Biomedical subjects

K S Lam

Publications and source records attributed to K S Lam.

At least 55 records · Page 3Linked to original sources

PubMed2000

Acute leukaemia in acromegaly patients.

Acromegaly patients are known to have an increased risk of malignancies, especially colonic adenocarcinoma. This may be as a result of the growth-stimulating effect of growth hormone (GH). The clustering of leukaemia in children treated with GH has also caused concern. There have been a few reports of leukaemia in acromegaly patients. We report two patients with acute lymphoblastic leukaemia and one patient with acute myeloid leukaemia among 106 acromegaly patients treated over a 15-year period. Two of the cases received radiotherapy as part of their treatment. Adjusted for age and follow-up years, the incidence of leukaemia in this cohort is significantly higher than the general population. The incidence is also higher than would be expected as a result of radiotherapy alone, suggesting that GH may play a synergistic role.

Acromegaly↗

PubMed2000

The prevalence of diabetes, association with cardiovascular risk factors and implications of diagnostic criteria (ADA 1997 and WHO 1998) in a 1996 community-based population study in Hong Kong Chinese. Hong Kong Cardiovascular Risk Factor Steering Committee. American Diabetes Association.

AIMS: While the American Diabetes Association (ADA) 1997 diagnostic criteria advocate the use of fasting plasma glucose only, the World Health Organization (WHO) criteria retain the use of the standard oral glucose tolerance test (OGTT). The present study evaluated the relative merit of the respective diagnostic criteria in Chinese. METHODS: Data collected for the Hong Kong Cardiovascular Risk Factor Prevalence Study was analysed. This was a representative population-based study, conducted from 1995 to 1996 among 2,900 Chinese subjects aged 25-74 years using a 75-g OGTT. RESULTS: The prevalence of diabetes (known plus unknown) was 6.2% (95% confidence interval 5.3-7.1%), 9.2% (8.1-10.3%), and 9.8% (8.7-10.9%) based on ADA 1997, WHO 1985 and WHO 1998 criteria, respectively, with a very high prevalence in older subjects. The 2,451 subjects classified as normal under ADA 1997 criteria were heterogenous: 15.3% had impaired glucose tolerance; 2.1% had diabetes under WHO 1998 criteria. These latter two smaller groups had cardiovascular risk profiles comparable to that found among the impaired fasting glucose subjects (under ADA), but worse than that among the concordant normal glucose tolerance subjects. CONCLUSIONS: The ADA criteria underestimate both diabetes prevalence and cardiovascular risk in this population. Hence fasting glucose alone is an inadequate approach and OGTT should be retained to identify at-risk individuals in both clinical diagnosis and epidemiological studies.

Adult↗

PubMed2000

Fibrinogen, other cardiovascular risk factors and diabetes mellitus in Hong Kong: a community with high prevalence of Type 2 diabetes mellitus and impaired glucose tolerance.

AIMS: To determine the prevalence of Type 2 diabetes mellitus and impaired glucose tolerance (IGT) and their relationships to fibrinogen and other cardiovascular risk factors in Hong Kong Chinese. METHODS: A probability sample of 1,316 men and 1,348 women aged 25-74 years were examined in a population-based cross-sectional study. RESULTS: A total of 3.0% (95% confidence interval 2.1-3.9) of men had previously diagnosed (known) and 6.4% (5.0-7.8) newly diagnosed (unknown) diabetes, 14.4% (12.4-16.5) had IGT and 79.2% were normal by 1985 WHO diagnostic criteria; corresponding prevalences in women were 3.7% (2.7-4.7), 5.9% (4.6-7.2), 17% (14.8-19.2) and 73.4%. The age-standardized prevalence of Type 2 diabetes for the 35-64 age group was 9.5% (7.5-11.6) in men and 10.2% (8.0-12.4) in women. Age-adjusted mean fibrinogen levels in these four groups (normal/IGT/unknown diabetes/known diabetes) with decreasing degrees of glucose tolerance (diabetes status) were 2.80, 2.57, 2.51 and 2.47 g/l (P = 0.003) in men, and 2.86, 2.72, 2.67, 2.61 g/l (P = 0.005) in women. Age, obesity, systolic blood pressure and triglycerides were significantly associated with diabetes status in both sexes, fibrinogen in men only and high density lipoprotein cholesterol negatively in women. CONCLUSIONS: The prevalence of Type 2 diabetes mellitus was very high especially in older subjects, and fibrinogen was associated with increasing glucose intolerance in men but not in women. The detection and better control of cardiovascular risk factors, particularly hypertension in this developed Chinese community with a high prevalence of diabetes and glucose intolerance, is particularly important.

