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Biomedical subjects

C S Cockram

Publications and source records attributed to C S Cockram.

At least 91 records · Page 5Linked to original sources
PubMed1999

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.

Adult↗
PubMed1999

Gastrointestinal symptoms in Chinese patients with Type 2 diabetes mellitus.

AIMS: To examine and compare gastrointestinal (GI) symptoms in Hong Kong Chinese Type 2 diabetic outpatients and non-diabetic control subjects. METHODS: A total of 149 Chinese Type 2 diabetic patients (66 men and 83 women, age (mean +/- SD) 46.8+/-11.1 years) newly referred to the diabetes clinic of the Prince of Wales Hospital, Hong Kong were examined. Sixty-five age and sex-matched non-diabetic subjects were recruited from the community as controls (22 men and 43 women, age (mean +/- SD) 46.5+/-6.6 years, P = 0.820). All patients were interviewed regarding GI symptoms over the past year, using a questionnaire that covered 14 items. A scoring system from 0 to 4 was used to grade severity. RESULTS: Diabetic patients had higher blood pressure, fasting plasma glucose and glycated haemoglobin and were more often smokers than control subjects. Of the 149 diabetic subjects, 105 (70.5+/-45.8%) had GI symptoms while only 20 (30.8%) of the 65 control subjects had GI symptoms (P<0.001). The respective percentages of upper and lower GI symptoms in diabetic and normal subjects were 44.3% vs. 24.6% (P = 0.006) and 54.4% vs. 13.9% (P<0.001). The three commonest GI symptoms in diabetic patients were diarrhoea (34.9%), constipation (27.5%) and epigastric fullness (16.8%). After adjustment for age, sex, duration of diagnosed diabetes and smoking, patients with or without metformin had similar percentages or scores for GI symptoms. On multivariate analysis using age, body mass index, fasting plasma glucose, glycated haemoglobin, duration of diagnosed diabetes and presence of peripheral neuropathy as independent variables, duration of diabetes was the only independent parameter associated with total score for GI symptoms (beta = 0.116, P = 0.003), for upper GI symptoms (beta = 0.073, P = 0.005) and for lower GI symptom (beta = 0.043, P = 0.020). CONCLUSIONS: Up to 70% of the Chinese Type 2 diabetic outpatients have GI symptoms, which is a much higher rate than in non-diabetic control subjects. Duration of diabetes is the most important factor associated with the presence of such GI symptoms.

Adult↗
PubMed1999

Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.

AIMS: To examine the prevalence of identified MODY-related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes. METHODS: Ninety-two unrelated Chinese subjects with diabetes diagnosed before the age of 40 years who had a positive family history of diabetes were screened for mutations in hepatocyte nuclear factors (HNF-1alpha and HNF-4alpha) and glucokinase genes by direct sequencing. The family members of patients with mutations and 100 healthy controls were also examined. RESULTS: Mutations in the HNF-1alpha and the glucokinase genes were found in 5% and 3% of the diabetic subjects, respectively but no mutations were found in the coding region of the HNF-4alpha gene. Three mutations found in the glucokinase gene were novel missense mutations (I110T, A119D and G385V). The mutations in the HNF-1alpha gene were also new and included four missense mutations (G20R, R203H, S432C, I618M) and one splice acceptor site mutation (IVS2nt-1G-->A). Patients with mutations in these genes were clinically heterogeneous with respect to phenotype and basal pancreatic beta cell function. CONCLUSIONS: Genetic factors such as mutations in the HNF-1alpha and glucokinase genes may be important in the development of diabetes in Chinese people, especially when the disease is of early onset.

Adolescent↗
PubMed1999

Clinical characteristics of acromegaly in Hong Kong.

