Hyperlipidemias: Critchley JA

Chan JC, Tong PC, Critchley JA. · Departmentof Medicine Therapeutics,Prince of Wales Hospital,TheChinese University of Hong Kong Shatin, Hong Kong. · Semin Vasc Med. · Pubmed #16222595 No free full text.

Abstract: For more than a decade, insulin resistance has been proposed as the key linking factor for the metabolic syndrome disease cluster of glucose intolerance, hypertension, dyslipidemia, obesity, and cardiovascular disease. Although most of the epidemiological, experimental, and clinical evidence still support the role of insulin resistance as an important component of this multifaceted syndrome, there is evidence amassing that a neurohormonal mechanism, including an endocrine role for adipocytes, probably plays a more fundamental role. This is supported by the strong associations between obesity, especially central adiposity, and all components of the metabolic syndrome, in contrast to the inconsistent relationships between blood pressure and markers of insulin resistance. However, much of the effect of visceral fat on cardiovascular risk factors is mediated through the metabolic actions of free fatty acids (FFA) on insulin resistance, thus resolving any obesity versus insulin resistance controversy. In addition to the roles of obesity and FFA in the development of insulin resistance syndrome, the high prevalence rates of this disease cluster among subjects from low socioeconomic groups as well as from developing countries have led to alternative hypotheses to better our understanding of the contributory roles of socioeconomic, in utero, and genetic factors in this syndrome. More recently, the pathogenetic roles of iron overload and liver dysfunction have also been re-examined. In this article, the various hypotheses which have been put forward to explain the diverse clinical manifestations of the metabolic or insulin resistance syndrome are summarized and put into perspective. While there is clinical and experimental evidence to support many of these independent pathways, alternative statistical methods such as factor analysis or structural equation modeling may be needed to unravel the complex nature of these interacting pathways. Finally, these hypotheses, if proven, will add new dimensions to our current strategies and emphasize the need to focus on behavioral and socioeconomic interventions in addition to the use of pharmacological therapy in our attempt to control this epidemic disease of modern societies.

Critchley JA, Zhao HL, Tomlinson B, Leung W, Thomas GN, Chan JC, Cockram CS. · Divisions of Clinical Pharmacology and Endocrinology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China. · Chin Med J (Engl). · Pubmed #11930647 links to  free full text

Abstract: PURPOSE: To review evidence-based management of nephropathy in patients with type 2 diabetes. DATA SOURCES: A literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed. STUDY SELECTION: Well-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected. DATA EXTRACTION: Data and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients. RESULTS: Hypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions. CONCLUSIONS: Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.

Chan JC, Ko GT, Leung DH, Cheung RC, Cheung MY, So WY, Swaminathan R, Nicholls MG, Critchley JA, Cockram CS. · Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong. · Kidney Int. · Pubmed #10652036 links to  free full text

Abstract: Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. BACKGROUND: In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. METHODS: After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). RESULTS: In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). CONCLUSION: In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.

Cheng J, Zhao D, Zeng Z, Critchley JA, Liu J, Wang W, Sun J, Capewell S. · Department of Epidemiology, Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing Anzhen Hospital affiliated to the Capital Medical University, Beijing, PR China. · BMC Public Health. · Pubmed #19159492 links to  free full text

Abstract: BACKGROUND: Recent, dramatic increases in coronary heart disease (CHD) mortality in China can be mostly explained by adverse changes in major cardiovascular risk factors. Our study aimed to assess the potential impact of subsequent changes in risk factors and population ageing on CHD deaths in Beijing between 1999 and 2010. METHODS: The previously validated IMPACT model was used to estimate the CHD deaths expected in 2010, with treatment uptakes being held constant at levels measured in 1999, comparing three scenarios: a) taking into account the ageing of the population but assuming no further changes in major risk factor levels from 1999 or, b) if recent risk factor trends continued until 2010 or, c) if there was a 0.5% annual reduction in each risk factor. RESULTS: Population ageing alone would result in approximately 1990 additional deaths in 2010 compared with 1999, representing an increase of 27%. Continuation of current risk factor trends would result in approximately 3,015 extra deaths in 2010, [a 40% increase]; three quarters of this increase would be attributable to rises in total cholesterol levels. Thus, demographic changes and worsening risk factors would together result in a 67% increase in CHD deaths. Conversely, assumed 0.5% annual reductions in risk factors (a mean population level decline of 0.3 mmol/L for total cholesterol in both genders, and smoking prevalence declining by 3.0% for men and 4.1% for women, body mass index by 1.3 kg/m2 for men and 1.4 kg/m2 for women, diabetes prevalence by 0.4% in both genders, and diastolic blood pressure by 4.7 mmHg for men and 4.4 mmHg for women) would result in some 3,730 fewer deaths, representing a 23% decrease overall. These findings remained consistent in sensitivity analyses. CONCLUSION: CHD death rates are continuing to rise in Beijing. This reflects worsening risk factor levels, compounded by demographic trends. However, the adverse impact of population ageing on CHD burden could be completely offset by eminently feasible improvements in diet and smoking.

