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Context: Age-related declines in testosterone and IGF-I are associated with deposition of visceral fat, a component of the metabolic syndrome (MES)., Objective: Testosterone and IGF-I may interact with familial disposition to diabetes mellitus to increase the association with MES., Design: We conducted a cross-sectional cohort study., Setting: The study was conducted in a university teaching hospital., Subjects: Study subjects included 179 middle-aged men with a family history of diabetes (FH) (aged 39.1 +/- 8.1 yr) and 128 men without FH (aged 43.8 +/- 8.5 yr)., Main Outcome Measures: Clinical characteristics, frequency of MES using the World Health Organization criteria with Asian definitions of obesity (body mass index > or = 25 kg/m2), and serum levels of total testosterone, IGF-I, and high-sensitive C-reactive protein (hs-CRP) were measured., Results: Men with FH had higher frequency of MES than those without FH [39.1 vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (former and current smokers), low total testosterone, and IGF-I but elevated hs-CRP levels explained 35% of the MES variance in men with FH. The frequency of MES increased with declining tertiles of total testosterone and IGF-I but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES, which explained 14% of the variance., Conclusions: Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.

Background: The G-308A polymorphism in the promoter region of the tumor necrosis factor alpha (TNF-alpha) gene has been reported to be associated with insulin resistance and obesity, both of which may increase the risk of diabetic nephropathy. We hypothesized that this polymorphism might interact with obesity to affect development of diabetic nephropathy., Methods: A consecutive cohort of 1281 Chinese type 2 diabetic patients was enrolled for analysis. Genotyping of TNF-alpha G-308A polymorphism was performed using a PCR-based RFLP method with NcoI digestion. The mean value of the albumin creatinine ratio (ACR) of a random spot urine sample and a timed urinary collection was used to determine albuminuric status. Diabetic nephropathy was defined as serum creatinine > or =150 micromol/L and/or mean ACR > or =25 mg/mmol. Obesity was defined as body mass index > or =25 kg/m2 using Asian criteria., Results: The G-308A polymorphism was not associated with either obesity or nephropathy. Clinical characteristics were similar between GG and GA/AA genotype carriers. Amongst the obese patients, GG genotype carriers had a higher median (interquartile range) urinary ACR [3.16 (0.70, 59.10) vs 1.28 (0.48, 12.28) mg/mmol; p = 0.01] and albumin excretion rate [38.7 (12.1, 620.3) vs 21.4 (8.9, 224.0) microg/min, p = 0.03] than GA/AA carriers. On multiple logistic regression analysis, compared with non-obese GA/AA carriers, obese subjects with the GG genotype had a 2.5-fold increased risk (95% CI: 1.04-6.03; P = 0.04) of nephropathy after adjustment for confounding factors. Other independent factors for diabetic nephropathy included male sex, systolic blood pressure, triglycerides (logarithmically transformed value), and the presence of cardiovascular and microvascular complications., Conclusion: Our findings suggest that the GG genotype of TNF-alpha G-308A polymorphism or a genetic variant in close linkage disequilibrium may interact with obesity to increase the risk of nephropathy in Chinese Type 2 diabetic patients. Apart from the need for replication of these results, functional studies are required to clarify its significance.

Despite the high cardiovascular risk of diabetic patients, there is a paucity of data on isolated systolic hypertension (ISH) in diabetic patients. In this cross-sectional study, we examined the risk of ISH and its associated factors in Chinese type 2 diabetic patients. Isolated systolic hypertension was defined as systolic blood pressure (SBP) > or =140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg. The mean value of two BP measurements taken 1 min apart was used. There were 1048 type 2 diabetic patients recruited from the Prince of Wales Hospital Diabetes Clinic. Another 1043 age- and sex-matched non-diabetic subjects were recruited from the community. The mean age of the 2091 subjects was 40.6 +/- 7.6 years (median: 40 years, range: 16-69 years). Diabetic patients had an increased risk of ISH compared to non-diabetic subjects (7.6% vs. 3.4%, p < 0.001) with an odd ratio of 2.38. On multivariate analysis, age, body mass index, total cholesterol and duration of diabetes in diabetic subjects while age and waist-hip ratio (WHR) in non-diabetic subjects were independently associated with ISH. In conclusion, Chinese type 2 diabetic patients had increased risk to develop ISH than non-diabetic subjects. Age, obesity, lipid and duration of diabetes were independent associated with ISH. These findings suggest that control of body weight and metabolic profile might have beneficial effects on ISH.

This study was designed to compare the short-term (1-y) tolerability and antiproteinuric efficacy of enalapril and valsartan in patients with type 2 diabetes. Forty-two patients with normal renal function or early-stage nephropathy were recruited in Hong Kong and randomized to valsartan 80 mg/day or enalapril 5 mg/day; the doses were increased to 160 mg and 10 mg daily, respectively, as tolerated. Early-morning urine was analyzed for albumin and creatinine and 24-hour urinary albumin excretion at baseline and 1 year after therapy began. Twenty-two patients were randomized to valsartan and 20 to enalapril. The 2 treatment groups were similar in terms of age, sex distribution, and duration of diabetes or hypertension. Blood pressure decreased to a similar extent (-2.5% to -5.0%) with each drug. Similarly, the 24-hour urinary albumin excretion decreased by 5% to 6% with each drug. The albumin-creatinine ratio in early-morning urine samples and plasma creatinine levels decreased in the valsartan group and increased in the enalapril group, but the difference was not significant. Plasma potassium levels were stable in both groups at the end of study. Cough was reported by 7 (35%) patients receiving enalapril and none of those receiving valsartan (P=.003). In conclusion, enalapril and valsartan both reduced blood pressure and albuminuria to a similar extent with 1 year of therapy in Chinese patients with type 2 diabetes and normal renal function or early-stage nephropathy. Fewer adverse events were reported with valsartan, but both drugs appear to be relatively safe.

Waist girth (WG) is regarded as the most significant anthropometric parameter associated with cardiovascular risk. The objective of the present study was to strengthen WG as an obesity marker by basing WG assessment not on gender but on individually measured body build characteristics that need not coincide with gender. We formulated a new marker, the Waist Reference Girth (WRG) and two corollaries, the Waist Deviation (WD) and the Percent Waist Deviation (%WD). The present research centered on deriving an equation for WRG from relevant trunk skeletal measurements that closely predicted WG in lean individuals. This equation would determine any individual's WRG and current WD. Trunk skeletal widths and chest depth as well as WG were measured on 507 physically active subjects (247 men and 260 women), predominantly lean young adults. Multiple regression analysis with the skeletal measurements as independent variables was performed on this data to predict WG. The unisex WRG equation WRG = Chest Sum x 1.635 predicted WG of 282 lean subjects (maximum WD of 4 cm) with R(2) of 0.87 (SEE of 3.0 cm). Male and female WG cutoff values for central obesity are usually taken at 94 cm and 80 cm respectively. For the average male and female WRG in this study (79 cm and 67.4 cm), these cutoff values are equivalent to WD of 15 cm and 12.6 cm respectively and to 19%WD for both genders (15/79 and 12.6/67.4). With %WD normalized for WRG, hence unaffected by intra-group or inter-group variations in the Chest Sum, %WD thresholds may better identify health risks linked to abdominal obesity than existing WG thresholds.

Aims: To assess the effect of regular diabetic health education on cardiovascular risk factors in Chinese Type 2 diabetic patients., Methods: This was a 1-year prospective randomized study. One hundred and eighty Type 2 diabetic subjects were recruited from three regional diabetic centres in Hong Kong. Ninety received additional structured reinforcement of diabetic health education by a trained nurse after the doctors' consultations every 3 months (intervention group). The others received the same medical care except no nursing reinforcement (control group). Outcome measures included fasting plasma glucose, HbA(1c), body mass index, waist circumference, blood pressure and lipid profiles, which were assessed before the study and after 1 year., Results: Two of the controls defaulted follow-up. The intervention group and controls had similar age and sex distribution. At the end of study, the intervention group had reducted their waist circumference, diastolic blood pressure, HbA(1c), total cholesterol and low-density lipoprotein cholesterol levels. The controls had reduced their total cholesterol and low-density lipoprotein cholesterol levels. Other cardiovascular risk factors were not significantly changed in the controls. Addition of drugs and/or dosage increment of anti-diabetic drugs, lipid-lowering agents and anti-hypertensive agents were similar between the two groups., Conclusions: Regular structured reinforcement with diabetic health education is useful. It helps to control more successfully some of the cardiovascular risk factors in Chinese Type 2 diabetic patients.

