J. K. Y. Li

Simple anthropometric indexes and cardiovascular risk factors in Chinese

OBJECTIVE: Obesity is a major public health problem due to its associations with multiple cardiovascular risk factors. Although there are sophisticated methods, such as imaging, to document total body fat and its distributions, anthropometric measurements remain important in clinical practice. We examined the relationships between cardiovascular risk factors and the three commonest anthropometric measurements for obesity, body mass index (BMI), waist–hip ratio (WHR) and waist circumference (WC), in Hong Kong Chinese subjects. DESIGN AND SETTING: The data are obtained from a prevalence survey for glucose intolerance and lipid abnormality in a representative Hong Kong Chinese working population. All employees from a public utility company and a regional hospital were invited to participate. SUBJECTS: There were 1513 subjects (910 men and 603 women, mean age ± s.e.m.: 37.5±0.2 y). All of them had no significant past medical history. MEASUREMENTS: BMI, WHR and WC of the 1513 subjects were assessed for their relationships with various cardiovascular risk factors. These include blood pressure, fasting and 2 h plasma glucose and insulin, glycated haemoglobin, total cholesterol, triglyceride, high density and low density lipoprotein cholesterol, and urine albumin concentration. RESULTS: After age adjustment, all three anthropometric indexes were significantly correlated with the major cardiovascular risk factors in both men and women. When BMI, WHR and WC were analysed according to quartiles, there was a significant trend for blood pressure, plasma triglyceride, fasting and 2 h plasma glucose and insulin to increase, and high density lipoprotein cholesterol to decrease, with increasing obesity after adjustment for age and smoking. Using stepwise regression analysis with the three indexes as independent variables, most of the variance in blood pressure, plasma lipid, insulin, glucose and urinary albumin concentration were explained either by WC or WHR. In women, BMI was the main explanatory variable for reduced high density lipoprotein cholesterol. CONCLUSIONS: In Hong Kong Chinese, BMI, WHR and WC provide important information in assessing cardiovascular risks. In men, central adiposity as reflected by WC and to some extent, WHR, explained most of the variance in blood pressure, plasma glucose, lipid, insulin and albuminuria. In women, all three indexes reflecting general and central obesity contribute to the variance in these risk factors.

Combined Use of a Fasting Plasma Glucose Concentration and HbA1c or Fructosamine Predicts the Likelihood of Having Diabetes in High-Risk Subjects

OBJECTIVE To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG ≥ 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) ≥ 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG ≥ 5.6 mmol/l and an HbA1c ≥ 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG ≥ 5.4 mmol/l and a fructosamine ≥ 235 μmol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG ≥ 5.6 mmol/l and < 7.8 mmol/l and a fructosamine ≥235 μmol/1 (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408 – 526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/1, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach ∼ 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.

Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus

The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young‐onset diabetes from the Hong Kong Family Diabetes Study.

The linkage and association of the gene encoding upstream stimulatory factor 1 with type 2 diabetes and metabolic syndrome in the Chinese population

Aims/hypothesisThe transcription factor upstream stimulatory factor 1 (USF1) regulates the expression of genes involved in glucose and lipid metabolism and has been associated with familial combined hyperlipidaemia. USF1 is located on chromosome 1q22–23, a region with evidence for linkage to type 2 diabetes and various traits of the metabolic syndrome in Chinese and other populations. The aim of this study was to investigate the linkage and association of USF1 with type 2 diabetes and the metabolic syndrome in Chinese individuals.Materials and methodsWe genotyped three haplotype-tagging single nucleotide polymorphisms (SNPs) (rs3737787, rs2516841 and rs2516839) at USF1 in three samples of the Hong Kong Chinese population, including members of 179 families from the Hong Kong Family Diabetes Study, 1,383 hospital cases with type 2 diabetes and/or the metabolic syndrome and 454 normal control subjects.ResultsWe found significant association of individual polymorphisms and haplotypes with type 2 diabetes and/or metabolic syndrome-related traits in the family samples using either family-based or unrelated normal control subjects. However, these variants could not explain much of the evidence for linkage in this region. Moreover, they were not associated with type 2 diabetes and/or the metabolic syndrome in the hospital cases.Conclusions/interpretationThe results are consistent with the hypothesis that variation at USF1 contributes to the risk of type 2 diabetes and the metabolic syndrome in families with strong evidence for linkage in the chromosome 1q region. However, they provide little support for USF1 as the susceptibility locus that generates the observed evidence for linkage at 1q21–25 for type 2 diabetes and/or the metabolic syndrome, and USF1 does not appear to have a major contribution to these phenotypes in the general Chinese population.

Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor‐1α genes in patients with early‐onset Type 2 diabetes mellitus/MODY

Aims To examine the prevalence of identified MODY‐related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes.

Serum bilirubin and cardiovascular risk factors in a Chinese population.

