K. F. Lui

Anti-GAD antibodies in Chinese patients with youth and adult-onset IDDM and NIDDM

Summary An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies – islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that 39.6 % IDDM and 16.1 % NIDDM patients had GADab, and 20.1 % and 4.8 %, respectively had detectable ICAs. Frequency of GADab positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes. NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who were GADab negative. Presence of GADab therefore did not serve to identify a sub-group of patients with latent or slow-onset IDDM. Half (53 %) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be the major factor in the pathogenesis of IDDM. [Diabetologia (1997) 40: 1425–1430]

Systemic levels of cytokines and GAD-specific autoantibodies isotypes in Chinese IDDM patients

It is not clear if a Th1/Th2 imbalance in Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) would lead to a particular antigen-specific IgG subclass dominant as had been shown in the mouse model. In new-onset Type 1 diabetics, an autoantibody response to glutamate decarboxylase (GADab) is frequently observed but the GADab subclass repertoire is not well-established. We determined the systemic levels of representative Th1 and Th2 cytokines and the GADab IgG subclass distribution in 41 Chinese IDDM patients of whom 26 were recently diagnosed (< or = 1 year) and 32 had GADab, to ascertain a likely association of antigen-specific antibody isotype and the Th1/Th2 dichotomy. With high-sensitivity ELISA systems that measure sub-picogram cytokine concentrations, 26 of the 41 patients (63.4%) had at least one of the pro-inflammatory Th1 cytokines (TNF-alpha, IFN-gamma and IL-12) detected. Fewer patients (4/41) had the anti-inflammatory Th2 cytokine IL-4 detected. For IL-10, all subjects had measurable quantities but only three diabetics had levels above the upper limit for healthy subjects (n = 20). Grouped according to the profile of detectable cytokines, there were 24 Th1, 2 Th2 and 2 Th0 patterns. GAD-specific IgG1 antibody was more frequently expressed; 22 of 32 GADab[+] patients. The rank order for the GADab subclasses was IgG1 > 4 > 3 > 2; IgG2 was found in 11 GADab[+] patients. Recent-onset diabetics have a similar ranking of the GAD-specific IgG subclasses. In human Type 1 diabetes, a predominance of GAD-specific IgG1 antibody response is observed together with a dominant Th1 cytokine pattern.

Low prevalence of autoimmune diabetes markers in a mixed ethnic population of Singaporean diabetics

Abstract

Three new glucose reflectance meters: Diascan, Glucometer II, and Reflolux II

More and more frequently, diabetics use portable blood glucose meters to assess their own glycemic control. New meters are constantly being introduced commercially. We evaluated three recently marketed meter/strip systems in terms of accuracy, precision, and the stability of the colors on the test strips. We compared the results from the meters with those from a Beckman Glucose Analyser and calculated the correlation and regression coefficients (Diascan, r = 0.93, y = 0.64x + 41.76; Glucometer II, r = 0.94, y = 0.86x + 2.32; and Reflolux II, r = 0.99, y = 0.99x + 5.15). Both the Diascan and Glucometer II meters tended to underestimate blood glucose whereas Reflolux II gave unbiased measurements throughout the clinical range. Reflolux II was also the most precise of the three. Furthermore, the Reflolux test strips kept their color over 6 days of storage at 4 degrees C, while strips from the other two systems faded. All three meters are compact, simple to calibrate, and convenient. They remain, however, relatively expensive, as do the test strips.

Testosterone and leptin in a group of Chinese with and without diabetes.

Aim: Leptin levels in the overweight and differences between men and women may be confounded by sex hormones in obesity‐related type 2 diabetes. We carried out a study of leptin and testosterone and the effect of diabetes on this relationship in 71 Chinese subjects (51 with type 2 diabetes and 20 healthy non‐diabetics) of whom 32 were overweight (body mass index (b.m.i.) > 25.0 kg/m2).

Soluble T-cell markers and serum cytokines in type I (insulin-dependent) diabetes mellitus

Markers of cell-mediated immune activation were studied in 32 Chinese patients with recent-onset insulin-dependent diabetes mellitus (IDDM) as compared with 12 patients with recent-onset non-insulin-dependent diabetes mellitus (NIDDM) and 34 normal subjects. Sera were assessed for soluble markers of T-cell activation (sCD4, sCD8, sIL-2R); the cytokines (IL-1 beta, TNF-alpha, IL-2, IL-6), and T-cell subsets were also determined. Only 1 of the 32 IDDM patients had increased sCD4 levels, 5 had increased sCD8, and 3 had increased sIL-2R. None of the sera from NIDDM patients and control subjects showed such increased levels of soluble markers. Three IDDM patients had detectable IL-1 beta and this weakly so (< 3.5 pg/ml). However, the other cytokine data and the frequency of activated T-cells, CD4+, CD8+ T-cell subsets and CD4:CD8 ratio showed no significant differences among the IDDM, NIDDM and normal subjects. Our data suggest that in addition to a low frequency of islet cell antibodies, Chinese patients with recent onset IDDM also showed a lack of serum markers of cellular activation.

IgG-Class Insulin Autoantibodies in Autoimmune Thyroid Disease

We studied the incidence of insulin autoantibodies (IAA) in 97 patients with autoimmune thyroid disease with an enzyme-linked immunosorbent assay. The sera were also tested for islet cell antibodies (ICA) and thyrotropin receptor antibodies (TRAb). IAA as assessed by a standard deviation score were present in 7 patients (7.2%). None of the patients were seropositive for ICA. Data from this random sampling and a retrospective study of 12 patients on antithyroid drug treatment indicated that the presence of IAA was not associated with TRAb.