Nature or nurture: an insightful illustration from a Chinese family with hepatocyte nuclear factor-1 alpha diabetes (MODY3)
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Adolescent↗
Biomedical subjects
J C Chan
Publications and source records attributed to J C Chan.
Effects and pharmacokinetics of oral glibenclamide and glipizide in Caucasian and Chinese patients with type-2 diabetes.
The effects and kinetics of oral glibenclamide (Gb) and glipizide (Gz) were studied in Caucasian and Chinese patients (ten in each group) with type-2 diabetes. In randomised order, 2.5 mg Gb, 2.5 mg Gz or placebo was given orally before the administration of 75 g oral glucose. Concentrations of insulin and proinsulin were determined using radioimmunoassay (RIA) without cross-reactivities, and sulphonylurea concentrations were determined using high-performance liquid chromatography (HPLC). There were no significant interethnic differences in Gb or Gz effects whether on glucose, insulin or proinsulin/insulin ratio at any time point. Following Gz, however, Chinese patients had greater increments of serum proinsulin at 10-30 min compared with Caucasians. Apart from the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of Gz being higher among the Chinese, no significant interethnic differences in pharmacokinetics were found. It appears that the same dosage principles could be used for Caucasian and Chinese patients with type-2 diabetes when Gb or Gz are prescribed.
Adult↗
Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes.
OBJECTIVE: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. BACKGROUND: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. MATERIAL AND METHODS: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. RESULTS: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l x min vs 2.6 mmol/l x min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l x min vs 54 pmol/l x min) and 30 min (2286 pmol/l x min vs 1198 pmol/l x min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (-1 min), proinsulin/insulin ratios (RPI) were lowest at 10-30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l x min vs 550 pmol/l x min) and a lower RPI at 30 min (6. 0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. CONCLUSION: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.
Adult↗
Phospholipase A(2) activity, heat shock protein, and superoxide dismutase in rat remnant kidney.
Male Sprague-Dawley rats (150-200 g) were randomly assigned to sham operation (n=6) or 5/6 nephrectomy (n=12) procedures. Two weeks after the completion of the 5/6 nephrectomy, these animals were again randomly assigned to two groups: non-treatment or treatment with vitamin E supplementation at 200 IU/kg chow. Two weeks later, all animals were sacrificed and the kidneys harvested. The secretory phospholipase A(2) (PLA(2)) activity was elevated (150%) in the untreated remnant kidney but returned to sham values in the vitamin E-treated kidneys. The cytoprotective heat shock protein (HSP70) and the intracellular antioxidant superoxide dismutase (MnSOD, Cu/ZnSOD) were similar in sham, remnant, and vitamin E-treated remnant kidneys. We conclude that the sudden reduction of renal mass secondary to the 5/6 nephrectomy procedure stimulates PLA(2) activity but not HSP70, MnSOD, or Cu/ZnSOD. This increased activity of PLA(2) in the remnant kidney returned to sham values after vitamin E treatment. The intrinsic cellular antioxidant enzymes, MnSOD, Cu/ZnSOD, as well as the cytoprotective heat shock protein HSP70, showed no significant changes in either vitamin E-treated or untreated kidneys compared with sham. These data are suggestive that the elevation of PLA(2) is a specific and localized response to the sudden reduction of renal mass.
Animals↗
Gene expression after intrarenal injection of plasmid DNA in the rat.
