Sidney Tam

Hypoadiponectinemia as a Predictor for the Development of Hypertension. A 5-Year Prospective Study

Low circulating levels of adiponectin, an adipokine with insulin-sensitizing, antiatherogenic, and anti-inflammatory properties, are found in hypertensive patients. Adiponectin replenishment ameliorated hypertension in adiponectin-deficient mice or obese, hypertensive mice with hypoadiponectinemia, suggesting an etiologic role of adiponectin in hypertension. We aimed to determine, in this 5-year prospective study, whether hypoadiponectinemia could predict the development of hypertension in a nondiabetic Chinese cohort. A total of 577 subjects (249 men and 328 women) were recruited from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study and prospectively followed up for 5 years. The relationship of serum adiponectin with the development of hypertension (sitting blood pressure ≥140/90 mm Hg) was investigated in a nested case–control study consisting of 70 subjects who had developed hypertension on follow-up and 140 age- and sex-matched control subjects who were normotensive both at baseline and at year 5. At baseline, serum adiponectin level in the lowest sex-specific tertile was more likely to be associated with hypertension (P=0.003 versus the highest tertile, after adjusting for age, body mass index, fasting insulin, and high-sensitivity C-reactive protein). At year 5, baseline serum adiponectin was a significant independent predictor of incident hypertension in the nested case–control study (P=0.015; age adjusted), together with mean arterial pressure (P<0.001), high-sensitivity C-reactive protein (P=0.018), and body mass index (P=0.004). Normotensive subjects with baseline serum adiponectin levels in the lowest sex-specific tertile had an increased risk of becoming hypertensive (adjusted odds ratio: 2.76; 95% CIs: 1.06 to 7.16; P=0.037 versus highest tertile). Our data suggest that hypoadiponectinaemia may be involved in the pathogenesis of hypertension in humans.

Diagnosis and spectrum of melamine-related renal disease: plausible mechanism of stone formation in humans.

BACKGROUND An epidemic of urinary stones affecting children after consumption of melamine tainted milk is unfolding. We defined clinicopathological features of the disease for diagnosis, monitoring, and treatment of this group of patients. METHODS A clinicopathological study on exposed children with ultrasonographic evidence of urolithiasis was conducted. Melamine and cyanuric acid levels in the urine were determined by mass spectrometry. RESULTS Disease severity varied from acute renal failure with hydronephrosis to symptomatic or asymptomatic stones with or without abnormal urinalysis. All cases were aged <3 y with >50% cases having predisposing urinary metabolic risk factors for urolithiasis. Most of the stones were located in the renal pelvis and measured 2.5-18 mm by ultrasonography. We found a strong correlation between renal stone size and urinary melamine concentration. For stones <10 mm, a 10 microg/mmol creatinine increase in urinary melamine concentration is associated with approximately 1 mm increase in the size of the stone. The high degree of correlation strongly suggests that melamine is related to stone formation in humans. Using ROC analysis, we propose that patients who have a persistent melamine level above the optimal cut-off value of 7.1 microg melamine/mmol creatinine in urine might have a significant exposure of melamine-tainted products. Unlike melamine, urinary cyanuric acid is not significantly different between cases and controls. Pathophysiological findings from feeding animals with melamine and cyanuric acid may not be directly applicable to humans. CONCLUSION Both melamine and urine metabolic lithogenic factors are important for the formation of melamine-related stones. Apart from aiding with case screening and confirmation, the urine melamine level might as well be an indicator of residual melamine load in the body and thus is useful for following-up and monitoring of the confirmed cases. As the stones are small and can be passed out spontaneously, follow-up of these patients with urine melamine will be a convenient tool for monitoring the melamine load of the patients.

Development of Diabetes in Chinese With the Metabolic Syndrome A 6-year prospective study

OBJECTIVE—We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. RESEARCH DESIGN AND METHODS—We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose ≥7.0 mmol/l with fasting and/or ≥11.1 mmol/l at 2 h. RESULTS—The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8–6.0] and 3.5 [2.3–5.2], respectively. HRs for fasting plasma glucose (FPG) ≥6.1 or 5.6 mmol/l were 6.9 [4.1–11.5] and 4.1 [2.8–6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, ∼20%, but their negative predictive values were ∼95%. CONCLUSIONS—The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes.

