Zoe S.K. Lee

Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality.

OBJECTIVES: To evaluate whether there is one central abnormality contributing to the conditions associated with the metabolic syndrome (MES), or whether one abnormality is contributing on multiple levels.METHODS: We recruited 145 Chinese subjects aged 17–68 y with varying degrees of insulin-sensitivity (IS): 33 healthy, 59 with type 2 diabetes mellitus, 32 essential hypertensives and 21 dyslipidaemics. IS was evaluated by the short insulin sensitivity test using a 0.1 U/kg intravenous bolus dose of insulin. Blood pressure, anthropometric measures and biochemical parameters associated with IS were also measured. Exploratory factor analyses (EFA) were performed in the entire group of 145 subjects and in the 76 with normal glucose tolerance.RESULTS: EFA in all 145 subjects defined three distinct, independent factors. Factor 1 was interpreted as general and central adiposity, impaired IS and glucose intolerance, Factor 2 was associated with hypertension and general and central obesity, whilst Factor 3 was strongly related to low HDL-cholesterol and high triglyceride concentrations and weakly to waist circumference. In patients with impaired glucose tolerance, only two factors were identified; factor 1 related to reduced IS, impaired glucose tolerance, dyslipidaemia and general and central adiposity, and factor 2 which was related to blood pressure and general and central adiposity.CONCLUSIONS: These models suggest that the clustering of variables in MES is a result of multiple factors linked by adiposity and not a single aetiology. Furthermore, increases in blood pressure are related to obesity in these Chinese subjects rather than decreased IS per se.

Visceral Fat and Cardiovascular Risk Factors in Chinese NIDDM Patients

OBJECTIVE The interrelations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance are well recognized. These relationships are of particular interest in Hong Kongs Chinese population, in whom increasing affluence has coincided with a marked increase in the prevalence of NIDDM. We designed a pilot study to examine the relationships between visceral fat and cardiovascular risk factors in Chinese NIDDM patients. RESEARCH DESIGN AND METHODS We studied 21 Chinese NIDDM patients whose visceral fat was quantified by magnetic resonance imaging. Cardiovascular risk factors including plasma lipids and 24-h ambulatory blood pressure (BP) were measured. In addition, insulin resistance was determined by a short insulin tolerance test (SITT). RESULTS Increased visceral adiposity was significantly correlated with plasma triglycerides (r = 0.63, P = 0.004), the total cholesterol/HDL cholesterol ratio (r = 0.61, P = 0.008), the urinary albumin/creatinine ratio (r = 0.49, P = 0.04), and decreased insulin sensitivity as measured by the SITT (r = 0.47, P = 0.03). When the data were analyzed by tertiles, increasing visceral fat area was associated with higher plasma triglycerides, lower HDL cholesterol, and a smaller plasma glucose decrement during the SITT. In addition, the diurnal rhythm in BP and heart rate tended to be best preserved in those with the least visceral obesity. CONCLUSIONS This pilot study demonstrates that visceral fat accumulation is associated with dyslipidemia, hypertension, insulin resistance, and albuminuria in Chinese patients with NIDDM.

An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome

Insulin resistance has been described as a possible underlying link for the clustering of Type 2 diabetes mellitus, hypertension, obesity, and dyslipidemia, known as the metabolic syndrome. Mutations within the insulin receptor have been associated with hypertension in some white and Oriental populations. We examined the relationship between the insulin receptor NsiI restriction fragment-length polymorphism (RFLP) and biochemical and anthropometric parameters associated with these disorders in 933 Chinese subjects. Of the 933 subjects, 117 were control subjects and 816 had one or more components of the metabolic syndrome: 59.7% hypertension, 64.6% glucose intolerance, 55.3% dyslipidemia, and 53.3% obesity. The prevalences of the N1 allele and N1N1 genotype were 74.4% and 55.8%, respectively, in the whole population. No differences were observed in the genotype and allele frequency distributions between the control group and the cohorts with glucose intolerance, hypertension, or dyslipidemia alone or in combination. Using one-way ANOVA, there was a weak relationship between the insulin receptor genotypes and diastolic blood pressure (DBP), P = .069. The DBP was significantly higher in subjects carrying the N1N1 genotype in both the total population (80 +/- 13 v 76 +/- 12 mm Hg, P = .038) and subjects with glucose intolerance (80 +/- 12 v 76 +/- 10 mm Hg, P = .048). Using stepwise multiple regression, the insulin receptor NsiI polymorphism was found to be an independent predictor of DBP in this Chinese population, P = .018. Age, gender, and body mass index (BMI) were also included in the analysis and were all significantly associated with diastolic DBP. To conclude, the insulin receptor gene NsiI RFLP is associated with DBP in these Chinese subjects.