Background: The RENAAL Study has confirmed the renoprotective effects of Losartan in type 2 diabetes. In this subgroup analysis from the RENAAL Study, we hypothesized that the intensive care received by patients in a clinical trial setting also reduced the rate of decline in renal function through optimization of all risk factors., Methods: We compared the rate of deterioration in renal function, expressed as the regression coefficient of the monthly serum creatinine (SeCr) reciprocal (beta-1/Cr) in 55 Chinese type 2 diabetic patients before and after entry into the RENAAL Study., Results: Of the 55 patients, 44 had at least three out-patient SeCr measurements both before (2.9+/-2.4 years) and after (3.3+/-0.8 years) entry into the study for evaluation. In the Losartan group (n = 24), the median beta-1/Cr fell from -11.4 x 10(-5) l micro mol(-1) month(-1) before entry into the trial to -4.7 x 10(-5) l micro mol(-1) month(-1) following entry (P = 0.001). The respective figures were -9.1 x 10(-5) and -5.0 x 10(-5) l micro mol(-1) month(-1) (P = 0.01) in the placebo group (n = 20). A decrease in beta-1/Cr was observed in 21 (87.5%) and 14 (70.0%) patients in the Losartan and placebo groups, respectively. Spot urinary albumin-to-creatinine ratio was reduced by 56% (P = 0.001) in the Losartan group but the change was not significant in the placebo group. At the end of the study, patients in both groups had lower blood pressure and better lipid control. The frequency of patient visits to doctors and nurses were doubled., Conclusions: The rate of renal function decline was significantly reduced in the majority of patients allocated to either Losartan or placebo following entry into the RENAAL study. These results suggest that in patients with diabetic nephropathy, implementation of a structured care protocol in a clinical trial setting facilities intensive treatment of risk factors confering renoprotective effects in addition to those resulting from Losartan treatment.

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by cardiac and extracardiac myxomas in the setting of spotty skin pigmentation and endocrinopathy. We previously identified PRKAR1A (regulatory subunit 1alpha of protein kinase A) mutations in CNC. Mutational analyses of the PRKAR1A gene in 51 unrelated CNC probands now detect mutations in 65%. All mutations, except for one unique missense mutation, lead to PRKAR1A haploinsufficiency. Therefore, we studied the consequences of prkar1a haploinsufficiency in mice. Although we did not observe cardiac myxomas or altered pigmentation in prkar1a(+/-) mice, we did observe some phenotypes similar to CNC, including altered heart rate variability. Moreover, prkar1a(+/-) mice exhibited a marked propensity for extracardiac tumorigenesis. They developed sarcomas and hepatocellular carcinomas. Sarcomas were frequently associated with myxomatous differentiation. Tumors from prkar1a(+/-) mice did not exhibit prkar1a loss of heterozygosity. Thus, we conclude that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation.

We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on survival and cardiorenal outcomes in a consecutive cohort of Chinese type 2 diabetic patients with varying degree of albuminuria, ranging from normoalbuminuria to macroalbuminuria. A total of 3773 consecutive Chinese type 2 diabetic patients were followed prospectively for a mean period of 35.8 months. Clinical end points included all-cause mortality, with cardiovascular end point defined as first hospitalization because of ischemic heart disease, congestive heart failure, revascularization procedures, or cerebrovascular accident as well as renal end point defined as dialysis, doubling of baseline plasma creatinine, or plasma creatinine > or =500 micromol/L. The use of ACE inhibitor was 26.3% in normoalbuminuric (NA), 70.1% in microalbuminuric (MI), and 82.6% in macroalbuminuric (MA) groups. Albuminuria was a major predictor for all-cause mortality with 4-fold difference between NA and MA patients. The 7-year cumulative mortality rate was 7.1%, 10.8%, and 21.7% in the NA, MI, and MA groups, respectively. The use of ACE inhibition was associated with significant reduction of mortality (hazard ratio 0.41 and 95% confidence interval, 0.29, 0.58) in the entire group and was most evident in high-risk patients who had cardiorenal complications or retinopathy at baseline for all albuminuric groups (NA 0.76 [0.31,1.87]; MI 0.32 [0.16, 0.65]; and MA 0.20 [0.13, 0.33]). The prognostic value of albuminuria for death in type 2 diabetes and the beneficial effects of ACE inhibitors in Chinese type 2 diabetic patients with micro- or macroalbuminuria has been confirmed. The effects of ACE inhibitors in type 2 diabetic patients with normoalbuminuria require further evaluation.

Objectives: Mutation in KCNE3 gene (Isk-related family potassium voltage-gated channel member 3 gene) was recently associated with the aetiology of thyrotoxic periodic paralysis (TPP). We studied 79 Chinese TPP patients by DNA sequencing of the entire coding sequence of KCNE3 to determine if this gene is the cause of TPP in Chinese patients., Design and Measurements: A case-control genetic association study was carried out to determine the role of mutation/polymorphism in KCNE3 gene in the pathogenesis of TPP. Genomic DNA was extracted from peripheral blood samples. DNA sequencing was performed to cover the coding region of the KCNE3 gene for the TPP subjects. Restriction fragment length polymorphism was used to genotype specific sequence variants. subjects Seventy-nine TPP patients (cases) and 111 male thyrotoxic patients without history of paralysis (controls) were identified from thyroid clinic and during acute admission in a teaching hospital., Results: No pathogenic mutation in KCNE3 was found in the TPP patients. The reported R83H mutation was also not found in the Chinese TPP patients. In addition, another silent polymorphism, 290T/C, was also not associated with TPP., Conclusion: The results indicate that mutation in KCNE3 is not a cause of TPP in Chinese patients.

Objective: To assess the effects of BMI on progression to diabetes in Hong Kong Chinese and to analyze the optimal cutoff for overweight and obesity in Hong Kong Chinese., Research Methods and Procedures: This is a prospective study with a mean follow-up of 2.1 years (median 1.4 years, range 0.9 to 8.4 years). We recruited 172 nondiabetic high-risk subjects, of whom 115 had normal glucose tolerance (NGT) and 57 had impaired glucose tolerance (IGT). BMI and 75-gram oral glucose tolerance tests were assessed at baseline and then at yearly intervals., Results: The crude rates of progression to diabetes for subjects with NGT or IGT were 8.4% and 11.5% per year, respectively. For subjects with NGT, the progression rate to diabetes differed with different BMI ranges. For subjects with NGT and BMI > or = 25 kg/m2, the crude rates of progression to diabetes or glucose intolerance (diabetes or IGT) were 12.5% per year and 14.6% per year, respectively. The corresponding rates for subjects with NGT and BMI > or = 28 kg/m2 were 14.6% and 18.9% per year, respectively. Among subjects with NGT, those with BMI between 25 and 28 kg/m2 had the highest Youden index and likelihood ratio to predict the conversion to diabetes or glucose intolerance., Discussion: Obese subjects with NGT had higher rates of progression to diabetes than nonobese subjects. We recommend redefining BMI cutoffs, with 23 kg/m2 for overweight and 28 kg/m2 for obesity. This definition may be more sensitive to identify at-risk subjects and more specific to identify "patients" for therapeutic management.

