A. W. K. Tso

Acute effect of orlistat on post-prandial lipaemia and free fatty acids in overweight patients with Type 2 diabetes mellitus.

Aims Post‐prandial lipaemia is prolonged and exaggerated in patients with Type 2 diabetes mellitus, with an accumulation of atherogenic triglyceride‐rich lipoprotein remnants. We postulate that orlistat, a gastrointestinal lipase inhibitor, may cause changes in post‐prandial lipoprotein metabolism by reducing dietary triglyceride absorption.

Association between raised blood pressure and dysglycemia in Hong Kong Chinese.

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia. RESEARCH DESIGN AND METHODS—We studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. We determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline. RESULTS—Diabetes and hypertension were both related to age, obesity indexes, blood pressure, glucose, HDL cholesterol, and triglycerides. Of subjects with diabetes, 58% had raised blood pressure. Of subjects with hypertension, 56% had dysglycemia. BMI and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new-onset diabetes. Age, systolic blood pressure, and 2-h glucose were independent predictors of new-onset hypertension. BMI, systolic blood pressure, and 2-h glucose were independent predictors of the development of diabetes and hypertension together. CONCLUSIONS—Diabetes and hypertension share common etiological factors. Patients with diabetes or hypertension should be screened and managed for the precursor of the other condition.

C-reactive protein as a predictor of hypertension in the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort

Inflammation contributes to the development of hypertension. Whether C-reactive protein (CRP) has a causal role in hypertension remains unknown. We studied the relationship between circulating CRP levels and hypertension. The role of single-nucleotide polymorphisms (SNPs) in the CRP gene as determinants of its plasma levels and the propensity to develop hypertension was investigated. Plasma CRP and genotypes of nine SNPs were determined in 1925 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004. Among 1378 subjects normotensive in CRISPS-2, 1115 subjects had been followed up in CRISPS-3 after a median interval of 5.3 years, 236 of whom had developed hypertension. Plasma CRP was independently associated with the development of hypertension in CRISPS-3 (odds ratio per quartile=1.26, P=0.010). Six SNPs were associated with plasma CRP (all P<0.001). However, none of the SNPs was significantly associated with blood pressure, prevalent or incident hypertension, or change in blood pressure. In conclusion, plasma CRP predicts the development of hypertension. Genetic variants in the CRP gene are significantly associated with plasma CRP but not with hypertension. The future risk of hypertension is therefore more related to plasma CRP than SNPs in the CRP gene in this population.

Genetic variants associated with persistent central obesity and the metabolic syndrome in a 12-year longitudinal study

OBJECTIVE Central obesity predisposes to various cardiometabolic diseases and is a key component of the metabolic syndrome (MetS). We have previously demonstrated that three obesity-susceptible single nucleotide polymorphisms (SNPs), rs10938397 (GNPDA2), rs8050136 (FTO) and rs17782313 (MC4R), were associated with obesity and waist circumference in cross-sectional studies in the Chinese population. In this study, we investigate whether these SNPs could also predict the persistence of central obesity and MetS in subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) cohort. DESIGN AND METHODS We genotyped these SNPs in i) 354 subjects with and 994 subjects without central obesity at both baseline and a 12-year follow-up, ii) 2214 subjects (816 cases and 1398 controls) in an MetS cross-sectional case-control study and iii) 225 subjects with and 1221 subjects without MetS at both baseline and the 12-year follow-up. RESULTS Both FTO rs8050136 (P(age, sex-adjusted)=0.019; odds ratio (OR) (95% confidence intervals (CI)): 1.35 (1.05, 1.73)) and GNPDA2 rs10938397 (P(age, sex-adjusted)=3 × 10(-3); OR (95% CI): 1.34 (1.11, 1.63)) were significantly associated with persistent central obesity. GNPDA2 rs10938397 was also significantly associated with MetS (P(age, sex-adjusted)=0.011, OR (95% CI): 1.20 (1.04, 1.38)) in the case-control study. However, none of these SNPs showed an individual association with persistent MetS. In the combined genetic risk analyses for persistent central obesity and persistent MetS, the combined genetic risk score of the three SNPs showed an OR of 1.25 (95% CI: 1.10, 1.42; P(age, sex-adjusted)=4.92 × 10(-3)) and 1.19 (95% CI: 1.03, 1.38; P(age, sex-adjusted)=0.019) for each additional risk allele respectively. CONCLUSION This study demonstrated that FTO and GNPDA2 variants predicted persistent central obesity in the Chinese population, further supporting their importance as obesity-susceptible genes.

Effect of Sandostatin® LAR® on serum leptin levels in patients with acromegaly

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin® LAR® on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans.

Multiple endocrine neoplasia type 1 (MEN1): genetic and clinical analysis in the Southern Chinese

objective Multiple endocrine neoplasia type 1 (MEN1) is characterized by a triad of neoplasia affecting the parathyroid glands, enteropancreatic endocrine tissue and the anterior pituitary gland.

A genetic variant in the gene encoding fibrinogen beta chain predicted development of hypertension in Chinese men.

Fibrinogen, a major determinant of blood viscosity, is an acute phase protein associated with cardiovascular disease. We studied the association of hypertension with single nucleotide polymorphisms (SNPs) in the gene encoding the fibrinogen beta chain (FGB). Three tagging SNPs (rs1025154, rs4220 and rs1044291) were selected from the HapMap database on Han Chinese. Genotypes were determined in 1,294 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. There were 199 hypertensive subjects at baseline. Among 1,095 subjects normotensive at baseline, 178 developed hypertension during a median follow-up period of 6.4 years. Among the three tagging SNPs, rs4220 showed significant association with hypertension at both baseline (odds ratio [OR]=1.49, p=0.004) and at follow-up (OR=1.32, p=0.013). The minor A allele of this SNP was associated with higher plasma fibrinogen level (beta=0.144, p<0.001 at baseline and beta=0.130, p<0.001 at follow-up). Among subjects normotensive at baseline, this SNP was also associated with the development of hypertension in men (OR=1.52, p=0.022), but not in women. The SNP rs4220 in FGB , which leads to the substitution of arginine by lysine at position 448, is independently associated with plasma fibrinogen level and hypertension in Hong Kong Chinese. This suggests a possible causal role of fibrinogen in hypertension development, especially in men.

Association of two adiponectin gene variants with ischemic stroke in a Chinese cohort

Disrupted-In-Schizophrenia (DISC1) is a candidate susceptibility gene for major psychiatric diseases including schizophrenia, depression and bipolar disorder, while biological roles of the DISC1 protein have not yet been fully explained. In the present study, a 129 substrain-specific 25-bp deletion in exon 6 of Disc1 that introduces a termination codon at exon 7 and abolishes production of the full-length protein was transferred to the C57BL/6J genetic background. We used behavioral assays to assess Disc1-deficient mice for depression-like behaviors. Immobility time in the forced swimming test and the tail suspension test was comparable between wildtype and Disc1-null mice. Brain sections of Disc1-deficient mice were examined in the microscopy. Gross brain morphology appeared normal in Disc1-null mice. Immunofluorescent staining was performed to compare the expression pattern of DISC1-related proteins in wild-type and Disc1-deficient mice. Further analysis of mice carrying the 129 substrain-derived deletion variant might help to explain how DISC1 variation contributes to susceptibility in humans.