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Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 19 recordsLinked to original sources
PubMed2006

Appropriateness of antiviral prescribing for influenza in primary care: a retrospective analysis.

BACKGROUND AND OBJECTIVE: Antiviral medications cost-effectively reduce influenza-related morbidity and potentially mortality. We sought to assess the appropriateness of antiviral prescribing for influenza. METHOD: We performed a retrospective analysis of visits by adults to primary care clinics during influenza seasons from 1 October 2000 to 31 May 2004 with a claims diagnosis of influenza (n=535) or with an electronic antiviral prescription (n=25). We defined appropriate antiviral prescribing as the patient having (a) symptoms for 2 or fewer days, (b) fever and (c) any two of headache, sore throat, cough, or myalgias. RESULTS AND DISCUSSION: Physicians diagnosed patients with influenza in 102 of 535 (19%) visits with a claims diagnosis of influenza. Physicians prescribed antivirals at 15 of 102 (15%) of these visits. The addition of 25 additional electronic antiviral prescriptions gave a sample of 127 visits and 40 (31%) antiviral prescriptions. Twenty-eight (70%) antiviral prescriptions were appropriate. Among patients who did not receive antivirals, 21 of 87 (24%) met criteria for appropriate antiviral prescribing. Antiviral prescribing was associated with a shorter median symptom duration (2 days vs. 3 days; P<0.01) and higher median temperature (37.8 degrees C vs. 36.9 degrees C; P<0.01). Physicians prescribed antivirals more frequently to patients who had myalgias (37% vs. 18%; P=0.04) and an influenza test (67% vs. 28%; P<0.01). Physicians prescribed antivirals more frequently to Blacks (44%) and patients with other race/ethnicity (67%) than to Whites (20%) or Hispanics (20%; P<0.0001). CONCLUSIONS: To improve antiviral prescribing for influenza in primary care, interventions need to target the accurate identification of influenza visits, undertreatment, as well as inappropriate treatment.

Adult↗
PubMed2003

Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia.

BACKGROUND: The best overall treatment strategy for patients with acute promyelocytic leukaemia (APL) in relapse with chemotherapy, bone marrow transplantation (BMT) or arsenic trioxide (As(2)O(3)) based therapy remains undefined. PATIENTS AND METHODS: We reviewed the clinical course and treatment outcome of 143 APL cases seen in four major hospitals in Hong Kong over a 10-year period. RESULTS: Complete remission (CR) was attained in 113 cases (79%) with all-trans retinoic acid (ATRA) and chemotherapy. Relapse occurred at a median of 16 months in 54 cases, with a 3-year disease free survival of 56%. Post-relapse treatment was successful in 41 cases (76%), giving an actuarial 3-year overall survival (OS) of 81% from CR1. Three different protocols were used: chemotherapy alone (n = 19), allogeneic BMT (n = 14) and an As(2)O(3)-based regimen (n = 21). Chemotherapy was associated with the highest treatment-related mortality (TRM) at 53%, giving a CR2 rate of 47%. TRM was 36% for BMT. The CR2 rate for the As(2)O(3)-based regimen was 100%, with no TRM. However, 38% of As(2)O(3) treated patients had subsequent relapses, which were further salvaged in 75% by combined As(2)O(3) plus ATRA. The actuarial OS for the three protocols leveled off by 2 years at 82% for As(2)O(3), 43% for BMT and 23% for chemotherapy (P = 0.0004). CONCLUSIONS: Our results suggest that As(2)O(3) may be superior to chemotherapy and BMT for the treatment of APL in relapse.

Adolescent↗
PubMed2001

Gene targeting in hemostasis. Factor VII.

Factor VII (FVII), in concert with its natural cofactor and receptor, Tissue Factor (TF), initiates the process of blood coagulation following vascular injury. Mice completely deficient in FVII were generated via specific deletion of exons 2 to 8, thus deleting the entire coding region of the mature protein. In contrast to the early lethality observed in TF-deficient embryos (TF-/-), embryos deficient in FVII (FVII-/-) developed normally, without incidence of hemorrhage. However, FVII-/- neonates succumbed to either early intraabdominal or intracranial hemorrhage in later life.