Background: The aim of this study was to investigate whether chronic infections with Helicobacter pylori and hepatitis B virus (HBV) might affect clinical outcomes in Chinese type 2 diabetic patients with advanced nephropathy., Methods: A prospective study of 97 type 2 diabetic patients with clinical proteinuria and renal insufficiency (median serum creatinine 200 micro mol/l)., Results: During a median follow-up period of 2 years, 34 developed end-stage renal disease (ESRD), 28 had cardiovascular endpoints and 11 patients had died (seven men and four women), and 52.7% developed a combined endpoint. Female patients had longer disease duration, higher blood pressure, lower body weight but higher serum creatinine and spot urine albumin : creatinine ratio as well as lower haemoglobin than male patients. On logistic regression analysis, female gender (hazard ratio: 5.91, p = 0.02), negative H. pylori serology (8.39, p = 0.004), baseline serum creatinine (1.04, p = 0.001) and haemoglobin (1.86, p = 0.01) were independent predictors for ESRD. Systolic blood pressure (1.04, p = 0.003), prior treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists (3.41, p = 0.04) and positive hepatitis B surface antigen (4.88, p = 0.025) were independent predictors for cardiovascular endpoints. Female gender (7.89, p = 0.002) and baseline serum creatinine (1.05, p < 0.001) were independent predictors for combined death and cardio-renal endpoints., Conclusions: In Chinese type 2 diabetic patients with clinical proteinuria renal insufficiency, there were high rates of death and cardio-renal outcomes. Female gender, low haemoglobin and negative H. pylori serology were important predictors for ESRD, whereas chronic HBV infection was associated with increased cardiovascular risks.

Information on the beneficial effects of exercise in Chinese concerning weight reduction and fat loss is limited. We studied 18 young, healthy Chinese volunteers and assessed the short-term effects of exercise on their anthropometric and biochemical parameters. They had not done regular exercise before the study and were randomly assigned to aerobic or anaerobic exercise group (9 subjects in each group). Professional trainers on aerobic and anaerobic exercise were invited to teach and supervise the whole group on the exercise programme. The study lasted 3 months with exercise of at least 3 sessions per week of 30 min each. Of the 18 subjects, 7 (38.9%) were men and 11 (61.1%) women. Their mean age was 28.9 +/- 3.6 yr (men: 29.6 +/- 4.2 yr, women: 28.5 +/- 3.4 yr, p value: NS). After the 3-month exercise programme, body weight and body mass index reduction were significant only in the aerobic group but not in the anaerobic one, while body fat percentage was improved in both groups. This suggests anaerobic exercise may increase the lean to fat body mass ratio. Plasma glucose was reduced in the aerobic group but not in the anaerobic one. Plasma insulin level was, otherwise, similar before and after exercise in both groups. This is compatible with a blunted insulin hormonal response to endurance exercise and an improved tissue sensitivity to insulin.

Objective: To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care., Study Design: Descriptive analysis of a prospective cohort., Patients and Methods: During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records., Results: Patients receiving structured care had lower mortality (relative risk [RR] = 0.21; 95% confidence interval [CI] = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P < .01) and 15.7-fold (P < .01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%)., Conclusion: Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.

Objective: To assess whether valvular lesions are associated with the use of dexfenfluramine in Chinese patients with type 2 diabetes., Design: Case-control study., Patients and Methods: Thirty-six obese Chinese patients with type 2 diabetes and a history of dexfenfluramine use during the period January 1992 and September 1997 were recruited into the study, while another 43 age- and sex-matched Chinese patients with type 2 diabetes were recruited as controls. The mean age for the cases was 44.1 years (standard deviation, 11.2 years; median, 42.5 years; range, 20-64 years). The 43 control subjects were age- and sex-matched, and had a mean age of 48.5 years (standard deviation, 10.9 years; median, 51.0 years; range, 16-63 years; P>0.05). The male-to-female ratio was confirmed as similar between the two groups (10:26 versus 12:31; P>0.05). All patients were clinically free from cardiovascular disease. Patients with a history of underlying valvular disease from any cause were excluded from the study. All patients underwent echocardiographic assessment, and the presence of any valvular lesions was documented., Results: The mean duration of dexfenfluramine use by the cases was 21.8 weeks (standard deviation, 29.0 weeks; median, 18.0 weeks; range, 1-160 weeks). Subjects with a history of dexfenfluramine use had higher rates of significant aortic regurgitation, tricuspid regurgitation of any severity, and of any valvular regurgitation, compared to controls (11.1% versus 0%, P<0.05; 30.6% versus 4.7%, P<0.01; and 61.1% versus 34.9%, P<0.05, respectively). Logistic stepwise regression analysis to predict the risk of valvular lesion was conducted, with age, sex, history of dexfenfluramine use, body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, lipid profile, and duration of diabetes as independent variables. A history of dexfenfluramine use was the only significant parameter entered into the model (significant aortic regurgitation: beta=9.19, standard error=46.6, P<0.05; any tricuspid regurgitation: beta=2.76, standard error=10.8, P<0.05)., Conclusion: In Chinese patients with type 2 diabetes, a history of dexfenfluramine use is associated with heart-valve regurgitation, particularly aortic regurgitation.

We assessed the effects of amlodipine and nifedipine retard on 24-h blood pressure (BP) control, nocturnal fall in BP and their significance on left ventricular systolic functions in 54 Chinese hypertensive type 2 diabetic patients. Patients being recruited were openly randomised to amlodipine or nifedipine retard. Ambulatory 24-h BP and echocardiogram (in 42 patients) were measured before and 1 year after treatment. At the end of study, there was 17% reduction in systolic BP; 17% reduction in diastolic BP and 12% reduction in mean arterial pressure (MAP) (no difference between amlodipine and nifedipine). Of the 42 subjects underwent echocardiograms, eight became 'new-dippers' at the end of study (non-dippers before treatment and restored nocturnal fall of MAP> or =10% after treatment). The other 34 patients were either non-dippers before and after treatment (n=27); dippers before and after treatment (n=3) or dippers before treatment and non-dippers after treatment (n=4). The eight 'new-dippers' had improved ejection fraction (69.6+/-7.2 to 75.8+/-7.4%, P<0.05) and increased left ventricular diastolic diameter (43.7+/-7.9 to 47.9+/-8.8 mm, P<0.05) after the 1-year treatment of calcium antagonist. Compared to the other 34 subjects, the eight 'new-dippers' showed significant improvement in ejection fraction (9.4+/-10.9 vs. -1.2+/-11.8%, P<0.05). In conclusion, both amlodipine and nifedipine retard are effective in controlling the 24-h BP in Chinese hypertensive type 2 diabetic patients. For those who have restored nocturnal dip in BP have significantly increased left ventricular systolic ejection fraction after 1-year treatment of long acting calcium antagonists. The clinical significance and underlying mechanisms require further studies.

Diabetes is associated with an increased risk of cardiovascular disease (CVD). We studied risk factors for CVD in a cohort of Chinese type 2 diabetic patients recruited between July 1994 and August 1998. Ischemic heart disease (IHD) was defined as a history of: (i) confirmed coronary artery disease (with typical electrocardiographic changes or a positive exercise tolerance test) in patients under care of a cardiologist; (ii) documented myocardial infarction; or (iii) coronary interventions such as angioplasty or coronary artery bypass graft. Cerebrovascular accident (CVA) was defined as any definite cerebral vascular event with or without residual neurological deficit. CVD was defined as a history of IHD or CVA. The study enrolled 3333 patients, including 1370 men (41.1%) and 1963 women (58.9%) of mean age 55.9+/-13.3 years (range, 16-91 years; median, 57 years). A total of 279 patients (8.4%) had CVD (including 4.1% with CVA, 4.9% with IHD, and 0.6% with both CVA and IHD). Men had an overall higher rate of CVD than women (10.1% vs. 7.1%, p=0.002). All cardiovascular diseases showed a progressive increase in prevalence with increasing age with the peak among those aged

The effect of biphosphonate therapy on bone mineral density (BMD) in patients with primary hyperparathyroidism (PHP) is unknown. Forty postmenopausal women (mean age, 70 yr) with PHP were randomized to receive alendronate 10 mg/d or placebo for 48 wk, followed by treatment withdrawal for 24 wk. The mean (+/-SD) changes in BMD at femoral neck (+4.17 +/- 6.01% vs. -0.25 +/- 3.3%; P = 0.011) and lumbar spine (+3.79 +/- 4.04% vs. 0.19 +/- 2.80%; P = 0.016) were significantly higher with alendronate at 48 wk. Serum calcium was reduced with alendronate but not placebo (-0.09 vs. +0.01 mmol/liter; P = 0.018). Serum bone-specific alkaline phosphatase activity was lower with alendronate from 12 wk onward and increased 24 wk after treatment withdrawal (21.1 +/- 12.8 to 7.3 +/- 4.9 IU/liter at 48 wk, and 15.0 +/- 14.8 IU/liter 24 wk after withdrawal; P = 0.002 for trend). Osteocalcin concentration decreased at 48 wk and increased 24 wk after alendronate withdrawal (P = 0.019 for trend of change over time) but not with placebo. Urinary N-telopeptide/creatinine ratio decreased with alendronate at 48 wk and increased 24 wk after treatment withdrawal (P = 0.008 for trend). N-telopeptide/creatinine ratio did not change with placebo. Alendronate improves BMD and reduces bone turnover markers in postmenopausal women with PHP.

