Type 1 diabetes: Pathogenesis and prevention

ArticleinCanadian Medical Association Journal 175(2):165-70 · August 2006with19 Reads
DOI: 10.1503/cmaj.060244 · Source: PubMed
Type 1 diabetes results from the autoimmune destruction of insulin-producing beta cells in the pancreas. Genetic and, as yet undefined, environmental factors act together to precipitate the disease. The excess mortality associated with the complications of type 1 diabetes and the increasing incidence of childhood type 1 diabetes emphasize the importance of therapeutic strategies to prevent this chronic disorder. Why is it considered that type 1 diabetes might be preventable? Different strands of diabetes research are coming together to suggest therapeutic targets. Islet cell autoantibody assays make it possible to accurately identify people at risk of future disease. In most cases, a long prodrome provides a window of opportunity to reverse the autoimmune process. Although no current "cure" exists, recent genetic data and preliminary trial results suggest T cells as a target for preventive strategies. Another potentially attainable target is induction of tolerance to the beta-cell proteins such as insulin that are inappropriately recognized. Other strategies involve beta-cell replacement, but currently there are insufficient donor cells available. This may be overcome as the processes controlling the differentiation of pancreatic and nonpancreatic progenitors as well as replication of existing islet beta cells are unravelled.
    • "Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease in which insulin-producing beta cells in pancreatic islets of Langerhans are selectively destroyed, leading to insulin deficiency and dysregulation of glucose metabolism (Atkinson and Maclaren, 1994; Eisenbarth, 1986; Gillespie, 2006; Zhang et al., 2008). The incidence of diabetes highly varies in different countries, and this is probably related to genetic and environmental factors, such as nutrition or lifestyle (Patterson et al., 2001 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.
    Article · May 2016
    • "Furthermore, patients with APSIII may also be diagnosed with celiac disease (CD). Despite the genetic variation in human leukocyte antigen (HLA) and its involvement in T1D development, new genes have been identified as potentially important in disease's susceptibility and modulation outside HLA range (Gillespie, 2006; Liang et al., 2012). Signal transducer and activator of transcription 4 (STAT4) is a latent cytoplasmic transcription factor activated by phosphorylation in response to proinflammatory cytokines, such as interleukin (IL)-12, IL-15, and IL-23 (Levy and Darnell, 2002). "
    [Show abstract] [Hide abstract] ABSTRACT: Type 1 diabetes mellitus (T1D) is an organ-specific autoimmune disease characterized by T-cell mediated self-destruction of insulin-producing β cells in the pancreas. T1D patients are prone to develop other glandular autoimmune disorders, such as autoimmune thyroid disease that occurs simultaneously with autoimmune polyglandular syndrome type III (APSIII). Signal transducer and activator of transcription 4 (STAT4) is a well-known regulator of proinflammatory cytokines, and interferon-induced with helicase C domain 1 (IFIH1) is activated in the interferon type I response. Both genes have been examined separately in autoimmune diseases and, in this study, we assessed their joint role in T1D and APSIII. We conducted a case-control study, enrolling 173 T1D patients and 191 healthy controls from northeastern Brazil, to assess the distribution of the rs7574865 and rs3024839 SNPs in STAT4 and the rs3747517 and rs1990760 SNPs in IFIH1 in T1D and APSIII patients. Additionally, we conducted a metaanalysis with the rs7574865 SNP in STAT4 (1392 T1D patients and 1629 controls) and the rs1990760 SNP in IFIH1 (25092 T1D patients and 28544 controls) to examine their association with T1D. Distribution of STAT4 and IFIH1 allelic frequencies did not show statistically significant differences between T1D patients and controls in our study population; however, the meta-analysis indicated that SNPs in STAT4 and IFIH1 are associated with T1D worldwide. Our findings indicate that although STAT4 and IFIH1 SNPs are not associated with T1D in a Brazilian population, they might play a role in susceptibility to T1D on a larger worldwide scale.
    Full-text · Article · Dec 2015
    • "Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by beta cell destruction [1]. Its incidence has increased by ∼3% per year in children under the age of 5 and represents 10% of all the cases of diabetes [2]. In Mexico, the incidence of T1D among children under 19 years of age is 6.2 per 100,000 insured cases in the Instituto Mexicano del Seguro Social (IMSS), the largest social health care provider throughout the country [3]. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cutoff point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (í µí±› = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.
    Full-text · Article · Aug 2015
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