ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) is a major health concern worldwide. There are limited studies which look into the actual knowledge level of CKD among the general population both locally and internationally. This study aims to assess the knowledge level of CKD among patients in a secondary hospital in Malaysia. METHODS: Consecutive sampling of patients attending the Medical Outpatient Clinic was performed in this crosssectional study. Respondents were given self-administered questionnaires which contain questions on demographic characteristics and knowledge on CKD. RESULTS: Out of 300 respondents, 78.6% (n=236) of the respondents completed the questionnaire. Majority of respondents (73.7%, n=174) scored less than 4 out of 7 marks on knowledge on CKD. Respondents who were younger, males, having higher education status, professionals/executives and earned higher monthly income were more likely to have a higher mean knowledge score of CKD. Respondents who have heard of CKD were also significantly associated with higher mean knowledge score of CKD. CONCLUSION: The study findings suggest that our Malaysian population is still inadequately informed on CKD, especially those who are at risk of developing CKD and its complications, and also among those of the lower socioeconomic group. In order for successful primary and secondary prevention of CKD, more importance should be placed on increasing awareness on CKD among these atrisk groups.
Subject(s)
Health Knowledge, Attitudes, Practice , Renal Insufficiency, Chronic , Adult , Aged , Ambulatory Care Facilities , Cross-Sectional Studies , Female , Humans , Malaysia , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
UNLABELLED: Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type 2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI). RESULT: Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations (P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5 +/- 16.8 ng/ml, DM: 14.6 +/- 10.5 ng/ml and control: 9.1 +/- 7.1 ng/ml). Women had higher serum leptin concentration than men in the control group (12.5 +/- 7.3 ng/ml versus 4.2 +/- 2.0 ng/ml, P=0.001) and in the DM group (18.9 +/- 11 ng/ml versus 8.6 +/- 5.9 ng/ml, P=0.07) whereas this gender difference was not observed in the DMN group (18.6 +/- 17.0 ng/ml versus 16.8 +/- 17.0 ng/ml, P=0.754). On multivariate analysis, ACR (=0.411, P<0.001) and BMI (=0.240, P=0.002) were independently associated with serum leptin concentrations (R2=0.194, F=22.1, P<0.001) in the whole group. In the DMN group, ACR (=0.370, P=0.016) was the only independent determinant of serum leptin concentrations (R2=0.159, F=11.4, P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Leptin/blood , Sex Characteristics , Adult , Albuminuria/etiology , Analysis of Variance , Body Mass Index , Case-Control Studies , Creatinine/urine , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/urine , Female , Humans , Male , Middle Aged , Osmolar ConcentrationABSTRACT
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.
Subject(s)
Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Obesity/complications , Adolescent , Adult , Aged , Albuminuria/complications , Albuminuria/genetics , Anthropometry , Asian People , Blood Glucose , Blood Pressure , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Female , Hong Kong/epidemiology , Humans , Hyperlipidemias/complications , Hyperlipidemias/genetics , Hypertension/complications , Hypertension/genetics , Male , Middle Aged , Obesity/genetics , Prevalence , Risk Factors , Sex DistributionABSTRACT
An interesting phenomenon was observed that the existence of the intact cell membrane can enhance the D-amino acids production from D,L-5-substituted hydantoins by reacting with the whole cells of Agrobacterium radiobacter. Two intracellular enzymes were involved in the reaction process. The first enzyme D-hydantoinase converted hydantoins to carbamoyl derivatives which were further converted to D-amino acids by D-amidohydrolase. The amount of D-amino acids produced from hydantoins by the intact cells were 1.8-2.4 fold higher than the toluene treated cells. In addition, by using the intact cells the amount of D-amino acids produced from hydantoins was about 10 fold higher than that produced directly from carbamoyl derivatives. The relatively lower permeability of cell membrane to the reaction intermediate carbamoyl derivatives was confirmed by a simple mathematical model to be the main factor for the better performance of the intact cells for D-amino acid production. Besides, the low intracellular enzymes activities also contributed to the effect of intact cell membrane on enhancing the D-amino acid production.
Subject(s)
Asian People/genetics , Carrier Proteins/genetics , Glycoproteins , Introns/genetics , Mutation , RNA Splicing/genetics , Carrier Proteins/blood , Cholesterol Ester Transfer Proteins , Cholesterol, HDL/blood , Cholesterol, HDL/genetics , Female , Heterozygote , Homozygote , Hong Kong/epidemiology , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
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.
