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C S Cockram

Publications and source records attributed to C S Cockram.

At least 19 recordsLinked to original sources

Triglyceride, albuminuria and blood pressure are the major associations of non-fatal cardiovascular disease in Chinese type 2 diabetes.

Diabetes is associated with an increased risk of cardiovascular disease (CVD). We studied risk factors for CVD in a cohort of Chinese type 2 diabetic patients recruited between July 1994 and August 1998. Ischemic heart disease (IHD) was defined as a history of: (i) confirmed coronary artery disease (with typical electrocardiographic changes or a positive exercise tolerance test) in patients under care of a cardiologist; (ii) documented myocardial infarction; or (iii) coronary interventions such as angioplasty or coronary artery bypass graft. Cerebrovascular accident (CVA) was defined as any definite cerebral vascular event with or without residual neurological deficit. CVD was defined as a history of IHD or CVA. The study enrolled 3333 patients, including 1370 men (41.1%) and 1963 women (58.9%) of mean age 55.9+/-13.3 years (range, 16-91 years; median, 57 years). A total of 279 patients (8.4%) had CVD (including 4.1% with CVA, 4.9% with IHD, and 0.6% with both CVA and IHD). Men had an overall higher rate of CVD than women (10.1% vs. 7.1%, p=0.002). All cardiovascular diseases showed a progressive increase in prevalence with increasing age with the peak among those aged </=60 years. Logistic regression analysis was used to examine the predictive value of age, body mass index, waist-to-hip ratio, blood pressure, fasting plasma glucose, glycated hemoglobin, lipid profiles, albuminuria, smoking and family history of diabetes on the risk of CVD. In women, age, systolic blood pressure and triglyceride level and in men, age and albuminuria, were predictive for CVD. In conclusion, 8.4% of Hong Kong Chinese type 2 diabetic patients being followed in a hospital out-patient setting have a history of established and confirmed cardiovascular disease. Age, systolic blood pressure, triglyceride and albuminuria were the major independent risk factors for non-fatal cardiovascular diseases.

Adolescent↗

Peripheral vascular disease in Type 2 diabetic Chinese patients: associations with metabolic indices, concomitant vascular disease and genetic factors.

AIMS: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of vascular disease, but do not explain the lower burden of cardiac and peripheral vascular disease (PVD) in Chinese compared with Caucasians. The role of renin-angiotensin system (RAS) gene polymorphisms and conventional vascular risk factors has not been determined. METHODS: A total of 3097 Chinese diabetic subjects were screened for PVD, which was identified in 194 of the 2967 patients with Type 2 diabetes. Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms were then compared between the PVD patients and 1046 age, gender and diabetes duration-matched patients without PVD. RESULTS: PVD identified in 6.5% was associated with significantly worse glycaemic control, lipid profile and renal function. Smoking was more common, as were the other macro- and microvascular diseases. The prevalence of hypertension was similar between the groups, yet diastolic blood pressure was slightly lower in the PVD group. The ACE D allele was significantly more frequent in patients with PVD compared with the matched diabetic controls (38.1 vs. 29.8%, P = 0.039). No differences in the AT1R or AGT polymorphisms were observed. CONCLUSIONS: PVD was associated with a worse metabolic profile and greater concomitant vascular disease than controls. The ACE I/D polymorphism was associated with PVD in these Type 2 diabetic patients.

Aged↗

The contribution of metformin to glycaemic control in patients with Type 2 diabetes mellitus receiving combination therapy with insulin.

Combination therapy of oral hypoglycaemic agents and insulin is a therapeutic option for those who have deterioration in glycaemic control. We examined the contribution of metformin by withdrawing it from Type 2 diabetic patients who had been stabilised on combination therapy. Fifty-one subjects with Type 2 diabetes and secondary oral hypoglycaemic agent failure were studied in a randomised, open and parallel study. In the first phase of 36 weeks, subjects were stabilised on combined therapy of sulphonylureas and nocturnal insulin, with or without metformin. During the second phase, metformin was withdrawn. The primary variables for efficacy were HbA(1c), fasting plasma glucose and 3-point capillary blood glucose profiles. After stabilisation with combination therapy, those subjects on metformin used less insulin to maintain glycaemic control (13.7+/-6.8 vs. 23.0+/-9.4 U/day, P=0.001) and had lower HbA(1c) values (8.13+/-0.89 vs. 9.05+/-1.30%, P=0.003) compared with those not given metformin. Withdrawal of metformin therapy caused deterioration in HbA(1c) (P=0.001). This study confirms that metformin plays an important role in the success of the combination therapy. The rational use of metformin and sulphonylurea together with insulin will help to improve metabolic control in Type 2 diabetes patients who have secondary drug failure.

