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 µmol/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 µmol/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.
Objective: To assess the effects of BMI on progression to diabetes in Hong Kong Chinese and to analyze the optimal cutoff for overweight and obesity in Hong Kong Chinese.
Research Methods and ...Procedures: This is a prospective study with a mean follow‐up of 2.1 years (median 1.4 years, range 0.9 to 8.4 years). We recruited 172 nondiabetic high‐risk subjects, of whom 115 had normal glucose tolerance (NGT) and 57 had impaired glucose tolerance (IGT). BMI and 75‐gram oral glucose tolerance tests were assessed at baseline and then at yearly intervals
Results: The crude rates of progression to diabetes for subjects with NGT or IGT were 8.4% and 11.5% per year, respectively. For subjects with NGT, the progression rate to diabetes differed with different BMI ranges. For subjects with NGT and BMI ≥ 25 kg/m2, the crude rates of progression to diabetes or glucose intolerance (diabetes or IGT) were 12.5% per year and 14.6% per year, respectively. The corresponding rates for subjects with NGT and BMI ≥ 28 kg/m2 were 14.6% and 18.9% per year, respectively. Among subjects with NGT, those with BMI between 25 and 28 kg/m2 had the highest Youden index and likelihood ratio to predict the conversion to diabetes or glucose intolerance.
Discussion: Obese subjects with NGT had higher rates of progression to diabetes than nonobese subjects. We recommend redefining BMI cutoffs, with 23 kg/m2 for overweight and 28 kg/m2 for obesity. This definition may be more sensitive to identify at‐risk subjects and more specific to identify “patients” for therapeutic management.
Diabetes in Hong Kong Chinese: evidence for familial clustering and parental effects.
S C Lee ,
Y B Pu ,
C C Chow ,
V T Yeung ,
G T Ko ,
W Y So ,
J K Li ,
W B Chan ,
R C Ma ,
J A Critchley ,
C S ...Cockram and
J C Chan
Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, SAR. shaochin@ctimail.com
Abstract
OBJECTIVE: To investigate transmission patterns of diabetes and their relationships with clinical characteristics in Hong
Kong Chinese patients with late-onset (age > or =35 years) type 2 diabetes. RESEARCH DESIGN AND METHODS: This study involved
2,310 patients consecutively selected from a hospital clinic-based diabetes registry. These patients all reported the diabetes
status of their parents as well as siblings. RESULTS: Approximately 36% of the 2,310 patients reported at least 1 affected
parent or sibling (25 and 21% reported at least 1 diabetic parent and sibling, respectively). These patients, irrespective
of their sex, were more likely to have a diabetic mother than a diabetic father (17 vs. 13% of the male patients and 18 vs.
9% of the female patients, P<0.01). The male patients were more likely than the female patients to have a diabetic father
(13 vs. 9%, P<0.01). The female patients with a diabetic mother were found to have higher levels of plasma total cholesterol
compared with the female patients with a diabetic father in multiple comparisons with adjustment for significance (5.56+/-1.30
vs. 5.09+/-0.95 mmol/l, P<0.05). In 2-group comparisons, there was also evidence that the male patients with a diabetic father
had higher BMI values than the male patients with a diabetic mother (25.9+/-3.5 vs. 25.0+/-3.5 kg/m2, P<0.05). CONCLUSIONS:
We found familial clustering of diabetes in the Hong Kong Chinese population as well as a significant maternal influence and
a male sex-specific paternal effect. We suggest that both maternal and paternal factors may be implicated in the development
of type 2 diabetes in the Chinese population.
Background: The aim of this study was to investigate whether chronic infections with Helicobacter pylori and hepatitis B virus (HBV) might affect clinical outcomes in Chinese type 2 diabetic ...patients with advanced nephropathy.
Methods: A prospective study of 97 type 2 diabetic patients with clinical proteinuria and renal insufficiency (median serum creatinine 200 µmol/l).
Results: During a median follow‐up period of 2 years, 34 developed end‐stage renal disease (ESRD), 28 had cardiovascular endpoints and 11 patients had died (seven men and four women), and 52.7% developed a combined endpoint. Female patients had longer disease duration, higher blood pressure, lower body weight but higher serum creatinine and spot urine albumin : creatinine ratio as well as lower haemoglobin than male patients. On logistic regression analysis, female gender (hazard ratio: 5.91, p = 0.02), negative H. pylori serology (8.39, p = 0.004), baseline serum creatinine (1.04, p = 0.001) and haemoglobin (1.86, p = 0.01) were independent predictors for ESRD. Systolic blood pressure (1.04, p = 0.003), prior treatment with angiotensin‐converting enzyme inhibitors or angiotensin II receptor antagonists (3.41, p = 0.04) and positive hepatitis B surface antigen (4.88, p = 0.025) were independent predictors for cardiovascular endpoints. Female gender (7.89, p = 0.002) and baseline serum creatinine (1.05, p < 0.001) were independent predictors for combined death and cardio‐renal endpoints.
Conclusions: In Chinese type 2 diabetic patients with clinical proteinuria renal insufficiency, there were high rates of death and cardio‐renal outcomes. Female gender, low haemoglobin and negative H. pylori serology were important predictors for ESRD, whereas chronic HBV infection was associated with increased cardiovascular risks.
