The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Three-dimensional assessment of the normal Japanese glenoid and comparison with the normal French glenoid.

INTRODUCTION: In 2014, reverse total shoulder arthroplasty was approved in Japan. We were concerned that the base plate might be incompatible with Japanese who were generally smaller than Westerners. Therefore, we investigated the dimensions and morphology of the normal Japanese glenoid and compared with the normal French glenoid. MATERIALS AND METHODS: One hundred Japanese shoulders without glenoid lesions (50 men and 50 women) were investigated and compared with 100 French shoulders (50 men and 50 women). Computed tomography was performed with 3-dimensional image reconstruction and images were analyzed using Glenosys software. Glenoid parameters (width, height, retroversion and inclination) were compared between Japanese and French subjects. RESULTS: In Japanese subjects, the mean glenoid width was 25.5mm, height was 33.3mm, retroversion was 2.3° and inclination was 11.6° superiorly. In French subjects, the mean glenoid width was 26.7mm, height was 35.4mm, retroversion was 6.0° and inclination was 10.4° superiorly. Glenoid width and height were significantly smaller in Japanese subjects than French subjects (P=0.001 and P<0.001), while retroversion was significantly greater in French subjects (P<0.001). There was no significant difference of inclination. CONCLUSIONS: These findings will help surgeons to identify suitable patients for RSA and perform the procedure with appropriate preoperative planning. LEVEL OF EVIDENCE: IV: retrospective or historical series.

High risk of conversion to diabetes in first-degree relatives of individuals with young-onset type 2 diabetes: a 12-year follow-up analysis.

AIM: Family history of diabetes is an established risk factor for Type 2 diabetes, but the impact of a family history of young-onset diabetes (onset < 40 years) on future risk of diabetes among first-degree relatives is unclear. In this prospective study, we examined the influence of family history of late- versus young-onset diabetes on the development of diabetes in a young to middle-aged Chinese population. METHODS: Some 365 siblings identified through probands with Type 2 diabetes and 452 participants from a community-based health awareness project (aged 18-55 years) who underwent metabolic assessment during the period 1998-2002 were followed to 2012-2013 to determine their glycaemic status. Multivariate logistic regression was performed to investigate the association of family history of diabetes presented at different age categories with development of diabetes. RESULTS: In this cohort, 53.4% (n = 167) of participants with a family history of young-onset diabetes, 30.1% (n = 68) of those with a family history of late-onset diabetes and 14.4% (n = 40) of those without a family history developed diabetes. Using logistic regression, family history of diabetes presented at ages ≥ 50, 40-49, 30-39 and < 30 years, increased conversion to diabetes with respective odds ratios of 2.4, 5.8, 9.4 and 7.0 (P < 0.001 for all), after adjustment for socio-economic status, smoking, obesity, hypertension and dyslipidaemia. Among participants without diabetes at baseline, risk association of family history of late-onset diabetes with incident diabetes was not sustained, whereas that of family history of young-onset diabetes remained robust on further adjustment for baseline glycaemic measurements. CONCLUSIONS: First-degree relatives of people with Type 2 diabetes, especially relatives of those with young-onset diabetes, are at high risk for diabetes.

Fast x-ray detector system with simultaneous measurement of timing and energy for a single photon.

We developed a fast X-ray detector system for nuclear resonant scattering (NRS) experiments. Our system employs silicon avalanche photo-diode (Si-APD) as a fast X-ray sensor. The system is able to acquire both timing and energy of a single X-ray photon simultaneously in a high rate condition, 106 counts per second for one Si-APD. The performance of the system was investigated in SPring-8, a synchrotron radiation facility in Japan. Good time resolution of 120 ps (FWHM) was achieved with a slight tail distribution in the time spectrum by a level of 10-9 at 1 ns apart from the peak. Using this system, we successfully observed the NRS from the 26.27-keV level of mercury-201, which has a half-life of 630(50) ps. We also demonstrated the reduction of background events caused by radioactive decays in a radioactive sample by discriminating photon energy.

A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes.

AIMS: To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. METHODS: The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse-coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). RESULTS: Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs -0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). CONCLUSIONS: Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364).