Adult↗

PubMed2000

Sand pits and bucket handles: A case of bilateral traumatic bucket-handle tears of the medial menisci.

Bucket-handle tears of the medial menisci are a common injury in young adult athletes. The incidence of acute bilateral tears occurring simultaneously is anecdotally very small and its occurrence has not been reported. We present the case of an 18-year-old man who sustained bilateral bucket-handle tears of the medial menisci while long jumping. We propose that the mechanism of injury may be analogous to that in footballers. This case report raises awareness of the occurrence of bilateral bucket-handle tears.

Adolescent↗

PubMed2000

Value of intra-arterial calcium stimulated venous sampling for regionalization of pancreatic insulinomas.

BACKGROUND: Intra-arterial calcium stimulation with hepatic venous sampling (ASVS) for insulin gradients has been reported to be the most sensitive preoperative localizing technique for insulinomas. We reviewed our experience with ASVS to localize and guide the treatment of insulinomas over the past decade. METHODS: Eighteen patients who underwent ASVS before surgical exploration for insulinoma were studied. The accuracy of ASVS was compared with intraoperative findings and other localizing studies. RESULTS: There were no complications arising from the procedures. A more than 2-fold step-up in insulin level 30 to 60 seconds after injection to at least 1 feeding artery was observed in 16 patients. Fourteen of the 16 solitary tumors (87.5%) were correctly located; 100% (6/6 tumors) at the head and 80% (8/10 tumors) at the body/tail. The overall accuracy of this test was 89%, compared with 11%, 33%, 38%, and 63% of ultrasonography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, respectively. Six enucleations and 10 distal resections were performed, which included 2 laparoscopic procedures. The combination of intraoperative ultrasonography with preoperative ASVS identified all tumors. CONCLUSIONS: ASVS is the most accurate preoperative localization tool for the localization of insulinomas and, in combination with intraoperative ultrasonography, can enhance surgical success.

Adult↗

PubMed2000

Serum leptin and vascular risk factors in obstructive sleep apnea.

STUDY OBJECTIVES: To define the metabolic profile relevant to vascular risks in obstructive sleep apnea (OSA) and the role of leptin resistance in this risk profile. DESIGN: Case control study. SETTING: Sleep Laboratory, Queen Mary Hospital, University of Hong Kong, China. METHODS: Thirty OSA subjects were matched with 30 non-OSA subjects for body mass index (BMI), age, sex, and menopausal status. Neck, waist, and hip girth, skinfold thickness, and fasting serum levels of lipids, glucose, insulin, and leptin were compared between these two groups. RESULTS: Compared with control subjects with a similar BMI but without OSA, the OSA group had a significantly more adverse vascular risk factor profile, including dyslipidemia, higher diastolic BP, insulin resistance, and greater adiposity reflected by skinfold thickness. OSA subjects also had higher circulating leptin levels (9.18+/-4.24 ng/mL vs 6.54+/-3.81 ng/mL, mean +/- SD, p = 0.001). Serum leptin levels correlated positively with BMI, skinfold thickness, serum cholesterol, low-density lipoprotein cholesterol, insulin, insulin/glucose ratio, apnea-hypopnea index, and oxygen desaturation time; multiple stepwise regression analysis identified skinfold thickness, waist/hip ratio, serum low-density lipoprotein cholesterol, and diastolic BP as independent correlates, while only serum insulin and diastolic BP were independent correlates in OSA subjects. After treatment with nasal continuous positive airway pressure for 6 months, there was a significant decrease in circulating leptin (p = 0.01) and triglyceride levels (p = 0.02) without change in other parameters. CONCLUSION: Despite controlling for BMI, OSA subjects showed distinct profiles with clustering of vascular risk factors. Hyperleptinemia was present in the OSA subjects, but it can be normalized by treatment with nasal continuous positive airway pressure, suggesting that increased leptin resistance was not the cause of OSA or its associated vascular risks.

Adult↗

PubMed2000

Metabolic and immunologic features of Chinese patients with atypical diabetes mellitus.