Blood Glucose↗

Obesity and cardiovascular risk factors in Hong Kong Chinese.

The purpose of this cross-sectional study was to examine the risk associations between obesity indexes [body mass index (BMI) and waist circumference (WC)], cardiovascular risk factors [plasma glucose and lipids, blood pressure and urinary albumin excretion (UAE)] and morbidity conditions (Type 2 diabetes mellitus, hypertension, dyslipidaemia and/or albuminuria) in Hong Kong Chinese. Seven-hundred and two Hong Kong Chinese subjects (18-65 years of age, 59.4% of whom had at least one morbidity condition) were recruited from the Prince of Wales Hospital, Hong Kong SAR. The measurements taken of the subjects included: height; weight; waist and hip circumferences; blood pressure; fasting plasma glucose and lipids; and 24-h UAE. The mean BMI was 22.4 and 25.7 kg m(-2) in healthy subjects and patients, respectively. The mean WC measurements of healthy subjects and patients were 77.1 and 86.4 cm in males and 71.0 and 81.8 cm in females, respectively. There were increasing trends between obesity indexes and the severity of cardiovascular risk factors and the prevalence of morbidity conditions (all P-values for trend <0.05). Using 19.0-20.9 kg m(-2) and <70 cm as a referent, subjects with a BMI of > or =25.0 kg m(-2) (in both sexes) and/or a WC of > or =85 cm in males and > or =75 cm in females had an age-adjusted odds ratio between 3.2 and 4.4 for the occurrence of at least one morbidity condition. Patients with a greater number of comorbidities also had higher BMI and WC measurements (all P-values for the trend were <0.05 with adjustment for age and gender). Hence, despite Hong Kong Chinese being less obese than Caucasians, the intimate relationships among obesity, cardiovascular risk factors and morbidity conditions remain. Our data support using lower BMI and WC levels to define obesity and its associated health risks rather than using the criteria established from Caucasians who generally have larger body frames.

Adolescent↗

Diabetes mellitus--a special medical challenge from a Chinese perspective.

As we enter the new millennium, Asia is being hit by an epidemic of diabetes and its related diseases. The rising prevalence of young onset diabetes which is closely associated with obesity and genetic factors as well as the increased propensity to develop kidney disease are special challenges in the management of Chinese diabetic patients. Although diabetic patients have earlier mortality and increased risks for micro and macrovascular complications, there is strong evidence that these devastating complications can be largely prevented by patient education, periodic assessments and use of appropriate therapeutic agents to optimize metabolic control and improve cardiovascular risk factors. However, a multidisciplinary approach is often required to deliver these complex disease management protocols. Hence, it is not surprising that large scale studies often revealed substandard diabetes management in both the hospital and community settings. This is often due to a combination of factors such as non-adherence to recommended guidelines both by patients and doctors as well as the 'non-urgent' and 'silent nature' of diabetes and its complications. To minimize the impacts of diabetes on quality of life, society productivity and utilization of health care resources, concerted efforts between health care professionals and public bodies are urgently needed to increase awareness, improve standards of care and develop better diagnostics and treatment modalities.

Asia↗

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.

Adult↗

Risk factors for cataract in Chinese patients with type 2 diabetes: evidence for the influence of the aldose reductase gene.

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5' of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over-presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non-Z; 38 vs. 50%, p<0.01), but under-presented the allele Z-4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z-4, Z-4+Z-4,non-Z-4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z-4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.

Aged↗

Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality.

OBJECTIVES: To evaluate whether there is one central abnormality contributing to the conditions associated with the metabolic syndrome (MES), or whether one abnormality is contributing on multiple levels. METHODS: We recruited 145 Chinese subjects aged 17-68 y with varying degrees of insulin-sensitivity (IS): 33 healthy, 59 with type 2 diabetes mellitus, 32 essential hypertensives and 21 dyslipidaemics. IS was evaluated by the short insulin sensitivity test using a 0.1 U/kg intravenous bolus dose of insulin. Blood pressure, anthropometric measures and biochemical parameters associated with IS were also measured. Exploratory factor analyses (EFA) were performed in the entire group of 145 subjects and in the 76 with normal glucose tolerance. RESULTS: EFA in all 145 subjects defined three distinct, independent factors. Factor 1 was interpreted as general and central adiposity, impaired IS and glucose intolerance, Factor 2 was associated with hypertension and general and central obesity, whilst Factor 3 was strongly related to low HDL-cholesterol and high triglyceride concentrations and weakly to waist circumference. In patients with impaired glucose tolerance, only two factors were identified; factor 1 related to reduced IS, impaired glucose tolerance, dyslipidaemia and general and central adiposity, and factor 2 which was related to blood pressure and general and central adiposity. CONCLUSIONS: These models suggest that the clustering of variables in MES is a result of multiple factors linked by adiposity and not a single aetiology. Furthermore, increases in blood pressure are related to obesity in these Chinese subjects rather than decreased IS per se.