Effective gene therapy requires efficient delivery and expression of the necessary genetic information to the target tissue. We demonstrate here that plasmid DNA, injected as naked, uncomplexed DNA into the cortical region of rat kidney, or intravenously, is localized and expressed in the kidney. The plasmid pRSVZ contained the Rous sarcoma virus promoter and a reporter gene, the beta-galactosidase gene, derived from bacteria. The beta-galactosidase gene hydrolyzes the artificial substrate X-gal to produce an intense blue color in cells that have taken up and expressed the plasmid genes. We have used X-gal staining and Western blotting to study plasmid gene expression 1, 4, and 8 days and 6 months after intrarenal injection of 50 microg of plasmid DNA and at 1 and 4 days after intravenous injection. Expression was apparent in the kidneys and several other tissues 24 h after injection and persisted for at least 8 days; expressed proteins could still be detected in the injected kidney 6 months later. These observations were corroborated by use of a plasmid, pEGFP-Puro, harboring the cytomegalovirus promoter in conjunction with a different reporter gene, the green fluorescent protein (GFP). Histological localization and Western blotting analysis of GFP expression after intrarenal injection of pEGFP-Puro paralleled results obtained with the plasmid pRSVZ. Our findings support the suggestion that intrarenal or intravenous injection of naked plasmid DNA may be an effective means of delivering therapeutic genes to the kidney and several other tissues.
Animals↗
Cardiovascular disease in chinese type 2 diabetic women is associated with a prolonged QTc interval.
We studied the relationships between QT interval and cardiovascular disease status in 192 Chinese type 2 diabetic patients. Of these 192 subjects, 132 (68.8%) were women and 60 (31.2%) were men. The mean age (+/-S.D.) was 56.6+/-12.9 years (range: 23-84, median: 58.0 years). Women had longer QTc interval compared to men (0.402+/-0.030 s vs. 0.387+/-0.026 s, P<0.01). Of the 192 subjects, 18 women and two men had prolonged QTc interval (QTc >0.433 s). Women with prolonged QTc interval have a 2.8-fold greater rate of cardiovascular disease as compared to those with normal QTc interval (38.9% vs. 14.0%, P<0.05). Using multiple regression analysis (stepwise) to assess the relationship with QTc interval with age, sex, body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, glycated haemoglobin, lipid profiles, smoking and duration of diabetes as independent variables (R(2)=0.146, F=8.88, P<0.001), systolic blood pressure (beta=0.198, P=0.017), age (beta=0. 189, P=0.023) and female gender (beta=0.157, P=0.037) were found to be independently associated with QTc interval. In conclusion, we have shown a significant association between prolonged QTc interval, ischaemic heart disease and cardiovascular disease in Chinese type 2 diabetic women. Age, systolic blood pressure and female gender are independently correlated to QTc interval.
Adult↗
Sporadic bilateral adrenal medullary hyperplasia: apparent false positive MIBG scan and expected MRI findings.
Adrenal medullary hyperplasia is a rare cause of clinical symptoms and biochemical findings identical to pheochromocytoma occurring mostly in multiple endocrine neoplasia patients. The scenario of positive MIBG scan, but no focal lesion found on CT and MRI led to diagnostic and management difficulties. Like pheochromocytoma, surgical excision can lead to clinical and biochemical recovery. We report this unusual case of sporadic bilateral adrenal medullary hyperplasia, with hypertension and biochemical abnormalities alleviated after surgical adrenalectomy. Based on T2 values reported in literature, high signal focal lesions may not appear on T2-weighted MRI images until development of frank pheochromocytoma. MIBG scan remains the most sensitive imaging modality for this condition.
3-Iodobenzylguanidine↗
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.
Adult↗
The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome.
BACKGROUND: In regions such as Hong Kong, rapid economic development has led to lifestyle alterations characterized by increases in energy and fat intake and reduction in physical activity. These changes have been associated with a dramatic increase in the prevalence of diabetes and related diseases of the metabolic syndrome. OBJECTIVE: To investigate if a common polymorphism (Trp64Arg) of the beta3-adrenergic receptor gene, previously implicated as predisposing to type 2 diabetes mellitus or obesity in other populations, has a role in the apparent susceptibility of Hong Kong Chinese to diabetes and related disorders. METHOD: A PCR-based protocol was used to genotype 802 Southern Chinese subjects who were either healthy or had one or more of the metabolic disorders including diabetes, hypertension or dyslipidaemia. RESULTS: The frequencies of the mutant A allele (12.7%) and AA genotype (1.7%) did not differ, by the chi2 test, in any patient group with diabetes, hypertension or dyslipidaemia, alone or in combination, compared to healthy controls. Using the t-test in the 802 subjects, those carrying the mutant A allele had evidence of increased obesity with a significantly (all P<0.05) higher body mass index (BMI, kg/m2) and also lower HDL-cholesterol. BMI was also elevated in subjects with the A allele in the separate groups with diabetes, dyslipidaemia or hypertension. Stepwise multiple regression showed this polymorphism to be an independent predictor of BMI. CONCLUSION: These data do not support any direct involvement of the Trp64Arg polymorphism in the development of diabetes, hypertension or dyslipidaemia in Chinese subjects, but do suggest a relationship with obesity.