OBJECTIVE: To determine whether atypical diabetes mellitus (ADM) is present in the Chinese population in Hong Kong. RESEARCH DESIGN AND METHODS: The records of Chinese patients who attended the Diabetes Clinic at Queen Mary Hospital were reviewed. We identified 11 patients who initially presented with acute diabetic ketoacidosis but subsequently displayed clinical features more typical of type 2 diabetes. Metabolic studies and HLA typing were performed to characterize this group of Chinese patients with ADM. RESULTS: C-peptide response of the patients with ADM 1 h after a standard meal was intermediate between that of type 1 diabetic patients (matched for age and duration of diabetes) and that of nondiabetic control subjects (matched for age and BMI) (analysis of variance, P = 0.02). Insulin sensitivity measured by a short insulin tolerance test was not significantly different between patients with ADM and their matched nondiabetic control subjects. HLA typing showed that none of the patients with ADM had the DR3 allele and that the frequency of DR9 was not increased. Only one patient had significantly increased levels of antibodies to GAD and islet cell antigen 512. CONCLUSIONS: ADM, which was first described in African-Americans, is seen also in Chinese subjects. These patients have significant residual C-peptide secretory capacity and should not be misdiagnosed and treated as patients with type 1 diabetes with life-long insulin therapy.

Adolescent↗

PubMed2000

Diabetic complications and their implications on health care in Asia.

Diabetes mellitus is a growing health problem in the Asia-Pacific region. The acute and chronic complications of diabetes mellitus are major causes of hospital admissions, blindness, renal failure, amputations, stroke, and coronary heart disease in this region. Compared with the general population, the annual per capita health care expenditure is estimated to be four-fold for people with diabetes. Recent prospective studies have provided unequivocal evidence for the crucial role of prolonged hyperglycaemia in the development of chronic diabetic complications. Although the aetiology of hyperglycaemia-induced damage of the kidneys, eyes, nerves, and arteries still remain to be elucidated, observational and interventional studies show that the occurrence and progression of these complications can be prevented by the optimal control of blood glucose, hypertension, and dyslipidaemia. Lifestyle changes such as weight control, increased physical exercise, and smoking cessation are also potentially beneficial in preventing diabetes mellitus and coronary artery disease. Furthermore, the morbidity and mortality caused by diabetes mellitus can be reduced by secondary prevention through regular screening, early detection, and appropriate treatment of chronic complications. Improved diabetes education is needed among health professionals as well as the general and diabetic populations. Government and public health officials should be mindful of the economic impact of this major health problem so that adequate health care resources can be allocated for the primary and secondary prevention of diabetic complications.

Diabetes Complications↗

PubMed1999

Effects of fluvastatin on prothrombotic and fibrinolytic factors in type 2 diabetes mellitus.

The effects of fluvastatin therapy on parameters of coagulation and fibrinolysis were evaluated in patients with diabetic dyslipidemia in a randomized, placebo-controlled study. Fluvastatin therapy was associated with a small reduction in factor VII coagulant activity, von Willebrand factor, and in plasminogen activator inhibitor 1 and tissue plasminogen activator antigens, but the effects of fluvastatin on hemostatic factors were much less marked than its effects on plasma lipids.

Analysis of Variance↗

PubMed1999

The importance of an intact abdominal musculature mechanism in maintaining spinal sagittal balance. Case illustration in prune-belly syndrome.

STUDY DESIGN: A rare case of thoracic hypokyphotic deformity secondary to prune-belly syndrome is presented. OBJECTIVES: To discuss the role of an intact abdominal musculature mechanism in maintaining spinal sagittal balance, and to present a case illustration of prune-belly syndrome. SUMMARY OF BACKGROUND DATA: There has been an ongoing debate concerning the integrity of the abdominal musculature unit in maintaining spinal support and stability. It is now believed that intra-abdominal pressure hitherto generated plays an important role in the stabilization of the spine. Congenital aplasia of the abdominal musculature, termed prune-belly syndrome, might therefore result in the loss of spinal function and stability. The literature also is reviewed for the incidence of spinal deformities related to this condition. METHODS: A unique case of prune-belly syndrome in a 33-year-old man with congenital aplasia of the abdominal musculature is presented. RESULTS: The patient exhibited loss of the spinal sagittal balance, with resultant development of a thoracic hypokyphotic deformity and thoracolumbar scoliosis. CONCLUSIONS: Scoliosis appears to be the most commonly reported spinal deformity. Unequal compressive forces on the vertebral endplates may be the proposed mechanism for the spinal deformities. Compensatory lumbar paraspinal overactivity resulting from the inability to generate normal intra-abdominal pressures because of a deficient abdominal wall musculature mechanism seems to be the plausible explanation for the observed thoracic hypokyphatic deformity.