This study analyses the clinical characteristics of acromegalic patients in Hong Kong. All patients with acromegaly under follow up in Prince of Wales Hospital, Hong Kong between January 1984 and December 1992 were reviewed retrospectively. Detailed hospital notes were available for review in 28 out of 34. Of the 28 patients with full records available, 27 were Chinese and 1 was Nepalese. There were 8 (28.6%) males and 20 (71.4%) females. The mean age (+/- SD) at presentation was 51.2+/-16.8 years (range: 28 to 84 years) (male, 49.9+/-13.9 years [range: 28-66]; female, 51.7+/-18.1 years [range: 31-84]; p-value: NS). The commonest mode of presentation (n=22, 78.6%) was clinical suspicion by medical staff during consultation for other conditions, acromegaly being later confirmed. The estimated duration of symptoms, before diagnosis, was 14 years (range: 1 to 30 years). CT scan imaging of the pituitary gland showed that 12 patients (42.9%) had pituitary macro-adenomas (> or =1 cm), 3 (10.7%) had micro-adenomas (<1 cm), 6 (21.4%) had normal imaging, 1 (3.6%) had an empty sella and 6 (21.4%) had suspicious but inconclusive lesions in the pituitary gland. Surgery was offered as initial treatment to all patients. 4 to 6 weeks after surgery, if the maximal growth hormone response following glucose loading exceeded 10 microg/L, radiotherapy was offered. Of the 28 patients, 13 received surgery and radiotherapy, 2 surgery only, 4 radiotherapy only, 4 no treatment and 5 defaulted. At presentation, 50% had some abnormality of glucose tolerance. The mean early morning fasting baseline growth hormone was 52.8+/-37.0 microg/L (mean +/- SD, median: 48.1 microg/L) and the maximal growth hormone response during an extended oral glucose tolerance test was 63.2+/-34.9 microg/L (median: 61.3 microg/L). Forty five percents of patients had a maximal growth hormone response exceeding 60 microg/L. Of the 19 patients who underwent surgery and/or radiotherapy, 15 had their pituitary function reassessed 6 months after intervention. Their early morning fasting growth hormone and maximal growth hormone response in an extended oral glucose tolerance test were 21.3+/-25.8 and 35.4+/-37.5 microg/L, respectively. In conclusion, acromegaly in Hong Kong has an estimated annual incidence of 3.8 per million. There is a female preponderance, tendency to late presentation (>10 years) and low number of large tumors. Up to 80% were referred following observer suspicion.

Acromegaly↗
PubMed1999

Glucose intolerance and other cardiovascular risk factors in chinese women with a history of gestational diabetes mellitus.

Women with a history of gestational diabetes (GDM) are at increased risk of developing diabetes compared with other women. There are few data on associations between GDM and cardiovascular risk factors. Between 1988 and 1995, 801 Chinese women with a history of GDM were recruited for a 75g oral glucose tolerance test (OGTT) and assessment of various cardiovascular risk factors, namely obesity, hypertension and dyslipidaemia, 6 weeks after delivery at the Diabetes Centre of the Prince of Wales Hospital. Another 431 women with no past history of diabetes or GDM recruited in a diabetes prevalence study were used as control subjects. After adjustment for age, body mass index and smoking, the prevalence of glucose intolerance remained higher in women with a history of GDM when compared to normal controls. The relative risks of obesity, hypertension, dyslipidaemia, diabetes and impaired glucose tolerance in women with a history of GDM comparing to normal subjects were, respectively, 2.4, 7.5, 2.4, 8.1 and 5.0. After excluding those with abnormal glucose tolerance, subjects with a history of GDM still had more adverse cardiovascular risk factors, including higher blood pressure, glycaemic and lipid parameters, than control subjects (after adjustment for age, body mass index and smoking). In conclusion, compared with normal subjects, Chinese women with a history of GDM had an 8-fold increased risk of having diabetes based on their OGTTs performed 6 weeks postdelivery. These women also have increased rates of other cardiovascular risk factors including obesity, high blood pressure and dyslipidaemia.

Adolescent↗
PubMed1999

Gynaecomastia as a presenting feature of thyrotoxicosis.