Animals↗
PubMed2001

Gene targeting in hemostasis. tissue factor pathway inhibitor.

Tissue Factor Pathway Inhibitor (TFPI) is a serine protease inhibitor of the Factor VIIa/Tissue Factor (FVIIa/TF)-initiated clotting cascade. Mice expressing a mutant form of TFPI, in which its Kunitz-1 domain has been deleted (TFPIKu1delta/delta), die prematurely in embryogenesis between E9.5dpc and birth. These results provide a rationale for the absence of TFPI-deficient patients. This early mortality can be ameliorated by an accompanying heterozygous or homozygous deficiency in FVII. Thus, diminishment of FVII activity precludes the requirement for TFPI-mediated inhibition of the FVIIa/TF pathway during embryogenesis.

Animals↗
PubMed2001

Progression after release of obstructive nephropathy.

Progressive glomerular and tubulointerstitial fibrosis develop in 1-year-old rats even after relief (R) of unilateral ureteral obstruction (UUO) at 5 days of age. The present study investigated whether a progressive renal injury model of UUO could be achieved after reversal of UUO (RUUO) in adult instead of neonatal rats. The potential for alpha-tocopherol modulation of mRNA for the fibrogenic cytokine, transforming growth factor-beta1 (TGFbeta1), apoptosis (TUNEL assay), and the presence of the stress protein, heat shock protein-70 (HSP-70), was also studied in this post-obstructive model. Male Sprague-Dawley rats weighing 125-150 g were randomly assigned to groups of 4 animals each for durations of 7 or 14 days of alpha-tocopherol supplementation after RUUO. The groups included: (i) sham, regular chow; (ii) RUUO, regular chow; (iii) RUUO, contralateral nephrectomy (NX); and (iv) RUUO, NX plus alpha-tocopherol supplementation. We found a significant increase in the ratio of kidney weight/body weight in the RUUO+NX group at 14 days compared with the sham and RUUO groups. This rise in the RUUO+NX group was significantly reduced after 14 days of alpha-tocopherol administration. The elevated level of kidney TGFbeta1 mRNA in the RUUO+NX group was only partially reduced at 7 days. But at 14 days this became significantly reduced with the continued alpha-tocopherol treatment. The HSP-70 staining and the apoptosis of the kidney showed results parallel to those of TGFbeta mRNA at 14 days. To separate the effects of hypertrophy after unilateral NX from the RUUO studies, we carried out a second experiment in control animals subjected to NX, with and without alpha-tocopherol supplementation. Fourteen days after NX, the apoptosis and TGFbeta1 mRNA showed no significant differences from the control animals. Our data suggest that a model of progressive renal injury in RUUO can be established in adult rats. After contralateral NX, the progressive injury is evidenced by the increase in the ratio of kidney weight/total body weight, the apoptotic counts, as well as fibrogenic cytokine TGFbeta1 mRNA in the post-obstructed kidney. Finally, our data also support the concept that alpha-tocopherol is renal protective, as judged by TGFbeta1 mRNA, apoptosis, and HSP-70 staining, even in the progressive disease process of the post-obstructed model.

Animals↗
PubMed2001

Accelerated skin wound healing in plasminogen activator inhibitor-1-deficient mice.

Components of the fibrinolytic system have been implicated in cell migratory events associated with tissue remodeling. Studies in plasminogen-deficient mice (PG(-/-)) indicated that skin wound healing is impaired, but is resolved with an additional fibrinogen deficiency. Plasminogen activator inhibitor-1 (PAI-1) expression by keratinocytes has been identified shortly after wound injury. PAI-1 expression could affect wound healing by regulating the fibrinolytic environment of the wounded area, as well as influencing events associated with cell attachment and detachment through interactions with matrix proteins. The present study directly assesses PAI-1 involvement in skin wound healing through analyses of a dermal biopsy punch model in PAI-1-deficient (PAI-1(-/-) mice. While the cellular events associated with the healing process are similar between wild-type (WT) and PAI-1(-/-) mice, the rate of wound closure is significantly accelerated in PAI-1(-/-) mice.

