Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes

Aims/hypothesis The aim of this study was to investigate the prevalence of fulminant type 1 diabetes and the clinical characteristics of the disease among newly diagnosed Korean patients. Methods Using data retrieved from the Seoul National University Hospital database, we identified all patients newly diagnosed with type 1 diabetes from 1 January 1999 to 31 July 2006. Information on clinical manifestations and laboratory data, including the presence of islet autoantibodies detected at diagnosis, were obtained by reviewing medical records. Results We identified 99 patients newly diagnosed with type 1 diabetes. Seven patients (7.1%) fulfilled the criteria for fulminant type 1 diabetes. Among the patients aged ≥18 years at onset, 30.4% had fulminant type 1 diabetes. Patients with this diabetes subtype tested negative for islet autoantibodies, had a higher age of onset (median 28 vs 10 years, p < 0.001) and a markedly shorter duration from onset of hyperglycaemic symptoms to first hospital visit (median 3 vs 30 days, p < 0.001) than patients with non-fulminant type 1 diabetes, and showed trends of increased serum aspartate aminotransferase and amylase levels and a decreased glucagon-stimulated serum C-peptide response. Conclusions/interpretation In Korea, the prevalence of fulminant type 1 diabetes was 7.1% among all patients newly diagnosed with type 1 diabetes and 30.4% among patients with adult-onset diabetes. The clinical and metabolic characteristics of the patients with fulminant type 1 diabetes were similar to those reported in Japanese studies. Y. M. Cho and J. T. Kim contributed equally to this work.     

Congenital anomalies in the offspring of women with type 1, type 2 and gestational diabetes.

AIM: To determine the frequency of major congenital anomalies in the offspring of women with gestational diabetes (GDM), classified according to their postpartum glucose tolerance status. METHODS: A prospective study of pregnancies in women with Type 1 diabetes (n = 221), Type 2 diabetes (n = 317) and GDM (n = 1822) between 1985 and 2000 (15 years). Congenital anomalies were detected by antenatal ultrasound or postnatal examination. RESULTS: The frequency of major congenital anomalies in the offspring was 5.9% (95% confidence interval (CI) 3.2-9.8) for women with Type 1 diabetes; 4.4% (95% CI 2.4-7.3) for women with Type 2 diabetes; and 1.4% (95% CI 0.9-2.0) for women with GDM. Two hundred and thirty-seven women with GDM (13%) had diabetes diagnosed on early (6-week) postpartum glucose tolerance testing. The frequency of major congenital anomalies in their offspring was 4.6% (95% CI 2.3-8.2), compared with 0.9% (95% CI 0.5-1.5) for the remainder of the GDM group (P < 0.0001). CONCLUSIONS: GDM is not a homogeneous group with regard to the risk of major congenital anomalies. In those with diabetes on early postpartum testing, who are likely to have had unrecognized Type 2 diabetes antedating their pregnancy, the rate of major congenital anomalies is the same as for women with established Type 1 or Type 2 diabetes. In the remainder of the GDM group, the rate does not differ from the non-diabetic background rate.     

Ovarian morphology and prevalence of polycystic ovary syndrome in Japanese women with type 1 diabetes mellitus

Aims/Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder including polycystic ovary morphology (PCOM), ovulatory dysfunction and hyperandrogenism. PCOS is frequently associated with type 2 diabetes mellitus; however, it is unknown whether PCOM and PCOS are prevalent in Japanese patients with type 1 diabetes mellitus. The purpose of our study was to determine the frequency of PCOM and PCOS in women with type 1 diabetes mellitus.

Materials and Methods

We evaluated clinical, hormonal and ovarian ultrasound data from 21 type 1 diabetes mellitus patients whose average glycated hemoglobin levels were 7.9 ± 1.5%.

Results

Ultrasound identified PCOM in 11 patients (52.4%) and these patients also had higher levels of the androgen dehydroepiandrosterone sulfate (DHEA‐S) than those without PCOM (P < 0.05). Of the patients with PCOM, five presented menstrual irregularities (45.5%) and three met the Japanese criteria for PCOS (27.2%); whereas all patients without PCOM had a normal menstrual cycle (P < 0.05).

Conclusions

Japanese premenopausal women with type 1 diabetes mellitus had a high frequency of PCOM as well as PCOS. This is the first research of this area carried out in an Asian population.     

