Emergence of anti-islet autoantibodies in Japanese patients with type 1 diabetes

Abstract

Abstract. Circulating anti-islet autoantibodies in sera are used as a predictive marker for type 1 diabetes (T1D). We here report two Japanese patients with autoimmune thyroid disease complicated with T1D in whom the time course of anti-islet autoantibodies were observed before the clinical onset of diabetes. Case 1: A woman who had developed Graves' disease at age 25 was diagnosed with type 2 diabetes at age 31; six months later, insulin therapy was started. At age 36 she was diagnosed with T1D due to glutamic acid decarboxylase 65 autoantibodies (GAD65Ab)-positive status and decreased C-peptide levels. With stored sera we retrospectively followed her anti-islet autoantibodies. GAD65Ab, zinc transporter 8 autoantibodies (ZnT8Ab) and insulin autoantibodies (IAA) were found to be positive at age 25. IAA soon turned negative, but GAD65Ab and ZnT8Ab remained positive with high levels. Insulinoma-associated antigen-2 autoantibodies (IA-2Ab) emerged 2 years before the initiation of insulin therapy. She has T1D-susceptible HLA-DRB1-DQB1 haplotypes, *0405-*0401/*0802-*0302. Case 2: A 49-year-old woman with hypothyroidism due to 19 years' history of atrophic thyroiditis noticed marked thirst, polyuria and weight loss. On admission she was diagnosed as T1D due to GAD65Ab-positive findings and poor C-peptide response to i.v. glucagon. Retrospective serology revealed the emergence of GAD65Ab and IAA just after the clinical onset. IA-2Ab and ZnT8Ab never developed. She has T1D-susceptible and -resistant HLA-DRB1-DQB1 haplotypes, *0901-*0303/*1502-*0601. The autoantibody profile and the mode of diabetes onset in the two cases were remarkably different. These cases imply that anti-islet autoantibodies do not always precede the onset of T1D.

Type 1 Diabetes Mellitus Diagnosed during Follow-up of Gestational Diabetes Mellitus in the Early Postpartum Period

“…We searched PubMed and the Japanese Igaku-Chuo-Zassi database using a combination of the key words, “slowly progressive type 1 diabetes mellitus” and “gestational diabetes mellitus”. The characteristics of five patients, including the present patient, were consistent with SPIDDM following a diagnosis of GDM (Table 2) (32-34). The mean age of these patients was 34 years, and the mean BMI was 19.5 kg/m 2 , which was relatively low.…”

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma‐associated antigen‐2 and zinc transporter 8

“…Furthermore, in longitudinal studies of genetically at‐risk children followed from birth, it has been reported that the presence of multiple anti‐islet autoantibodies greatly increases the probability for type 1 diabetes 25 , and IA‐2A and ZnT8A are shown to appear later, in general, during the subclinical disease process and to herald more rapid progression to type 1 diabetes than GADA 26,27 . These data imply that anti‐GAD response might be a sign of general autoimmunity, whereas IA‐2A and ZnT8A might be a surrogate indicator of residual β‐cell mass 28–30 , although there is a study showing that the prevalence of IA‐2A and ZnT8A at and after type 1 diabetes onset did not strongly correlate with endogenous insulin secretion 31 . To avoid autoimmune thyroid disease convoluting the results of the present study, we excluded the type 1 diabetic patients with autoimmune thyroid disease who were persistently positive for GADA 9 .…”

Utility of autoantibodies in insulin-dependent diabetes mellitu

“…Наиболее критичес-ким периодом для возникновения этого заболевания у детей считают возраст от 1 до 5 лет. Именно в этом возрасте отмеча-ют высокий титр аутоантител в крови [4]. Одновременное выявление у ребёнка дру-гих диабетогенных аллелей человеческого лейкоцитарного антигена (HLA), нали-чие инсулинзависимого сахарного диабе-та в семье ещё больше увеличивают этот риск [5].…”