Animals↗
PubMed2001

The characterization of mice with a targeted combined deficiency of protein c and factor XI.

Activated protein C functions directly as an anticoagulant and indirectly as a profibrinolytic enzyme. To determine whether the fibrin deposition previously observed in PC(-/-) murine embryos and neonates was mediated through the FXI pathway, PC(+/-)/FXI(-/-) mice were generated and crossbred to produce double-deficient progeny (PC(-/-)/FXI(-/-)). PC(-/-)/FXI(-/-) mice survived the early lethality observed in the PC(-/-)/FXI(+/+) neonates, with the oldest PC(-/-)/FXI(-/-) animal living to 3 months of age. However, the majority of these animals was sedentary and significantly growth-retarded. On sacrifice or natural death, all of these PC(-/-)/FXI(-/-) mice demonstrated massive systemic fibrin deposition with concomitant hemorrhage and fibrosis, as confirmed through histological analyses. Several of these animals also presented with enlarged lymph nodes and extensive lymphatic fluid in the thoracic cavity. Thus, although a number of the PC(-/-)/FXI(-/-) mice survived the lethal perinatal coagulopathy seen in the PC(-/-) neonates, they nonetheless succumbed to overwhelming thrombotic disease in later life. This combined deficiency state provided the first clear indication that the course of a severe thrombotic disorder could be manipulated by blocking the intrinsic pathway and provided the first opportunity to study a total protein C deficiency in an adult animal.

Animals↗
PubMed2001

Diabetes mellitus--a special medical challenge from a Chinese perspective.

As we enter the new millennium, Asia is being hit by an epidemic of diabetes and its related diseases. The rising prevalence of young onset diabetes which is closely associated with obesity and genetic factors as well as the increased propensity to develop kidney disease are special challenges in the management of Chinese diabetic patients. Although diabetic patients have earlier mortality and increased risks for micro and macrovascular complications, there is strong evidence that these devastating complications can be largely prevented by patient education, periodic assessments and use of appropriate therapeutic agents to optimize metabolic control and improve cardiovascular risk factors. However, a multidisciplinary approach is often required to deliver these complex disease management protocols. Hence, it is not surprising that large scale studies often revealed substandard diabetes management in both the hospital and community settings. This is often due to a combination of factors such as non-adherence to recommended guidelines both by patients and doctors as well as the 'non-urgent' and 'silent nature' of diabetes and its complications. To minimize the impacts of diabetes on quality of life, society productivity and utilization of health care resources, concerted efforts between health care professionals and public bodies are urgently needed to increase awareness, improve standards of care and develop better diagnostics and treatment modalities.

Asia↗
PubMed2001

A low socio-economic status is an additional risk factor for glucose intolerance in high risk Hong Kong Chinese.

To examine whether a low socio-economic status (SES) is an additional risk factor for glucose intolerance in Hong Kong Chinese with known risk factors for glucose intolerance, a total of 2847 Chinese subjects (473 men and 2374 women) were recruited from the community for assessment. They had known risk factors for glucose intolerance including a previous history of gestational diabetes, positive family history of diabetes in first degree relatives and equivocal fasting plasma glucose concentrations between 7 and 8 mmol/l or random plasma glucose concentrations between 8 and 11 mmol/l. The 2847 subjects were classified according to their education levels and occupations: education group 1 = high school or university, group 2 = middle school, group 3 = illiterate or up to elementary school; occupational group 1 = professional or managerial, group 2 = non-manual, group 3 = manual, group 4 = unskilled, group 5 = housewife or unemployed. Different socio-economic groups were well represented in this selected population. The distribution of educational groups in this study was similar to that recorded in the 1991 Hong Kong Census. When analysed according to education levels and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes, body mass index, blood pressure and plasma glucose concentrations. Men with the lowest education level had the highest prevalence of diabetes after age adjustment. The age-adjusted odds ratio (95% confidence intervals) of having diabetes was 2.3 (1.3. 4.3) in female subjects and 2.5 (1.2, 5.4) in male subjects with the lowest SES compared to subjects with the highest SES. When categorised according to occupation and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes and glycaemic indexes. The age-adjusted odds ratio of having diabetes was 4.5 (1.9, 10.9) in female subjects with the lowest SES compared to those with the highest SES. The corresponding age-adjusted odds ratio in male subjects was 1.9 (0.9, 3.9) but this was not statistically significant. In conclusion, a lower socio-economic class, categorised either by occupational or educational level, was an additional risk factor for diabetes in Hong Kong Chinese who had known risk factors for glucose intolerance. These subjects should have increased priority for health education and regular diabetes screening. Our findings further emphasise the complex relationships between societal affluence, personal income and educational level.

