.

Patients with type I (insulin-dependent) diabetes mellitus maintain B-cell function for a varying period of time after onset. This is commonly held to account for post-initial remission. To estimate residual B-cell function we measured plasma and 24-h urinary C-peptide in 68 type I diabetic patients (age range 4-35 years, within 10-180 days of the onset of symptoms, typed for HLA-A, -B, -C and DR loci. A positive correlation (r = 0.26; p less than 0.05) was found between urinary C-peptide levels and the age of the patient. The analysis of variance of urinary C-peptide values on the basis of the presence or absence of DR3 and DR4 antigens revealed that the DR3-positive patients had reduced e…

Influences of obesity and weight loss on thyroid hormones. A 3-3.5-year follow-up study on obese subjects with surgical bilio-pancreatic by-pass

The effects of changing body size, energy intake and substrate oxidation on serum T4, FT4, T3, FT3 and TSH were investigated in ten morbidly obese subjects (4 men/6 women; age: 37 ± 6 years; BMI: 53.8 ± 6.5 kg/m2; mean ± SD) who had undergone a surgical bilio-pancreatic by-pass in order to reduce their body weight. The starting value of serum FT3 was inversely related to the BMI (r = -0.63; p < 0.05). After 1-3 months, all the subjects were losing weight and their intake of carbohydrates was almost negligible; at this time a significant reduction of T3 (-14.6%, p < 0.0001), T4 (-19.5%, p < 0.0001), and FT3 (-10.5%, p < 0.001) was observed. Nine to 16 months after surgery, all th…

Insulin resistance and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in humans, affecting approximately 7-8% of women of reproductive age. Despite the criteria adopted, PCOS is considered to be a predominantly hyperandrogenetic syndrome and the evaluation of metabolic parameters and insulin sensitivity is not mandatory. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Acknowledging the strong impact of insulin-resistance in the genesis of PCOS co…

Hypothyroidism induced by esophageal adenocarcinoma metastates: a case report

Decremento delle cellule T regolatorie (Treg) CD4+CD25+FOXP3+ nei linfociti periferici dei pazienti affetti da diabete di tipo 1.

Corrigendum to “Off-line control of the postprandial glycemia in type 1 diabetes patients by a fuzzy logic decision support” [Expert Systems with Applications 39 (12) (2012) 10693–10699]

Differential regulation of Fas-mediated apoptosis in both thyrocyte and lymphocyte cellular compartments correlates with opposite phenotypic manifestations of autoimmune thyroid disease.

Several mechanisms are probably involved in determining the evolution of autoimmune thyroid disease (AITD) towards either hypothyroidism and the clinical syndrome known as Hashimoto's thyroiditis (HT) or toward hyperthyroidism and the symptoms of Graves' disease (GD). To gain further insight into such mechanisms we performed an exhaustive comparative analysis of the expression of key molecules regulating cell death (Fas, Fas ligand [FasL], Bcl-2) and apoptosis in both thyrocytes and thyroid infiltrating lymphocytes (TILs) from patients with either GD or HT. GD thyrocytes expressed less Fas/FasL than HT thyrocytes, whereas GD TILs had higher levels of Fas/FasL than HT TILs. GD thyrocytes exp…

Oligomenorrhea in PCOS is characterized by a high visceral adiposity index (VAI): a likely condition of cardiometabolic risk.

BRAFV600E Mutation and p27kip1 Expression in Papillary Carcinomas of the Thyroid ≤1 cm and Their Paired Lymph Node Metastases

BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real-time, allele-specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E …

Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial.

Background As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic control in adults with inadequately controlled type 2 diabetes mellitus taking oral hypoglycaemic agents. Methods In the 44-week, parallel, open study that was undertaken in 69 study sites across Europe and Australia, 418 patients with type 2 diabetes mellitus that was inadequately controlled by oral hypoglycaemic agents were randomly assigned to either insulin glargine taken once daily at the same ti…

Low hrTSH-Tg levels in patients affected by papillary thyroid microcarcinoma are influenced by pre-surgery L-thyroxine therapy.

Amplificazione real-time allele-specifica per l'individuazione della mutazione V600E del B-RAF nel carcinoma papillare su agoaspirato tiroideo.

Defective T cell receptor/CD3 complex signaling in human type I diabetes

The autoimmune process leading to the destruction of pancreatic β-cells is mediated by T lymphocytes. Peripheral T cells from subjects with preclinical and clinical type I diabetes respond weakly in vitro to lectin stimulation. We, therefore, investigated in a group of newly diagnosed diabetic patients the presence of a defect in the signal transduction pathway of the T cell receptor (TcR)/CD3 complex. Following stimulation with anti-CD3-coupled beads, the proliferative response in diabetic T cells was significantly decreased in comparison with that from normal T cells. Interestingly, addition of either recombinant interleukin (IL)-2 or phorbol 12-myristate 13-acetate to the cell culture wa…

Development of a fuzzy expert system for the control of glycemia in type 1 diabetic patients

Abstract The paper describes the structure and the characteristics of an expert system that allows the optimization of postprandial glycemia in type 1 diabetic patients. The expert system is able to provide patients with the number of rapid insulin units that must be taken in order to keep the blood glucose level close to the omeostatic condition in the hours following a meal.

Use of glargine in pregnant women with type 1 diabetes mellitus: a case-control study.

BACKGROUND: Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy. OBJECTIVE: The aim of this study was to retrospectively evaluat…

Differente pattern di espressione di citochine a fenotipo Th1 e Th2 nei pazienti affetti da diabete di tipo 1 (T1DM) e con associata tireopatia autoimmune (AITD)

Relative Hypoleptinemia in poor controlled patients with Type 1 Diabetes

L’espressione del “peroxisome proliferator-activated gamma” (PPARgamma) nelle tireopatie croniche autoimmuni

Regulation of Apoptosis in Endocrine Autoimmunity

Dysregulation of apoptosis is associated with the pathogenesis of organ-specific autoimmune diseases, through altered target organ susceptibility. Apoptosis signaling pathways can be initiated through activation of death receptors such as Fas. A comparative analysis of the expression of Fas and FasL, the antiapoptotic molecule Bcl-2, and apoptosis in both thyrocytes and thyroid-infiltrating lymphocytes (TILs) from patients with either Graves' disease (GD) or Hashimoto's thyroiditis (HT) was performed. GD thyrocytes expressed less Fas than HT thyrocytes, whereas GD TILs had higher levels of Fas and FasL than HT TILs. GD thyrocytes expressed higher levels of Bcl-2 compared with HT thyrocytes.…

Antitumor effect of aminobisphosphonates on anaplastic thyroid carcinoma cell lines.