Analysis of pathogenesis of juvenile new-onset diabetes

Abstract

Background Measurement of anti-islet autoantibodies at the time of disease onset contributes greatly to the differentiation of Type 1A diabetes with HLA Class II subtyping also contributing. Methods Blood samples were obtained from 900 patients with age from 1 month to 25 years (median age 11.1 years) within 2 weeks of diabetes onset to test anti-islet autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma antigen (IA-2AA), the zinc transporter-8 (ZnT8AA), and islet-cell antibodies (ICA). Polymorphisms of the HLA Class II gene were typed in 547 randomly selected patients. Results Of the 900 subjects analyzed, 145 (16.1%) were negative for all five anti-islet autoantibodies, and autoantibody negativity significantly increased with age: 10.2% (38/372) among children <10 years of age, 14.2% (46/325) in those 10–14 years of age, and 30.1% (61/203) in those >14 years of age (P < 0.001). The prevalence of IA-2AA was the highest among young children. The prevalence of GADA increased with age while the prevalence of IAA was inversely correlated with age. At diagnosis, the subjects with negative antibodies had a higher body mass index (P < 0.001) and less high risk HLA genotype DR3-DQ2/DR4-DQ8 (P < 0.01). Conclusion A large percentage of children and youths negative for all anti-islet autoantibodies at the onset of diabetes are likely to have the non-immune form, especially those without DR3/DR4 and obese patients. Among autoantibody-positive Type 1A patients, IAA and GADA showed a reciprocal prevalence, suggesting differential disease pathogenesis.

HLA-DR, HLA-DQ Haplotypes and Diabetic Autoantibodies in Nondiabetic Siblings of Type I Diabetes

“…The ethnic variation in the prevalence of autoantibodies among T1DM was highlighted in many early studies [26,27]. In the current study, GAD antibody and anti-IA-2 were significantly higher in siblings compared to controls.…”

Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR

“…Insulin insufficiency and impairment in pancreatic islet β-cells is also found combined with insulin resistance in type 2 diabetes 2 , the most prevalent form of diabetes. Although the cause of insulin insufficiency is generally considered to be a result of β-cell damage by autoimmunity, a high percentage of diabetic patients with insulin insufficiency show negative of those autoantibodies 3 . Notably, whereas most CFRD cases exhibit insulin insufficiency 4 5 , the exact cause remains elusive although destruction of the insulin-secreting pancreatic islets secondary to the obstruction of the pancreatic duct due to defective CFTR has long been considered the underlying cause 6 7 .…”

Diabetes in youth: A dilemma of pathogenesis

“…In those <10 years of age, those 10–14 years of age, and in those >14 years of age, 10%, 14%, and 30% were negative to an entire panel of five diabetes‐related antibodies. A lower prevalence of antibody positivity was seen not only with increasing age, but also with increasing body mass index–standard deviation score, an age‐independent measure 6 . This study highlights the difficulty in identifying the type of diabetes in this age group.…”

“…A lower prevalence of antibody positivity was seen not only with increasing age, but also with increasing body mass index-standard deviation score, an age-independent measure. 6 This study highlights the difficulty in identifying the type of diabetes in this age group. Should the antibody-negative diabetic youths to be considered as having Type 2 diabetes?…”

“…In the current issue of the Journal of Diabetes , Wang et al 6 . present an analysis of Type 1 diabetes‐related antibody characteristics of a cohort of 900 people aged 25 years or less presenting to the University of Colorado between 1992 and 2004.…”