Prevention strategies for type 1 diabetes

Type 1 diabetes (T1D) is a common chronic disease of childhood. Patients with T1D are at significant risk for developing serious health complications. Understanding of the genetics, environmental factors, and natural history of diabetes has lead to greater understanding of the etiology and epidemiology of T1D. Furthermore, technology has greatly improved glycemic control and reduction of complications. However, prevention of the development of diabetes remains elusive. This review article describes the past, current and upcoming strategies for diabetes prevention for patients at risk for developing autoimmunity, after antibody production, and patients with new onset diabetes.     

Disease burden of rheumatic diseases in India: COPCORD perspective

The maiden WHO ILAR COPCORD (community oriented program for control of rheumatic diseases) Bhigwan (1996–2014) demonstrated that musculoskeletal (MSK) pain was the commonest self-reported ailment in the community, soft tissue rheumatism, ill-defined MSK symptoms and osteoarthritis (OA) were the predominant disorders and about 10% cases suffered from inflammatory arthritis. The burden of rheumatoid arthritis (RA) was high with point prevalence of 0.7%. Bone and joint decade (BJD) India conducted several standardized and uniform surveys (2004–2010) all over India and collected data from over 55,000 persons at 12 sites. The pooled age sex adjusted (India census population 2001) prevalence reported by the recent surveys was – RA (0.34), OA knees (3.34), undifferentiated inflammatory arthritis (0.22), Spondyloarthritis (0.23), ankylosing spondylitis (0.03), psoriatic arthritis (0.01) soft tissue rheumatism (1.39), gout (0.05) lupus (0.01); prevalence percent in parenthesis. Several forms of collagen vascular disorders and vasculitis are described in hospital based case series. Musculoskeletal infections including tuberculosis remain an important clinical burden. The 2006 India Chikungunya epidemic has put an additional burden of chronic MSK pain and arthritis. The recently launched national health programs pertaining to non-communicable diseases, rural and women health does not even mention rheumatic diseases thus there is urgent need to study the burden of rheumatic diseases and its impact on society.     

Dietary quality and markers of inflammation: No association in youth with type 1 diabetes

Background

Systemic inflammation is a key process underlying cardiovascular disease (CVD) development, and CVD risk is significantly elevated in persons with type 1 diabetes (T1D). Youth with T1D exhibit increased levels of inflammation. Studies in persons without diabetes suggest that dietary quality influences inflammation, yet little is known about dietary influences on inflammation in youth with T1D.

The rise and fall of insulin secretion in type 1 diabetes mellitus

An understanding of the natural history of beta cell responses is an essential prerequisite for interventional studies designed to prevent or treat type 1 diabetes. Here we review published data on changes in insulin responses in humans with type 1 diabetes. We also describe a new analysis of C-peptide responses in subjects who are at risk of type 1 diabetes and enrolled in the Diabetes Prevention Trial-1 (DPT-1). C-peptide responses to a mixed meal increase during childhood and through adolescence, but show no significant change during adult life; responses are lower in adults who progress to diabetes than in those who do not. The age-related increase in C-peptide responses may account for the higher levels of C-peptide observed in adults with newly diagnosed type 1 diabetes compared withhose in children and adolescents. Based on these findings, we propose a revised model of the natural history of the disease, in which an age-related increase in functional beta cell responses before the onset of autoimmune beta cell damage is an important determinant of the clinical features of the disease. Electronic Supplementary Material Supplementary material is available for this article at     

Type 1 diabetes mellitus in patients with recurrent acute and chronic pancreatitis: A case series

Background/objectivesPancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing β-cell autoimmunity in susceptible individuals.MethodsWe describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy.ResultsAll 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis.ConclusionsThese cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of β-cell antigens and neoepitope generation, which are potential initiating events for loss of β-cell self-tolerance.     

调节性B细胞与1型糖尿病

1型糖尿病主要是由T细胞介导的针对胰岛β细胞的自身免疫性疾病,然而B细胞在1型糖尿病发生、发展中也发挥重要作用,B细胞去除可用于治疗1型糖尿病.调节性B细胞是近来研究发现的一群具有免疫负向调控作用的B细胞亚群.在1型糖尿病中存在调节性B细胞数量和功能的异常.探索调节性B细胞在1型糖尿病发病机制中所起的作用将提供更多的理论依据,为1型糖尿病免疫治疗提供新靶点和新思路.     

