GAD65Abs Are Not Associated With Beta-Cell Dysfunction in Patients With T2D in the GRADE Study.

Context: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.

Type 1 Diabetes Genetic Risk Score Differentiates Subgroups of Ketosis-Prone Diabetes.

Objective: To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aβ subgroups of ketosis-prone diabetes (KPD), where A+ and A- define the presence or absence of islet autoantibodies and β+ and β- define the presence or absence of β-cell function.

Research Design And Methods: We compared T1D genetic risk scores (GRS) of patients with KPD across subgroups, race/ethnicity, β-cell function, and glycemia.

Results: Among 426 patients with KPD (54% Hispanic, 31% African American, 11% White), rank order of GRS was A+β- > A+β+ = A-β- > A-β+.

Subgroups of adult-onset diabetes: a data-driven cluster analysis in a Ghanaian population.

Adult-onset diabetes mellitus (here: aDM) is not a uniform disease entity. In European populations, five diabetes subgroups have been identified by cluster analysis using simple clinical variables; these may elucidate diabetes aetiology and disease prognosis. We aimed at reproducing these subgroups among Ghanaians with aDM, and establishing their importance for diabetic complications in different health system contexts.

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case-cohort study.

Aims/hypothesis: Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes.

Methods: We used the European EPIC-InterAct case-cohort study including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals.

Hypothesis: Viral infections of pregnant women may be early triggers of childhood type 1 diabetes and other autoimmune disease.

Children and adolescents with early onset autoimmune diseases have a different seasonality of month of birth than the general population. This pattern is consistent with an infection during pregnancy affecting the fetus or an infection immediately after birth that act as early triggers of the autoimmune diseases. We present data supporting the use of Rotavirus vaccinations in the reduction of incidence of childhood T1D and propose further investigations into whether other anti-virus vaccinations may reduce the burden of other autoimmune diseases such as multiple sclerosis, atopic dermatitis, psoriasis and subtypes of rheumatoid arthritis, Hashimoto thyroiditis.

Data Mining Framework for Discovering and Clustering Phenotypes of Atypical Diabetes.

Context: Some individuals present with forms of diabetes that are "atypical" (AD), which do not conform to typical features of either type 1 diabetes (T1D) or type 2 diabetes (T2D). These forms of AD display a range of phenotypic characteristics that likely reflect different endotypes based on unique etiologies or pathogenic processes.

Objective: To develop an analytical approach to identify and cluster phenotypes of AD.

Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.

Islet autoantibodies, including autoantibodies directed against the 65kDa isoform of glutamate decarboxylase (GAD65Ab), are present in the majority of patients with newly diagnosed type 1 diabetes (T1D). Whereas these autoantibodies are historically viewed as an epiphenomenon of the autoimmune response with no significant pathogenic function, we consider in this study the possibility that they impact the major islet function, namely glucose-stimulated insulin secretion. Two human monoclonal GAD65Ab (GAD65 mAb) (b78 and b96.

Islet Autoimmunity is Highly Prevalent and Associated With Diminished β-Cell Function in Patients With Type 2 Diabetes in the Grade Study.

Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin alone.

A randomized double-blind placebo controlled pilot study of probiotics in adolescents with severe obesity.

Purpose: The purpose of the study is to assess the effect of probiotic supplementation on gut microbiota and insulin resistance in adolescents with severe obesity.

Methods: Through a randomized, double blind, placebo-controlled, 12-week pilot clinical trial, 15 adolescents with severe obesity received either an oral probiotic 'Visbiome®' ( = 8) or placebo ( = 7). Anthropometry, fasting glucose, insulin, hs-CRP and stool for microbiome and calprotectin were collected at baseline (week 0) and 12 weeks after intervention.

Differences in MPS I and MPS II Disease Manifestations.

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation.

Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs.

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

Objective: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.

Research Design And Methods: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries.

Dysostosis Multiplex in Human Mucopolysaccharidosis Type 1 H and in Animal Models of the Disease.

