Clive S. Cockram

Prediction of hypertension, diabetes, dyslipidaemia or albuminuria using simple anthropometric indexes in Hong Kong Chinese

OBJECTIVE: It is important to determine what values of simple anthropometric measurements are associated with the presence of adverse cardiovascular risk factors such as diabetes or hypertension to provide an indication for further detailed investigations. In this analysis, we aimed to assess which anthropometric cutoff values are best at predicting the likelihood of diabetes, hypertension, dyslipidaemia and albuminuria in Hong Kong Chinese.DESIGN AND SETTING: The data were obtained from a previously reported prevalence survey for glucose intolerance in a representative Hong Kong Chinese working population.SUBJECTS: 1513 subjects (910 men and 603 women) with mean age±s.d. 37.5±9.2 y.MEASUREMENTS: We examined the likelihood ratios of having diabetes, hypertension, dyslipidaemia and albuminuria in subjects with various cutoff values of the four simple anthropometric indexes, namely, body mass index, waist-hip ratio, waist circumference and the ratio of waist-to-height.RESULTS: We developed a nomogram to show the predictive values of different indexes for the cardiovascular risk factors using likelihood ratio analysis. Using Caucasian mean levels of the simple anthropometric indexes to predict diabetes or hypertension in Hong Kong Chinese gave a high likelihood ratio of 2:3:5.CONCLUSION: Higher levels of body mass index, waist-hip ratio, waist circumference and the ratio of waist-to-height are associated with risk of having diabetes mellitus or hypertension in Hong Kong Chinese as in Caucasians. However, the cutoff values of those anthropometric indexes to define obesity used in Caucasians may not be applicable to Chinese.

Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza

Abstract BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 [95% confidence interval, +0.03 to +1.68]). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β [standard error], −1.19 [0.43] and −0.68 [0.33] log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 [95% confidence interval, 0.03–0.35] and 0.30 [0.10–0.90] for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001) ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance

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.

Outcomes of adults hospitalised with severe influenza

Background The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza. Methods A prospective, observational cohort study was conducted over 24 months (2007–2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates. Results 754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70±18 years; co-morbidities and serious complications were common (61–77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation. Conclusions Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.

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.

The prevalence of diabetes mellitus and impaired glucose tolerance among Hong Kong Chinese adults of working age

We studied 1513 employees (910 men and 603 women) from a public utility company and a regional hospital to document the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the Chinese working population of Hong Kong using a 75-g oral glucose tolerance test and World Health Organisation (1985) criteria. The overall prevalence of DM was 4.5 (95% confidence interval: 3.5-5.7%) and that of IGT 7.3 (6.0-8.6%). The prevalence of DM was 5.1 (3.7-6.5%) in men and 3.6 (2.1-5.1%) in women, while that of IGT was 7.4 (5.7-6.5%) in men and 7.1 (5.1-9.1%) in women. The truncated age-adjusted rate of DM for age 30-64 is 7.7% which is comparable to the age-adjusted prevalence rates among Chinese living in Singapore and Mauritius but in marked contrast to the low prevalence rate in Chinese living in Mainland China. Among the diabetic subjects, 38.2% had been previously diagnosed and 32% gave a family history affecting at least one first degree relative. Using polychotomous logistic regression analysis, the independent predictive factors for the development of DM include age (t = 7.31, P < 0.001), family history (t = 5.1, P < 0.001), waist hip ratio (t = 4.05, P < 0.001) and body mass index (t = 4.62, P < 0.001). Our data further confirm that Hong Kong Chinese have a moderate to high susceptibility to non-insulin-dependent diabetes (NIDDM) when exposed to sufficient environmental and lifestyle factors. The high prevalence of IGT indicates a potential for the prevalence of DM to continue to rise unless effective preventive measures are implemented.

Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak

Background: The outcome is reported of a prospective uncontrolled study based on a stepwise treatment protocol during an outbreak of severe acute respiratory syndrome (SARS) in Hong Kong. Method: One hundred and thirty eight patients were treated with broad spectrum antibiotics, a combination of ribavirin and low dose corticosteroid, and then intravenous high dose methylprednisolone according to responses. Sustained response to treatment was defined as (1) defervescence for ⩾4 consecutive days, (2) resolution of lung consolidation by >25%, and (3) oxygen independence by the fourth day without fever. Patients with defervescence who achieved either criterion 2 or 3 were classified as partial responders. Patients who fell short of criteria 2 and 3 were non-responders. Results: Laboratory confirmation of SARS coronavirus infection was established in 132 (95.7%). None responded to antibiotics but 25 (18.1%) responded to ribavirin + low dose corticosteroid. Methylprednisolone was used in 107 patients, of whom 95 (88.8%) responded favourably. Evidence of haemolytic anaemia was observed in 49 (36%). A high level of C-reactive protein at presentation was the only independent predictor for use of methylprednisolone (odds ratio 2.18 per 10 mg/dl increase, 95% confidence interval 1.12 to 4.25, p = 0.02). Thirty seven patients (26.8%) required admission to the intensive care unit and 21 (15.2%) required invasive mechanical ventilation. There were 15 deaths (mortality rate 10.9%), most with significant co-morbidities, whereas 122 (88.4%) had been discharged home 4 months after the outbreak onset. Conclusion: The use of high dose pulse methylprednisolone during the clinical course of a SARS outbreak was associated with clinical improvement, but randomised controlled trials are needed to ascertain its efficacy in this condition.