Subject(s)
Epinephrine/urine , Insulin/blood , Norepinephrine/urine , Obesity/blood , Obesity/urine , Adult , Age Factors , Albuminuria/blood , Albuminuria/metabolism , Albuminuria/urine , Anthropometry , Asian People , Catecholamines/blood , Catecholamines/metabolism , Catecholamines/urine , Cohort Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/urine , Female , Hong Kong , Humans , Hyperlipidemias/blood , Hyperlipidemias/metabolism , Hyperlipidemias/urine , Hypertension/blood , Hypertension/metabolism , Hypertension/urine , Lipid Metabolism , Male , Models, Biological , Obesity/metabolism , Sex Factors , Statistics as Topic , SyndromeABSTRACT
BACKGROUND: Albuminuria predicts nephropathy-related mortality in Caucasian and Chinese populations. The involvement of renin-angiotensin system (RAS) gene polymorphisms in the pathogenesis of nephropathy has been described predominantly in Caucasian populations. We have previously suggested that the angiotensinogen 235T variant may be associated with nephropathy in diabetic Chinese. PATIENTS AND METHODS: To validate these findings and extend them to include non-diabetic nephropathy, we examined the association of albuminuria and gene polymorphisms of the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type I receptor A1166C polymorphisms in 614 Chinese subjects (66% type 2 diabetic, 16% normoglycemic hypertensives and 18% controls). RESULTS: Obesity and higher blood pressure were associated with albuminuria in both diabetes and normoglycemic hypertension. In the diabetic group, albuminuria was also associated with increased insulin resistance and glycemic indices, duration of diabetes and adverse lipid profiles. Only the ACE gene polymorphism showed evidence of association with albuminuria, with the D allele being less frequent in the normoglycemic hypertensive patients with albuminuria (25.0%) than the controls (41.4%) or normoalbuminuric group (39.6%) and in those hypertensives at increased risk (albumin-to-creatinine ratio > 5.6 mg/mmol) of end-stage renal disease than those at lower risk (all p < 0.05), but not in the diabetic group. The D allele was also less prevalent in the total (31.9%) and normoalbuminuric (32.2%) diabetic groups than in the controls (p < 0.05). CONCLUSION: In this cohort of Chinese subjects, the ACE gene polymorphism D allele was less frequent in normoglycemic hypertensive patients with albuminuria and in type 2 diabetes.
Subject(s)
Albuminuria , Blood Glucose/analysis , Diabetes Mellitus, Type 2/genetics , Hypertension/genetics , Polymorphism, Genetic , Renin-Angiotensin System/genetics , Adult , Albuminuria/genetics , Angiotensinogen/genetics , China , Diabetes Mellitus, Type 2/urine , Female , Gene Frequency , Humans , Hypertension/blood , Hypertension/urine , Male , Middle Aged , Peptidyl-Dipeptidase A/genetics , Receptors, Angiotensin/geneticsABSTRACT
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.
Subject(s)
Adipose Tissue/anatomy & histology , Hypertension/complications , Insulin Resistance/physiology , Metabolic Syndrome/physiology , Obesity/complications , Abdomen , Adolescent , Adult , Aged , Body Constitution , China , Factor Analysis, Statistical , Female , Glucose Intolerance , Humans , Male , Middle Aged , Triglycerides/bloodABSTRACT
1. To assess the role of renal dopamine (DA), sympathetic nervous system (SNS) activity and the renal kallikrein-kinin system in sodium excretion in Chinese subjects, we studied the effects of intravenous saline infusion on the urinary excretions of sodium, free DA, free noradrenaline (NA) and kallikrein in eight healthy males aged 23-25 years. 2. After a baseline period of 1 h (hour 0), these subjects received 11 of 0.9% saline over 2 h (hours 1 and 2), followed by a 4-h recovery period (hours 3-6). From hours 0-4, subjects remained in the supine position, except to void urine. Distilled water was given orally throughout the study to ensure an adequate diuresis. 3. A 31-39% increase in sodium excretion (P < 0.05) was seen during hours 2 and 3. Urinary DA did not change throughout the study period. Urinary free NA showed no changes while the subjects remained supine, but an increase of 91-105% (P < 0.02) was seen after the subjects became ambulatory. However, there was a 103-140% increase in urinary kallikrein excretion (P < 0.05) during the saline infusion. Urinary kallikrein was still much higher (by 74%) than the basal level 1 h after the completion of the saline infusion. 4. There is no evidence from the present study that renal DA or SNS play any role in the natriuretic response to saline infusion in Chinese subjects. The brisk urinary kallikrein response, despite a relatively small salt load, suggests that the renal kallikrein-kinin system may play an important role in extracellular fluid volume and sodium homeostasis in Chinese subjects.