Adult↗
PubMed2001

Risk factors for cataract in Chinese patients with type 2 diabetes: evidence for the influence of the aldose reductase gene.

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5' of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over-presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non-Z; 38 vs. 50%, p<0.01), but under-presented the allele Z-4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z-4, Z-4+Z-4,non-Z-4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z-4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.

Aged↗
PubMed2001

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

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

Abdomen↗
PubMed2001

Change of glycaemic status in Chinese subjects with impaired fasting glycaemia.

AIMS: To examine the risk of progression to diabetes in Chinese subjects with impaired fasting glycaemia (IFG) or normal fasting glucose (NFG). METHODS: Between 1988 and 1996, 657 Hong Kong Chinese subjects underwent annual screening, using an oral glucose tolerance test, until they had developed diabetes, or until June 1997, when the data were analysed. All subjects had a risk factor associated with the development of diabetes such as a history of gestational diabetes or a family history of diabetes. The follow-up interval for the subjects ranged from 0.87 to 8.54 years and of the 657, 319 had fasting plasma glucose levels of < 7.0 mmol/L where a fasting glucose level of > or = 7.0 mmol/L was used to diagnose diabetes RESULTS: Of the 319 nondiabetic subjects, 55 had IFG and 264 had NFG. After a median follow-up of 1.12 years (range: 0.87-8.54 years), 27 progressed to diabetes. The Kaplan-Meier analysis of progression to diabetes showed significant differences between subjects with IFG and subjects with NFG. Using Cox regression analysis, IFG (beta = 3.51, SE = 1.63, P = 0.032) and smoking (beta = 3.60, SE = 1.50, P = 0.017) were found to be independently associated with progression to diabetes. CONCLUSIONS: In Hong Kong Chinese with risk factors for glucose intolerance, IFG status is an independent risk factor for progression to diabetes.

Adult↗
PubMed2001

The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects: evidence for associations with type 2 diabetes and cholesterol levels.

BACKGROUND AND OBJECTIVES: There has been evidence that the S20G mutation in the islet amyloid polypeptide (amylin) gene may be associated with type 2 diabetes. In the present study, we investigated the distribution of the mutation in Hong Kong Chinese, and examined whether there was evidence for associations between the mutation and type 2 diabetes and/or metabolic profiles. SUBJECTS AND METHODS: This study involved 227 early and 235 late-onset (defined as onset age < or = 40 and > 40 years, respectively) type 2 diabetic patients, as well as 126 nondiabetic subjects. The mutation was detected using a PCR-RFLP method. RESULTS: We identified six (2.6%) and one (0.4%) patients heterozygous for the mutation from the early and late-onset groups, respectively (P = 0.05). None of the nondiabetic subjects had the mutation. Insulin deficiency and poor glycaemic control were not common findings amongst carriers of the mutation. In the early onset group, the patients with the mutation had lower plasma levels of total (4.3 +/- 0.9 mmol/l vs. 5.3 +/- 1.1 mmol/l, P = 0.02) and low density lipoprotein (LDL)-cholesterol (2.3 +/- 0.7 mmol/l vs. 3.2 +/- 0.9 mmol/l, P = 0.01) than those without the mutation. CONCLUSIONS: Our data suggest that the islet amyloid polypeptide gene mutation might be associated with early occurrence of type 2 diabetes and lower plasma levels of total and low density lipoprotein-cholesterol in the Chinese population.

Adolescent↗
PubMed2001

Relationships between the taqI polymorphism of the dopamine D2 receptor and blood pressure in hyperglycaemic and normoglycaemic Chinese subjects.

BACKGROUND: We have previously reported an association of the A2 allele of the dopamine D2 receptor (DRD2) TaqI polymorphism with increased blood pressure in normoglycaemic Chinese subjects, but conversely possibly with decreased indices of obesity. Hypertension is also a common feature of patients with type 2 diabetes, with up to 50% being hypertensive. OBJECTIVE: To compare the relationship between the DRD2 TaqI polymorphism, blood pressure and obesity in Chinese patients with and without fasting hyperglycaemia. METHOD: The DRD2 TaqI polymorphism was determined by PCR-RFLP in 519 normoglycaemic and 471 hyperglycaemic Chinese subjects, of whom 53.2 and 48.8% were hypertensive, respectively. RESULTS: In the normoglycaemic subjects there was a significant increase in mean arterial pressure (P= 0.041) with increasing proportions of the A2 allele, 95 +/- 16, 96 +/- 17 and 100 +/- 17 mmHg for the A1A1, A1A2 and A2A2 genotypes, respectively. However, the relationship was not observed in the subjects with fasting hyperglycaemia either in the total group or in the subgroup who were not receiving blood pressure-lowering medication (n = 383, 97 +/- 15, 98 +/- 14 and 97 +/- 15 mmHg, respectively). When the whole group was divided into those subjects obese by either body mass index or waist-to-hip ratio (n = 484) and those subjects not obese by both these criteria (n= 506), the A1 allele (49.2 vs. 43.8%, P = 0.02) and A1 allele containing genotypes (P = 0.03) were more frequent in the obese subjects. Similar relationships were seen in the normoglycaemic and hyperglycaemic groups separately, although these did not reach significance. CONCLUSIONS: In the normoglycaemic subjects, the A2 allele was associated with increased blood pressure and possibly lower indices of obesity, but in the hyperglycaemic subjects only the possible association with obesity was noted.

Adult↗
PubMed2001

HLA typing and immunological characterization of young-onset diabetes mellitus in a Hong Kong Chinese population.

AIMS: A study of the Hong Kong Chinese showed that the majority of subjects with young-onset diabetes (age of diagnosis < 35 years) present with a phenotype suggestive of Type 2 diabetes mellitus, although up to 50% subsequently need insulin treatment. The aim of this study was to use a combination of clinical, genetic and immunological markers to characterize the disease phenotype further in such individuals and to determine whether the requirement for insulin is the result of autoimmune disease. METHODS: One hundred and thirty-seven Hong Kong Chinese with young-onset diabetes were studied, irrespective of their mode of presentation. The subjects were typed for alleles of the HLA-DR and -DQ genes and investigated for the presence of autoantibodies to glutamic acid decarboxylase (GAD). Plasma C-peptide concentration and requirement for insulin were also determined. RESULTS: One hundred and three subjects presented with a syndrome resembling Type 2 diabetes, while 34 presented with Type 1 diabetes. Of the former group, 35 patients (34.0%) were insulin-deficient, 16 (15.5%) were insulin-treated and seven (6.9%) were positive for GAD autoantibodies. Among the GAD-positive subjects presenting with Type 2 diabetes, the HLA-DRB1*03 allele may be a marker of early progression to insulin therapy. CONCLUSIONS: Seven subjects with Type 2 diabetes at presentation had autoantibodies to GAD. Causes other than GAD autoimmunity, however, must be sought to explain the high prevalence of insulin deficiency observed in the Chinese patients. This study highlights the heterogeneity of the pathogenic processes leading to the diabetic phenotype.