Abdomen↗

Change of glycaemic status in Chinese subjects with impaired fasting glycaemia.

AIMS: To examine the risk of progression to diabetes in Chinese subjects with impaired fasting glycaemia (IFG) or normal fasting glucose (NFG). METHODS: Between 1988 and 1996, 657 Hong Kong Chinese subjects underwent annual screening, using an oral glucose tolerance test, until they had developed diabetes, or until June 1997, when the data were analysed. All subjects had a risk factor associated with the development of diabetes such as a history of gestational diabetes or a family history of diabetes. The follow-up interval for the subjects ranged from 0.87 to 8.54 years and of the 657, 319 had fasting plasma glucose levels of < 7.0 mmol/L where a fasting glucose level of > or = 7.0 mmol/L was used to diagnose diabetes RESULTS: Of the 319 nondiabetic subjects, 55 had IFG and 264 had NFG. After a median follow-up of 1.12 years (range: 0.87-8.54 years), 27 progressed to diabetes. The Kaplan-Meier analysis of progression to diabetes showed significant differences between subjects with IFG and subjects with NFG. Using Cox regression analysis, IFG (beta = 3.51, SE = 1.63, P = 0.032) and smoking (beta = 3.60, SE = 1.50, P = 0.017) were found to be independently associated with progression to diabetes. CONCLUSIONS: In Hong Kong Chinese with risk factors for glucose intolerance, IFG status is an independent risk factor for progression to diabetes.

Adult↗

The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects: evidence for associations with type 2 diabetes and cholesterol levels.

BACKGROUND AND OBJECTIVES: There has been evidence that the S20G mutation in the islet amyloid polypeptide (amylin) gene may be associated with type 2 diabetes. In the present study, we investigated the distribution of the mutation in Hong Kong Chinese, and examined whether there was evidence for associations between the mutation and type 2 diabetes and/or metabolic profiles. SUBJECTS AND METHODS: This study involved 227 early and 235 late-onset (defined as onset age < or = 40 and > 40 years, respectively) type 2 diabetic patients, as well as 126 nondiabetic subjects. The mutation was detected using a PCR-RFLP method. RESULTS: We identified six (2.6%) and one (0.4%) patients heterozygous for the mutation from the early and late-onset groups, respectively (P = 0.05). None of the nondiabetic subjects had the mutation. Insulin deficiency and poor glycaemic control were not common findings amongst carriers of the mutation. In the early onset group, the patients with the mutation had lower plasma levels of total (4.3 +/- 0.9 mmol/l vs. 5.3 +/- 1.1 mmol/l, P = 0.02) and low density lipoprotein (LDL)-cholesterol (2.3 +/- 0.7 mmol/l vs. 3.2 +/- 0.9 mmol/l, P = 0.01) than those without the mutation. CONCLUSIONS: Our data suggest that the islet amyloid polypeptide gene mutation might be associated with early occurrence of type 2 diabetes and lower plasma levels of total and low density lipoprotein-cholesterol in the Chinese population.

Adolescent↗

Relationships between the taqI polymorphism of the dopamine D2 receptor and blood pressure in hyperglycaemic and normoglycaemic Chinese subjects.