The association between gynaecomastia and thyrotoxicosis is well recognised. However, the reported frequency of the association is variable, partly depending upon the defining criteria used. Here we report two patients with thyrotoxicosis in whom gynaecomastia was the presenting feature. Both patients had other contributing factors, which are assumed to have predisposed to gynaecomastia. In both patients, the gynaecomastia resolved with successful treatment of the thyrotoxicosis. When gynaecomastia is a presenting, or prominent feature of thyrotoxicosis, the possibility of additional underlying pathology should be considered.

Adult↗
PubMed1999

Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients.

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.

Adolescent↗
PubMed1998

Glycated haemoglobin and cardiovascular risk factors in Chinese subjects with normal glucose tolerance.

Increased plasma glucose concentration is a predictive factor for mortality in both diabetic and non-diabetic subjects. Although glycated haemoglobin (HbA1c) is a useful index of mean blood glucose concentrations over the preceding 1 to 3 months, there are few data regarding its relationship to cardiovascular risk. We have examined the relationship between HbA1c and cardiovascular risk factors in 1280 subjects with normal glucose tolerance. Based on HbA1c tertiles (tertile 1: n = 427, 262 men and 165 women, HbA1c level: 2.9-4.7% in men and 3.2-4.2% in women; tertile 2: n = 426, 261 men and 165 women, HbA1c level: 4.7-5.1% in men and 4.2-4.6% in women; tertile 3: n = 427, 262 men and 165 women, HbA1c level: 5.1-6.7% in men and 4.6-6.9% in women), increasing HbA1c was associated with increasing age, blood pressure, waist-hip ratio, fasting and 2-h plasma glucose, 2-h insulin, cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and urate concentrations. When age and sex were included as covariates, increasing HbA1c remained associated with increasing fasting and 2-h plasma glucose, 2-h insulin, total cholesterol, and low-density lipoprotein cholesterol concentrations. These findings emphasize the importance of hyperglycaemia, as reflected by HbA1c, as a continuum in the evaluation of cardiovascular risk. Furthermore, these findings support the hypothesis that cardiovascular disease risk commences with rising glucose concentrations before 'conventionally-defined' glucose intolerance occurs.

Adult↗
PubMed1998

Short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes mellitus and mixed dyslipidemia.

In type 2 diabetes, it is not uncommon to find an elevated serum triglyceride and/or reduced high-density lipoprotein (HDL) cholesterol levels; elevated total cholesterol levels often occur as well. To evaluate the short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes who have mixed dyslipidemia, an open-label 6-month trial was conducted. All patients had type 2 diabetes (n = 33) with total cholesterol > or = 6.2 mmol/L and fasting triglyceride > or = 2.8 mmol/L, which had been confirmed twice and persisted for at least 12 weeks after introduction of diet control. After a 4-week run-in period, they were given lovastatin 40 mg daily at night for 12 weeks. Acipimox 250 mg three times a day was then added for a further 12 weeks. After 12 weeks of treatment with lovastatin alone, improvement was observed in total cholesterol (21% reduction), triglyceride (32% reduction), low-density lipoprotein (LDL) cholesterol (5.5% reduction), HDL cholesterol (11.6% elevation), apolipoprotein A-I (4.6% elevation), and apolipoprotein B (20.5% reduction). The addition of acipimox to lovastatin for an additional 12 weeks further reduced serum total cholesterol, triglyceride, LDL cholesterol, and apolipoprotein B, but this additional decrease was not statistically significant. However, HDL cholesterol and apolipoprotein A-I levels were significantly increased by the addition of acipimox (a 14.2% and 9.0% elevation, respectively). Serum creatine phosphokinase increased slightly after 12 weeks of lovastatin but decreased to a concentration similar to baseline after 12 weeks of combination treatment. No patients reported muscle pain or weakness or other side effects. Combination treatment with lovastatin and acipimox appears to be a safe and effective therapy in patients with type 2 diabetes and mixed dyslipidemia, and has particular benefit in elevating serum HDL cholesterol and apolipoprotein A-I levels.

