Chung Shun Ho

Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease.

To the Editors:Curcumin is a polyphenolic molecule that comprises approximately 5% of turmeric, giving the spice its color but not flavor. It is used in processed foods as a yellow coloring. 1 Because of its anti-inflammatory and antioxidant properties, curcumin has been tested in animal models of A

Development and Validation of an All-Cause Mortality Risk Score in Type 2 Diabetes: The Hong Kong Diabetes Registry

BACKGROUND Diabetes reduces life expectancy by 10 to 12 years, but whether death can be predicted in type 2 diabetes mellitus remains uncertain. METHODS A prospective cohort of 7583 type 2 diabetic patients enrolled since 1995 were censored on July 30, 2005, or after 6 years of follow-up, whichever came first. A restricted cubic spline model was used to check data linearity and to develop linear-transforming formulas. Data were randomly assigned to a training data set and to a test data set. A Cox model was used to develop risk scores in the test data set. Calibration and discrimination were assessed in the test data set. RESULTS A total of 619 patients died during a median follow-up period of 5.51 years, resulting in a mortality rate of 18.69 per 1000 person-years. Age, sex, peripheral arterial disease, cancer history, insulin use, blood hemoglobin levels, linear-transformed body mass index, random spot urinary albumin-creatinine ratio, and estimated glomerular filtration rate at enrollment were predictors of all-cause death. A risk score for all-cause mortality was developed using these predictors. The predicted and observed death rates in the test data set were similar (P > .70). The area under the receiver operating characteristic curve was 0.85 for 5 years of follow-up. Using the risk score in ranking cause-specific deaths, the area under the receiver operating characteristic curve was 0.95 for genitourinary death, 0.85 for circulatory death, 0.85 for respiratory death, and 0.71 for neoplasm death. CONCLUSIONS Death in type 2 diabetes mellitus can be predicted using a risk score consisting of commonly measured clinical and biochemical variables. Further validation is needed before clinical use.

BMI and Waist Circumference in Predicting Cardiovascular Risk Factor Clustering in Chinese Adolescents

Objective: To derive the optimal BMI and waist circumference (WC) cut‐off values to predict clustering of cardiovascular risk factors in Hong Kong Chinese adolescents.

Risk factors in V‐shaped risk associations with all‐cause mortality in type 2 diabetes—The Hong Kong Diabetes Registry

Body mass index (BMI) is associated with death in a V‐shaped manner in general populations but it is unknown whether BMI or other risk factors also exhibit V‐shaped relationships with death in type 2 diabetic patients.

Association between obesity and atopy in Chinese schoolchildren.

Background: Despite parallel increases in asthma and obesity prevalence, there is little data on obesity as a risk factor for atopy. The latter is an important phenotype in asthmatic patients. This study investigates the association between asthma traits, atopy and obesity-related markers in Chinese adolescents. Methods: 486 schoolchildren were recruited among participants of our population-based study on the epidemiology of obesity, and their allergy status was ascertained using a standardized questionnaire. Subjects’ anthropometry was recorded on-site, and fasting blood was collected for allergen-specific immunoglobulin E (IgE), lipids and systemic inflammatory biomarkers. Results: 98 (20.2%) subjects were classified as overweight or obese. Obesity status was not associated with asthma, allergic rhinitis or eczema (p > 0.25). Atopy was not associated with age-adjusted body mass index (BMI) or waist circumference. Atopy and presence of allergen-specific IgE did not differ between overweight or obese children and those with normal BMI (p > 0.25), although subgroup analysis suggested that cockroach sensitization was more common among males who were obese or overweight (p = 0.045). White cell count (WCC) was higher among atopic than nonatopic children (mean values 6.5 × 109/l vs. 6.2 × 109/l, p = 0.006). Logistic regression revealed WCC to be the only risk factor for atopy (OR 18.97, p = 0.004). Conclusions: Obesity is not associated with asthma or atopy in Chinese children. High WCC is an important risk factor for atopy in both males and females. Gender does not exert any consistent effect on the association between obesity and allergen sensitization in children.

Severe Hypoglycemia Identifies Vulnerable Patients With Type 2 Diabetes at Risk for Premature Death and All-Site Cancer: The Hong Kong Diabetes Registry

OBJECTIVE We examined the associations of clinical profiles in type 2 diabetic patients who developed severe hypoglycemia and their clinical outcomes, including death and all-site cancer. RESEARCH DESIGN AND METHODS A consecutive cohort of 8,767 type 2 diabetic patients with and without severe hypoglycemia in the 12 months before enrollment were recruited between 1995 and 2007, with follow-up until 2009. Severe hypoglycemia was defined by ICD-9 codes as hospitalizations resulting from hypoglycemia. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% CIs of clinical factors collected at enrollment for severe hypoglycemia. RESULTS In this cohort, mean age was 57.4 (SD 13.2) years and median disease duration of diabetes was 5 (interquartile range [IQR] 1–11) years. During a median follow-up of 6.71 (IQR 3.47–10.38) years, 235 patients had severe hypoglycemia (incidence 3.96 [95% CI 3.45–4.46] per 1,000 patient-years). At enrollment, patients with and without severe hypoglycemia had similar cancer rates. During follow-up, patients with severe hypoglycemia had a higher incidence of all-site cancer (13.4 vs. 6.4%, P < 0.0001) and mortality (32.8 vs. 11.2%, P < 0.0001) than those without severe hypoglycemia. After adjusting for confounders, old age, low BMI, high glycated hemoglobin, low triglyceride (TG), low LDL cholesterol (LDL-C), albuminuria, and chronic kidney disease were independent predictors for severe hypoglycemia. CONCLUSIONS In type 2 diabetes, severe hypoglycemia is associated with advanced age, renal dysfunction, poor glycemic control, and cancer subphenotypes (low BMI, low LDL-C, and low TG).