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder, caused by deficiency of α-L-iduronidase, and consequent accumulation of dermatan and heparan sulfates. Severity of the disease ranges from mild (Scheie) to moderate (Hurler-Scheie) to severe (Hurler or MPS-IH). A prominent clinical manifestation of MPS-IH is dysostosis multiplex, a constellation of skeletal abnormalities.

For Debate: The Controversy whether Rotavirus Vaccination Attenuates the Incidence of Childhood Type 1 Diabetes.

Recent epidemiological surveys performed in Australia, USA and Israel demonstrate that Rotavirus vaccination correlates with an attenuated prevalence and/or incidence of early childhood diabetes (T1D). Other studies failed to confirm the above.

Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology.

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive inherited disease, caused by deficiency of the enzyme α-L-iduronidase, resulting in accumulation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate in organs and tissues. If untreated, patients with the severe phenotype die within the first decade of life. Early diagnosis is crucial to prevent the development of fatal disease manifestations, prominently cardiac and respiratory disease, as well as cognitive impairment.

Geographic location determines beta-cell autoimmunity among adult Ghanaians: Findings from the RODAM study.

Introduction: Beta-cell autoantibodies are established markers of autoimmunity, which we compared between Ghanaian adults with or without diabetes, living in rural and urban Ghana and in three European cities.

Methods: In the multicenter cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) study (N = 5898), we quantified autoantibodies against glutamic acid decarboxylase (GAD65Ab) by radioligand binding assay (RBA) and established cut-offs for positivity by displacement analysis. In a subsample, we performed RBA for zinc transporter-8 autoantibodies (ZnT8Ab).

Placental Barrier and Autism Spectrum Disorders: The Roles of Prolactin and Dopamine in the Developing Fetal Brain-Part II.

The inverse relationship between prolactin and dopamine is important in the context of treatment with antipsychotic medications in men and nonpregnant women with thought disorders. Likewise, increased levels of prolactin as confirmation of recent seizure and the reciprocal levels of prolactin and dopamine in both eclampsia (seizures) and pre-eclampsia might have significant potential effects on a growing fetus. In this article, we attempt to outline the influence of these associations on autism spectrum disorders (ASDs) in children born to mothers with established diagnoses of eclampsia and/or pre-eclampsia.

Serum C-peptide and osteocalcin levels in children with recently diagnosed diabetes.

Background: We explored the association of C-peptide (marker of secreted insulin), proinsulin and proinsulin ⁄C-peptide ratio (PI/C) (markers of beta-cell endoplasmic reticulum [ER] stress) with undercarboxylated (uOC) and carboxylated osteocalcin (cOC) and their ratio (uOC/cOC) in children with recently diagnosed type 1 (T1D) or type 2 diabetes (T2D), and the correlation of these variables with partial remission (PR) in children with T1D.

Methods: Demographic and clinical data of children with new-onset diabetes (n = 68; median age = 12.2 years; 33.

Autoimmunity plays a role in the onset of diabetes after 40 years of age.

Aims/hypothesis: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.

Contribution of the Cerebellum to Predictive Motor Control and Its Evaluation in Ataxic Patients.

Goal-directed movements are predictive and multimodal in nature, especially for moving targets. For instance, during a reaching movement for a moving target, humans need to predict both motion of the target and movement of the limb. Recent computational studies show that the cerebellum predicts current and future states of the body and its environment using internal forward models.

Anti-GAD Antibodies and the Cerebellum: Where Do We Stand?

Anti-GAD65 antibodies (anti-GAD65 Abs) are associated with cerebellar ataxia (CA). The significance of anti-GAD65 Abs has been a focus of debates. Since GAD65 is intracellularly located and associated with type 1 diabetes mellitus and different clinical neurological phenotypes such as CA, stiff-person syndrome, and epilepsy, some researchers have argued that anti-GAD65 Abs have no pathogenic roles.