Search

OBJECTIVE—The study aims to test whether biological interaction between hyperglycemia and albuminuria can explain the inconsistent findings from epidemiological studies and clinical trials about effects of hyperglycemia on stroke in type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 6,445 Hong Kong Chinese patients with type 2 diabetes and free of stroke at enrollment were followed up for a median of 5.37 years. Spline Cox proportional hazard regression was used to obtain hazard ratio curves, which were used to identify cutoff points of A1C and spot urinary albumin–to–creatinine ratio for increased ischemic stroke risk. The identified cutoff point of A1C was used to check biological interaction between A1C and albuminuria (micro- and macroalbuminuria). The biological interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index. RESULTS—During the follow-up period, 4.45% (n = 287) of patients developed ischemic stroke. A1C was associated with increased hazard ratios of ischemic stroke in a near-linear manner except for two points—6.2 and 8.0%—where the slope between these two points accelerated. For A1C values CONCLUSIONS—A1C ≥6.2% and micro/macroalbuminuria interact to markedly increase the ischemic stroke risk, which explains a large proportion of risk in patients with type 2 diabetes harboring both risk factors.

OBJECTIVE—The purpose of this study was to compare the predictive value for coronary heart disease (CHD) of the International Diabetes Federation (IDF) definition (with Asian criteria for central obesity) of the metabolic syndrome with existing criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—Subjects with type 2 diabetes and without macrovascular diseases or end-stage renal disease were categorized by the criteria of the IDF and the NCEP ATP III. CHD was defined as myocardial infarction, ischemic heart disease, coronary revascularization, heart failure, and death related to CHD. RESULTS—Of 4,350 patients (aged 54.4 ± 13.4 years; median follow-up period 7.1 [interquartile range 5.2–8.5] years), 65.9% had metabolic syndrome according to either IDF or NCEP ATP III criteria. The NCEP ATP III definition identified metabolic syndrome in 786 subjects (18.1%) who did not fulfill the criteria of the IDF. HDL cholesterol and systolic blood pressure were predictors of CHD after adjustment for other confounding factors. Compared with subjects without metabolic syndrome, the IDF criteria failed to predict CHD (hazard ratio 1.13 [95% CI 0.86–1.48], P = 0.374). In contrast, the NCEP ATP III definition (2.51 [1.80–3.50], P < 0.001) predicted an increased risk of CHD with the NCEP-only group having the highest risk (2.49 [1.66–3.73], P < 0.001). CONCLUSIONS—With established type 2 diabetes, the IDF definition of the metabolic syndrome failed to identify a subgroup of patients who had the highest risk for CHD. Practitioners must recognize the appropriate setting for its application.

OBJECTIVE—Anemia and chronic kidney disease (CKD) are risk factors for cardiovascular diseases in diabetes. We examined the association between hematocrit, stratified by the presence of CKD, and cardiovascular events in a cohort of Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 3,983 patients who underwent assessment for diabetes complications were recruited. Subjects were categorized into five groups. Group I included subjects with hematocrit below the normal sex-specific range. The cutoff points for groups II–V were selected to represent the distribution of the hematocrit for each sex. CKD was defined by the estimated glomerular filtration rate RESULTS—A total of 294 subjects (7.4%) developed cardiovascular events during the median of 36.4 months. The rate of cardiovascular events was highest in subjects with low hematocrit (group I, 18.6%) compared with group V (3.4%, P < 0.001). The multivariate-adjusted hazard ratio for cardiovascular events diminished with increasing hematocrit (group I, 1.0; group II, 0.73 [95% CI 0.51–1.04]; group III, 0.57 [0.39–0.83]; group IV, 0.61 [0.39–0.95]; and group V, 0.36 [0.17–0.79]). After stratifying by the presence of CKD, the previously observed reduction in the risk of developing cardiovascular events with increasing hematocrit was abolished in the cohort with CKD but persisted in the non-CKD cohort. CONCLUSIONS—In Chinese subjects with type 2 diabetes, low levels of hematocrit and the presence of CKD are associated with increased risk of developing adverse cardiovascular events.

OBJECTIVE—Chronic kidney disease (CKD) predicts cardiovascular disease (CVD) in the general population. We investigated the effects of stages of renal function using the estimated glomerular filtration rate (eGFR) on all-cause mortality and cardiovascular end points in a prospective cohort of Chinese type 2 diabetic patients.RESEARCH DESIGN AND METHODS—Between 1995 and 2000, 4,421 patients without macrovascular disease or end-stage renal disease were recruited. Renal function was assessed by eGFR, as calculated by the abbreviated Modification of Diet in Renal Disease Study Group formula. Clinical end points included all-cause mortality, cardiovascular end point (cardiovascular death, new admissions due to angina, myocardial infarction, stroke, revascularization, or heart failure), and renal end point (reduction in eGFR by >50%, progression of eGFR to stage 5, or dialysis or renal death).RESULTS—After a median follow-up period of 39.4 months (interquartile range 20.3–55), all-cause mortality rate increased from 1.2% (95% CI 0.8–1.7) to 18.3% (9.1–27.5) (P for trend CONCLUSIONS—Chinese type 2 diabetic patients with reduced eGFR were at high risk of developing cardiovascular end points and all-cause mortality, independent of albuminuria and metabolic control.