Background: We examined the weight-losing effect of orlistat treatment on insulin sensitivity and cardiovascular risk factors in a group of severely obese young Chinese patients with or without type 2 diabetes mellitus., Methods: Obese patients with diabetes (n = 33) and obese nondiabetic patients (n = 27) were given orlistat, 120 mg 3 times daily, without a concomitant hypocaloric diet for 6 months (body mass index [calculated as weight in kilograms divided by the square of height in meter; kg/m2] range, 27.8-47.4). The efficacy measures were (1) insulin sensitivity indices derived from the homeostasis model assessment and a composite measure of whole-body insulin sensitivity index; (2) glycemic control; (3) cardiovascular risk factors, including anthropometry, blood pressure, lipid profiles, and albuminuria; and (4) body composition determined by dual-energy x-ray absorptiometry., Results: At baseline, patients with diabetes had lower body mass index and percentage of body fat but higher waist-hip ratios and were more insulin resistant. Orlistat therapy reduced body weight, waist and hip circumferences, percentage of total body fat, blood pressure, fasting plasma glucose and lipid levels, albuminuria, and insulin sensitivity indices in both groups (all, P<.05). Despite less weight reduction, we found a greater percentage of reduction from baseline in glycosylated hemoglobin level (-11.6% vs -3.6%; P<.001), fasting plasma glucose level (-18.2% vs -5.0%; P<.001), and systolic blood pressure (-7.1% vs -3.1%; P =.02) in patients with diabetes. Obese subjects without diabetes had greater improvements in triglyceride levels, albuminuria, and the homeostasis model assessment (all, P<.01)., Conclusion: Short-term orlistat treatment without the use of a hypocaloric diet significantly improved insulin sensitivity and cardiovascular risk profiles in severely obese Chinese patients with or without type 2 diabetes.

The purpose of this cross-sectional study was to examine the risk associations between obesity indexes [body mass index (BMI) and waist circumference (WC)], cardiovascular risk factors [plasma glucose and lipids, blood pressure and urinary albumin excretion (UAE)] and morbidity conditions (Type 2 diabetes mellitus, hypertension, dyslipidaemia and/or albuminuria) in Hong Kong Chinese. Seven-hundred and two Hong Kong Chinese subjects (18-65 years of age, 59.4% of whom had at least one morbidity condition) were recruited from the Prince of Wales Hospital, Hong Kong SAR. The measurements taken of the subjects included: height; weight; waist and hip circumferences; blood pressure; fasting plasma glucose and lipids; and 24-h UAE. The mean BMI was 22.4 and 25.7 kg m(-2) in healthy subjects and patients, respectively. The mean WC measurements of healthy subjects and patients were 77.1 and 86.4 cm in males and 71.0 and 81.8 cm in females, respectively. There were increasing trends between obesity indexes and the severity of cardiovascular risk factors and the prevalence of morbidity conditions (all P-values for trend <0.05). Using 19.0-20.9 kg m(-2) and <70 cm as a referent, subjects with a BMI of > or =25.0 kg m(-2) (in both sexes) and/or a WC of > or =85 cm in males and > or =75 cm in females had an age-adjusted odds ratio between 3.2 and 4.4 for the occurrence of at least one morbidity condition. Patients with a greater number of comorbidities also had higher BMI and WC measurements (all P-values for the trend were <0.05 with adjustment for age and gender). Hence, despite Hong Kong Chinese being less obese than Caucasians, the intimate relationships among obesity, cardiovascular risk factors and morbidity conditions remain. Our data support using lower BMI and WC levels to define obesity and its associated health risks rather than using the criteria established from Caucasians who generally have larger body frames.

Hypothesis: The multi-faceted components of the metabolic syndrome now include markers of inflammation and endothelial activation. Despite this growing body of epidemiological data, standard statistical methods fail to evaluate the nature of these associations adequately. In this pilot study, we hypothesize that obesity may lead to endothelial activation which is in part mediated by dyslipidaemia and proinflammatory cytokines. These factors interact to give rise to hyperinsulinaemia, hypertension and an anti-fibrinolytic state. To test this hypothesis, we used confirmatory factor analysis and structural equation modelling to fit these data to a model designed on theoretical grounds., Methods: Metabolic syndrome variables, cytokines (IL6 and TNFalpha), markers of inflammation and endothelial activation were measured in 107 Caucasian non-diabetic subjects aged 40-75 y. Using confirmatory factor analysis, we identified six factors to represent composite measurements of blood pressure, obesity, dyslipidaemia, hyperinsulinaemia, endothelial activation and the anti-fibrinolytic state. We fitted these variables to two separate models, one using IL-6 and the other TNFalpha as the cytokine, and examined the inter-relationships (path analysis) amongst these variables, based on the above hypothesis., Results: Men were centrally more obese and had increased markers of endothelial activation, inflammation and the anti-fibrinolytic state as well as hyperinsulinaemia and dyslipidaemia, compared with women. Obesity indexes (both body mass index and waist-hip ratio) were strongly associated with multiple cardiovascular risk factors. Both IL6 and TNFalpha were correlated with age, male gender, obesity indexes and markers of endothelial activation. Only IL-6 was associated with smoking while TNFalpha was correlated with hyperinsulinaemia. In the TNFalpha model, 61% of the obesity variance was explained by male gender, 36% of TNFalpha variance by age and dyslipidaemia, 43% of dyslipidaemia variance by age and obesity, 33% of hyperinsulinaemia variance by dyslipidaemia and a non-smoking state, 29% of anti-fibrinolytic state variance by hyperinsulinaemia, 65% of endothelial activation variance by TNFalpha, dyslipidaemia and hyperinsulinaemia, 34% of blood pressure variance by hyperinsulinaemia and endothelial activation. In the IL-6 model, we observed similar relationships except that 23% of IL6 variance was explained by smoking and age., Conclusions: Using confirmatory factor analysis and structural equation modelling, we found that obesity, dyslipidemia and cytokines were the principal explanatory variables for the various components of the metabolic syndrome, with IL6 and TNFalpha having different explanatory variables and effects. These complex inter-relationships were in part mediated by hyperinsulinaemia and endothelial activation. While this hypothetical model was based on scientific evidence, supported by rigorous analysis, it requires further confirmation in large-scale prospective studies. Given the complexity of the biological system and its interactions with exogenous factors, structural equation modelling provides a useful scientific tool for hypothesis testing, complementary to the more traditional experimental and cohort studies.