Higher incidence of childhood-onset type 1 diabetes mellitus in remote areas: a UK regional small-area analysis

Aims/hypothesis We investigated the association between the incidence of type 1 diabetes mellitus and remoteness (a proxy measure for exposure to infections) using recently developed techniques for statistical analysis of small-area data.Subjects, materials and methods New cases in children aged 0 to 14 years in Northern Ireland were prospectively registered from 1989 to 2003. Ecological analysis was conducted using small geographical units (582 electoral wards) and area characteristics including remoteness, deprivation and child population density. Analysis was conducted using Poisson regression models and Bayesian hierarchical models to allow for spatially correlated risks that were potentially caused by unmeasured explanatory variables.Results In Northern Ireland between 1989 and 2003, there were 1,433 new cases of type 1 diabetes, giving a directly standardised incidence rate of 24.7 per 100,000 person-years. Areas in the most remote fifth of all areas had a significantly (p=0.0006) higher incidence of type 1 diabetes mellitus (incidence rate ratio=1.27 [95% CI 1.07, 1.50]) than those in the most accessible fifth of all areas. There was also a higher incidence rate in areas that were less deprived (p<0.0001) and less densely populated (p=0.002). After adjustment for deprivation and additional adjustment for child population density the association between diabetes and remoteness remained significant (p=0.01 and p=0.03, respectively).Conclusions/interpretation In Northern Ireland, there is evidence that remote areas experience higher rates of type 1 diabetes mellitus. This could reflect a reduced or delayed exposure to infections, particularly early in life, in these areas.Electronic supplementary material Supplementary material is available for this article at and is accessible for authorized users.     

Immunoglobulin heavy chain switch region polymorphisms are not associated with type 1 diabetes

In order to ascertain whether the immunoglobulin heavy chain genes are important in the aetiology of Type 1 diabetes, we have used restriction fragment length polymorphism (RFLP) analysis of genomic DNA to study 148 Caucasoid subjects with Type 1 diabetes and 146 normal Caucasoid subjects. A DNA probe homologous to the switch regions for the IgM (S mu) and IgA1 (S alpha 1) genes when used in conjunction with the restriction endonuclease Sst I detects RFLPs at both these loci. There were no significant differences in phenotype or gene frequencies for the alleles of S mu or S alpha 1 in the patients when compared with control subjects; nor were there significant associations of S mu or S alpha 1 with HLA-DR type or gender.     

人高迁移率族蛋白B1在风湿免疫性疾病中的研究进展

人高迁移率族蛋白B1(HMGB1)是细胞核内典型的非组蛋白。HMGB1在细胞和组织中分布十分广泛,受到炎症刺激后能从坏死或损伤细胞被动释放,并可诱导树突状细胞上调其成熟的表面抗原。本文详细介绍了HMGB1的结构、功能特点及HMGB1在系统性红斑狼疮、类风湿关节炎、肌炎、系统性硬化症、干燥综合征等风湿免疫性疾病中的表达情况。随着对HMGB1研究的不断深入,HMGB1在风湿性疾病诊断、治疗等中的潜力将进一步得到发展。     

Evaluation of type 1 diabetes in black African-heritage populations: no time for further neglect. Diabetes Epidemiology Research International Group.

Heritage studies involving populations that share a common genetic background but reside in different geographic areas have provided important insights into the aetiology of Type 1 diabetes. While Type 1 diabetes heritage research has focused on Iberian, Arab, Italian, Indian (Asian), and Oriental groups, little attention has been paid to the evaluation of the disease in populations with black African ancestry. Epidemiological data on the occurrence of Type 1 diabetes in New World black populations have thus far been limited to a few studies conducted mainly in African-Americans. Moreover, much of the available data is not population-based and are of limited value for making generalizations about the black populations studied. Despite the limitations, there is evidence that these populations may be important for studying the aetiology and natural history of Type 1 diabetes. Increased research in this area is warranted and should be based on population-based cohorts.     