Adult↗
PubMed1998

The association between dyslipidaemia and obesity in Chinese men after adjustment for insulin resistance.

Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.

Adult↗
PubMed1998

No evidence for allelic association of a human CTLA-4 promoter polymorphism with autoimmune thyroid disease in either population-based case-control or family-based studies.

OBJECTIVE: The cytotoxic T lymphocyte associated-4 (CTLA-4) gene is a candidate for T-cell mediated autoimmune disease and polymorphism has been reported to be associated with both type 1 diabetes and autoimmune thyroid disease. A previously unreported polymorphism of the promoter region of the human CTLA-4 gene has recently been described in a sample of a normal control population. We investigated the distribution of this polymorphism, situated at position -318 to the ATG start codon and resulting in a C-T change leading to an Mse I restriction site, in both population based case control studies and family studies in patients with Graves' disease (Caucasian and Hong Kong Chinese), autoimmune hypothyroidism and systemic lupus erythematosus (SLE). DESIGN: Target DNA was amplified using the polymerase chain reaction and the resulting product was digested using the Mse I restriction enzyme. PATIENTS: One hundred and ninety-one white UK Caucasian and 98 Hong Kong Chinese patients with Graves' disease, 78 white UK Caucasian patients with Graves' disease plus family members, 92 white UK Caucasian patients with autoimmune hypothyroidism, 13 white UK Caucasian patients with autoimmune hypothyroidism plus family members, 132 white UK Caucasian patients with systemic lupus erythematosus, 355 white UK Caucasian control subjects and 82 Hong Kong Chinese control subjects. MEASUREMENTS: Frequencies of the C and T alleles were compared between patients and control subjects using the chi 2-test and Fisher's exact test for small numbers. RESULTS: No association with the T allele was observed in any of the patient groups studied. CONCLUSION: These data suggest that the C-T change in exon 1 of the promoter region of the CTLA-4 gene does not play a role, nor is in linkage disequilibrium with a disease causing mutation, in the development of autoimmune disease.

Abatacept↗
PubMed1998

A novel PCR-based methodology to determine TAP allele frequencies in population studies.

The TAP genes have been extensively studied as candidate susceptibility genes for autoimmune and infectious diseases. TAP1 and TAP2 have two and three polymorphic sites respectively which are used for the allele assignment following WHO nomenclature. The usual techniques employed to determine the TAP alleles cannot unequivocally ascertain the alleles present in subjects which are heterozygous at more than one polymorphic position within the genes. This results in an inability to determine absolute TAP allele frequencies in population studies. The aim of this study was to devise a PCR-based method to unambiguously assign TAP alleles to all subjects. The novel method was tested in Oriental Type I diabetic and control subjects. The technique is a valuable tool for allele assignment in heterozygous subjects solely using PCR.

Alleles↗
PubMed1998

Evaluation of glucose intolerance in pregnancy using biochemical markers of fetal hyperinsulinemia.

We aimed to evaluate gestational impaired glucose tolerance (GIGT) in untreated patients using umbilical cord blood insulin and connecting peptide (C-peptide) concentrations to indicate fetal hyperinsulinemia. A 75 g, 2-hour oral glucose tolerance test, evaluated using WHO criteria, was performed in 722 antenatal patients. Cord C-peptide (p = 0.001) and insulin (p = 0.008) concentrations were significantly higher in patients with GIGT in comparison to those with normal glucose tolerance. The WHO test failed to identify abnormal C-peptide concentrations (p = 0.057), but did identify abnormal insulin concentrations (p = 0.006) and cases where either or both were raised (p = 0.002), with a low Youden's index (range 8.1-11.3) in all 3 cases. A significant biochemical difference exists in patients with GIGT. The WHO criteria for GIGT predict abnormal biochemical outcomes, but they do so poorly.

Biomarkers↗