Abdominal Muscles↗

PubMed1999

Beta-fibrinogen gene G/A-455 polymorphism in relation to fibrinogen concentrations and ischaemic heart disease in Chinese patients with type II diabetes.

AIMS/HYPOTHESIS: We investigated the relation between the G/A-455 (Hae III) beta-fibrinogen gene polymorphism and plasma fibrinogen concentration and its role in ischaemic heart disease in 264 Chinese patients with Type II (non-insulin-dependent) diabetes mellitus and 182 non-diabetic control subjects. METHODS: The G/A-455 polymorphism was determined in genomic DNA using polymerase chain reaction and Hae III restriction enzyme digestion. Fibrinogen was measured with the Claus method. RESULTS: Fibrinogen concentrations were higher in diabetic patients (3.3 +/- 0.5 vs 2.5 +/- 0.9 g/l in controls, p < 0. 0001) and in women (p < 0.03 vs men). Allele frequency of the variant A allele was 27 % in both diabetic patients and control subjects' similar to findings in Caucasians. In control subjects, the AA genotype was associated with higher fibrinogen concentrations (2.8 +/- 0.38 g/l vs 2.5 +/- 0.5 in GG or GA, p < 0.03), contributing to 4 % of the variance in plasma fibrinogen. The genotype effect was smaller and not significant among non-smokers, women and diabetic patients. Higher fibrinogen concentrations and AA genotype frequency were found in diabetic patients with ischaemic heart disease (p < 0.05 and p < 0.005, respectively vs unaffected patients). In a multiple logistic regression model, AA genotype, age and mean arterial pressure were associated with ischaemic heart disease, with odds ratios of 4.19 (p < 0.01), 1.05 (p < 0.0001) and 1.03 (p < 0.03), respectively. CONCLUSION/INTERPRETATION: The G/A-455 polymorphism is a genetic determinant of fibrinogen concentrations and ischaemic heart disease in this Chinese cohort. It also interacts with environmental influences associated with smoking, the female sex and Type II diabetes in determining plasma fibrinogen concentrations. [Diabetologia (1999) 42: 1250-1253]

Age Factors↗

PubMed1999

Thyroid hormones regulate the expression of somatostatin receptor subtypes in the rat pituitary.

Circulating TSH levels are increased in hypothyroidism and suppressed in hyperthyroidism. On the other hand, the hypothalamic hormone somatostatin suppresses basal and TRH-induced TSH release, an effect which is enhanced by thyroid hormones. To investigate whether the effects of thyroid hormones on TSH secretion may be mediated in part through alterations in the gene expression of pituitary somatostatin receptors (SSTR), 3-week-old male Sprague-Dawley rats were rendered hypothyroid with antithyroid drugs for 3 weeks. Total RNA extracted from anterior pituitaries were analysed for SSTR mRNA levels, using Northern blot hybridization. Compared to controls, hypothyroid rats had significantly lower pituitary mRNA levels of SSTR1 and SSTR2 (p < 0.0001 for both, n = 16); the reductions could be prevented by T4 supplementation (3 microgram/100 g body weight/day i.p.). In vitro studies using GH4C1 rat pituitary cells showed that the addition of T3 10(-8) M to cells cultured in charcoal-stripped bovine calf serum resulted in significant increases in mRNA levels of SSTR1 (p < 0.0001; n = 7) and the two transcripts of SSTR2 (p < 0.0005; n = 7). The increase for SSTR1 showed no further increase with higher doses of T3, but was time-dependent and could be seen consistently after 8 h of incubation. We conclude that thyroid hormones regulate the gene expression of SSTR subtypes in the pituitary, via a direct action on anterior pituitary cells. Changes in SSTR gene expression may contribute to the increase in circulating TSH levels in hypothyroidism.

Animals↗

PubMed1999

Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes.

Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceridemia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the susceptibility of LDL to oxidation in vitro, and endothelial function in type 2 diabetes mellitus. LDL subfractions were measured by density gradient ultracentrifugation. The susceptibility of LDL to oxidation was determined by measuring the kinetics of conjugated dienes formation during copper-mediated oxidation of LDL. Endothelium-dependent and independent vasodilation of the brachial artery were assessed by high resolution vascular ultrasound. Diabetic patients had a higher concentration of small dense LDL-III than matched controls (P < 0.01). The lag phase of conjugated dienes formation was shorter in the diabetic patients (P < 0.05), and the rate of LDL oxidation was faster (P < 0.05). Both endothelium-dependent (P < 0.01) and independent dilation of the brachial artery (P < 0.01) were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III concentration accounted for 12% and 6%, respectively, of the variation in endothelium-dependent vasodilation (adjusted r2 = 0.18; P < 0.05), whereas LDL-III concentration and the maximum amount of conjugated dienes formed accounted for 27% and 5%, respectively, of the variation in endothelium-independent vasodilation (adjusted r2 = 0.32; P < 0.01) in the diabetic patients. In conclusion, endothelial and smooth muscle cell dysfunction in type 2 diabetes were related to abnormalities in LDL subfractions and in LDL oxidation.

Adult↗

PubMed1999

Changes in gingival crevicular fluid levels of immunoglobulin A following therapy: association with attachment loss.

BACKGROUND: In previous studies, we demonstrated that increased levels of immunoglobulin A (IgA) in gingival crevicular fluid (GCF) may be "protective", while increased levels of the polymorphonuclear lysosomal enzyme, beta-glucuronidase, in GCF were associated with increased risk of disease activity. In this study, we examined the effect of scaling and root planing (SRP) on the levels of beta-glucuronidase, IgG, and IgA in GCF over a 24-week period and compared these to clinical attachment loss (CAL). METHODS: Twenty-nine patients with periodontal disease were examined for attachment level, probing depth, plaque, and bleeding on probing at 6 sites per tooth. GCF was collected from the mesial aspect of all teeth excluding third molars and analyzed for beta-glucuronidase, IgG, and IgA. After baseline data were collected, each patient received SRP, and GCF was collected again at 2, 4, 6, 8, 12, and 24 weeks post-SRP while clinical data were obtained at 4, 8, 12, and 24 weeks. In addition, we analyzed whether the magnitude of the IgA response to SRP would affect the rate of periodontal disease progression by examining GCF IgA levels at 2 time intervals: 2 to 4 weeks post-SRP and 6 to 12 weeks post-SRP. RESULTS: Seventeen patients (58.6%) exhibited at least 1 site losing > or =2.5 mm of CAL during the 24-week study. Beta-glucuronidase in GCF was significantly decreased at 2 weeks following SRP and then demonstrated a gradual increase throughout the study period. Levels of IgA in GCF significantly increased following SRP, reaching a peak at 6 weeks and then gradually decreasing throughout the study. Furthermore, we found an inverse relationship between GCF IgA levels at 6 to 12 weeks post-SRP and the occurrence of CAL. CONCLUSIONS: These results support the hypothesis that maintenance of high levels of IgA in GCF may be "protective" against periodontal attachment loss. Furthermore, levels of beta-glucuronidase appear to be a more sensitive indicator of gingival inflammation than clinical measures.

Adult↗

PubMed1998

Comparison of the intrinsic kinase activity and substrate specificity of c-Abl and Bcr-Abl.

We studied the intrinsic tyrosine kinase activity and substrate specificity of c-Abl and Bcr-Abl protein tyrosine kinases (PTKs) using the peptide substrates discovered from a synthetic combinatorial peptide library. Our data indicate that the phosphorylation of these peptides by Bcr-Abl was consistently stronger than that by c-Abl. Bcr-Abl also showed substrate preference towards those peptides with one or more positive charges.

Amino Acid Sequence↗

PubMed1998

Discovery of a novel series of potent and selective substrate-based inhibitors of p60c-src protein tyrosine kinase: conformational and topographical constraints in peptide design.

On the basis of the efficient substrate for p60c-src protein tyrosine kinase (PTK) YIYGSFK-NH2 (1) (Km = 55 microM) obtained by combinatorial methods, we have designed and synthesized a series of conformationally and topographically constrained substrate-based peptide inhibitors of this enzyme, which showed IC50 values in the low-micromolar range (1-3 microM). A "rotamer scan" was performed by introducing the four stereoisomers of beta-Me(2')Nal in the postulated interaction site of the peptide inhibitor 23(IC50 = 1.6 microM). This substitution led to selective and potent inhibitors of p60c-src PTK; however, no substantial difference in potency was observed among them. This and the results of the "stereochemical scan" performed at residues 2 and 7 of 3 (peptides 19-21), which form the disulfide bond, may suggest that the enzyme active site does not have rigid topographic requirements and thus is able to achieve important conformational changes to bind the ligand as long as the pharmacophore pattern in the inhibitor is conserved. Two new potent iodo-containing nonphosphorylatable tyrosine analogues were also incorporated into our lead inhibitory sequence 23, producing the most potent inhibitors for p60c-src PTK identified thus far in our studies. Compounds 29 and 30 exhibit IC50 values of 0.13 and 0.54 microM, respectively. Peptide 29 is 420-fold more potent than the parent peptide 1. Selectivity studies of peptides 23-30 toward p60c-src, Lyn, and Lck PTK showed in general high Lyn/Src and moderate Lck/Src selectivity ratios. We found that the chi1 space constraints of the specialized amino acids, introduced at position 3 of the peptide lead 23, were not as important as the configuration of the Calpha of that residue to recognize the subtle chemical environment surrounding the active site of Src and Lck PTK, as reflected on the obtained Lck/Src selectivity ratios.