Background Many risk factors for cardiovascular disease (CVD) have been identified. Recently, an association between low concentration of serum bilirubin and increased risk of CVD has been reported. However, information on this topic remains scarce. Methods We examined the relationships between serum bilirubin and CVD risk factors in 1508 Hong Kong Chinese. We divided the subjects into four quartiles based on serum bilirubin concentrations. Cardiovascular risk factors studied include age, sex, smoking, obesity, glycaemic status and lipid indices. Results Decreasing serum bilirubin concentration was associated with older age, increased prevalence of smoking, higher body mass index and systolic blood pressure, increased glycated haemoglobin, fasting and 2 h insulin, triglyceride, very-low-density lipoprotein and apolipoprotein B concentrations, and lower high-density lipoprotein concentration. Women had lower bilirubin concentrations than men. After adjustment for age, sex, smoking and insulin levels as covariates, the associations between serum bilirubin concentration and glycated haemoglobin, triglyceride, high-density lipoprotein and very-low-density lipoprotein persisted. The prevalence rates of abnormal glucose tolerance (impaired glucose tolerance or diabetes) were similar amongst the four quartiles of bilirubin concentrations. However, the mean bilirubin concentration was significantly lower in subjects with abnormal glucose tolerance (9.3 ± 3.5 μmol/l, n = 178) than in normal subjects (10.1 ± 5.2 μmol/l, n = 1330, P = 0.039). When analysed as a continuous variable by age-adjusted partial correlation coefficients, serum bilirubin concentration was inversely correlated with fasting insulin, triglyceride, very-low-density lipoprotein and glycated haemoglobin level. Conclusions There were close associations between low serum bilirubin concentration and increased CVD risk factors. Subjects with abnormal glucose tolerance also had lower serum bilirubin concentration than normal subjects. Some of these associations (body mass index, systolic blood pressure) could be explained by differences in insulin level. These relationships between bilirubin and CVD risk factors require further clarification, although abnormal intermediary metabolism and antioxidant deficiency may be possible linking factors.

The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects: Evidence for associations with type 2 diabetes and cholesterol levels

BACKGROUND and OBJECTIVES There has been evidence that the S20G mutation in the islet amyloid polypeptide (amylin) gene may be associated with type 2 diabetes. In the present study, we investigated the distribution of the mutation in Hong Kong Chinese, and examined whether there was evidence for associations between the mutation and type 2 diabetes and/or metabolic profiles.

Mitochondrial DNA A3243G mutation in patients with early‐ or late‐onset type 2 diabetes mellitus in Hong Kong Chinese

The mitochondrial DNA A to G mutation at nucleotide 3243 (mt3243) is associated with a subtype of diabetes characterized by maternal transmission and deafness. We have previously reported a 2.7% prevalence of this mutation in a cohort of young patients with either type 1 or type 2 diabetes. In this study, we aimed to confirm this finding by examining for the prevalence of this mutation in a large‐scale study.

Antibodies to glutamic acid decarboxylase in young Chinese diabetic patients

Antibodies to glutamic acid decarboxylase (GAD) are a useful autoimmune marker for type 1 diabetes mellitus in Caucasians. We examined antibodies to GAD and their relationships with clinical features and pancreatic β cell function in 140 young Chinese diabetic patients. Over an 18-month period beginning in 1995, 140 young Chinese diabetic subjects with age of onset of disease ⩽ 35 years and age < 40 years were recruited consecutively, irrespective of their modes of presentation. Clinical features, antibodies to GAD and pancreatic β cell function (using a glucagon stimulation test) were examined. Increased levels of antibodies to GAD (>18 units) were detected in 12·1% (n> = 17) of these subjects. Forty-three (31%) patients had a classical type 1 presentation and 65 (46%) patients were insulin-deficient based on post-glucagon plasma C-peptide levels. Patients who were insulin-deficient and had a type 1 presentation had the highest prevalence of antibodies to GAD (29·0%) compared with patients who had a type 2 presentation and were non-insulin deficient (6·4%, P = 0·003). Patients who had antibodies to GAD had lower body mass index and waist—hip ratio, earlier onset of disease, lower blood pressure, plasma triglyceride and C-peptide, and higher concentrations of plasma high-density lipoprotein cholesterol and glycated haemoglobin, and were more likely to require drug treatment, compared with those without antibodies to GAD. In conclusion, there was a low prevalence of antibodies to GAD in Chinese young diabetic patients although such antibodies remained a relatively specific marker for insulin deficiency and acute presentation. Causes other than autoimmunity should be sought to explain the high prevalence of insulin deficiency in these young Chinese patients.

Glycated haemoglobin and cardiovascular risk factors in Chinese subjects with normal glucose tolerance.

Increased plasma glucose concentration is a predictive factor for mortality in both diabetic and non‐diabetic subjects. Although glycated haemoglobin (HbA1c) is a useful index of mean blood glucose concentrations over the preceding 1 to 3 months, there are few data regarding its relationship to cardiovascular risk. We have examined the relationship between HbA1c and cardiovascular risk factors in 1280 subjects with normal glucose tolerance. Based on HbA1c tertiles (tertile 1: n = 427, 262 men and 165 women, HbA1c level: 2.9–4.7 % in men and 3.2–4.2 % in women; tertile 2: n = 426, 261 men and 165 women, HbA1c level: 4.7–5.1 % in men and 4.2–4.6 % in women; tertile 3: n = 427, 262 men and 165 women, HbA1c level: 5.1–6.7 % in men and 4.6–6.9 % in women), increasing HbA1c was associated with increasing age, blood pressure, waist–hip ratio, fasting and 2‐h plasma glucose, 2‐h insulin, cholesterol, low‐density lipoprotein cholesterol, apolipo‐ protein B and urate concentrations. When age and sex were included as covariates, increasing HbA1c remained associated with increasing fasting and 2‐h plasma glucose, 2‐h insulin, total cholesterol, and low‐density lipoprotein cholesterol concentrations. These findings emphasize the importance of hyperglycaemia, as reflected by HbA1c, as a continuum in the evaluation of cardiovascular risk. Furthermore, these findings support the hypothesis that cardiovascular disease risk commences with rising glucose concentrations before ‘conventionally‐defined’ glucose intolerance occurs.