Fat redistribution and adipocyte transformation in uninephrectomized rats.

Dyslipidemia complicates renal function leading to disturbances of major homeostatic organs in the body. Here we examined the effect of chronic renal dysfunction induced by uninephrectomy on fat redistribution and lipid peroxidation in rats treated with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for up to 10 months. Uninephrectomized rats developed fat redistribution and hypercholesterolemia typical of chronic renal failure when compared with sham-operated rats or lisinopril-treated uninephrectomized rats. The weight of the peri-renal fat was significantly less in the untreated compared to the lisinopril-treated uninephrectomized rats or those rats with a sham operation. We also found that there was a shift of heat-protecting unilocular adipocytes to heat-producing multilocular fat cells in the untreated uninephrectomized rats. Similarly in these rats we found a shift of subcutaneous and visceral fat to ectopic fat with excessive lipid accumulation and lipofuscin pigmentation. Lisinopril treatment prevented fat redistribution or transformation and lipid peroxidation. This study shows that ACE inhibition may prevent the fat anomalies associated with chronic renal dysfunction.

Low LDL Cholesterol, Albuminuria, and Statins for the Risk of Cancer in Type 2 Diabetes: The Hong Kong Diabetes Registry

OBJECTIVE LDL cholesterol <2.80 mmol/l was associated with increased cancer risk in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol and albuminuria and 2) interaction between copresence of these two risk factors and statin use for cancer in type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained naive for statin treatment and 1,483 patients in whom statin treatment was initiated during a median follow-up period of 5.24 years. All patients were free of cancer at baseline. Biological interactions were estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates biological interaction. RESULTS In 3,793 statin-naive type 2 diabetic patients, copresence of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard ratio 2.77 [95% CI 1.78–4.31]) with significant biological interactions (RERI 1.05 [0.04–2.06]; AP 0.38 [0.09–0.66]). In the whole cohort of 5,276 type 2 diabetic patients, there was interaction between nonuse of statins and copresence of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87 [0.64–5.09] and AP 0.60 [0.29–0.90]). Statin nonusers with LDL cholesterol <2.80 mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users with or without both risk factors. CONCLUSIONS In type 2 diabetes, there was interaction between low LDL cholesterol and albuminuria with increased cancer risks. The latter was attenuated in the presence of statin treatment.

Distribution of melamine in rat foetuses and neonates.

Pharmacokinetics of melamine has not been studied in pregnancies despite of the many reports on the effect on renal damage in adult and neonates. In this study, Sprague-Dawley rats have been used as a model to study the single-dose effect of melamine administration in late pregnancy and in neonates within 24h. Melamine concentrations in maternal serum, breast milk, whole foetus, amniotic fluid, neonatal serum and neonatal kidney was measured by liquid chromatography coupled with mass spectrometry. Melamine was detected in all the samples, including foetal rats and amniotic fluid in utero. Melamine was able to pass through placenta and reach the foetus, and to accumulate in lactating mammary gland and neonatal kidney. Moreover, melamine was eliminated through the placenta of the foetus and the kidneys of the neonates, and later excreted into the amniotic fluid. The study characterised for the first time the distribution of melamine in foetuses and neonates, providing reference for toxicological study of melamine during pregnancy.

Associations between microRNA (miR-21, 126, 155 and 221), albuminuria and heavy metals in Hong Kong Chinese adolescents

BACKGROUND AND AIM Pathogenetic mechanisms underlying albuminuria are not completely understood. Heavy metals might lead to atherosclerosis and kidney damage. miR-21, 126, 155 and 221 regulated endothelial function and might contribute to the development of albuminuria. To date, no clinical trial has explored the relationship between miRNAs, microalbuminuria and heavy metals in human. In this study, we aimed to examine the association between microalbuminuria, miRNAs and heavy metals in adolescents. MATERIALS AND METHODS From a cross-sectional, population-recruited study, we identified 60 school children aged 12-19 years with microalbuminuria (defined as spot urine albumin-creatinine ratio >3.5 mg/mmol). We compared the urine heavy metals (arsenic, mercury, cadmium and lead) and miRNAs levels (miR-21,126, 155 and 221) with another 60 age-and sex-matched normoalbuminuric adolescents as control. RESULTS Mean age of the study cohort was 15.5±2.1 years. 43% were boys. Among the four miRNAs tested, only miR-21 was associated with microalbuminuria (p=0.02). Urinary arsenic and lead levels had a negative association with both miR-21 and miR-221. No significant association was found between heavy metals examined and microalbuminuria. CONCLUSION The results of our study suggest an association between microalbuminuria, miR-21 and heavy metals (arsenic and lead). This might imply that miR-21 is involved in the pathogenetic mechanisms linking heavy metals exposure and albuminuria.