Adult↗
Mitochondrial DNA A3243G mutation in patients with early- or late-onset type 2 diabetes mellitus in Hong Kong Chinese.
BACKGROUND AND OBJECTIVES: The mitochondrial DNA A to G mutation at nucleotide 3243 (mt3243) is associated with a subtype of diabetes characterized by maternal transmission and deafness. We have previously reported a 2.7% prevalence of this mutation in a cohort of young patients with either type 1 or type 2 diabetes. In this study, we aimed to confirm this finding by examining for the prevalence of this mutation in a large-scale study. SUBJECTS AND METHODS: Nine hundred and six unrelated Chinese patients with type 2 diabetes and 213 nondiabetic controls were studied. The presence of mt3243 mutation was determined by polymerase chain reaction amplification and ApaI digestion. RESULTS: This mutation was found in four of 133 (3.0%) patients with early onset (</= 40 years) diabetes who also had a positive maternal family history, and in one of 348 (0.3%) patients with late-onset (> 40 years) diabetes and no family history. Basal pancreatic beta-cell function, as assessed by fasting plasma C-peptide, was variable amongst mutation carriers, and did not correlate with the level of heteroplasmy of mutation. CONCLUSIONS: In agreement with most studies, our results suggest that despite the high prevalence of positive maternal family history of diabetes amongst our type 2 diabetic patients, mt3243 mutation was not a major cause of diabetes in either early- or late-onset diabetic patients in Hong Kong. The role of other genetic, environmental and intrauterine factors needs further investigation.
Adult↗
Late forming supernumerary tooth in the premaxilla: a case report.
A case of late forming supernumerary tooth in the premaxilla is presented in this report. The patient has been followed-up radiographically from the age of 9 years but the supernumerary tooth could only be detected radiographically when the patient was 11 years old. This emphasises the importance of thorough clinical and radiographic examination of the developing dentition in children.
Child↗
Renal kallikrein-kinin system, but not renal dopamine system, mediates the natriuretic response to intravenous saline infusion in healthy Chinese subjects.
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.
Adult↗
Young Chinese adults with new onset of diabetic ketoacidosis--clinical course, autoimmune status and progression of pancreatic beta-cell function.
AIMS: To examine the clinical course, autoimmune status and pancreatic beta cell function, over a 2-year period, in young Chinese subjects newly presenting with diabetic ketoacidosis (DKA). METHODS: A prospective study involving 562 out of 27,893 patients who were admitted to the medical ward with a principal diagnosis of diabetes mellitus during the recruitment period of 1 year. RESULTS: Of these 562 patients, 27 were aged less than 35 years and admitted with a diagnosis of DKA and 11 (six males and five females) of these were newly diagnosed. Antibodies to glutamic acid decarboxylase (GAD) were present in five patients. Anti-ICA 512 was not detected in any of the patients. Basal and post-glucagon stimulated plasma C-peptide remained in the insulin-deficient range although showing improvement at 2 years. CONCLUSIONS: These findings confirm the relative rarity of autoimmune Type 1 diabetes in young Chinese. Even when the clinical presentation takes the extreme form of acute DKA, less than 50% have positive autoimmune markers.
Adult↗
Impact of uremia on female reproductive cyclicity, ovulation, and luteinizing hormone in the rat.
