A.C. Thai

Cardiovascular diseases in Chinese, Malays, and Indians in Singapore. II. Differences in risk factor levels.

STUDY OBJECTIVE--The aim of the study was to examine cardiovascular risk factors to see how these might explain differences in cardiovascular disease mortality among Chinese, Malays, and Indians in the Republic of Singapore. DESIGN--The study was a population based cross sectional survey. Stratified systematic sampling of census districts, reticulated units, and houses was used. The proportions of Malay and Indian households were increased to improve statistical efficiency, since about 75% of the population is Chinese. SETTING--Subjects were recruited from all parts of the Republic of Singapore. SUBJECTS--2143 subjects aged 18 to 69 years were recruited (representing 60.3% of persons approached). There were no differences in response rate between the sexes and ethnic groups. MEASUREMENTS AND MAIN RESULTS--Data on cardiovascular risk factors were collected by questionnaire. Measurements were made of blood pressure, serum cholesterol, low and high density lipoprotein cholesterol, fasting triglycerides and plasma glucose. In males the age adjusted cigarette smoking rate was higher in Malays (53.3%) than in Chinese (37.4%) or Indians (44.5%). In both sexes, Malays had higher age adjusted mean systolic blood pressure: males 124.6 mm Hg v 121.2 mm Hg (Chinese) and 121.2 mm Hg (Indians); females 122.8 mm Hg v 117.3 mm Hg (Chinese) and 118.4 mm Hg (Indians). Serum cholesterol, low density lipoprotein cholesterol and triglyceride showed no ethnic differences. Mean high density lipoprotein cholesterol in males (age adjusted) was lower in Indians (0.69 mmol/litre) than in Chinese (0.87 mmol/litre) and Malays (0.82 mmol/litre); in females the mean value of 0.95 mmol/litre in Indians was lower than in Chinese (1.05 mmol/litre) and Malays (1.03 mmol/litre). Rank prevalence of diabetes for males was Indians (highest), Malays and then Chinese; for females it was Malays, Indians, Chinese. CONCLUSIONS--The higher mortality from ischaemic heart disease found in Indians in Singapore cannot be explained by the major risk factors of cigarette smoking, blood pressure and serum cholesterol; lower high density lipoprotein cholesterol and higher rates of diabetes may be part of the explanation. The higher systolic blood pressures in Malays may explain their higher hypertensive disease mortality.

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.

Islet autoimmunity status in Asians with young-onset diabetes (12–40 years): Association with clinical characteristics, beta cell function and cardio-metabolic risk factors

In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.

Islet cell and thyroid autoimmunity in Chinese patients with IDDM.

tion (ADA) recommends that screening be confined to individuals with more than one risk factor for diabetes (4). The ADA Diabetes Risk Test (5) is a tool that is used to educate people about diabetes and encourage individuals at high risk of diabetes to seek further diagnostic testing. Two research groups have recently investigated the usefulness of the ADA Diabetes Risk Test and the ADA Diabetes Screening Position Statement. Using the Risk Test, Burden and Burden (6) found poor test sensitivity (46%) and specificity (59.5%) in England. In a U.S. Study (7), 8.3% of participants without risk factors were found to have abnormal screening glucose tests, and 9.2% of those with more than one risk factor were found to have abnormal screening glucose tests (NS). As part of a diabetes education and intervention project, we used the ADA Risk Test as an initial screening tool for finding individuals with undiagnosed diabetes. A revised version of the ADA Diabetes Risk Test was sent to all households occupied by individuals >60 years of age in the Everett, WA, area. These individuals were asked to complete and return the test. Test results were scored using the ADA Diabetes Risk Test scoring guidelines (5). All individuals in the high risk category were asked to have their fasting plasma glucose (FPG) tested. All FPG tests were done through our laboratory using the hexokinase-ultraviolet method. Individuals with FPG levels >6.38 mmol/1 were advised to visit their physicians for further diagnostic testing. We received 349 completed returns (return rate 4.7%). One hundred and eighty-one Risk Tests were classified as high risk by ADA criteria. One hundred and ten (61%) of those people with high risk test scores had FPG testing. Eleven of these people (10%) had FPG tests that exceeded 6.38 mmol/1. Of these 11,7 had FPG levels >7.77 mmol/1. Six new cases of diabetes were diagnosed. Results from individuals with known diabetes were eliminated from data analysis. We compared revised ADA Diabetes Risk Test total scores with FPG values using ^ and Fishers exact tests. The revised ADA Diabetes Risk Test total scores were not significantly related to FPG results (P = 0.961). The ADA Diabetes Risk Test positive predictive value was 9.8% when an FPG level of ^6.38 mmol/1 was used and 6.3% when a FPG level oil.11 mmol/1 was used. The revised ADA Diabetes Risk Test did not prove to be a useful instrument for detecting undiagnosed diabetes in our population of older, primarily Caucasian individuals. We recommend that ADA convert the ADA Diabetes Risk Test to an educational tool that lists common symptoms of diabetes and supports work to analyze the predictive value of various diabetes risk factors with an emphasis on changes that occur with aging and with relative occurrence of each risk factor.

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.)u2003>u200325.0u2003kg/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.