Objectives: Dyslipidaemia plays a major role in the increased mortality in diabetes. Our aim was to address the quantitative abnormalities and determinants for lipid abnormalities in Chinese Type 2 diabetic patients., Material and Methods: In this study, we examined 1 279 Chinese type 2 diabetic patients and compared them with 959 non-diabetic control subjects., Results: Of the 1 279 Type 2 diabetic patients, 588 (46.0%) were men and 691 (54.0%) were women. The mean age was 40.4 +/- 8.1 years (median: 41.0 years, range: 16-72 years). Compared to the 959 age- and sex-matched non-diabetic controls, diabetic patients were more obese, had higher blood pressure and adverse lipid profile characterized by high triglycerides and low high-density lipoprotein cholesterol. After adjusting for age, sex, smoking, obesity, use of lipid-lowering drugs and anti-diabetic agents, diabetic patients had higher risk of having hypertriglyceridaemia (>=2.3 mmol/L) and low high-density lipoprotein cholesterol (<0.9 mmol/L) than non-diabetic subjects. The corresponding odds ratios were 2.9 and 1.5, respectively. With multiple regression analysis (stepwise), dyslipidaemia was mainly associated with glycaemia, obesity and age in diabetic patients, and obesity, male gender and age in non-diabetic subjects., Conclusion: We have confirmed the high prevalence and increased risk of dyslipidaemia in Chinese type 2 diabetic patients. The long-term significance of these lipid abnormalities and their synergism on clinical outcomes requires further evaluation.

Aims: To examine the risk of progression to diabetes in Chinese subjects with impaired fasting glycaemia (IFG) or normal fasting glucose (NFG)., Methods: Between 1988 and 1996, 657 Hong Kong Chinese subjects underwent annual screening, using an oral glucose tolerance test, until they had developed diabetes, or until June 1997, when the data were analysed. All subjects had a risk factor associated with the development of diabetes such as a history of gestational diabetes or a family history of diabetes. The follow-up interval for the subjects ranged from 0.87 to 8.54 years and of the 657, 319 had fasting plasma glucose levels of < 7.0 mmol/L where a fasting glucose level of > or = 7.0 mmol/L was used to diagnose diabetes, Results: Of the 319 nondiabetic subjects, 55 had IFG and 264 had NFG. After a median follow-up of 1.12 years (range: 0.87-8.54 years), 27 progressed to diabetes. The Kaplan-Meier analysis of progression to diabetes showed significant differences between subjects with IFG and subjects with NFG. Using Cox regression analysis, IFG (beta = 3.51, SE = 1.63, P = 0.032) and smoking (beta = 3.60, SE = 1.50, P = 0.017) were found to be independently associated with progression to diabetes., Conclusions: In Hong Kong Chinese with risk factors for glucose intolerance, IFG status is an independent risk factor for progression to diabetes.

Aim: Recent studies have shown that the risk of developing coronary heart disease in subjects with 'isolated low high-density-lipoprotein cholesterol (HDL-C)' (defined as HDL-C < 0.9 mmol/l and total cholesterol (TC) < 5.2 mmol/l) was similar to those with hypercholesterolaemia. We examined the prevalence of isolated low HDL-C in Hong Kong Chinese and its relationship with insulin resistance and triglyceride (TG) level., Methods: Hong Kong Chinese subjects (n = 1493) recruited in a population-based prevalence survey for cardiovascular risk factors were examined. Insulin resistance was calculated using a computer-solved homeostasis model assessment method., Results: Of the 1493 subjects, 72 (4.8%) had isolated low HDL-C, in whom half (n = 36) had TG > or = 1.7 mmol/l and half (n = 36) had TG < 1.7 mmol/l. Compared with the 'controls' (subjects with TC < 5.2 mmol/l and HDL-C > or = 0.9 mmol/l; TC > or = 5.2 mmol/l and HDL-C < 0.9 mmol/l; or TC > or = 5.2 mmol/l and HDL-C > or = 0.9 mmol/l, n = 1421), subjects with isolated low HDL-C and high TG were more obese, had higher plasma glucose, fasting and 2 h plasma insulin concentrations and insulin resistance. Subjects with isolated low HDL-C and TG < 1.7 mmol/l had similar insulin concentrations and insulin resistance, but were more obese than the 'controls'. Subjects with isolated low HDL-C and high TG also had higher fasting PG, insulin and insulin resistance than those with isolated low HDL-C and low TG., Conclusions: In this population-based study, 4.8% of Hong Kong Chinese had isolated low HDL-C, which was closely associated with obesity. The coexistence of high TG suggests an insulin-resistant state.

Objective: In this 1-year clinical study, we compared the efficacy and tolerability of amlodipine and nifedipine retard in 64 Chinese Type 2 diabetic patients with hypertension., Subjects and Methods: There were 25 (39.1%) men and 39 (60.9%) women with mean age 60.7+/-9.9 years. Thirty-four patients were randomized to receive amlodipine 5 mg daily and 30 to receive nifedipine retard 20 mg twice daily. The daily dose of amlodipine and nifedipine retard was increased from 5 mg to 10 mg daily and 20 mg to 40 mg twice daily, respectively, if sitting BP > 140/90 mmHg., Results: Of the 64 patients, 9 dropped out early because they experienced adverse effects related to the drugs. If all treatment-related adverse effects were taken into account, 6 (19.4%) patients were from the amlodipine group and 14 (53.8%) from the nifedipine group (p = 0.011). After 1 year, 48 patients finished the study, 28 were on amlodipine and 20 were on nifedipine retard. Of the 28 patients from the amlodipine group, 11 (39.3%) required additional antihypertensive agents. Of the 20 patients from the nifedipine group, 5 (25%, p value: NS, comparing the 2 groups) required additional antihypertensive agents. Both groups showed similar and significant reduction in blood pressure from Week 6 to Week 52., Conclusion: Both amlodipine and nifedipine retard are relatively safe and useful in the treatment of hypertension in Chinese Type 2 diabetic patients. Nifedipine retard, when compared to amlodipine, showed significantly more adverse effects and these may hamper long-term compliance.

Introduction: Obesity has now become an epidemic with increasing prevalence in most parts of the world. However, information on the problem of obesity in Asians is limited., Subjects and Methods: From April 1996 to August 1997, 17,121 Chinese adult subjects from the community of Hong Kong presented themselves voluntarily at the United Christian Nethersole Community Health Service Centers for primary health care check-up. Demographic data including height and weight were documented. Their body mass indexes (BMI) were measured. The prevalence rates of overweight and obese subjects were calculated according to the 1995 World Health Organization criteria., Results: There were 4781 (27.9%) men and 12,340 (72.1%) women. The mean age (+/- SD) was 51.3 +/- 16.0 years (range 20 to 96 years, median 49.8 years). Of the 17,121 subjects, 4939 (28.85%) were overweight and 656 (3.83%) were obese. Based on the 1997 Hong Kong Census statistics of the overall Hong Kong population data, the age-standardised prevalence rates of overweight and obese subjects were 30.52% and 3.19% in men and 22.14% and 3.35% in women, respectively. Of the 10,937 subjects of working age (20 to 65 years), the prevalence rates of overweight and obese subjects were 28.98% and 3.55%, respectively. Of the 6648 subjects aged > or = 60 years, the prevalence rates of overweight and obese subjects were 36.31% and 4.81%, respectively., Conclusions: In Hong Kong, the age-standardised prevalence rate of overweight and obese subjects were 30.5% and 3.2% in men and 22.1% and 3.4% in women, respectively. This information provides some useful estimations of the extent of an important public health problem, obesity, in Hong Kong.

Recent experimental data suggest that a microsatellite polymorphism at 5' end of the aldose reductase gene may be associated with the development of diabetic retinopathy. In the present study, we examined the allele distribution of the polymorphism in 384 Hong Kong Chinese patients who had late-onset (age at diagnosis > or =35 years) Type 2 diabetes, but no clinical evidence of cataract. Approximately 17% of them (n = 64) had retinopathy. The patients with retinopathy were older (52 +/- 11 years vs. 60 +/- 9 years, p < 0.01) and had a higher HbA1c (8.9 +/- 2.2% vs. 7.7 +/- 2.0%, p < 0.01 with adjustment for age) than those without the complication. Amongst all of the patients, we detected 10 microsatellite alleles and found that allele Z-4 was overpresented in those with retinopathy (9% vs. 4%, p < 0.05). There were no significant differences in allelic distributions of the major alleles Z + 2, Z, and Z-2, which accounted for more than 80% of the overall frequency, between the two groups of patients. Using multiple logistic regression analysis (R2 = 0.17, p < 0.01), we found that age (p < 0.01) and HbA1c (p < 0.05) were associated with retinopathy. In conclusion, our data suggest that the occurrence of diabetic retinopathy in the Chinese population may be influenced by clinical and metabolic factors. The aldose reductase gene may be implicated, but is not likely to play a major role.