Kabir Z, Bennett K, Shelley E, Unal B, Critchley JA, Capewell S. · Harvard School of Public Health, Division of Public Health Practice, Boston, USA. <> · BMC Public Health. · Pubmed #17584932 links to  free full text

Abstract: BACKGROUND: To investigate whether primary prevention might be more favourable than secondary prevention (risk factor reduction in patients with coronary heart disease(CHD)). METHODS: The cell-based IMPACT CHD mortality model was used to integrate data for Ireland describing CHD patient numbers, uptake of specific treatments, trends in major cardiovascular risk factors, and the mortality benefits of these specific risk factor changes in CHD patients and in healthy people without recognised CHD. RESULTS: Between 1985 and 2000, approximately 2,530 fewer deaths were attributable to reductions in the three major risk factors in Ireland. Overall smoking prevalence declined by 14% between 1985 and 2000, resulting in about 685 fewer deaths (minimum estimate 330, maximum estimate 1,285) attributable to smoking cessation: about 275 in healthy people and 410 in known CHD patients. Population total cholesterol concentrations fell by 4.6%, resulting in approximately 1,300 (minimum estimate 1,115, maximum estimate 1,660) fewer deaths attributable to dietary changes(1,185 in healthy people and 115 in CHD patients) plus 305 fewer deaths attributable to statin treatment (45 in people without CHD and 260 in CHD patients). Mean population diastolic blood pressure fell by 7.2%, resulting in approximately 170 (minimum estimate 105, maximum estimate 300) fewer deaths attributable to secular falls in blood pressure (140 in healthy people and 30 in CHD patients), plus approximately 70 fewer deaths attributable to antihypertensive treatments in people without CHD.Of all the deaths attributable to risk factor falls, some 1,715 (68%) occurred in people without recognized CHD and 815(32%) in CHD patients. CONCLUSION: Compared with secondary prevention, primary prevention achieved a two-fold larger reduction in CHD deaths. Future national CHD policies should therefore prioritize nationwide interventions to promote healthy diets and reduce smoking.

Unal B, Critchley JA, Capewell S. · Department of Public Health, Dokuz Eylul University School of Medicine, 35340 Izmir, Turkey. · BMJ. · Pubmed #16107431 links to  free full text

Abstract: OBJECTIVE: To investigate whether population based primary prevention (risk factor reduction in apparently healthy people) might be more powerful than current government initiatives favouring risk factor reduction in patients with coronary heart disease (CHD) (secondary prevention). DESIGN, SETTING, AND PARTICIPANTS: The IMPACT model was used to synthesise data for England and Wales describing CHD patient numbers, uptake of specific treatments, trends in major cardiovascular risk factors, and the mortality benefits of these specific risk factor changes in healthy people and in CHD patients. RESULTS: Between 1981 and 2000, CHD mortality rates fell by 54%, resulting in 68,230 fewer deaths in 2000. Overall smoking prevalence declined by 35% between 1981 and 2000, resulting in approximately 29,715 (minimum estimate 20 035, maximum estimate 44,675) fewer deaths attributable to smoking cessation: approximately 5035 in known CHD patients and approximately 24,680 in healthy people. Population total cholesterol concentrations fell by 4.2%, resulting in approximately 5770 fewer deaths attributable to dietary changes (1205 in CHD patients and 4565 in healthy people) plus 2135 fewer deaths attributable to statin treatment (1990 in CHD patients, 145 in people without CHD). Mean population blood pressure fell by 7.7%, resulting in approximately 5870 fewer deaths attributable to secular falls in blood pressure (520 in CHD patients and 5345 in healthy people) plus approximately 1890 fewer deaths attributable to antihypertensive treatments in people without CHD. Approximately 45,370 fewer deaths were thus attributable to reductions in the three major risk factors in the population: some 36 625 (81%) in people without recognised CHD and 8745 (19%) in CHD patients. CONCLUSIONS: Compared with secondary prevention, primary prevention achieved a fourfold larger reduction in deaths. Future CHD policies should prioritise population-wide tobacco control and healthier diets.

Thomas GN, Hong AW, Tomlinson B, Lam CW, Critchley JA, Sanderson JE, Woo J, Lau E. · Department of Medicine and Therapeutics, The Chinese University of Hong Kong Prince of Wales Hospital, Shatin, Hong Kong. · Diabetes Res Clin Pract. · Pubmed #15063605 No free full text.

Abstract: OBJECTIVE: To investigate the impact of insulin resistance on cardiovascular risk factors in the elderly. RESEARCH DESIGN AND METHODS: A cross-sectional, community-based study of 225 older Chinese participants (65-74 years, 55.6% female) recruited from community centres for the elderly in Shatin. Anthropometric measures and DXA body fat, blood pressure, insulin sensitivity (fasting insulin, fasting insulin-glucose product, short insulin tolerance test (SITT)), glycaemic (fasting glucose, glycated haemoglobin A1c) and lipid (total, HDL-, and LDL-cholesterol, triglycerides) indices and albuminuria (24h albumin-to-creatinine ratio) were measured. RESULTS: There was a close correlation between the SITT and insulin-glucose product indices of insulin resistance. Decreasing tertiles of insulin sensitivity were associated with increasing indices of glycaemic control, and general and central obesity, including DXA lean and fat mass, albuminuria, and triglycerides, with decreasing HDL-cholesterol. There were no differences in blood pressure or electrolyte levels between these tertile groups. These subjects were more insulin resistant than a group of younger diabetics. CONCLUSIONS: Insulin resistance was associated with indices of obesity and an atherogenic lipid and hyperglycaemic profile and may in part contribute to the high frequency of metabolic syndrome components in these older Chinese subjects.

