Social support, self-efficacy and their correlation among patients with Type 2 Diabetes Mellitus: A primary care perspective.

INTRODUCTION: Social support and self-efficacy are factors that influence patients' health behaviour. However, the relationship between these two factors among patients with Type 2 Diabetes Mellitus (T2DM) has not been adequately explored. This study aims to report social support and selfefficacy of Malaysian T2DM patients, and their correlations. METHODS: This cross-sectional questionnaire study involved 329 patients with T2DM who received their follow up at a public primary care clinic. Patients were selected via systematic random sampling. Patients self-completed locally adapted versions of the Medical Outcomes Study (MOS) Social Support Survey and Diabetic Management Self Efficacy Scale (DMSES). The scores of both tools were analysed to determine the association and correlation between social support and self-efficacy. RESULTS: The mean score for overall social support was 72.7±21.40 score range (0-100). "Affectionate support" was rated the highest averaged mean score at 78.31±23.71 (score range: 0-100). The mean DMSES score was 147.6±35.5 (score range :0-200), of which "medications" subscale was rated the highest with averaged mean scores 9.07±1.67 (score range: 0-10). Overall social support and self-efficacy were found to be weakly correlated (r=0.197, p<0.001). However, all subscales of social support were moderately correlated with "medications" subscale of self-efficacy. CONCLUSION: Social support is significantly associated with patients' self-efficacy in handling their own medications.

Swallowed foreign bodies in children: report of four unusual cases.

INTRODUCTION: Although a majority of ingested foreign bodies (FBs) pass down the gastrointestinal tract spontaneously, those that are sharp, pointed or large in size need removal to avert serious complications. We highlight the urgent need and utility of endoscopic accessories and technical artistry in safe retrieval of FBs in children. CLINICAL PICTURE: Four children had accidentally swallowed a nail, metallic dumbbell, open safety pin and a cushion pin respectively. They were symptom-free and the abdominal plain radiographs revealed foreign body in the stomach in all the cases. TREATMENT: Oesophago-gastro-duodenoscopy (OGD) was done in all the patients and could retrieve the nail, metallic dumbbell and open safety pin successfully using a Dormia basket, a polypectomy snare and a pair of rat-tooth forceps respectively. The cushion pin had migrated to the duodeno-jejunal junction within 4 hours of ingestion and necessitated open duodenotomy and retrieval. OUTCOME: All patients did well after the procedure with no complications. CONCLUSIONS: Swallowed FBs with pointed or sharp ends or large enough to cross the pylorus and duodenal sweep need removal and in the majority of the cases they can be retrieved by OGD. Sharp or pointed FBs that have crossed the second part of the duodenum necessitate urgent laparotomy for retrieval to prevent complications.

Duodenal duplication cyst communicating with an aberrant pancreatic duct.

Duodenal duplication cyst (DDC) is an uncommon congenital anomaly and is the rarest site for intraabdominal duplications. We report a case of DDC communicating with an aberrant pancreatic duct in a 2-year-old girl, with features of possible occult relapsing pancreatitis. The duplication cyst was successfully enucleated with excision of the aberrant pancreatic duct. The literature is reviewed, and the diagnostic modalities and management options are discussed.

The lipoprotein lipase S447X polymorphism and plasma lipids: interactions with APOE polymorphisms, smoking, and alcohol consumption.

We studied 4,058 subjects from a representative sample of the Singapore population 1) to determine the association between the S447X polymorphism at the LPL locus and serum lipid concentration in Chinese, Malays, and Asian Indians living in Singapore and 2) to explore any interactions with apolipoprotein E (APOE) genotype, exercise, obesity, cigarette smoking, and alcohol intake. Information on obesity, lifestyle factors (including smoking, alcohol consumption, and exercise frequency), glucose tolerance, and fasting lipids was obtained. Male and female carriers of the X447 allele had lower serum triglyceride concentrations and higher HDL cholesterol (HDL-C) concentrations. The association between the X447 allele and serum HDL-C concentration was modulated by APOE genotype in males and cigarette smoking and alcohol intake in females. The effect of the X447 allele was greatest in men who carried the E4 allele and women who smoked or consumed alcohol. The X447 allele at the LPL locus is common and associated with a less atherogenic lipid profile in Asian populations. Interactions with APOE genotype, cigarette smoking, and alcohol intake reinforce the importance of examining genetic associations, such as this one, in the context of the population of interest.

APOE polymorphism and lipid profile in three ethnic groups in the Singapore population.

BACKGROUND: Serum lipid concentrations are modulated by environmental factors such as exercise, alcohol intake, smoking, obesity and dietary intake and genetic factors. Polymorphisms at the Apolipoprotein E (APOE) locus have consistently shown a significant association with total and LDL-cholesterol (LDL-C). However, their impact on HDL-cholesterol (HDL-C) may be population dependent. Having three major ethnic groups within a similar social environment allows us to study the role of genetics and their interactions with lifestyle factors on the serum lipid profile and coronary risk in Asians. METHODS: This study included 1740 males (1146 Chinese, 327 Malays and 267 Asian Indians) and 1950 females (1329 Chinese, 360 Malays and 261 Asian Indians) with complete data on anthropometric indices, fasting lipids, smoking status, alcohol consumption, exercise frequency and genotype at the APOE locus. RESULTS: Malays and Asian Indians were more obese compared with the Chinese. Smoking was uncommon in all females but Malay males had significantly higher prevalence of smokers. Malays had the highest LDL-C whilst Indians had the lowest HDL-C, The epsilon 3 allele was the most frequent allele in all three ethnic groups. Malays had the highest frequency of epsilon 4 (0.180 and 0.152) compared with Chinese (0.085 and 0.087) and Indians (0.108 and 0.075) in males and females, respectively. The epsilon 2 allele was the least common in Asian Indians. Total cholesterol (TC) and LDL-C was highest in epsilon 4 carriers and lowest in epsilon 2 carriers. The reverse was seen in HDL-C with the highest levels seen in epsilon 2 subjects. The association between ethnic group and HDL-C differed according to APOE genotype and gender. Asian Indians had the lowest HDL-C for each APOE genotype except in Asian Indian males with epsilon 2, where HDL-C concentrations were intermediate between Chinese and Malays. CONCLUSION: Ethnic differences in lipid profile could be explained in part by the higher prevalence of epsilon 4 in the Malays. Ethnicity may influence the association between APOE genotypes and HDL-C. APOE genotype showed no correlation with HDL-C in Malay males whereas the association in Asian Indians was particularly marked. Further studies of interactions between genes and environmental factors will contribute to the understanding of differences of coronary risk amongst ethnic groups.

Statin therapy and small fibre neuropathy: a serial electrophysiological study.

We describe three patients who developed small fibre neuropathy after 1 month of statin therapy with clinical resolution upon prompt drug withdrawal. All patients showed abnormal sympathetic skin responses (SSR) in comparison with controls. SSRs returned to normal in tandem with clinical improvement. One patient redeveloped small and large fibre neuropathy when the similar drug was readministered. The SSR is of value in the electrophysiological assessment and follow-up of statin-related small fibre neuropathy.

The TaqIB and -629C>A polymorphisms at the cholesteryl ester transfer protein locus: associations with lipid levels in a multiethnic population. The 1998 Singapore National Health Survey.

The Singapore population comprises Chinese, Malays and Asian Indians. Within this population, Asian Indians have the highest rates of coronary heart disease, whereas Chinese have the lowest. Conversely, Indians have the lowest high-density lipoprotein cholesterol (HDL-C) concentrations, followed by Malays and Chinese. We studied the TaqIB and -629C>A polymorphisms at the CETP locus in 1300 Chinese, 364 Malay and 282 Asian Indian men, and in 1558 Chinese, 397 Malay and 306 Asian Indian women, to determine whether these polymorphisms are responsible for the ethnic difference in HDL-C concentration. The frequency of the B2 allele in Chinese, Malays and Indians was 0.384, 0.339 and 0.449 in men, and 0.379, 0.329 and 0.415 in women, respectively (p < 0.001). For the A-629 allele, the relative frequencies were 0.477, 0.423 and 0.592 in men and 0.486, 0.416 and 0.575 in women (p < 0.001). The two polymorphisms were in linkage disequilibrium (D / Dmax= 0.9772, p < 0.00001). The B2 and the A-629 alleles were associated with increased HDL-C concentrations in a dose-dependent manner. The B2 allele continued to show an association with HDL-C concentration, even after controlling for the genotype at position -629. Dietary cholesterol showed a significant interaction with the TaqIB polymorphism in determining HDL-C concentrations in Indians and Malays, but not in Chinese. In conclusion, the high frequencies of these polymorphisms in Asian Indians could not explain the observed ethnic differences in HDL-C concentration. Moreover, we observed an ethnic-specific interaction among dietary cholesterol, the TaqIB polymorphism and HDL-C concentrations.

Do Singapore patients require lower doses of statins? The SGH Lipid Clinic experience.

A substantial number of physicians in Asian countries believe that Asian patients need lower doses of statins to achieve therapeutic lipid target because of the smaller size of patients. This belief is deep rooted and we looked at the SGH Lipid Clinic to determine if our experience bears out this belief. Between 1996 and August 2000, the Lipid Unit treated a total of 841 patients, of which 548 patients (77.5% Chinese, 12.1% Malays, 7.6% Asian Indians; 49.6% males, 50.4% females; 54.7% diabetics, 45.3% non-diabetic) were on statins alone. These patients had > or =2 coronary risk factors, diabetes mellitus or documented coronary heart disease. The pre-treatment lipid levels or the worst lipid levels available were entered as the baseline lipid values (mean LDL-C: 5.38+1.5 mmol/l). Duration of therapy ranged from six months to five years. The choice and titration of statins were determined by attending physicians. The median statin dose (Simvastatin equivalent) was 20.0 mg with 52.5% requiring 20 mg or more. Statin dose did not differ between diabetic and non-diabetic subjects. The median statin dose was 15 mg for the lower two tertiles and 20 mg for the upper tertile; this difference did not achieve statistical significance. The reduction in LDL cholesterol was 41.5% (40.1-42.8) and total cholesterol was 33.0% (32.9-34.1). Only 25% of our patients achieved LDL cholesterol of less than 2.6 mmol/l whilst 77.5% had LDL cholesterol less than 3.4 mmol/l. Our experience at the Lipid Clinic suggests that the Asian patients require similar statin doses to achieve target cholesterol levels.

The relationship between insulin resistance and cardiovascular risk factors in overweight/obese non-diabetic Asian adults: the 1992 Singapore National Health Survey.

OBJECTIVE: Insulin resistance (IR) is associated with cardiovascular risk factors including hypertension, dyslipidemia, glucose intolerance and hyperuricemia. The relationship between IR and these cardiovascular risk factors in obese non-diabetic individuals is not well studied. We explore this relationship by comparing the cardiovascular risk factors among insulin-sensitive and insulin-resistant overweight/obese non-diabetic Asian adults in the 1992 National Health Survey of Singapore. DESIGN AND MEASUREMENTS: A total of 3568 subjects were examined in the survey, which involved a combination of disproportionate stratified sampling and systematic sampling. Anthropometric measurements, level of physical activity, blood pressure, insulin, lipid profile, uric acid and standard 75 g oral glucose tolerance test were performed after a 10 h overnight fast. Subjects with diabetes were excluded from the analysis. Homeostasis model assessment (HOMA) was used to assess insulin sensitivity. Relative LDL size was derived from the formula LDL/ApoB. We defined insulin-sensitive individuals as having a HOMA value <1.479 (below median in individuals without diabetes; n=3226) and overweight/obesity as body mass index (BMI) >or=25.0 kg/m(2). RESULTS: There were 156 insulin-sensitive (S) and 679 insulin-resistant (R) overweight/obese individuals, respectively. The groups did not differ in terms of gender and ethnic distribution and level of physical activity. However, subjects in group S were younger than those in group R (mean+/-s.d.; 40.1+/-12.1 vs 42.4+/-12.7 y; P<0.05). Group R individuals were also slightly more obese globally and centrally than group S (BMI=28.2+/-3.2 vs 27.1+/-2.8 kg/m(2); waist circumference (WC)=86.7+/-9.3 vs 82.5+/-8.3 cm; P<0.01). There were more subjects with impaired glucose tolerance (IGT) in group R than in group S (29.7 vs 16.0%; P<0.01). After adjustment for age and indices of global and regional obesity (ie BMI and WC), insulin-resistant individuals showed higher apolipoprotein B, triglyceride, fasting (FPG) and 2 h post-load plasma glucose (2hPG) but lower HDL and LDL size. Further adjustment for FPG, 2hPG and level of physical activity had minimal impact on the results. CONCLUSIONS: Insulin-resistant overweight/obese non-diabetic Asian adults had greater burden of the cardiovascular dysmetabolic syndrome than insulin-sensitive overweight/obese individuals. This could not be fully explained by differences in global and regional obesity, glucose tolerance and level of physical activity.