Amino Acid Sequence↗

PubMed1998

Protein tyrosine kinases: structure, substrate specificity, and drug discovery.

Protein tyrosine kinases (PTKs) play a crucial role in many cell regulatory processes. It is therefore not surprising to see that functional perturbation of PTKs results in many diseases. Despite the diverse primary structure organization of various PTKs, the catalytic or kinase domains of various PTKs as well as that of Ser/Thr kinases are generally conserved. The high resolution crystal structure of a few PTKs has been solved in the last few years. In contrast to the well-defined linear peptide substrate motifs recognized by specific Ser/Thr kinases, the identification of specific substrate motifs for PTK has been slow. It is not until recently that through the use of combinatorial peptide library methods that specific recognition motifs for specific PTKs have begun to emerge. Efficient and specific peptide substrates for some PTKs with Km at the mid microM range have been identified. Based on these peptide substrates, relatively potent (IC50 at the low microM range) and highly selective pseudosubstrate-based peptide inhibitors have been developed. There has been enormous effort in the development of PTK inhibitors for diseases such as cancer, psoriasis, and osteoporosis. Several new high-throughput PTK assay technologies have recently been described. Small molecules against specific PTK have been developed. Most of them are competitive inhibitors at the ATP binding site. Some of these inhibitors have already been in clinical trial.

Amino Acid Sequence↗

PubMed1998

Genetic influence of the R/Q353 genotype on factor VII activity is overwhelmed by environmental factors in Chinese patients with Type II (non-insulin-dependent) diabetes mellitus.

We studied the effects of genetic and environmental influences on factor VII coagulant activity (VIIc) in Chinese diabetic patients (263 with Type II [non-insulin-dependent] diabetes mellitus, 78 with Type I [insulin-dependent] diabetes mellitus) and 143 normal control subjects. VIIc was measured by a one-stage biological assay. The R/Q353 or Msp1 polymorphism at codon 353 of the factor VII gene was detected after Msp1 digestion of polymerase chain reaction-amplified genomic DNA. In both diabetic and control subjects the allele frequencies of the R (M1) and Q (M2) alleles were 0.96 and 0.04; the corresponding reported frequencies in Caucasians being 0.90 and 0.10: VIIc were 21% lower in Chinese control subjects and Type I diabetic patients with R/Q, compared with R/R subjects (p < 0.001 and p < 0.05). The corresponding difference was 4% for Type II diabetc patients (p = NS). Type II diabetic patients had higher mean VIIc levels than control subjects and Type I diabetic patients (p < 0.01); they were also older, and had higher serum creatinine and triglyceride (all p < 0.01). They also had higher VIIc levels than an age-matched older control group (p < 0.01; n = 182) in whom the genotype effect was clearly seen. On stepwise linear regression analysis, the significant independent determinants of VIIc were serum triglyceride (contributing 20% and 25% to variance in control subjects and diabetic patients), the R/Q353 genotype (contributing to 12% of the variance in control subjects but only 1% in diabetic patients), age and total cholesterol in all subjects, and in the diabetic patients female sex, urinary albumin excretion rate and serum creatinine. VIIc was higher in diabetic patients with macroangiopathy and retinopathy (both p < 0.0001). We conclude that compared with Caucasians, the Q allele frequency is significantly lower in these Chinese subjects. Plasma VIIc is determined by both genetic and environmental influences such that in Chinese Type II diabetic patients, the effect of environmental factors predominates, almost negating the influence of the R/Q353 genotype. High VIIc may contribute to the increased cardiovascular risk in Type II diabetic patients.

Adult↗