Chun-Chung Chow

Erectile Dysfunction Predicts Coronary Heart Disease in Type 2 Diabetes

OBJECTIVES We examined the predictive power of erectile dysfunction (ED) on coronary heart disease (CHD) events in Chinese men with type 2 diabetes. BACKGROUND Subjects with diabetes are prone to develop cardiovascular complications. Erectile dysfunction is strongly associated with CHD in cross-sectional studies, but prospective data are lacking. METHODS A consecutive cohort of men with no clinical evidence of cardiovascular disease underwent comprehensive assessments for diabetic complications. Erectile dysfunction was defined according to the definition of the National Institutes of Health Consensus Conference 1992. Coronary heart disease events were censored with centralized territory-wide hospital databases in 2005. RESULTS Of 2,306 subjects (age: 54.2 +/- 12.7 years; follow-up: 4.0 [range 1.7 to 7.1] years), 26.7% had ED at baseline. The incidence of CHD events was higher in men with ED than those without (19.7/1,000 person-years, 95% confidence interval [CI] 14.3 to 25.2 person-years vs. 9.5/1,000 person-years, 95% CI 7.4 to 11.7 person-years). Men who developed CHD events were older; had a higher frequency of ED and microvascular complications; had longer duration of diabetes; and had higher blood pressure, total cholesterol, low-density lipoprotein cholesterol, and urinary albumin/creatinine ratio but lower high-density lipoprotein cholesterol and estimated glomerular filtration rate than those without CHD events. Erectile dysfunction remained an independent predictor for CHD events (hazard ratio 1.58, 95% CI 1.08 to 2.30, p = 0.018) after adjustment for other covariates along with age, duration of disease, and use of antihypertensive agents and albuminuria. CONCLUSIONS In type 2 diabetic men without clinically overt cardiovascular disease, the presence of ED predicts a new onset of CHD events. Symptoms of ED should be independently sought to identify high-risk subjects for comprehensive cardiovascular assessments.

The Reproducibility and Usefulness of the Oral Glucose Tolerance Test in Screening for Diabetes and other Cardiovascular Risk Factors

We examined the reproducibility of oral glucose tolerance tests (OGTT) using the World Health Organization criterion in 212 Chinese subjects (male 149, female 63) who underwent two 75 g OGTTs within a 6-week period. The overall reproducibility was 65.6% (139/212) of which 74 subjects had normal glucose tolerance, 24 had diabetes and 41 had impaired glucose tolerance (IGT) on two occasions. The subjects were divided into three groups [group 1: normal OGTTs on both occasions (n = 74); group 2: one abnormal OGTT (either diabetes or IGT (n = 51); group 3: 2 abnormal OGTTs (n = 87)]. Subjects in group 1 were younger, had lower blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), fasting and 2 h plasma insulin levels, triglyceride, very — low density lipoprotein and apolipoprotein-B concentrations than both groups 2 and 3. Group 2 had similar characteristics as group 3 except for a lower glycated haemoglobin (HbA1c), fasting and 2 h plasma glucose during the two OGTTs. With receiver operating characteristic curve (ROC) analysis, a HbA1c. of 5.3% gave an optimal sensitivity of 70.7% and specificity of 74.3% to predict diabetes as defined by a 2h plasma glucose value ≥ 11.1 mmol/L in the first OGTT. Of the 212 subjects, 73 had HbA1c ≥ 5.3%. The reproducibility of OGTT was 56.2% for these 73 subjects. With ROC analysis, a BMI of 25 kg/m2 gave an optimal sensitivity of 53.7% and specificity of 56.7% to predict diabetes. For the 36 subjects with BMI ≥ 25 kg/m2, the reproducibility of OGTT was 58.3%. Similarly, for the 140 subjects with WHR ≥ 0.9, the reproducibility of OGTT was 57.9%. These findings confirmed the poor reproducibility of OGTT which was not improved even amongst subjects with high HbA1c, BMI or WHR. Furthermore, subjects with one abnormal OGTT, whether reproducible or not, had a higher cardiovascular risk profile compared to subjects who had two normal OGTTs.

Associations of Hyperglycemia and Insulin Usage With the Risk of Cancer in Type 2 Diabetes: The Hong Kong Diabetes Registry

OBJECTIVE Insulin has mitogenic effects, although hyperglycemia may be a risk factor for cancer in type 2 diabetes. It remains uncertain whether use of insulin increases cancer risk because of its effect on cell growth and proliferation or decreases cancer risk because of its glucose-lowering effect. RESEARCH DESIGN AND METHODS A 1:2-matched new insulin user cohort on age (±3 years), smoking status, and likelihood of initiating insulin therapy (±0.05) was selected from a cohort of 4,623 Chinese patients with type 2 diabetes, free of cancer, and naive to insulin at enrollment. Stratified Cox regression analysis on the matched pairs was used to obtain hazard ratios (HRs) of insulin therapy and A1C for cancer risk. A structured adjustment scheme was used to adjust for covariates. RESULTS Of 973 new insulin users, 971 had matched nonusers (n = 1935). The cancer incidence in insulin nonusers was much higher than that in insulin users (49.2 vs. 10.2, per 1,000 person-years, P < 0.0001). After further adjustment for all other covariates with a P value less than 0.3 and nonlinear associations with cancer, A1C was associated with an increased cancer risk (HR per percentage 1.26, 95% CI 1.03–1.55), whereas use of insulin was associated with a decreased cancer risk (HR of insulin users vs. nonusers: 0.17, 0.09–0.32). Consistent results were found in analyses including all 973 insulin users and 3,650 nonusers. CONCLUSIONS In Chinese patients with type 2 diabetes, hyperglycemia predicts cancer, whereas insulin usage was associated with a reduced cancer risk.