OBJECTIVE To validate a Chinese version of the Diabetes Distress Scale (CDDS). RESEARCH DESIGN AND METHODS The CDDS was derived using forward-backward translation and administered in 189 Chinese type 2 diabetic patients with evaluation of its psychometric properties. RESULTS On the basis of principal-component analysis, three factors of the 15-item version of the CDDS (CDDS-15) accounted for 63% of the variance. The correlation coefficient between the original 17-item and 15-item scales was 0.99. The Cronbach α for internal consistency was 0.90, and the test-retest reliability coefficient was 0.74. The CDDS-15 score was significantly associated with glycemic control, obesity, depressive symptoms, and quality of life. CONCLUSIONS The CDDS-15 is a valid and reliable instrument to assess diabetes-related distress.

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

OBJECTIVE—The study aims to test whether biological interaction between hyperglycemia and albuminuria can explain the inconsistent findings from epidemiological studies and clinical trials about effects of hyperglycemia on stroke in type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 6,445 Hong Kong Chinese patients with type 2 diabetes and free of stroke at enrollment were followed up for a median of 5.37 years. Spline Cox proportional hazard regression was used to obtain hazard ratio curves, which were used to identify cutoff points of A1C and spot urinary albumin–to–creatinine ratio for increased ischemic stroke risk. The identified cutoff point of A1C was used to check biological interaction between A1C and albuminuria (micro- and macroalbuminuria). The biological interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index. RESULTS—During the follow-up period, 4.45% (n = 287) of patients developed ischemic stroke. A1C was associated with increased hazard ratios of ischemic stroke in a near-linear manner except for two points—6.2 and 8.0%—where the slope between these two points accelerated. For A1C values

OBJECTIVE—International guidelines recommend optimal control of risk factors in diabetes to prevent cardiovascular events. We examined risk associations between achieving treatment targets for glycemia, blood pressure and lipid control, and other risk factors on subsequent cardiovascular events in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Between 1995 and 2005, 6,386 Chinese type 2 diabetic patients without a history of coronary heart disease (CHD) or stroke were recruited. They were classified according to the number of treatment targets attained at baseline, and their cardiovascular outcomes were compared. Treatment targets were defined as A1C RESULTS—After a median follow-up of 5.7 years, cumulative incidence of CHD or stroke (n = 749) increased with decreasing numbers of treatment targets attained at baseline. Attainment of two or more targets at baseline was associated with reduced risk of CHD compared with those with no target achieved (hazard ratio 0.69 [95% CI 0.50–0.94], P = 0.020). However, the association lost its significance after adjustment for urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and hemoglobin. CONCLUSIONS—Reaching more treatment targets was associated with reduced risk of new onset of CHD in Chinese patients with type 2 diabetes.

OBJECTIVE— The insertion/deletion (I/D) polymorphism of the ACE gene has been reported to be associated with diabetic microvascular or macrovascular complications. The aim of the present study was to investigate the prognostic effect of I/D polymorphism on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS— A consecutive cohort of 1,281 Chinese patients with type 2 diabetes were followed for 41.3 ± 21.6 months. Renal end points were defined as renal death and events (need for dialysis, plasma creatinine ≥500 μmol/l, or doubling of plasma creatinine of baseline value ≥150 μmol/l). Cardiovascular end points were defined as cardiovascular death and events, which included ischemic heart disease, heart failure, cerebrovascular accident, and revascularization requiring hospital admission. The I/D polymorphism of the ACE gene was examined by PCR followed by agarose gel electrophoresis. RESULTS— The frequencies of ACE gene I/D polymorphisms were in Hardy-Weinberg equilibrium. Patients who developed a renal end point (n = 98) had higher frequencies of DD genotype (19.4 vs. 10.8%, P = 0.018) and D allele (41.3 vs. 31.8%, P = 0.006) compared with subjects who did not (n = 1,183). The cumulative rates of renal end points were 10.0, 19.2, and 24.4% in the II (n = 595), DI (n = 539), and DD genotype carriers (n = 147), respectively (log rank P = 0.004). In multiple Cox regression analysis, the occurrence of renal end points remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype (DD versus II, adjusted hazard ratio 2.80 [95% CI 1.49–5.29]). There was no prognostic effect of I/D polymorphism on cardiovascular end points. CONCLUSIONS— The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular end points in Chinese patients with type 2 diabetes.