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Early gene-diet interaction between glucokinase regulatory protein (GCKR) polymorphism, vegetable and fish intakes in modulating triglyceride levels in healthy adolescents.

BACKGROUND AND AIMS: The benefits of dietary vegetable and fish consumptions on improving glucose and lipid metabolism have been well established. Recently, the T-allele of a common genetic variant rs780094 at glucokinase regulatory protein (GCKR) was reported to be associated with elevated triglyceride (TG) levels but reduced fasting plasma glucose (FPG) and type 2 diabetes risk. However, the dietary modulation on genetic risk is not clearly understood. METHODS AND RESULTS: A cohort of 2095 Chinese adolescents (mean age 15.6 ± 2.0 years, 45.3% male) recruited from a population-based school survey for cardiovascular risk factor assessment, with dietary data including weekly vegetable and fish consumptions as well as clinical data were genotyped for the GCKR rs780094 polymorphism. In the linear regression analysis with adjustment for sex, age, body mass index, and socioeconomic status (school banding, paternal and maternal education levels), the frequency of vegetable intake per week was inversely associated with FPG (P = 0.044). Individuals with low fish intake generally had elevated TG levels but reduced TC, HDL-C and LDL-C (0.006 < P < 0.029). We also observed significant associations of the minor T-allele of GCKR rs780094 with decreased FPG (P = 0.013) and increased TG levels (P = 2.7 × 10(-8)). There were significant gene-diet interactions between rs780094 and vegetable consumption (P(interaction) = 0.009), and between rs780094 and fish consumption (P(interaction) = 0.031) in modulating TG levels. The T-allele of GCKR locus was associated with higher TG levels amongst individuals with ≥7 vegetable meals per week (P = 6.4 × 10(-9)), and among individuals with <7 fish meals per week (P = 0.020 and 7.0 × 10(-7) for 4-6 and ≤3 meals per week, respectively). High intake of vegetable exerted a reduction in TG levels only among CC genotype carriers (Ptrend = 0.020), while high intake of fish was associated with reduced TG levels only among TT genotype carriers (Ptrend = 0.026). CONCLUSIONS: In summary, our data indicated that the favorable associations of higher vegetable and fish intakes on TG levels are dependent on the genetic background of an individual. In particular, at-risk TT- genotype carriers of the GCKR variant may derive more benefits from a high fish intake, while the CC-genotype carriers may find further benefits from a high consumption of vegetable.

Non-linear relationship between birthweight and cardiometabolic risk factors in Chinese adolescents and adults.

AIM: To investigate the relationship between birthweight and cardiometabolic traits in two cohorts: one of Chinese adolescents and one of Chinese adults. METHODS: Birthweight and clinical data, including anthropometric traits, fasting plasma glucose and fasting plasma insulin levels, blood pressure and lipid profiles were collected from 2035 adolescents and 456 adults. A subset of 735 subjects underwent an oral glucose tolerance test to measure the glucose and insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents, birthweight showed U-shaped relationships with larger body size, obesity, abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 < P(quadratic) < 0.0499), as well as an inverse association with fasting plasma glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing birthweight was associated with elevated fasting plasma glucose levels, greater insulin resistance and worse lipid profiles (3.1 × 10⁻5 < P(linear) < 0.0058). Among adults, high birthweight was associated with larger body size and abdominal obesity in men, while low birthweight was associated with elevated glucose levels at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as well as with ß-cell dysfunction (6.5 × 10⁻5 < P(linear) < 0.0437). Adjustment for adult adiposity did not substantially change the relationships. There was significant interaction between birthweight and abdominal obesity in elevating fasting plasma insulin and homeostasis model assessment of insulin resistance (P > 0.05), with abdominally obese adolescents in the lowest birthweight category (≤ 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high and low birthweights are associated with an increased risk of cardiometabolic abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia and insulin resistance, as well as with ß-cell dysfunction.

Associations of uric acid and gamma-glutamyltransferase (GGT) with obesity and components of metabolic syndrome in children and adolescents.

BACKGROUND: The combined effect of uric acid, gamma-glutamyltransferase (GGT) and cardiovascular risk factors clustering in the youth remains under-explored. OBJECTIVE: The objective of this study was to examine the association between uric acid, GGT, obesity and the individual components of metabolic syndrome in children and adolescents. METHODS: We performed a cross-sectional observational study of 2067 children and adolescents (875 boys and 1192 girls) aged 6-20 years who were healthy volunteers and were recruited from primary and secondary schools in Hong Kong between 2007 and 2008. Subjects were divided into two strata (75th percentile as cut-off) for comparison between odds of cardiovascular risk factors. RESULTS: After adjustment by multivariable logistic regression, subjects in upper stratum, i.e., >75th percentile, of either serum uric acid or GGT levels were associated with obesity, low high-density lipoprotein cholesterol (HDL-C) level and high blood pressure (adjusted odds ratios [AOR] ranged from 1.63 to 5.82, all P < 0.005) compared with those in the lower stratum. There were combined effect for upper stratum of both uric acid and GGT in the association with obesity, low HDL-C and high blood pressure (AOR ranged from 2.60 to 10.69, all P < 0.05) after adjustment for age, sex and body mass index z-score (except for obesity status) as well as body height (for high blood pressure). CONCLUSION: Uric acid and GGT have combined effect in association with obesity and other cardiovascular risk factors in children and adolescents.

A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes.

AIM: To examine the efficacy, safety and tolerability of rivoglitazone, a novel thiazolidinedione (TZD), and explore its effects on glucose and lipid control compared to placebo and pioglitazone in Chinese type 2 diabetic patients who are treatment naÏve or treated with a single oral blood glucose-lowering drug. METHODS: This was a double-blind, randomized, placebo- and active-controlled study. A total of 287 Chinese type 2 diabetic patients with suboptimal glycaemic control (defined as HbA1c ≥6.5 to <10% and fasting plasma glucose ≥7 to ≤15 mmol/l) were enrolled. One hundred and seventy-four eligible patients were randomized into one of the five treatment arms for 12 weeks: placebo, pioglitazone 30 mg daily, rivoglitazone of dose 0.5, 1.0 or 1.5 mg daily. In a full set analysis, we used analysis of covariance to compare the primary endpoint defined as change in HbA1c from baseline to week 12/last observation carried forward in the rivoglitazone group at each dose level with the placebo group. RESULTS: Changes in HbA1c were -0.11% in the 0.5-mg group; -0.22% in the 1-mg group and -0.17% in the 1.5-mg rivoglitazone group; -0.06% in the 30-mg pioglitazone group and 0.61% in the placebo group. Compared to placebo, changes were significant in all active treatment groups (all p < 0.05). Increase in high-density lipoprotein cholesterol and decrease in triglyceride were observed in the rivoglitazone 1 and 1.5 mg groups, respectively, compared to placebo from baseline to week 12 (p < 0.05). Drug-related oedema was reported in eight patients (7.7%) in all rivoglitazone groups compared to six patients (16.2%) in the pioglitazone group and one patient (3.0%) in the placebo group. CONCLUSIONS: Rivoglitazone is an efficacious, safe and well-tolerated TZD which improved glycaemic control in Chinese type 2 diabetic patients up to 3 months.

A simple risk score to identify Southern Chinese at high risk for diabetes.

AIMS: To develop a simple scoring system for identifying Southern Chinese at risk of diabetes. METHODS: The score was derived from a risk factor matching cohort for Type 2 diabetes in Hong Kong Chinese (cohort 1, 2448 subjects without a history of diabetes; age, mean +/- sd 37.2 +/- 8.9 years, median 36.0 years; 1649 had risk factors for diabetes and 799 were age-matched control subjects from the community). Two other cohorts were used to validate the risk score (cohort 2, 3734 subjects with risk factors for diabetes; and cohort 3, 1513 participants of a community diabetes survey). All subjects had a 75 g oral glucose tolerance test (OGTT). RESULTS: In cohort 1, 270 (11%) of the subjects were found to have diabetes on OGTT. A risk score system was derived using the beta values of the corresponding predictors in the logistic regression analysis. The area under the curve (95% confidence intervals) of the score system was 0.735 (0.705, 0.765). The application of a risk score of > or = 16 increased the detection rate 2.5-4 times in all three cohorts. A high post-test probability of diabetes of > 60% was derived from a risk score of > or = 20. Only 10-20 and approximately 5% with a score of > or = 12 and > or = 16, respectively, are indicated for OGTT. This will considerably improve the yield of OGTT screening. CONCLUSIONS: A simple risk score identifies young-to-middle-aged Southern Chinese at high risk for diabetes. Subjects with a score of 16 or above (out of 30) should undergo OGTT for definitive diagnosis of diabetes.

Hypoadiponectinaemia enhances waist circumference as a predictor of glucose intolerance and clustering of risk factors in Chinese men.

AIM: This study aimed to confirm the hypothesis that adiponectin levels can enhance the discriminative value of waist circumference (WC) in predicting impaired glycaemic status and clustering of risk factors. METHODS: We used receiver operating characteristic (ROC) curve analysis to define the optimal cut-off value of adiponectin to predict diabetes in Chinese men with no relevant past medical history. This value was combined with WC to increase its discriminative power in ascertaining impaired glycaemic status and various cardiovascular risk factors. RESULTS: In 360 men (mean+/-S.D.; age: 41.3+/-9.2 years), the mean+/-S.D. adiponectin level was 5.2+/-2.7 microg/mL. Based on oral glucose tolerance tests (OGTTs), 84 men (23.3%) had undiagnosed diabetes, 52 (14.4%) had impaired glucose tolerance (IGT) and 224 (62.3%) had normal glucose tolerance. On ROC analysis, 5.7 microg/mL was the optimal cut-off value of adiponectin in this population to predict diabetes. Compared with subjects who had normal WC (defined as less than 90 cm) and high adiponectin levels (> or =5.7 microg/mL), the likelihood ratio of diabetes was 2.54 in those with central obesity and hypoadiponectinaemia. CONCLUSION: The combined use of low adiponectin levels and large WC measures has greater discriminative power than using either index alone to identify subjects at particular risk of glucose intolerance and clustering of risk factors.

Characteristics of liquid cluster ion beam for surface treatment.

A liquid cluster ion source, which is an ion source for the cluster beams produced with liquid materials, has been developed for the surface treatment of solid materials. The electrodes were designed for increasing the cluster beam intensity by a computer simulation of beam trajectories. The peaks of the cluster size distributions of the water and ethanol cluster ion beams of 3 atm vapor pressure were approximately at 2.4x10(3) and 1.6x10(3) molecules, respectively. The cluster size distributions of ethanol clusters were not sensitive to the variations of the acceleration voltages (V(e)) and currents (I(e)) of the electrons for ionization when the V(e) and I(e) were larger than approximately 200 V and 200 mA, respectively.

The NCEP-ATPIII but not the IDF criteria for the metabolic syndrome identify Type 2 diabetic patients at increased risk of chronic kidney disease.

AIM: To examine the association between chronic kidney disease (CKD) and the metabolic syndrome (MetS) using both International Diabetes Federation (IDF) and National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATPIII) definitions in Chinese subjects with Type 2 diabetes. METHODS: Subjects with Type 2 diabetes were categorized according to the presence or absence of MetS by IDF or NCEP-ATPIII criteria. CKD was considered present if glomerular filtration rate, calculated using the abbreviated equation developed by the Modification of Diet in Renal Disease study with Chinese modification, was < 60 ml/min per 1.73 m2. Multivariate logistic regression analysis of the association between CKD and MetS by either definition was performed. RESULTS: Of 6350 subjects (mean age 55.1 +/- 13.3 years), 3439 (54.2%) and 3204 (50.5%) had MetS by IDF and NCEP-ATPIII definitions, respectively. Using the IDF definition, the presence of MetS was not associated with CKD [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.71, 1.29, P = 0.784]. In contrast, the association with CKD was significant when MetS was defined by the NCEP-ATPIII definition (OR 1.75, 95% CI 1.37, 2.24, P < 0.001). In subjects who did not have MetS (n = 2911) as defined by IDF criteria, 997 fulfilled the MetS criteria of NCEP-ATP III. The association with CKD was stronger, after adjustment for covariates, in these subjects (OR 1.42, 95% CI 1.03, 1.97, P = 0.032) compared with subjects who met IDF criteria of MetS. CONCLUSION: In Type 2 diabetes, NCEP-ATPIII, but not the IDF definition of MetS, identifies a subgroup of patients who have a higher risk of CKD.

Interactive effect of retinopathy and macroalbuminuria on all-cause mortality, cardiovascular and renal end points in Chinese patients with Type 2 diabetes mellitus.

AIMS: To examine the effect of albuminuria and retinopathy on the risk of cardiovascular and renal events, and all-cause mortality in patients with Type 2 diabetes. METHODS: A post-hoc analysis of 4416 Chinese patients without macrovascular complications at baseline (age 57.6 +/- 13.3 years). Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease Study Group Formula, further adjusted for Chinese ethnicity. Clinical end points were all-cause mortality, cardiovascular events (heart failure or angina, myocardial infarction, lower limb amputation, re-vascularization procedures and stroke) and renal end points (reduction in eGFR by more than 50% or eGFR < 15 ml/min/1.73 m2 or death as a result of renal causes or need for dialysis). RESULTS: Compared with individuals without complications, subjects with retinopathy and macroalbuminuria had higher rates of cardiovascular events (14.1 vs. 2.4%), renal events (40.0 vs. 0.8%) and death (9.3 vs. 1.7%, P < 0.001). For composite event of death, cardiovascular and renal events, the presence of retinopathy, microalbuminuria alone, macroalbuminuria alone, retinopathy with microalbuminuria or retinopathy with macroalbuminuria increased the risk [hazard ratio (95% CI)] by 1.61 (1.05 to 2.47; P = 0.04), 1.93 (1.38 to 2.69; P < 0.001), 4.34 (3.02 to 6.22; P < 0.001), 2.59 [1.76 to 3.81; P < 0.001) and 6.83 (4.89 to 9.55; P < 0.001) fold, respectively. The relative excess risk as a result of interaction between retinopathy and macroalbuminuria was 15.31, implying biological interaction in the development of renal events. CONCLUSIONS: In Chinese patients with Type 2 diabetes, retinopathy interacts with macroalbuminuria to increase the risk of composite cardio-renal events.

The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients with moderate renal insufficiency.

BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.

Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients-- interaction with ACE insertion/deletion polymorphism.

Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin-angiotensin-aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (+/- standard deviation) age of 59.7 +/- 13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.

Assessment of glomerular filtration rate in addition to albuminuria is important in managing type II diabetes.

Although much emphasis has been placed on screening for albuminuria in type II diabetic patients, less attention has been focused on the role of glomerular filtration rate (GFR) in the assessment of risk. Herein, we examined the association between GFR and vascular complications in a consecutive cohort of 5174 type II diabetic patients between 1995 and 2000. Renal function was assessed by GFR (estimated by Modification of Diet in Renal Disease equation). The frequency of chronic kidney disease (CKD) as defined by GFR <60 ml/min/1.73 m(2), micro- and macrovascular complications, and their associations were analyzed. In this study cohort, 6% had serum creatinine > or =150 micromol/l and 15.8% had CKD. After adjustment for potential confounders, including urinary albumin excretion, odds ratios [95% confidence interval (CI)] across different stages of estimated GFR (> or =90, 60-89, 30-59, 15-29, <15 ml/min/1.73 m(2)) for macrovascular disease were 1.00, 1.42 [1.12-1.80], 1.80 [1.32-2.45], 2.74 [1.64-4.56], and 4.05 [1.77-9.26], respectively (P for trend <0.001); for retinopathy were 1.00, 1.23 [1.04-1.46], 1.80 [1.40-2.30], 2.05 [1.25-3.37], and 4.12 [1.56-10.90], respectively (P for trend <0.001); for sensory neuropathy were 1.00, 1.53[1.27-1.85], 2.09 [1.58-2.76], 4.32 [2.41-7.77], and 3.16 [1.25-8.02], respectively (P for trend <0.001); and for microalbumuria (with GFR <15 ml/min/1.73 m(2) excluded from the analysis) were 1.00, 1.51 [1.30-1.75], 5.80 [4.52-7.44], and 52.5 [16.4-168.2] respectively (P for trend <0.001). Measurement of serum creatinine alone without GFR may underestimate renal impairment in type II diabetic patients. Decreasing GFR was significantly associated with increasing frequency of micro- and macrovascular complications.