Background. The RENAAL Study has confirmed the renoprotective effects of Losartan in type 2 diabetes. In this subgroup analysis from the RENAAL Study, we hypothesized that the intensive care received ...by patients in a clinical trial setting also reduced the rate of decline in renal function through optimization of all risk factors. Methods. We compared the rate of deterioration in renal function, expressed as the regression coefficient of the monthly serum creatinine (SeCr) reciprocal (beta-1/Cr) in 55 Chinese type 2 diabetic patients before and after entry into the RENAAL Study. Results. Of the 55 patients, 44 had at least three out-patient SeCr measurements both before (2.9±2.4 years) and after (3.3±0.8 years) entry into the study for evaluation. In the Losartan group (n = 24), the median beta-1/Cr fell from −11.4 × 10−5 l µmol−1 month−1 before entry into the trial to −4.7 × 10−5 l µmol−1 month−1 following entry (P = 0.001). The respective figures were −9.1 × 10−5 and −5.0 × 10−5 l µmol−1 month−1 (P = 0.01) in the placebo group (n = 20). A decrease in beta-1/Cr was observed in 21 (87.5%) and 14 (70.0%) patients in the Losartan and placebo groups, respectively. Spot urinary albumin-to-creatinine ratio was reduced by 56% (P = 0.001) in the Losartan group but the change was not significant in the placebo group. At the end of the study, patients in both groups had lower blood pressure and better lipid control. The frequency of patient visits to doctors and nurses were doubled. Conclusions. The rate of renal function decline was significantly reduced in the majority of patients allocated to either Losartan or placebo following entry into the RENAAL study. These results suggest that in patients with diabetic nephropathy, implementation of a structured care protocol in a clinical trial setting facilities intensive treatment of risk factors confering renoprotective effects in addition to those resulting from Losartan treatment.
Despite the high cardiovascular risk of diabetic patients, there is a paucity of data on isolated systolic hypertension (ISH) in diabetic patients. In this cross-sectional study, we examined the risk ...of ISH and its associated factors in Chinese type 2 diabetic patients. Isolated systolic hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg. The mean value of two BP measurements taken 1 min apart was used. There were 1048 type 2 diabetic patients recruited from the Prince of Wales Hospital Diabetes Clinic. Another 1043 age- and sex-matched non-diabetic subjects were recruited from the community. The mean age of the 2091 subjects was 40.6±7.6 years (median: 40 years, range: 16–69 years). Diabetic patients had an increased risk of ISH compared to non-diabetic subjects (7.6% vs. 3.4%,
p<0.001) with an odd ratio of 2.38. On multivariate analysis, age, body mass index, total cholesterol and duration of diabetes in diabetic subjects while age and waist–hip ratio (WHR) in non-diabetic subjects were independently associated with ISH. In conclusion, Chinese type 2 diabetic patients had increased risk to develop ISH than non-diabetic subjects. Age, obesity, lipid and duration of diabetes were independent associated with ISH. These findings suggest that control of body weight and metabolic profile might have beneficial effects on ISH.
To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care.
Descriptive analysis of a ...prospective cohort.
During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records.
Patients receiving structured care had lower mortality (relative risk RR = 0.21; 95% confidence interval CI = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P < .01) and 15.7-fold (P < .01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%).
Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.
Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type ...2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI).
Result: Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations (
P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5±16.8
ng/ml, DM: 14.6±10.5
ng/ml and control: 9.1±7.1
ng/ml). Women had higher serum leptin concentration than men in the control group (12.5±7.3
ng/ml versus 4.2±2.0
ng/ml,
P=0.001) and in the DM group (18.9±11
ng/ml versus 8.6±5.9
ng/ml,
P=0.07) whereas this gender difference was not observed in the DMN group (18.6±17.0
ng/ml versus 16.8±17.0
ng/ml,
P=0.754). On multivariate analysis, ACR (
β=0.411,
P<0.001) and BMI (
β=0.240,
P=0.002) were independently associated with serum leptin concentrations (
R
2=0.194,
F=22.1,
P<0.001) in the whole group. In the DMN group, ACR (
β=0.370,
P=0.016) was the only independent determinant of serum leptin concentrations (
R
2=0.159,
F=11.4,
P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.
The relationship between diabetes and Helicobacter pylori (HP) infection is controversial. In this study, we examined the possible relationship between HP infection and type 2 diabetes in Chinese ...subjects. Sixty-three Chinese type 2 diabetic patients (mean age ± SD: 49.9 ± 12.0 years; range: 17-76 years) were recruited irrespective of the duration of diabetes or type of therapy. Twenty-nine (46%) of them had upper gastrointestinal symptoms and the other 34 (54%) did not. Another 55 age- and sex-matched non-diabetic subjects (mean age ± SD: 45.6 ± 15.6 years, p = 0.098; range 18-79 years) with dyspepsia indicated for upper endoscopy were recruited as a comparison group. Upper endoscopy was performed with antral mucosal biopsy specimens taken for rapid urease test (CLO test). HP infection was considered to be present if the rapid urease test was positive. The rates of HP infection of the diabetic and non-diabetic individuals were 50.8% and 56.4% respectively (p: NS). The rate of HP infection was similar between the 2 groups of diabetic patients with or without gastrointestinal symptoms (42.9% vs. 56.3%, p: NS). Using logistic regression analysis (forward stepwise) with age, sex, glycaemic control, duration of diabetes and upper gastrointestinal symptoms as independent variables to predict the risk of HP infection in diabetic patients, none of the parameters enter into the model. In conclusion, the rate of HP infection in Hong Kong Chinese subjects with type 2 diabetes is around 50%, which is similar to control subjects. No association was found between HP infection, glycaemic status, and duration of diabetes and upper gastrointestinal symptoms in these diabetic subjects.
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