Humoral immune response to islet autoantigens in Japanese patients with type 1 diabetes.

In this study, we evaluated autoantibodies to IA-2 (IA-2As), glutamic acid decarboxylase 65 (GADAs), and islet cell antibodies (ICAs) in 233 patients with type 1 diabetes (M:F = 90:143, mean duration 4.0 +/- 6.7 yr) as a cross-sectional study. Of 233 patients with type 1 diabetes, IA-2A was detected in 58% of patients with duration within 2 weeks, 61% of patients with duration <1 yr, 41% of patients with diabetes for 1-3 yr, 29% for 4-9 yr, and 21% for >or=10 yr. These prevalences were similar to those of ICA, while the prevalence of GADA was not influenced by duration of diabetes with positivity of 63-74%. Thus, as the duration of diabetes became longer, the frequency of GADA(+)/IA-2A(-) patients increased and the frequency of GADA(+)/IA-2A(+) patients decreased. However, the frequency of GADA(-)/IA-2A(+) patients was not influenced by duration of diabetes. The prevalence of IA-2A was significantly higher in abrupt-onset group (68%, n= 79) compared to the slowly progressive group (23%, n= 22) in new-onset patients (P= 0.0001). However, there was no difference in the IA-2A frequency between these two groups (abrupt-onset 26%, n= 53 vs. slowly progressive 24%, n= 21) in patients with long-standing disease, suggesting that IA-2A positivity might persist in patients with slowly progressive type 1 diabetes. These results emphasize the heterogeneity of humoral autoimmunity to protein tyrosine phosphatase-like molecules, but not to GAD, in patients with type 1 diabetes.

Coexistence of insulin resistance and inflammation effectively predicts cardiac disease but not stroke in Japanese patients with type 2 diabetes mellitus.

It is well known that insulin resistance (IR) and inflammation (IF) are associated with macroangiopathy. However, whether IR and IF are related to cardiac disease (myocardial infarction, angina pectoris, and heart failure), stroke or both remains elusive. The present hospital-based prospective study was designed to investigate this issue. The study subjects were 300 Japanese patients with type 2 diabetes mellitus and negative history of cardiac disease and stroke. IR (K index of insulin tolerance test; K(ITT)) and IF (high-sensitivity C-reactive protein [hs-CRP]) were measured in each patient at baseline. Patients were followed-up for a mean period of 5.5 years. The time of first evidenced cardiac disease or stroke was monitored. During the follow-up, 35 patients developed cardiac disease and 26 patients developed stroke. Age, smoking, K(ITT), and hs-CRP were independently related to cardiac disease, while age, systolic blood pressure, low HDL, and anti-platelet drug use were independently related to stroke. When patients were subdivided into IR(-) and IR(+), and IF(-) and IF(+), Kaplan-Meier survival analysis showed that the rate of cardiac disease, but not of stroke, was significantly higher in IR(+)IF(+) than IR(-)IF(-) patients (p < 0.01). In conclusion, coexistence of IR and IF effectively predicted cardiac disease but not stroke in Japanese patients with type 2 diabetes mellitus.

Distinct IA-2 autoantibody epitope recognition between childhood-onset and adult-onset type 1 diabetes.

Different autoimmune mechanisms may be involved in childhood- and adult-onset type 1 diabetes. Our aim was to explore the differences in IA-2 autoantibody epitope recognition between childhood- and adult-onset type 1 diabetes. Therefore, in vitro synthesized radiolabeled IA-2ic (amino acid 601-979), IA-2JM (amino acid 557-629), and IA-2PTP (amino acid 630-979) were used to analyze the IA-2 autoantibody epitope specificities in 93 patients with new-onset type 1 diabetes. Among 93 patients with type 1 diabetes the prevalences of autoantibodies to GAD, IA-2ic, and insulin were 69.9%, 58.1%, and 45.2%, respectively. The prevalence of IA-2ic autoantibodies in patients with childhood-onset type 1 diabetes (aged