Recently there is renewed interest in the association between type 2 diabetes and colorectal carcinoma (1). Some authorities have advocated more intensive colonoscopy screening in patients with diabetes (2). We recently managed two diabetic patients who developed acute renal failure following elective colonoscopy. The clinical presentation and biochemical parameters of these two patients are summarized in Table 1. Both of the patients described had normal renal function at baseline, yet presented with acute renal failure within a few days following bowel preparation and colonoscopy, thus strongly implicating the bowel preparation in the development of the acute renal failure. Both patients …

OBJECTIVE To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG ≥ 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) ≥ 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG ≥ 5.6 mmol/l and an HbA1c ≥ 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG ≥ 5.4 mmol/l and a fructosamine ≥ 235 μmol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG ≥ 5.6 mmol/l and < 7.8 mmol/l and a fructosamine ≥235 μmol/1 (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408 – 526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/1, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach ∼ 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.

OBJECTIVE To investigate the safety, efficacy, and metabolic effects of dexfenfluramine in obese Chinese NIDDM patients. RESEARCH DESIGN AND METHODS Thirty-two patients, mean (± SD) body weight 76.2 ± 8.5 kg with corresponding BMI 31.1 ± 2.1 kg/m2, were randomized into a two-phase study, after a 2-week single-blind run-in period on placebo. Phase 1 was a randomized 3-month double-blind placebo-controlled trial during which either dexfenfluramine or placebo was added to the existing treatment regimens of diet plus or minus sulfonylureas without metformin. Phase 2 was a further 3-month single-blind trial during which the placebo group was given dexfenfluramine without patients' knowledge of changing to active medication, while the active group continued with dexfenfluramine. Body weight, glycemic control, blood pressure, lipids, and quality of life were assessed before and at 3 and 6 months after randomization. A total of 27 patients were also followed for an additional period of 6–12 months (215 ± 53 days) after dexfenfluramine treatment was withdrawn. RESULTS During the run-in period, both groups were comparable for all parameters measured. At 3 months, mean changes in BMI were −1.2 ± 1.0 kg/m2 (dexfenfluramine) vs. −0.1 ± 0.5 kg/m2 (placebo) (P < 0.001). The mean changes in fasting plasma glucose were −1.14 ± 0.99 vs. 0.51 ± 1.34 mmol/l (dexfenfluramine vs. placebo, P = 0.004). HbA1c also significantly improved in the dexfenfluramine group (−0.80 ± 0.53 vs. 0.25 ± 0.64%, P < 0.001). During the 3-month single-blind dexfenfluramine treatment in the ex-placebo group, there were similar improvements in body weight and glycemic indexes. After cessation of dexfenfluramine therapy at 6 months, significant increases in body weight and glycemic indexes, almost back to the baseline, were observed for both groups. CONCLUSIONS Dexfenfluramine aids weight loss and improves glycemic control in obese Chinese NIDDM patients over a 3- to 6-month period. These effects are emphasized after withdrawal of treatment and further support the longer-term use of dexfenfluramine for chronic complicated obesity.

OBJECTIVES Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral Hypoglycemic agents (OHAs). RESEARCH DESIGN AND METHODS Fifty-three Chinese patients with NIDDM (mean age 53.9 ± 12.6 years, duration of diabetes 9.0 ± 4.9 years, body wt 60.4 ± 13.3 kg with corresponding body mass index 24.2 ± 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice–daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) RESULTS Both groups showed similar improvement of glycemie control. For the combination group, FPG decreased from 13.5 ± 2.7 to 8.9 ± 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 ± 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 ± 3.6 to 7.5 ± 3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 ± 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbAlc). Fructosamine fell from a mean of 458 to 365 μmol/l at 3 months (P < 0.0001) and to 371 μmol/l at 6 months (P < 0.0001) and from 484 to 325 μmol/1 at 3 months (P < 0.0001) and to 350 μmol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1cdecreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs. 57.2 U/day, P < 0.0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 ± 1.8 kg at 3 months and 2.1 ± 2.5 kg at 6 months (both P < 0.0001 vs. baseline), whereas for the insulin group, weight gain was 3.5 ± 4.3 and 5.2 ±4.1 kg, respectively (both P < 0.0001 vs. baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 ± 1.0 to 1.4 ± 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 ± 0.7 mmol/l at 6 months [P < 0.02]) but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe Hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group. CONCLUSIONS in NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement.