To: Holstein A, Stumvoll M (2005) Contraindications can damage your health--is metformin a case in point? Diabetologia 48:2454-2459.
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Biomedical subjects
Publications and source records attributed to R C W Ma.
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Although much emphasis has been placed on screening for albuminuria in type II diabetic patients, less attention has been focused on the role of glomerular filtration rate (GFR) in the assessment of risk. Herein, we examined the association between GFR and vascular complications in a consecutive cohort of 5174 type II diabetic patients between 1995 and 2000. Renal function was assessed by GFR (estimated by Modification of Diet in Renal Disease equation). The frequency of chronic kidney disease (CKD) as defined by GFR <60 ml/min/1.73 m(2), micro- and macrovascular complications, and their associations were analyzed. In this study cohort, 6% had serum creatinine > or =150 micromol/l and 15.8% had CKD. After adjustment for potential confounders, including urinary albumin excretion, odds ratios [95% confidence interval (CI)] across different stages of estimated GFR (> or =90, 60-89, 30-59, 15-29, <15 ml/min/1.73 m(2)) for macrovascular disease were 1.00, 1.42 [1.12-1.80], 1.80 [1.32-2.45], 2.74 [1.64-4.56], and 4.05 [1.77-9.26], respectively (P for trend <0.001); for retinopathy were 1.00, 1.23 [1.04-1.46], 1.80 [1.40-2.30], 2.05 [1.25-3.37], and 4.12 [1.56-10.90], respectively (P for trend <0.001); for sensory neuropathy were 1.00, 1.53[1.27-1.85], 2.09 [1.58-2.76], 4.32 [2.41-7.77], and 3.16 [1.25-8.02], respectively (P for trend <0.001); and for microalbumuria (with GFR <15 ml/min/1.73 m(2) excluded from the analysis) were 1.00, 1.51 [1.30-1.75], 5.80 [4.52-7.44], and 52.5 [16.4-168.2] respectively (P for trend <0.001). Measurement of serum creatinine alone without GFR may underestimate renal impairment in type II diabetic patients. Decreasing GFR was significantly associated with increasing frequency of micro- and macrovascular complications.
Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin-angiotensin-aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (+/- standard deviation) age of 59.7 +/- 13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.
BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.
OBJECTIVES: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria. DESIGN: Retrospective study. SETTING: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong. PATIENTS: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria. MAIN OUTCOME MEASURES: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance. RESULTS: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests. CONCLUSIONS: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.
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UNLABELLED: Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type 2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI). RESULT: Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations (P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5 +/- 16.8 ng/ml, DM: 14.6 +/- 10.5 ng/ml and control: 9.1 +/- 7.1 ng/ml). Women had higher serum leptin concentration than men in the control group (12.5 +/- 7.3 ng/ml versus 4.2 +/- 2.0 ng/ml, P=0.001) and in the DM group (18.9 +/- 11 ng/ml versus 8.6 +/- 5.9 ng/ml, P=0.07) whereas this gender difference was not observed in the DMN group (18.6 +/- 17.0 ng/ml versus 16.8 +/- 17.0 ng/ml, P=0.754). On multivariate analysis, ACR (=0.411, P<0.001) and BMI (=0.240, P=0.002) were independently associated with serum leptin concentrations (R2=0.194, F=22.1, P<0.001) in the whole group. In the DMN group, ACR (=0.370, P=0.016) was the only independent determinant of serum leptin concentrations (R2=0.159, F=11.4, P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.
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BACKGROUND: Chinese Type 2 diabetic subjects are generally less obese than their Caucasian counterparts. We hypothesized that lean and obese Chinese Type 2 diabetic subjects have different metabolic and insulin secretory profiles. We compared the clinical features, C peptide and metabolic status between lean/normal weight and obese diabetic subjects. STUDY DESIGN: We conducted a cross-sectional study on 521 consecutive diabetic subjects newly referred to a Diabetes Clinic in 1996. The subjects were categorized into underweight (< 18.5 kg/m(2)), normal weight (18.5-23 kg/m(2)) and overweight (>/= 23 kg/m(2)) according to the re-defined WHO criterion for obesity in Asia Pacific Region. Metabolic and anthropometric parameters were compared between groups with different levels of obesity. RESULTS: In this cohort, 5.8, 30.6 and 63.7% of subjects were underweight, normal weight and overweight, respectively, using the 'Asian' criteria. Of these 521 subjects, 20% had fasting C-peptide less than 0.2 nmol/l, suggesting insulin deficiency. Fasting C-peptide showed linear increasing trend (P < 0.001) while HbA(1c) showed decreasing trend (P = 0.001) with BMI after adjustment for duration of disease. There were more subjects in the underweight group who were treated with insulin (41.3% vs. 13.9 and 8.2%, P < 0.001). Although homeostasis model assessment was similar amongst the three groups, systolic (P = 0.006) and diastolic blood pressure (P < 0.001) and triglyceride (P < 0.001) showed increasing, while HDL-C (P < 0.001) showed decreasing, trends across different BMI groups. The underweight patients had the lowest C-peptide and highest HbA(1c) while overweight patients had the highest C-peptide, blood pressure, triglyceride but lowest HbA(1c) levels. CONCLUSION: In Chinese Type 2 diabetic patients, lean subjects had predominant insulin deficiency and obese subjects had features of metabolic syndrome. Clinicians should have low threshold to initiate insulin therapy in lean Type 2 diabetic patients with suboptimal glycaemic control. In obese diabetic patients, aggressive control of multiple cardiovascular risks is of particular importance.
We report on two patients with systemic lupus erythematosus, both of whom developed suppurative thyroiditis. One suffered from Staphylococcus aureus-induced thyroiditis and the other had tuberculous thyroiditis. The occurrence of tuberculous thyroiditis in systemic lupus erythematosus has not previously been reported. The diagnoses were made by fine-needle aspiration biopsy and subsequent bacteriological confirmation. Transient alteration of thyroid function was observed in both patients. In patients with systemic lupus erythematosus who present with fever and anterior neck pain, infection of the thyroid gland should be considered, and appropriate investigations undertaken.
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.
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BACKGROUND: To examine the lipid profile in Chinese type 2 diabetic patients and their relationship with anthropometric parameters, glycaemic control and cardiovascular mortality. METHODS: A consecutive cohort of 562 newly referred patients with type 2 diabetes to a hospital-based diabetes centre were examined in 1996. Subjects treated with lipid lowering drugs at the time of referral were excluded. A total of 517 subjects were followed up over a mean (+/-SD) period of 4.6 +/- 0.9 years. Glycated haemoglobin (HbA1c), fasting insulin and lipid profile and anthropometric parameters were documented at the time of recruitment. Cardiovascular mortality, mainly due to coronary heart disease and stroke, was ascertained using death registry and review of hospital case notes in 2001. RESULT: Of the 517 subjects (mean age of 54.0 +/- 14.0 years), 42.6% were men. In this cohort, 63.3% of subjects were either overweight (BMI > or = 23 kg/m2) or obese (BMI > or = 25 kg/m2) using Asian criteria. The mean (+/-SD) total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C) and geometric mean (x// antilog SD) of triglycerides (TG) were 5.6 +/- 1.3 mmol/L, 3.6 +/- 1.1 mmol/L, 1.3 +/- 0.3 mmol/L and 1.46x//1.90 mmol/L respectively. TC and LDL-C correlated positively with HbA1c, HDL-C negatively with BMI and WC (waist circumference), while TG positively with HbA1c, BMI, WC and HOMA (insulin resistance estimated using the homeostasis model assessment). During the 4.6 years follow-up period, there were 61 deaths giving a total mortality rate of 11.4%, of which 15 (25%) were because of cardiovascular events. Apart from age and disease duration, logarithm of TG was significantly associated with increased risk of cardiovascular mortality (p = 0.049, relative risk = 2.97, 95% CI 1.00-8.77). CONCLUSIONS: Chinese type 2 diabetic patients had a lower prevalence of obesity, lower TG and higher HDL-C than Caucasian patients. Despite the low incidence of cardiovascular death, TG, which was closely associated with obesity indexes, was significantly associated with cardiovascular death in these patients.