New clues for the developing human biliary system at the porta hepatis.

The human biliary system is formed from the hepatic diverticulum, a structure which develops from the embryonic foregut in the fourth week of gestation. The cephalic portion of the hepatic diverticulum lies within the septum transversum, and gives rise to entodermal cells which become the primitive hepatocytes. The caudal part of the hepatic diverticulum is molded by mesenchyme to form the gallbladder, cystic duct, and extrahepatic bile duct. The gallbladder is initially tubular in shape, and undergoes morphological changes to become saccular during the 11th week of gestation. The extrahepatic bile duct elongates and widens as gestation progresses, and intramural mucus glands develop. There is no solid stage during the development of the extrahepatic bile duct. The extrahepatic bile duct is a well-defined tubular structure by the 6th week of gestation, whereas the intrahepatic biliary system during this period of gestation is represented by the primitive ductal plate. The ductal plate undergoes structural changes from the 11th week of gestation, beginning at the porta hepatis and progressing through gestation to the periphery of the liver. This remodeling process shapes the ductal plate from a flat sheath of biliary epithelium surrounding the portal vein branches into a network of interconnecting tubular structures. Mesenchyme plays an important role in ductal plate remodeling. The intrahepatic biliary system is in luminal continuity with the extrahepatic bile duct throughout gestation at the porta hepatis. The major bile ducts at the porta hepatis are fully formed by the 16th week of gestation.

The prognostic value of ductal plate malformation and other histologic parameters in biliary atresia: an immunohistochemical study.

Ductal plate malformation, a term given to intrahepatic bile ducts that retain the fetal configuration, is observed in some cases of biliary atresia. We examined 21 livers from patients with biliary atresia; ductal plate malformation occurred in 38% of cases, and its presence was predictive of poor clinical outcome (P =.04).

Protection of salvia miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats dual mechanisms involved.

Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 microg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.

In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects.

OBJECTIVE: To investigate the effects of Absorbitol on body weight, anthropometry, body composition, blood pressures and lipid profiles in obese, hypercholesterolaemic subjects without dietary restriction. DESIGN: A randomised, double blind. Placebo-controlled study. SUBJECTS: Normal volunteers with no history of chronic illnesses (n=88) who were obese (body fat percentage > 20% in males and > 30% in females) and hypercholesterolaemic (total cholesterol > 5.20 mmol/L). Sixty-eight (72.3%) subjects completed the study. INTERVENTION: After a 4 week run in phase, 4 placebo/Absorbitol (250 mg) capsules were prescribed 3 times a day before meals. Subjects received written information on healthy lifestyle but there was no dietary restriction or monitoring. MAIN OUTCOME MEASURES: Weight, body mass index, lean body mass, waist, hip, blood pressure, fasting lipids and insulin levels were taken at baseline, 4th and 16th week of the study. STATISTICAL ANALYSIS PERFORMED: Analyses were on an intention-to-treat basis. Comparisons between groups were made using Student's t and Mann-Whitney tests for parametric and non-parametric data respectively. RESULTS: There was no significant change in the measured parameters in Absorbitol treated subjects compared to those on placebo, with exception of HDL-cholesterol which increased in the absorbitol group and decreased in the placebo group (p=0.048). The side effects of Absorbitol were also comparable to that of placebo. CONCLUSIONS: In the absence of dietary surveillance, Absorbitol does not bring about improvement in weight, anthropometry, body composition, blood pressure or lipid profile.