Vitamin D Deficiency Is Associated with Depletion of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Patients with Type 2 Diabetes

CONTEXT Vitamin D (Vit-D) deficiency is associated with type 2 diabetes mellitus (DM) and endothelial dysfunction. The relationship of Vit-D deficiency with circulating endothelial progenitor cells and endothelial dysfunction in type 2 DM patients nonetheless remains unclear. OBJECTIVE We aimed to investigate the cross-sectional association of Vit-D status with brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in type 2 DM patients. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional study of 280 patients (59% male, aged 68 ± 10 yr) with type 2 DM recruited in outpatient clinics during the winter period. MAIN OUTCOME MEASURE We measured serum 25-hydroxyvitamin D [25(OH)D] by an ELISA kit, circulating CD34+/kinase insert domain-containing receptor (KDR)+ and CD133+/KDR+ EPCs by flow cytometry and brachial artery FMD by vascular ultrasound, respectively. RESULTS The mean serum 25(OH)D concentration was 25.00 ± 9.17 ng/ml, and 34.3% of patients had Vit-D deficiency [25(OH)D < 20 ng/ml]. Serum 25(OH)D concentration had a significant correlation with hemoglobin A1c level [B = -0.018, 95% confidence interval (CI) -0.035 to -0.002, P = 0.032]. Patients with Vit-D deficiency status had significantly lower brachial FMD (mean difference -1.43%, 95% CI -2.31 to -0.55, P = 0.001) and CD133+/KDR+EPC counts (mean difference -0.12%, 95% CI -0.21 to -0.019, P = 0.022) than those with sufficient Vit-D status after adjustment for age, sex, and cardiovascular risk factors, including hemoglobin A1c levels. CONCLUSIONS Our results demonstrate that serum 25(OH)D status was significantly associated with brachial artery FMD and circulating CD133+/KDR+EPCs. This suggests that Vit-D deficiency might contribute to depletion of EPCs and endothelial dysfunction in patients with type 2 DM.

Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus

ABSTRACT Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus.

Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension

Recent studies suggest that reductions in circulating endothelial progenitor cells (EPCs) may contribute to the development of atherosclerosis. However, whether reduced circulating EPCs contribute to cerebrovascular disease remains undefined. We tested the hypothesis that reduced circulating EPCs was associated with an increased burden of carotid atherosclerosis. The level of circulating CD34+/KDR+ EPCs and the extent of carotid atherosclerosis were determined in 30 patients with a history of atherothrombotic ischaemic stroke and 30 age- and sex-matched controls (mean age: 63±2 years; 63% men). Stroke patients, compared with controls, had significantly higher carotid mean maximum intima-media thickness (mmIMT) (1.08±0.05 versus 0.90±0.02 mm, P=0.002), prevalence of carotid plaque (60.0 versus 23.3%, P=0.004) and a lower number of circulating CD34+/KDR+ EPCs (235.7±45.5 versus 400.4±56.8 cells/μl, P=0.027). The circulating CD34+/KDR+ EPC count correlated negatively with carotid mmIMT (r=−0.50, P<0.001), and was an independent risk factor for increased carotid mmIMT>1 mm (odds ratio (OR): 7.71; 95% confidence interval (CI): 1.62–36.74, P=0.010) and the presence of carotid plaque (OR: 7.04; 95% CI: 1.95–25.43, P=0.003). Furthermore, stroke patients with low (<25th percentile of controls) as compared to those with normal CD34+/KDR+ EPC count had a significantly greater carotid mmIMT (1.21±0.07 versus 0.93±0.05 mm, P=0.005) and a significantly higher prevalence of carotid plaque (87.5% versus 28.6%; P=0.001). Our observations suggested that reduced circulating EPC may contribute to the progression of carotid atherosclerosis. Circulating EPC count may provide a novel marker for the burden of carotid atherosclerosis.

Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area

Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake.

Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study

Safety of traditional Chinese medicine in patients with chronic hepatitis B is unknown.

Thyroxine suppressive therapy decreases bone mineral density in post‐menopausal women

OBJECTIVE Hyperthyroidism is associated with increased bone turnover and decreased bone mass. This study aimed to evaluate the bone mineral density (BMD) of post‐menopausal women on long‐term thyroxine suppressive therapy.

Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke.

AIMS To investigate the effect of oral isoflavone supplement on vascular endothelial function in patients with established cardiovascular disease. METHODS AND RESULTS A randomized, double-blinded, placebo-controlled trial was performed to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence interval (95% CI) 0.1-2.0, P = 0.035]. Adjusted for baseline differences in FMD, isoflavone treatment was independently associated with significantly less impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13-0.80, P = 0.014). The absolute treatment effect of isoflavone on brachial FMD was inversely related to baseline FMD (r = -0.51, P < 0.001), suggesting that vasoprotective effect of isoflavone was more pronounced in patients with more severe endothelial dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a significant decrease in serum high-sensitivity (hs)-C-reactive protein level (treatment effect -1.7 mg/L, 95% CI -3.3 to -0.1, P = 0.033). Nevertheless, isoflavone did not have any significant treatment effects on nitroglycerin-mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose and insulin, haemoglobin A1c, and oxidative stress as determined by serum superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05). CONCLUSION This study demonstrated that 12 week isoflavone treatment reduced serum hs-C-reactive protein and improved brachial FMD in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status. These findings may have important implication for the use of isoflavone for secondary prevention in patients with cardiovascular disease, on top of conventional interventions.