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5' of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over-presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non-Z; 38 vs. 50%, p<0.01), but under-presented the allele Z-4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z-4, Z-4+Z-4,non-Z-4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z-4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.

Objective: We examined the prevalence of different forms of diabetes in Hong Kong Chinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes., Research Design and Methods: A total of 145 young patients with early-onset diabetes (age and age at diagnosis < or = 40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4alpha, and HNF-1alpha. The mitochondrial DNA A-->G at nucleotide 3243 (mt3243) and amyLin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined., Results: The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4alpha, 5% for HNF-1alpha, 3% for mt3243, 2% for amylin 520G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria. CONCLUSIONS; Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined.

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., Subjects and Methods: This study involved 227 early and 235 late-onset (defined as onset age < or = 40 and > 40 years, respectively) type 2 diabetic patients, as well as 126 nondiabetic subjects. The mutation was detected using a PCR-RFLP method., Results: We identified six (2.6%) and one (0.4%) patients heterozygous for the mutation from the early and late-onset groups, respectively (P = 0.05). None of the nondiabetic subjects had the mutation. Insulin deficiency and poor glycaemic control were not common findings amongst carriers of the mutation. In the early onset group, the patients with the mutation had lower plasma levels of total (4.3 +/- 0.9 mmol/l vs. 5.3 +/- 1.1 mmol/l, P = 0.02) and low density lipoprotein (LDL)-cholesterol (2.3 +/- 0.7 mmol/l vs. 3.2 +/- 0.9 mmol/l, P = 0.01) than those without the mutation., Conclusions: Our data suggest that the islet amyloid polypeptide gene mutation might be associated with early occurrence of type 2 diabetes and lower plasma levels of total and low density lipoprotein-cholesterol in the Chinese population.

Smoking is a major cardiovascular risk factor and cause of death. Diabetes mellitus is also associated with an increased mortality and morbidity. Evidence concerning whether smoking increases the incidence of diabetes remains conflicting. Glycaemic status and smoking habits were analysed in 3718 Chinese subjects in order to assess the possible association between smoking and risk of diabetes in the Chinese population. The World Health Organisation 1998 criteria were used for the diagnosis of glucose intolerance. Smoking was defined as current cigarette smoking or ex-smoking without regard to daily consumption. The smoking habits of the studied subjects were correlated with glycaemic status. There were 3003 (80.8%) women and 715 (19.2%) men. The mean age (SD) was 38.4 (12.8) years (median 35.0, range 12-88 years). Of the 3718 subjects, 786 (21.1%) had diabetes, 708 (19.1%) had impaired glucose tolerance, and 2224 (59.8%) had normal results. Of the 3003 women, only 87 (2.9%) were smokers. The female smokers were younger, heavier, and had higher alcohol consumption than non-smokers. The prevalence of diabetes was similar between female smokers and non-smokers after adjustment for age, body mass index, family history of diabetes, and alcohol. Of the 715 men, 175 (24.5%) were smokers. The male smokers were younger, had lower blood pressure, and higher alcohol consumption. After adjustment for age, body mass index, family history of diabetes and alcohol, the male smokers had lower blood pressure, higher one hour plasma glucose, and more diabetes. Using logistic regression analysis (stepwise forward) with age, body mass index, alcohol, smoking, and family history of diabetes as independent variables to predict the risk of having diabetes, age and body mass index are independently associated with diabetes in both men and women. In addition, smoking is independently associated with the risk of diabetes in men, the odds ratio (95% confidence interval, CI) being 1.705 (1.106 to 2.630). Family history of diabetes is independently associated with the risk of diabetes in women, and the odds ratio (95% CI) is 1.643 (1.314, to 2.053). In conclusion, it was found that smoking is independently associated with diabetes after adjustment for age, body mass index, alcohol, and family history of diabetes in Hong Kong Chinese men, the odds ratio being 1.7. The prevalence of smoking in Hong Kong Chinese women is low and its association with diabetes is inconclusive.

Objective: To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese., Research Design and Methods: The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios., Results: Approximately 29% of the index patients were diagnosed with type 2 diabetes at < or = 35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at >35 years of age (hereby defined as late-onset) the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P < 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA1c waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal was well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted olderq age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA1c and sBP and a positive paternal history of diabetes Predictors for younger age at diagnosis in the female patients were higher HbA1c WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child parent pairs and clild-parent-grandparent trios there was a decrease in age at diagnosis in successive generations., Conclusions: Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation.

The relationship between diabetes and Helicobacter pylori (HP) infection is controversial. In this study, we examined the possible relationship between HP infection and type 2 diabetes in Chinese subjects. Sixty-three Chinese type 2 diabetic patients (mean age +/- SD: 49.9 +/- 12.0 years; range: 17-76 years) were recruited irrespective of the duration of diabetes or type of therapy. Twenty-nine (46%) of them had upper gastrointestinal symptoms and the other 34 (54%) did not. Another 55 age- and sex-matched non-diabetic subjects (mean age +/- SD: 45.6 +/- 15.6 years, p=0.098; range 18-79 years) with dyspepsia indicated for upper endoscopy were recruited as a comparison group. Upper endoscopy was performed with antral mucosal biopsy specimens taken for rapid urease test (CLO test). HP infection was considered to be present if the rapid urease test was positive. The rates of HP infection of the diabetic and non-diabetic individuals were 50.8% and 56.4% respectively (p: NS). The rate of HP infection was similar between the 2 groups of diabetic patients with or without gastrointestinal symptoms (42.9% vs. 56.3%, p: NS). Using logistic regression analysis (forward stepwise) with age, sex, glycaemic control, duration of diabetes and upper gastrointestinal symptoms as independent variables to predict the risk of HP infection in diabetic patients, none of the parameters enter into the model. In conclusion, the rate of HP infection in Hong Kong Chinese subjects with type 2 diabetes is around 50%, which is similar to control subjects. No association was found between HP infection, glycaemic status, and duration of diabetes and upper gastrointestinal symptoms in these diabetic subjects.

There is increasing evidence suggesting that the cut-off values for defining obesity used in the Western countries cannot be readily applied to Asians, who often have smaller body frames than Caucasians. We examined the BMI and body fat (BF) as measured by bioelectrical impedance in 5153 Hong Kong Chinese subjects. We aimed to assess the optimal BMI reflecting obesity as defined by abnormal BF in Hong Kong Chinese. Receiver operating characteristic curve (ROC) analysis was used to assess the optimal BMI predicting BF at different levels. The mean age and SD of the 5153 subjects (3734 women and 1419 men) was 51.5 (SD 16.3) years (range: 18.0-89.5 years, median: 50.7 years). Age-adjusted partial correlation (r) between BMI and BF in women and men were 0.899 (P < 0.001) and 0.818 (P < 0.001) respectively. Using ROC analysis, the BMI corresponding to the conventional upper limit of normal BF was 22.5-23.1 kg/m(2), and the BMI corresponding to the 90 percentiles of BF was 25.4-26.1 kg/m(2). Despite similar body fat contents, the BMI cut-off value used to define obesity in Hong Kong Chinese should be lower as compared to Caucasians. We suggest a BMI of 23 kg/m(2) and 26 kg/m(2) as the cut-off values to define overweight and obesity respectively in Hong Kong Chinese.