Simple anthropometric indexes and cardiovascular risk factors in Chinese

OBJECTIVE: Obesity is a major public health problem due to its associations with multiple cardiovascular risk factors. Although there are sophisticated methods, such as imaging, to document total body fat and its distributions, anthropometric measurements remain important in clinical practice. We examined the relationships between cardiovascular risk factors and the three commonest anthropometric measurements for obesity, body mass index (BMI), waist–hip ratio (WHR) and waist circumference (WC), in Hong Kong Chinese subjects. DESIGN AND SETTING: The data are obtained from a prevalence survey for glucose intolerance and lipid abnormality in a representative Hong Kong Chinese working population. All employees from a public utility company and a regional hospital were invited to participate. SUBJECTS: There were 1513 subjects (910 men and 603 women, mean age ± s.e.m.: 37.5±0.2 y). All of them had no significant past medical history. MEASUREMENTS: BMI, WHR and WC of the 1513 subjects were assessed for their relationships with various cardiovascular risk factors. These include blood pressure, fasting and 2 h plasma glucose and insulin, glycated haemoglobin, total cholesterol, triglyceride, high density and low density lipoprotein cholesterol, and urine albumin concentration. RESULTS: After age adjustment, all three anthropometric indexes were significantly correlated with the major cardiovascular risk factors in both men and women. When BMI, WHR and WC were analysed according to quartiles, there was a significant trend for blood pressure, plasma triglyceride, fasting and 2 h plasma glucose and insulin to increase, and high density lipoprotein cholesterol to decrease, with increasing obesity after adjustment for age and smoking. Using stepwise regression analysis with the three indexes as independent variables, most of the variance in blood pressure, plasma lipid, insulin, glucose and urinary albumin concentration were explained either by WC or WHR. In women, BMI was the main explanatory variable for reduced high density lipoprotein cholesterol. CONCLUSIONS: In Hong Kong Chinese, BMI, WHR and WC provide important information in assessing cardiovascular risks. In men, central adiposity as reflected by WC and to some extent, WHR, explained most of the variance in blood pressure, plasma glucose, lipid, insulin and albuminuria. In women, all three indexes reflecting general and central obesity contribute to the variance in these risk factors.

Combined Use of a Fasting Plasma Glucose Concentration and HbA1c or Fructosamine Predicts the Likelihood of Having Diabetes in High-Risk Subjects

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.

Comparison of Insulin With or Without Continuation of Oral Hypoglycemic Agents in the Treatment of Secondary Failure in NIDDM Patients

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) <7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemie control, and quality of life were assessed before and at 3 and 6 months after stabilization. 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.

Development and Validation of an All-Cause Mortality Risk Score in Type 2 Diabetes: The Hong Kong Diabetes Registry

BACKGROUND Diabetes reduces life expectancy by 10 to 12 years, but whether death can be predicted in type 2 diabetes mellitus remains uncertain. METHODS A prospective cohort of 7583 type 2 diabetic patients enrolled since 1995 were censored on July 30, 2005, or after 6 years of follow-up, whichever came first. A restricted cubic spline model was used to check data linearity and to develop linear-transforming formulas. Data were randomly assigned to a training data set and to a test data set. A Cox model was used to develop risk scores in the test data set. Calibration and discrimination were assessed in the test data set. RESULTS A total of 619 patients died during a median follow-up period of 5.51 years, resulting in a mortality rate of 18.69 per 1000 person-years. Age, sex, peripheral arterial disease, cancer history, insulin use, blood hemoglobin levels, linear-transformed body mass index, random spot urinary albumin-creatinine ratio, and estimated glomerular filtration rate at enrollment were predictors of all-cause death. A risk score for all-cause mortality was developed using these predictors. The predicted and observed death rates in the test data set were similar (P > .70). The area under the receiver operating characteristic curve was 0.85 for 5 years of follow-up. Using the risk score in ranking cause-specific deaths, the area under the receiver operating characteristic curve was 0.95 for genitourinary death, 0.85 for circulatory death, 0.85 for respiratory death, and 0.71 for neoplasm death. CONCLUSIONS Death in type 2 diabetes mellitus can be predicted using a risk score consisting of commonly measured clinical and biochemical variables. Further validation is needed before clinical use.

Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus

Background: The risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy. Methods: We examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis. Results: During a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20–2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29–2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19–1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01–1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up. Interpretation: Among patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.

Hyperinsulinaemia and Na+, K+ -ATPase activity in thyrotoxic periodic paralysis

OBJECTIVE Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na+, K+ ‐ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na+, K+ ‐ATPase activity In thyrotoxic periodic paralysis (TPP) was examined.

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.