Subject(s)
Dopamine/physiology , Kallikrein-Kinin System/physiology , Kidney/physiology , Natriuresis/physiology , Adult , Blood Pressure/drug effects , Heart Rate/drug effects , Humans , Infusions, Intravenous , Kallikrein-Kinin System/drug effects , Kidney/drug effects , Male , Natriuresis/drug effects , Sodium Chloride/administration & dosage , Sodium Chloride/pharmacology , Sympathetic Nervous System/drug effects , Water-Electrolyte Balance/drug effectsABSTRACT
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.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Hyperlipidemias/genetics , Hypertension/genetics , Obesity/genetics , Tumor Necrosis Factor-alpha/genetics , Diabetes Mellitus, Type 2/blood , Female , Genotype , Humans , Hyperlipidemias/blood , Hypertension/blood , Insulin Resistance/genetics , Male , Middle Aged , Obesity/blood , Polymorphism, Genetic , SyndromeABSTRACT
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.
Subject(s)
Asian People/genetics , Blood Pressure , Diabetes Mellitus, Type 2/genetics , Hypertension/genetics , Obesity/genetics , Polymorphism, Genetic/physiology , Receptor, Insulin/genetics , Adult , Alleles , China , Cohort Studies , Diabetes Mellitus, Type 2/physiopathology , Diastole , Female , Gene Frequency , Genotype , Humans , Hypertension/physiopathology , Male , Middle Aged , Obesity/physiopathology , Polymorphism, Restriction Fragment Length , Regression Analysis , SyndromeABSTRACT
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.
Subject(s)
Cardiovascular Diseases/epidemiology , Obesity/epidemiology , Adult , Body Mass Index , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Female , Hong Kong/epidemiology , Humans , Hyperlipidemias/epidemiology , Hypertension/epidemiology , Insulin/blood , Insulin Resistance , Male , Regression Analysis , Risk FactorsABSTRACT
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.
Subject(s)
Asian People , Blood Pressure , Insulin Resistance/physiology , Obesity/ethnology , Obesity/physiopathology , Adult , Blood Glucose/analysis , Body Mass Index , Female , Hong Kong , Humans , Hyperlipidemias/complications , Hypertension/blood , Hypertension/ethnology , Hypertension/etiology , Male , Middle Aged , Obesity/pathology , Reference ValuesABSTRACT
AIMS: To examine the prevalence of identified MODY-related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes. METHODS: Ninety-two unrelated Chinese subjects with diabetes diagnosed before the age of 40 years who had a positive family history of diabetes were screened for mutations in hepatocyte nuclear factors (HNF-1alpha and HNF-4alpha) and glucokinase genes by direct sequencing. The family members of patients with mutations and 100 healthy controls were also examined. RESULTS: Mutations in the HNF-1alpha and the glucokinase genes were found in 5% and 3% of the diabetic subjects, respectively but no mutations were found in the coding region of the HNF-4alpha gene. Three mutations found in the glucokinase gene were novel missense mutations (I110T, A119D and G385V). The mutations in the HNF-1alpha gene were also new and included four missense mutations (G20R, R203H, S432C, I618M) and one splice acceptor site mutation (IVS2nt-1G-->A). Patients with mutations in these genes were clinically heterogeneous with respect to phenotype and basal pancreatic beta cell function. CONCLUSIONS: Genetic factors such as mutations in the HNF-1alpha and glucokinase genes may be important in the development of diabetes in Chinese people, especially when the disease is of early onset.
Subject(s)
Asian People/genetics , DNA-Binding Proteins , Diabetes Mellitus, Type 2/genetics , Glucokinase/genetics , Mutation, Missense , Nuclear Proteins , Point Mutation , Transcription Factors/genetics , Adolescent , Adult , Age of Onset , Amino Acid Substitution , Child , China , Exons , Family , Female , Hepatocyte Nuclear Factor 1 , Hepatocyte Nuclear Factor 1-alpha , Hepatocyte Nuclear Factor 1-beta , Humans , Introns , Male , Middle AgedABSTRACT
OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.
Subject(s)
Asian People/genetics , Central Nervous System/physiopathology , Diabetes Mellitus, Type 2/blood , Human Growth Hormone/blood , Hydrocortisone/blood , Insulin/blood , Obesity/blood , Adolescent , Adult , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Female , Hong Kong/epidemiology , Humans , Male , PrevalenceABSTRACT
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.
Subject(s)
Boric Acids , Catecholamines/urine , Indicators and Reagents , Kallikreins/urine , Albuminuria/urine , Creatinine/urine , Humans , Hydrocortisone/urine , Hydrogen-Ion Concentration , Potassium/urine , Proteinuria/urine , Sodium/urineABSTRACT
OBJECTIVE: The interrelations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance are well recognized. These relationships are of particular interest in Hong Kong's 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.