Among the subjects with 'normal' fasting plasma glucose (PG) levels (< 7.0 mmol/L), some of them are actually suffering from impaired glucose tolerance and diabetes, which can only be diagnosed by 2hr PG levels. We aim to find out a proper clinical approach in order to minimize missing those subjects with high 2hr PG but 'normal' fasting PG levels. We analyzed data collected from a previously published population-based prevalence survey for glucose intolerance in 1486 Hong Kong Chinese subjects who had no past history of diabetes. Of the 1468 subjects, there were 138 subjects (9.4%) having "missed glucose intolerance". Compared to the diabetic subjects (fasting plasma glucose > or = 7.0 mmol/L) after adjustment for age, the subjects with missed glucose intolerance had similar characteristics except lower glycemic level. Compared to the normal subjects (fasting plasma glucose < 7.0 mmol/L) after adjustment for age, subjects with missed glucose intolerance had more obesity (both general and central), more hypertension, worse glycemic status and lipid profile in both men and women. There were 38 subjects (2.6%) having impaired fasting glucose. Of these 38 subjects, 24 (63.2%) had missed glucose intolerance. The detection of missed glucose intolerance increased from 9.7% of overall male subjects to 23.1% in men with hypertension to 52.9% in men with both hypertension and family history of diabetes. Similarly, the detection of missed glucose intolerance increased from 9.0% of overall female subjects to 25.7% in women with obesity to 45.2% in women with both obesity and hypertension. If only fasting plasma glucose is performed, 4% of subjects will be diagnosed to have diabetes or impaired fasting glucose while up to 10% of subjects having impaired glucose tolerance or diabetes will be missed in Hong Kong Chinese. The latter 2 groups of subjects have similar cardiovascular risk factors to those with fasting PG > or = 7.0 mmol/L. We recommend that for those with a family history of diabetes, hypertension or obesity, an oral glucose tolerance test instead of fasting plasma glucose should be used in the first place for the diagnosis of glucose intolerance. For those with impaired fasting glucose, a routine follow-up oral glucose tolerance test should also be performed. This clinical approach may improve the detection of those subjects with glucose intolerance, who will be otherwise missed by using fasting plasma glucose alone.

To examine whether a low socio-economic status (SES) is an additional risk factor for glucose intolerance in Hong Kong Chinese with known risk factors for glucose intolerance, a total of 2847 Chinese subjects (473 men and 2374 women) were recruited from the community for assessment. They had known risk factors for glucose intolerance including a previous history of gestational diabetes, positive family history of diabetes in first degree relatives and equivocal fasting plasma glucose concentrations between 7 and 8 mmol/l or random plasma glucose concentrations between 8 and 11 mmol/l. The 2847 subjects were classified according to their education levels and occupations: education group 1 = high school or university, group 2 = middle school, group 3 = illiterate or up to elementary school; occupational group 1 = professional or managerial, group 2 = non-manual, group 3 = manual, group 4 = unskilled, group 5 = housewife or unemployed. Different socio-economic groups were well represented in this selected population. The distribution of educational groups in this study was similar to that recorded in the 1991 Hong Kong Census. When analysed according to education levels and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes, body mass index, blood pressure and plasma glucose concentrations. Men with the lowest education level had the highest prevalence of diabetes after age adjustment. The age-adjusted odds ratio (95% confidence intervals) of having diabetes was 2.3 (1.3. 4.3) in female subjects and 2.5 (1.2, 5.4) in male subjects with the lowest SES compared to subjects with the highest SES. When categorised according to occupation and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes and glycaemic indexes. The age-adjusted odds ratio of having diabetes was 4.5 (1.9, 10.9) in female subjects with the lowest SES compared to those with the highest SES. The corresponding age-adjusted odds ratio in male subjects was 1.9 (0.9, 3.9) but this was not statistically significant. In conclusion, a lower socio-economic class, categorised either by occupational or educational level, was an additional risk factor for diabetes in Hong Kong Chinese who had known risk factors for glucose intolerance. These subjects should have increased priority for health education and regular diabetes screening. Our findings further emphasise the complex relationships between societal affluence, personal income and educational level.

Objective: We have previously suggested using the paired values of fasting plasma glucose (FPG) and HbA1c to identify potential diabetic subjects. In this article, we followed up on 208 nondiabetic subjects and examined their rates of progression to diabetes. We analyzed their likelihood of becoming diabetic according to their baseline FPG and HbA1c concentrations., Research Design and Methods: Between 1988 and 1995, 2,877 Chinese subjects with risk factors for diabetes underwent screening. Of these, 2,250 had FPG <7.8 mmol/l and 2-h plasma glucose (PG) <11.1 mmol/l. Of these 2,250 subjects, 265 were randomly recruited for an annual oral glucose tolerance test (OGTT) until they progressed to develop diabetes. Of those 265 subjects, 57 had baseline FPG > or =7.0 mmol/l and were excluded from the present analysis. Hence, the progression of glucose tolerance in 208 subjects who were nondiabetic according to the new American Diabetes Association diagnostic criteria (FPG < 7.0 mmol/l and 2-h PG < 11.1 mmol/l) was examined, Results: Of the 208 nondiabetic subjects, 26 (12.5%) were men and 182 (87.5%) were women. After a mean follow-up of 1.60 +/- 1.16 years (range 1-7, median 1), 44 (21.2%) progressed to develop diabetes and 164 (78.8%) remained nondiabetic. Those who were diabetic at the end of the study had a high likelihood ratio (LR) of 9.3 to have baseline FPG > or =6.1 mmol/l and baseline HbA1c > or =6.1%. This was compared with a low LR of 0.6-1.1 in diabetic subjects who had either FPG <6.1 mmol/l or HbA1c <6.1% or both at baseline. The crude rate of progression to diabetes was more than five times higher (44.1 vs. 8.1%) in those whose baseline FPG was > or =6.1 mmol/l and baseline HbA1c was > or =6.1% compared with those whose baseline FPG was <6.1 mmol/l and baseline HbA1c was <6.1%., Conclusions: For Chinese subjects with risk factors for glucose intolerance, the use of paired FPG and HbA1c values helped to identify potential diabetic subjects. Those with an FPG > or =6.1 mmol/l and HbA1c > or =6.1% had a rate of progression to diabetes more than five times higher than those with an FPG <6.1 mmol/l and an HbA1c <6.1% after a mean follow-up of 1.6 years. Those with an FPG > or =6.1 but <7.0 mmol/l, especially if their HbA1c was > or =6.1%, should undergo an OGTT to confirm diabetes. Subjects with an FPG <6.1 mmol/l and/or an HbA1c <6.1% should have regular screening using the paired values of FPG and HbA1c.

We studied the relationships between QT interval and cardiovascular disease status in 192 Chinese type 2 diabetic patients. Of these 192 subjects, 132 (68.8%) were women and 60 (31.2%) were men. The mean age (+/-S.D.) was 56.6+/-12.9 years (range: 23-84, median: 58.0 years). Women had longer QTc interval compared to men (0.402+/-0.030 s vs. 0.387+/-0.026 s, P<0.01). Of the 192 subjects, 18 women and two men had prolonged QTc interval (QTc >0.433 s). Women with prolonged QTc interval have a 2.8-fold greater rate of cardiovascular disease as compared to those with normal QTc interval (38.9% vs. 14.0%, P<0.05). Using multiple regression analysis (stepwise) to assess the relationship with QTc interval with age, sex, body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, glycated haemoglobin, lipid profiles, smoking and duration of diabetes as independent variables (R(2)=0.146, F=8.88, P<0.001), systolic blood pressure (beta=0.198, P=0.017), age (beta=0. 189, P=0.023) and female gender (beta=0.157, P=0.037) were found to be independently associated with QTc interval. In conclusion, we have shown a significant association between prolonged QTc interval, ischaemic heart disease and cardiovascular disease in Chinese type 2 diabetic women. Age, systolic blood pressure and female gender are independently correlated to QTc interval.