Epigenetics in autoimmune diseases with focus on type 1 diabetes

Autoimmune diseases arise when the body mounts an immune response against ‘self’ cells and tissues causing inflammation and damage. It is commonly accepted that these diseases develop because of the interplay of genetic and environmental factors. Evidence for genetic factors includes the higher concordance of disease in monozygotic twins than in dizygotic twins. However, monozygotic twins may remain discordant for disease indicating a role for environmental factors. Environmental factors may alter gene expression via epigenetic mechanisms. This is particularly pertinent in type 1 diabetes in which DNA methylation and histone modifications have been associated with altered gene expression. The low disease concordance rate in adult‐onset type 1 diabetes (<20%) suggests that environmental and epigenetic changes may play a predominant role. Defining the role of epigenetic changes could identify specific gene pathways and dysregulated expression of gene products that contribute to the pathogenesis of type 1 diabetes. This article reviews how epigenetic mechanisms may contribute to the development of autoimmune diseases with a focus on type 1 diabetes. Copyright © 2012 John Wiley & Sons, Ltd.     

Syphilis iridocyclitis in a patient with type 1 diabetes

We present a rare cause of iridocyclitis in a patient with vitiligo and type 1 diabetes who showed poor metabolic control, and suffered from remitting fever, weight loss, fatigue, diffuse arthralgias and reduced visual acuity. Mild systemic symptoms coupled with increased cholestasis enzymes, insulin resistance, mild inflammation and a functioning adrenal gland focused our clinical work‐up on granulomatous causes of iridocyclitis. Specific tests confirmed syphilis, with no involvement of the central nervous system. Ocular syphilis, despite being unusual, can be the only manifestation of the disease. The work‐up of any unexplained ocular inflammation should include testing for syphilis so as to not delay the diagnosis.     

Neutrophils in type 1 diabetes

Type 1 diabetes is an autoimmune disease that afflicts millions of people worldwide. It occurs as the consequence of destruction of insulin‐producing pancreatic β‐cells triggered by genetic and environmental factors. The initiation and progression of the disease involves a complicated interaction between β‐cells and immune cells of both innate and adaptive systems. Immune cells, such as T cells, macrophages and dendritic cells, have been well documented to play crucial roles in type 1 diabetes pathogenesis. However, the particular actions of neutrophils, which are the most plentiful immune cell type and the first immune cells responding to inflammation, in the etiology of this disease might indeed be unfairly ignored. Progress over the past decades shows that neutrophils might have essential effects on the onset and perpetuation of type 1 diabetes. Neutrophil‐derived cytotoxic substances, including degranulation products, cytokines, reactive oxygen species and extracellular traps that are released during the process of neutrophil maturation or activation, could cause destruction to islet cells. In addition, these cells can initiate diabetogenic T cell response and promote type 1 diabetes development through cell–cell interactions with other immune and non‐immune cells. Furthermore, relevant antineutrophil therapies have been shown to delay and dampen the progression of insulitis and autoimmune diabetes. Here, we discuss the relationship between neutrophils and autoimmune type 1 diabetes from the aforementioned aspects to better understand the roles of these cells in the initiation and development of type 1 diabetes.     

HLA antigens in spanish type 1 diabetic population. correlations with clinical,biological and autoimmune markers

Summary The HLA haplotype and its relationships with clinical, biological and immunological parameters were analyzed in a group of 87 Spanish type I diabetic patients at the clinical onset of the disease. The frequency of HLA-B18, DR3 and DR4 antigens was significantly increased whereas DR2, DR5 and DR7 were decreased in comparison with 189 healthy unrelated controls without family history of diabetes. DR3 showed a maximum relative risk for diabetes (5.5) whereas DR4 had a lower one (4.0). HLA-DR4 patients were younger at the time of diagnosis than DR4 negative (16.7vs 21.4 years). We found no statistically significant relationship between HLA antigens and the other variables studied including the presence of islet cell antibodies, complement fixing islet cell antibodies, insulin autoantibodies, organ-specific antibodies, fasting and maximal glucagon stimulated C-peptide levels, initial glycemia and glycosylated hemoglobin.     

Breast feeding and the development of type 1 diabetes mellitus.

A case-control study was conducted to study the proposed inverse relationship between breast feeding and incidence of Type 1 diabetes mellitus. All Danish diabetic men born in Copenhagen during 1959-1964 and/or residing there for the first year of life (n = 119) were identified and a search made for their post-natal health visitor records. These include data on birth weight, birth length, immunizations, and feeding habits. A total of 77 cases were re-identified. No differences were found with respect to clinical characteristics between these cases and those not identified. For each diabetic subject, two control children with date of birth identical to the diabetic cases were drawn from health visitor records. Cases and controls did not differ with respect to maternal age, or birth weight or length. Overall, the statistical analysis failed to confirm the hypothesis of an association between duration of breast feeding and subsequent diabetes risk.