BACKGROUND: We have previously reported an association of the A2 allele of the dopamine D2 receptor (DRD2) TaqI polymorphism with increased blood pressure in normoglycaemic Chinese subjects, but conversely possibly with decreased indices of obesity. Hypertension is also a common feature of patients with type 2 diabetes, with up to 50% being hypertensive. OBJECTIVE: To compare the relationship between the DRD2 TaqI polymorphism, blood pressure and obesity in Chinese patients with and without fasting hyperglycaemia. METHOD: The DRD2 TaqI polymorphism was determined by PCR-RFLP in 519 normoglycaemic and 471 hyperglycaemic Chinese subjects, of whom 53.2 and 48.8% were hypertensive, respectively. RESULTS: In the normoglycaemic subjects there was a significant increase in mean arterial pressure (P= 0.041) with increasing proportions of the A2 allele, 95 +/- 16, 96 +/- 17 and 100 +/- 17 mmHg for the A1A1, A1A2 and A2A2 genotypes, respectively. However, the relationship was not observed in the subjects with fasting hyperglycaemia either in the total group or in the subgroup who were not receiving blood pressure-lowering medication (n = 383, 97 +/- 15, 98 +/- 14 and 97 +/- 15 mmHg, respectively). When the whole group was divided into those subjects obese by either body mass index or waist-to-hip ratio (n = 484) and those subjects not obese by both these criteria (n= 506), the A1 allele (49.2 vs. 43.8%, P = 0.02) and A1 allele containing genotypes (P = 0.03) were more frequent in the obese subjects. Similar relationships were seen in the normoglycaemic and hyperglycaemic groups separately, although these did not reach significance. CONCLUSIONS: In the normoglycaemic subjects, the A2 allele was associated with increased blood pressure and possibly lower indices of obesity, but in the hyperglycaemic subjects only the possible association with obesity was noted.

Adult↗

Obesity, insulin resistance and isolated low high-density-lipoprotein cholesterol in Chinese subjects.

AIM: Recent studies have shown that the risk of developing coronary heart disease in subjects with 'isolated low high-density-lipoprotein cholesterol (HDL-C)' (defined as HDL-C < 0.9 mmol/l and total cholesterol (TC) < 5.2 mmol/l) was similar to those with hypercholesterolaemia. We examined the prevalence of isolated low HDL-C in Hong Kong Chinese and its relationship with insulin resistance and triglyceride (TG) level. METHODS: Hong Kong Chinese subjects (n = 1493) recruited in a population-based prevalence survey for cardiovascular risk factors were examined. Insulin resistance was calculated using a computer-solved homeostasis model assessment method. RESULTS: Of the 1493 subjects, 72 (4.8%) had isolated low HDL-C, in whom half (n = 36) had TG > or = 1.7 mmol/l and half (n = 36) had TG < 1.7 mmol/l. Compared with the 'controls' (subjects with TC < 5.2 mmol/l and HDL-C > or = 0.9 mmol/l; TC > or = 5.2 mmol/l and HDL-C < 0.9 mmol/l; or TC > or = 5.2 mmol/l and HDL-C > or = 0.9 mmol/l, n = 1421), subjects with isolated low HDL-C and high TG were more obese, had higher plasma glucose, fasting and 2 h plasma insulin concentrations and insulin resistance. Subjects with isolated low HDL-C and TG < 1.7 mmol/l had similar insulin concentrations and insulin resistance, but were more obese than the 'controls'. Subjects with isolated low HDL-C and high TG also had higher fasting PG, insulin and insulin resistance than those with isolated low HDL-C and low TG. CONCLUSIONS: In this population-based study, 4.8% of Hong Kong Chinese had isolated low HDL-C, which was closely associated with obesity. The coexistence of high TG suggests an insulin-resistant state.

Adult↗

Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese.

The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.

Adult↗

Platelet Na,K-adenosine triphosphatase as a tissue marker of hyperthyroidism.

Platelet Na(+),K(+)-adenosine triphosphatase (ATPase) activity was measured in 34 (15 males, 19 females) healthy subjects, 89 (35 males, 54 females) hyperthyroid patients, and 34 (7 males, 27 females) treated hyperthyroid patients to assess the potential of this measurement as a tissue marker and diagnostic test for hyperthyroidism. Platelet Na(+),K(+)-ATPase activity was measured in platelet lysates by the rate of release of phosphate from adenosine triphosphate (ATP) in the presence and absence of ouabain. Platelet Na(+),K(+)-ATPase activity (median and range) in the hyperthyroid group (271, 169 to 821 pmol/h/g protein) was significantly higher compared with the healthy group (125, 74 to 185 micromol/h/g protein, P <.001 by Mann-Whitney U test). The treated hyperthyroid group had slightly, but significantly higher, free triiodothyronine (FT3) and free thyroxine (FT4), as well as platelet Na(+),K(+)-ATPase activity (147, 98 to 246 micromol/h/g protein, P <.05). If a platelet Na(+),K(+)-ATPase activity of 190 micromol/h/g protein was used as a cut off value, the specificity and sensitivity were 90% and 93%, respectively. We conclude that platelet Na(+),K(+)-ATPase may be a useful tissue marker of hyperthyroidism.

Adolescent↗