c-peptide and Virus-Diseases

Fulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute-onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA-DR-DQ, HLA-B and CTLA-4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll-like receptor-3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti-viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction.

Topics: Acute Disease; Adult; Aged; Asia, Eastern; Blood Glucose; C-Peptide; CTLA-4 Antigen; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Enterovirus Infections; Female; Glycated Hemoglobin; HLA-B Antigens; HLA-DRB1 Chains; Humans; Insulin-Secreting Cells; Japan; Male; Middle Aged; Virus Diseases

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Early Diagnosis; Glycated Hemoglobin; HLA-DR4 Antigen; Humans; Insulin; Insulin-Secreting Cells; Japan; Linkage Disequilibrium; Prognosis; Th1 Cells; Time Factors; Virus Diseases

To clarify the characteristics of idiopathic type 1 (type 1B) diabetes mellitus (DM), we compared the clinical features of immune-mediated type 1 (type 1A) DM and type 1B DM in 85 Japanese children and adolescents with DM. The prevalence of type 1B DM was 16.5%. The patients with type 1B DM were significantly younger at diagnosis and had a higher frequency of preceding viral infection before onset, compared to those with type 1A DM. They displayed more severe metabolic decompensation with a higher frequency of ketoacidosis at diagnosis than patients with type 1A DM. They had strong, HLA-defined genetic susceptibility, similar to that in type 1A DM. Some patients with type 1B DM exhibited a remarkably abrupt onset and rapid loss of beta-cell capacity. From these findings, it is considered that type 1B DM differs from type 1A DM with respect to age at onset and the trigger event, such as viral infection, leading to rapid destruction of beta-cells without autoimmunity in the etiology of the disease.

Topics: Adolescent; Age of Onset; Bicarbonates; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hemoglobin; HLA-DR Antigens; Humans; Japan; Male; Virus Diseases

We studied the effect of interferon as an adjunct to conventional insulin therapy on the early course of Type 1 diabetes in 43 newly diagnosed patients. Compared with conventional therapy, interferon administration slightly delayed the improvement of glucose homeostasis and the rise of high density lipoprotein cholesterol, while C-peptide secretion was unaffected. Independent of the type of therapy, 18 patients (42%) entered partial remission. The remission began 2.0 +/- 0.6 months (mean +/- SEM) from the start of therapy and lasted for 4.1 +/- 1.1 months. Seven patients (16%) were still in remission 1 year after diagnosis. The patients who entered remission had higher initial C-peptide secretion, lower glycosylated haemoglobin levels and better initial control than patients without remission. Thus, interferon provided no benefits as an adjunct to conventional insulin therapy in unselected patients with newly diagnosed Type 1 diabetes. An important factor for the development of remission was the presence of C-peptide secretion at the time of diagnosis.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cholesterol, HDL; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Insulin; Interferon Type I; Male; Virus Diseases

Various immunological mechanisms help to understand the epidemiological and biological heterogenicity of type 1 Diabetes Mellitus. Immunological mechanisms are involved in the destruction of beta cells and perhaps explain the prevalence of Diabetes Mellitus among certain patients with well defined genetic markers. Certain cases of Diabetes Mellitus seem to be mediated by auto-immune processes (cellular or humoral) and thus have a common denominator with other endocrinological diseases. Other immunological mechanisms are incriminated in the development of insulin resistance during exogenous insulin treatment of type 1 Diabetes Mellitus. Resistance to endogenous insulin which characterizes type 2 Diabetes Mellitus is related to a decrease in number and density of peripheral insulin receptors.

Topics: Animals; C-Peptide; Diabetes Mellitus; HLA Antigens; Humans; Insulin Resistance; Islets of Langerhans; Virus Diseases