Lee ZS, Critchley JA, Ko GT, Anderson PJ, Thomas GN, Young RP, Chan TY, Cockram CS, Tomlinson B, Chan JC. · Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin. · Obes Rev. · Pubmed #12164469 No free full text.

Abstract: 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.

Ko GT, Cockram CS, Critchley JA, Chan JC. · Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, Hong Kong, ROC. · Diabetes Metab. · Pubmed #11852371 links to  free full text

Abstract: 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.

Lee ZS, Critchley JA, Tomlinson B, Young RP, Thomas GN, Cockram CS, Chan TY, Chan JC. · Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories. · Metabolism. · Pubmed #11229419 No free full text.

Abstract: The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.

Thomas GN, Tomlinson B, Chan JC, Sanderson JE, Cockram CS, Critchley JA. · Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin. · Diabetes Care. · Pubmed #11213892 links to  free full text

Abstract: OBJECTIVE: In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms--the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms--for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: The three gene polymorphisms of this cross-sectional study were detected using polymerase chain reaction-based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia using chi2 test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance. RESULTS: No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT1RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels. CONCLUSIONS: These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele-containing genotypes in those groups, but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects.

Thomas GN, Critchley JA, Tomlinson B, Anderson PJ, Lee ZS, Chan JC. · Department of Medicine and Therapeutics, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China. · Metabolism. · Pubmed #11145111 No free full text.

Abstract: Obesity and insulin resistance are considered important links underlying the development of hypertension. In Caucasians, there have been many reports of an association between insulin resistance and hypertension. However, this relationship is not consistently found in other ethnic groups. In this study, we examined the involvement of insulin resistance (assessed as fasting insulin-glucose product, FIGP) and general and central obesity as potential links in the development of hypertension in 413 normoglycemic Hong Kong Chinese (56.9% hypertensive) subjects. Anthropometric parameters (waist circumference [WC], waist-to-hip ratio [WHR], body mass index [BMI]), surrogate measures of insulin resistance (fasting plasma glucose, insulin, FIGP), fasting lipids and systolic (SBP) and diastolic (DBP) blood pressure were measured. Both male and female hypertensives were more obese and dyslipidemic, and the females had higher indices of insulin resistance than the normotensive subjects of the same gender. Before adjustment for age, gender, and adiposity, FIGP correlated with SBP in the total (r = .19, P = .009) and low BMI (r = .23, P < .05) and low WHR (r = .25, P < .01) groups. However, after adjustment, there was no significant relationship between FIGP and blood pressure. In contrast, BMI and WC were strongly associated with blood pressure (r > or = .41, P < .001 for both DBP and SBP in the total population), although in the group with general obesity, the strength of the relationship was weaker (r > or = .13). These relationships persisted after adjustment for age, gender, and FIGP. Obesity, therefore, appears to have a predominant role compared with insulin resistance in determining blood pressure in these normoglycemic Chinese.

Lee SC, Pu YB, Thomas GN, Lee ZS, Tomlinson B, Cockram CS, Critchley JA, Chan JC. · Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin. · Metabolism. · Pubmed #10954020 No free full text.

Abstract: Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine constitutively produced by adipose tissue that may mediate insulin resistance. Studies in Caucasian subjects have suggested that the G-308A transition in the 5' region of the TNF-alpha gene may be associated with insulin resistance and obesity. These factors have been proposed to underlie the clustering of type 2 diabetes, hypertension, and dyslipidemia found in the metabolic syndrome, the prevalence of which is reaching epidemic proportions in Hong Kong Chinese. We investigated the association of this gene polymorphism with the components of the metabolic syndrome including the lipid profile, as well as with the indices of obesity and insulin resistance as measured by the insulin-glucose product, in 440 Chinese subjects (healthy [27.5%] and overlapping groups with type 2 diabetes [54.1%], hypertension [38.8%], dyslipidemia [39.3%], or obesity [39.5%]). The frequency of the mutant A allele was 7.4% in 121 healthy controls and 9.0% in the total population. The mutation was not associated with any component of the metabolic syndrome or with the prevalence of albuminuria and retinopathy in these subjects. Furthermore, there was no difference in anthropometric measures, insulin resistance, or lipid levels between subjects with the GG genotype and those with the mutant allele. In summary, the TNF-alpha gene G-308A polymorphism is unlikely to play an important role in the development of these disorders in this population.

Lee ZS, Critchley JA, Chan JC, Anderson PJ, Thomas GN, Ko GT, Young RP, Chan TY, Cockram CS, Tomlinson B. · Divisions of Clinical Pharmacology and Endocrinology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. · Hong Kong Med J. · Pubmed #10793398 links to  free full text

Abstract: 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.