Objective: To investigate transmission patterns of diabetes and their relationships with clinical characteristics in Hong Kong Chinese patients with late-onset (age > or =35 years) type 2 diabetes., Research Design and Methods: This study involved 2,310 patients consecutively selected from a hospital clinic-based diabetes registry. These patients all reported the diabetes status of their parents as well as siblings., Results: Approximately 36% of the 2,310 patients reported at least 1 affected parent or sibling (25 and 21% reported at least 1 diabetic parent and sibling, respectively). These patients, irrespective of their sex, were more likely to have a diabetic mother than a diabetic father (17 vs. 13% of the male patients and 18 vs. 9% of the female patients, P<0.01). The male patients were more likely than the female patients to have a diabetic father (13 vs. 9%, P<0.01). The female patients with a diabetic mother were found to have higher levels of plasma total cholesterol compared with the female patients with a diabetic father in multiple comparisons with adjustment for significance (5.56+/-1.30 vs. 5.09+/-0.95 mmol/l, P<0.05). In 2-group comparisons, there was also evidence that the male patients with a diabetic father had higher BMI values than the male patients with a diabetic mother (25.9+/-3.5 vs. 25.0+/-3.5 kg/m2, P<0.05)., Conclusions: We found familial clustering of diabetes in the Hong Kong Chinese population as well as a significant maternal influence and a male sex-specific paternal effect. We suggest that both maternal and paternal factors may be implicated in the development of type 2 diabetes in the Chinese population.

Diabetic patients have higher cardiovascular risk than non-diabetic subjects, and fibrinogen has been reported to be one of the independent predictors for diabetic vascular complications. We examined 101 subjects (24 men, 77 women) who were newly diagnosed with type 2 diabetes. Thirty non-diabetic subjects were recruited as controls. The mean (standard deviation, SD) baseline fibrinogen concentrations in men and women were 3.87 (1.17) and 3.42 (1.00) g/L, respectively (not significantly different). Of these 101 subjects, 70 were treated with diet alone and 31 were treated with oral agents. After a mean (SD) follow-up period of 2.38 (0.63) years, there was an 18.5% increase in the fibrinogen concentration from 3.53 (1.06) g/L at baseline to 3.97 (1.07) g/L at follow-up (P < 0.001). The normal subjects had a mean (SD) follow-up period of 1.17 (0.38) years, and showed no significant change in their fibrinogen concentrations from 3.49 (0.90) g/L at baseline to 3.15 (0.61) g/L at follow-up. In the 101 diabetic subjects, only changes in plasma triglyceride correlated with the changes in fibrinogen concentration. Using multivariate analysis with age, sex, duration of diabetes, baseline and changes in body mass index, blood pressure, glycaemic and lipid parameters as independent variables (R2 = 0.106, F= 6.840, P = 0.011), triglyceride (beta = 0.282, P = 0.011) was identified as the only independent variable that predicted the changes in the fibrinogen concentrations. Improved glycaemic control was not accompanied by a reduction in plasma fibrinogen concentration.

Objective: To examine the significance of individual risk factors on the development of diabetes in subjects who underwent screening for diabetes., Research Design and Methods: A total of 1,649 Chinese subjects underwent screening for diabetes. They were asymptomatic but had known risk factors for diabetes, including a positive family history of diabetes, a past history of gestational diabetes, obesity, hypertension, and/or dyslipidemia. Another 799 age-matched subjects from the community who had no risk factors for diabetes were used as the comparison group., Results: Of the 1,649 subjects who underwent screening, 241 (14.6%) had diabetes. In these subjects, 989 (60.0%) had 1 risk factor, 502 (30.4%) had 2 risk factors, 141 (8.6%) had 3 risk factors, and 17 (1.0%) had 4 or 5 risk factors for diabetes. Of the 799 control subjects, 29 (3.6%) had diabetes. Compared with the comparison group, the odds ratio (95% CI) of having diabetes after adjustment for age was 5.2 (3.5-7.7) in the 1,649 subjects with known risk factors. The odds ratio of having diabetes increased from 3.7 in subjects with 1 risk factor to 28.4 in subjects with 4 or 5 risk factors., Conclusions: In men, age, BMI, family history of diabetes, and dyslipidemia, and in women, age, BMI, hypertension, dyslipidemia, total cholesterol, and history of gestational diabetes are associated with increased odds of developing diabetes. These risk factors have additive effects on the odds of having diabetes. Early and regular screening for diabetes and other cardiovascular risk factors is essential in these high-risk individuals.

Acromegaly patients are known to have an increased risk of malignancies, especially colonic adenocarcinoma. This may be as a result of the growth-stimulating effect of growth hormone (GH). The clustering of leukaemia in children treated with GH has also caused concern. There have been a few reports of leukaemia in acromegaly patients. We report two patients with acute lymphoblastic leukaemia and one patient with acute myeloid leukaemia among 106 acromegaly patients treated over a 15-year period. Two of the cases received radiotherapy as part of their treatment. Adjusted for age and follow-up years, the incidence of leukaemia in this cohort is significantly higher than the general population. The incidence is also higher than would be expected as a result of radiotherapy alone, suggesting that GH may play a synergistic role.

Background: Good results have been reported with combined use of octreotide and bromocriptine in acromegalic Caucasians. Data concerning the efficacy and tolerability of this combination treatment in Chinese acromegalic patients are scanty., Aim: The aim of this study was to assess the efficacy and tolerability of combined therapy using bromocriptine and octreotide in the treatment of acromegaly in Chinese patients and to compare the cost-effectiveness of various regimes., Methods: Sixteen Chinese acromegalic patients with growth hormone (GH) concentration not suppressible to below 5 mU/L (2 microg/L) during an extended OGTT were recruited to undergo four phases of the study. During the study period, the patients were given bromocriptine alone, bromocriptine and low dose octreotide, bromocriptine and medium dose octreotide, and medium dose octreotide alone. Plasma concentrations of GH and insulin-like growth factor-1 (IGF-1) were measured before and after the completion of each phase., Results: The number of patients reaching target GH concentrations was significantly higher when treated with octreotide compared to baseline (p<0.05). Bromocriptine alone had a significant effect but not to the extent of octreotide alone. A combination of low dose octreotide and bromocriptine is as efficacious in the treatment of acromegaly as high dose octreotide. None of the patients suffered from serious adverse effects., Conclusion: The results confirmed the usefulness and tolerability of bromocriptine and octreotide in Chinese acromegalics. The most cost-effective regime in this study was a combination of low dose octreotide and bromocriptine.

Objectives: To examine the interrelationships between obesity and various cardiovascular risk factors, and to investigate the relative importance of insulin and obesity in their associations with various pathophysiologies., Design: Cross-sectional clinic-based study., Setting: Medical clinics at a university teaching hospital, Shatin, Hong Kong., Participants: A heterogeneous cohort of 767 Hong Kong Chinese subjects with a mean age of 43 (standard deviation, 14) years., Main Outcome Measures: Body mass index, waist circumference, plasma insulin, insulin resistance index, fasting plasma glucose and lipid levels, blood pressure, and 24-hour urinary albumin excretion., Results: Pathophysiological abnormalities and risk factors are frequently clustered to varying degrees. Compared with the control subjects, patients with at least one component of the metabolic syndrome were more obese, hyperinsulinaemic, insulin resistant, hyperglycaemic, hypertensive, dyslipidaemic, and albuminuric (all variables, P<0.001). Increasing degrees of body mass index, waist circumference, plasma insulin level, and insulin resistance index were associated with an increasing number of risk factors after adjusting for age and sex (all variables, P<0.02). Multiple regression analysis showed that obesity, as reflected by either the body mass index or waist circumference, had a closer association than plasma insulin with the fasting plasma glucose concentration, blood pressure, and high-density lipoprotein-cholesterol and triglyceride concentrations. Using 19.0-20.9 kg/m(2) as the reference body mass index interval, the lowest cardiovascular risk was associated with a body mass index of <23.0 kg/m(2). There was an increased risk of 3.1 and 5 times when the body mass index was 23. 0-24.9 kg/m(2) and > or =25 kg/m(2), respectively., Conclusions: Obesity, hyperinsulinaemia, and insulin resistance are characteristic features of Hong Kong Chinese patients who have various components of the metabolic syndrome. Obesity has a greater effect than plasma insulin on various pathophysiologies.