Adolescent↗
PubMed2001

Obesity, insulin resistance and isolated low high-density-lipoprotein cholesterol in Chinese subjects.

AIM: Recent studies have shown that the risk of developing coronary heart disease in subjects with 'isolated low high-density-lipoprotein cholesterol (HDL-C)' (defined as HDL-C < 0.9 mmol/l and total cholesterol (TC) < 5.2 mmol/l) was similar to those with hypercholesterolaemia. We examined the prevalence of isolated low HDL-C in Hong Kong Chinese and its relationship with insulin resistance and triglyceride (TG) level. METHODS: Hong Kong Chinese subjects (n = 1493) recruited in a population-based prevalence survey for cardiovascular risk factors were examined. Insulin resistance was calculated using a computer-solved homeostasis model assessment method. RESULTS: Of the 1493 subjects, 72 (4.8%) had isolated low HDL-C, in whom half (n = 36) had TG > or = 1.7 mmol/l and half (n = 36) had TG < 1.7 mmol/l. Compared with the 'controls' (subjects with TC < 5.2 mmol/l and HDL-C > or = 0.9 mmol/l; TC > or = 5.2 mmol/l and HDL-C < 0.9 mmol/l; or TC > or = 5.2 mmol/l and HDL-C > or = 0.9 mmol/l, n = 1421), subjects with isolated low HDL-C and high TG were more obese, had higher plasma glucose, fasting and 2 h plasma insulin concentrations and insulin resistance. Subjects with isolated low HDL-C and TG < 1.7 mmol/l had similar insulin concentrations and insulin resistance, but were more obese than the 'controls'. Subjects with isolated low HDL-C and high TG also had higher fasting PG, insulin and insulin resistance than those with isolated low HDL-C and low TG. CONCLUSIONS: In this population-based study, 4.8% of Hong Kong Chinese had isolated low HDL-C, which was closely associated with obesity. The coexistence of high TG suggests an insulin-resistant state.

Adult↗
PubMed2001

Contribution of gene polymorphisms in the renin-angiotensin system to macroangiopathy in patients with diabetic nephropathy.

The renin-angiotensin system is important in the control of hemodynamic status and pathogenesis of macrovascular disease, which is a major cause of morbidity and mortality in patients with type 2 diabetes with nephropathy. Serum angiotensin-converting enzyme (ACE) and angiotensinogen (Atg) levels are related to their respective gene polymorphisms. Seventy patients with type 2 diabetes with overt nephropathy (serum creatinine >/= 1.5 mg/dL) were studied. Serum ACE activity was measured by the spectrophotometric method. ACE deletion/insertion (D/I) and Atg M235T genotypes were determined by polymerase chain reaction. Patients with and without macroangiopathy were compared. Those with macroangiopathy had increased ACE activity (median, 60.9 U/L; range, 37.9 to 100 U/L versus without macroangiopathy, 47.9 U/L; range, 11.2 to 84.5 U/L; P = 0.01) and prevalence of ACE DD/DI genotypes (DD/DI:II: with macroangiopathy, 61%:39% versus without macroangiopathy, 34%:66%; P = 0.03). Multivariate analysis using age; sex; duration of diabetes; glycemic, blood pressure, and lipid level control; serum creatinine level; and presence of the ACE D allele showed that presence of the D allele (P = 0.03; odds ratio, 1.8; confidence interval, 1.1 to 3.1) and serum creatinine level (P = 0.0007) were independent risk factors for macroangiopathy. Association of the D allele became insignificant after serum ACE activity was included in the analysis in which only serum ACE activity (P = 0.004) and serum creatinine level (P = 0.01) were independent risk factors. Neither Atg M235T nor its synergistic effect with the ACE D allele showed an association with macroangiopathy. In conclusion, the ACE D allele is associated with macroangiopathy in Chinese patients with type 2 diabetes with nephropathy. The association is dependent on its effect on serum ACE activity, which is an independent risk factor for the development of macroangiopathy.

Aged↗