Simultaneous measurement of catecholamines and kallikrein in urine using boric acid preservative

Catecholamines, dopamine and the renal kallikrein-kinin system may participate in the pathogenesis of hypertension. In the past these systems have been studied independently in isolation. Attempts to study the systems together have been hampered by incompatibility of the current urine preservatives for the two assays involved. In order to measure acid-stable catecholamines and acid-labile kallikrein enzyme together, we have established boric acid solution as a preservative by comparing the stability of urinary catecholamines stored in it with the commonly employed preservative, hydrochloric acid (HCl) as well as the stability of urinary kallikrein in untreated urine with and without boric acid at ambient temperatures for 24 and 48 h, and at -20 degrees C for 2 weeks and 1, 2 and 3 months. The stability of other common urine parameters including cortisol, electrolytes, creatinine and protein, was also investigated after storage with boric acid at ambient temperature for 24 h. Our results showed that there was a good agreement between the measurements of urinary catecholamines stored in both HCl and boric acid and that the latter did not interfere with measurements of urinary kallikrein or other common urine parameters.

Identification of the intron 14 splicing defect of the cholesteryl ester transfer protein gene in Hong Kong Chinese.

To the Editor: The plasma glycoprotein cholesteryl ester transfer protein (CETP) mediates transfer of cholesteryl esters from high-density lipoprotein (HDL) particles into triglyceride-rich lipoproteins with a reciprocal exchange of triglycerides. The CETP gene, located on the short arm of chromosome 16 (1), G/A mutation at the first nucleotide of the intron 14 splicing donor site was present in about 1–2% of a Japanese population sample (2), but not detected in a random sample of 25 unrelated Chinese subjects (3). Japanese AA homozygotes had markedly increased HDL-cholesterol levels (three to four times higher than those subjects without the mutation) and undetectable CETP activity, whereas the heterozygous subjects had intermediate levels of HDL-cholesterol and CETP activity (4, 5). Mutations in the CETP gene explained 10% of the variance of HDL cholesterol in Japanese men (6, 7). In recent decades, lipid levels in Hong Kong have been increasing towards those found in western countries, a process which is currently also occurring in mainland China (8). However, the incidence of coronary heart disease (CHD) events is still much lower in Hong Kong compared to most western countries (9). These differences may be the result of other environmental factors or a lag period between the rise in cholesterol levels and the impact on CHD, which may not be observed until much later. However, these differences may also be the result of genetic factors. As such, we are investigating possible genetic factors influencing lipid levels and now present data describing the frequency of an intron 14 mutation of CETP gene and its relationship to plasma lipid concentrations in Hong Kong Chinese.

Association of the D8S282 marker near the lipoprotein lipase gene locus with systolic blood pressure in healthy Chinese subjects

Objective To investigate the association between the marker D8S282 near the lipoprotein lipase (LPL) gene locus, and blood pressure, anthropometric and biochemical parameters in 229 healthy Chinese subjects. Method Genotyping was performed using an automated DNA sequencer and the Base ImageIR software. Eight different alleles were identified (272–286 bp) resulting in 15 genotypes in our population. We investigated the association between the common (28.8%) 278 bp allele and the anthropometric and biochemical parameters. Results In a tertile analysis, the frequency of the 278 bp allele increased linearly (P = 0.003) with increasing systolic blood pressure (SBP). The relationship was most evident in the females (n = 141); SBP was higher in homozygotes for the 278 bp allele (117 ± 10 mmHg, n = 12) than those without this allele (109 ± 9 mmHg, n = 77, P < 0.05) and was gene-dose dependent, and this difference was more significant after adjusting for age (P = 0.004). No relationship between the locus and the anthropometric or biochemical parameters investigated was observed. Conclusion The D8S282 marker near the LPL gene locus contributes to the variance of SBP in healthy Hong Kong Chinese subjects, particularly in females.