BACKGROUND: Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multiple ova during the normal estrous cycle. METHODS: Renal insufficiency (uremia) was induced by 5/6 nephrectomy. Two control groups comprised sham-operated animals fed ad libitum (sham) or pair-wise with the uremic animals (pair-fed). Estrous cycles were determined by cytology of vaginal lavage. We examined concomitant changes in the preovulatory luteinizing hormone (LH) surge by radioimmunoassay (RIA), immunoradiometric assay (IRMA), and bioassay. Repetitive LH measurements were made from blood samples taken by intra-atrial catheter throughout the afternoon and evening of proestrus. The following morning (estrus), ovaries were collected, and ova were enumerated per oviduct. RESULTS: Experimentally uremic animals manifested a threefold elevation of plasma creatinine and urea nitrogen and concomitantly a more than 50% impoverishment of ova production. Analyses of a large group of animals (N = 83) by RIA revealed uremia-associated attenuation of the preovulatory LH surge. Further measurements of the preovulatory LH surge by independent IRMA and LH bioassay (N = 26) corroborated this attenuation. Additional experiments indicated that these hormonal changes, but not changes in ovulation, might further reflect modulation of LH release by the anesthesia used in the preparative nephrectomy and catheterization surgeries. When normalized to body weight, the ovaries of uremic rats were found to weigh more than those of either the sham or pair-fed animals. CONCLUSIONS: The present experiments take advantage of an experimental uremic model to document a consistent decrease in the number of ova released during estrus in the uremic animal. Possible disruption of hypothalamic-pituitary-ovarian regulation is further highlighted by attenuation in the preovulatory LH surge. These results provide a basis for further studies of neuroendocrine pathophysiology in a rodent model of uremia-associated ovulatory disruption.
Amenorrhea↗
Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.
UNLABELLED: 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.
Aged↗
Association of plasminogen activator inhibitor-1 4G/4G genotype and type 2 diabetic nephropathy in Chinese patients.
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolytic pathway and extracellular matrix (ECM) turnover. Because diabetic nephropathy is characterized by the presence of basement membrane thickening and mesangial expansion, we examined the role of PAI-1 gene polymorphisms in the development of type 2 diabetic nephropathy. Evidence also suggested that the PA/plasmin system and the renin-angiotensin system (RAS) interact together to affect the risk of fibrosis and thrombosis. Hence, we also studied the synergistic effect between PAI-1 and angiotensin-converting enzyme (ACE) gene polymorphisms. METHODS: The PAI-1 and ACE (D/I) gene polymorphisms were examined in a cohort of Chinese type 2 diabetic patients who had diabetes for an average of 14 years. These patients were sex and age matched. Group A (N = 46) consisted of patients without diabetic nephropathy (normoalbuminuric with creatinine <120 micromol/L), and group B (N = 95) was with diabetic nephropathy (with albuminuria or renal impairment, including patients on dialysis). RESULTS: Patients with type 2 diabetic nephropathy had a higher frequency of PAI-1 (4G/4G) genotypes than those without nephropathy [4G/4G:4G/5G:5G/5G = 41:38:21 (%) vs. 15:65:20(%), P = 0.005]. Diabetic patients with coexistence of PAI-1 4G/4G genotype and ACE D alleles had a higher incidence of diabetic nephropathy (22 vs. 7%, P = 0.012) than those with other combinations of genotypes. Multivariate logistic regression analysis showed that PAI-1 4G/4G (P = 0.01) and the prevalence of hypertension (P < 0.0001) are independent risk factors of development of type 2 diabetic nephropathy. CONCLUSIONS: These results suggest that the PAI-1 4G/4G genotype is associated with an increased risk for type 2 diabetic nephropathy in Chinese patients, which is an independent risk factor for the development of nephropathy. The PAI-1 4G/4G genotype also exhibits a synergistic effect with the ACE D allele on development of diabetic nephropathy.
Aged↗
Obesity, independent of insulin resistance, is a major determinant of blood pressure in normoglycemic Hong Kong Chinese.
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.
Adult↗
Tumor necrosis factor alpha gene G-308A polymorphism in the metabolic syndrome.
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.
Diabetes Mellitus, Type 2↗