Compound heterozygous familial hypercholesterolemia and familial defective apolipoprotein B-100 produce exaggerated hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) represent ligand-receptor disorders that are complementary. Individuals with both FH and FDB are unusual. We report a family with both disorders and the impact of the mutations on the phenotypes of the family members. METHODS: We used single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) for genetic analysis of all 18 exons and the promoter region of the LDL receptor and DGGE for genetic analysis of the apolipoprotein B-100 (apo B-100) gene. The functional significance of the apo B-100 mutation was studied using a U937 cell proliferation assay. Fasting serum lipid profiles were determined for the index case and seven first-degree relatives. RESULTS: One of the patient's sisters had a missense mutation (Asp(407)-->Lys) in exon 9 of the LDL receptor and a serum LDL-cholesterol concentration of 4.07 mmol/L. Four other first-degree relatives had hyperlipidemia but no LDL-receptor mutation. However, these subjects had a mutation of the apo B-100 gene (Arg(3500)-->Trp). The cell proliferation rate of U937 cells fed with LDL from other subjects with the same mutation was fourfold less than that of controls. The index case had both FH- and FDB-related mutations. Her serum LDL-cholesterol (9.47 mmol/L) was higher than all other relatives tested. CONCLUSIONS: Existence of both FH and FDB should be considered in families with LDL-receptor mutations in some but not all individuals with hypercholesterolemia or when some individuals in families with FH exhibit exaggerated hypercholesterolemia.

Diabetes mellitus abolishes ethnic differences in cardiovascular risk factors: lessons from a multi-ethnic population.

AIMS: To compare cardiovascular risk factors in diabetic subjects of different ethnic groups, and between new and known diabetic subjects, in the Singapore National Health Survey '92. METHODS: Disproportionate stratified sampling followed by systematic sampling were used in 3568 (total) respondents of whom 2743 were non-diabetics, 179 newly diagnosed diabetics and 150 known diabetics. Amongst the diabetics, there were 185 Chinese, 66 Malays and 78 Asian Indians. Diagnosis of diabetes mellitus (DM) was based on the 2 h glucose alone, after a 75 g oral glucose tolerance test. Blood pressure (BP), lipid profile, glucose, insulin and anthropometric indices were obtained from all subjects. RESULTS: Subjects with diabetes (new and known) exhibited significantly higher triglyceride (TG), lower high density lipoprotein cholesterol (HDL-C) and low density lipoprotein (LDL)/apolipoprotein B (apo B) ratio (LDL size) compared with normoglycaemic subjects. They were more obese (generalised and central) and had higher systolic and diastolic BP. There was no difference in lipid risk factors between the two groups with diabetes although those with new diabetes were more obese whilst those with known diabetes had higher fasting glucose. Amongst subjects with diabetes, there were no significant differences between ethnic groups in TG, HDL-C, LDL/apo B ratio, or waist to hip ratio (WHR). Female Malays with diabetes had higher total cholesterol and were more obese whilst male Asian Indians with diabetes had higher fasting insulin. CONCLUSION: Asian Indians had lower HDL-C and LDL/apo B ratio than Chinese or Malays amongst normoglycaemic subjects. However, these differences between ethnic groups were not seen in subjects with DM.

Cardiovascular risk factors and LDL subfraction profile in Type 2 diabetes mellitus subjects with good glycaemic control.

OBJECTIVES: To compare cardiovascular risk factors and LDL particle size in well-controlled Type 2 diabetes mellitus and normal subjects. METHODS: Ninety-three Type 2 diabetic males and 186 age-matched, male controls were studied. Glycaemic control was stable for at least 3 months prior to recruitment. None were on insulin or lipid lowering therapy. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A1 and B, LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h. RESULTS: Diabetic subjects (mean HbA(1c) 6.6%+/-0.10) did not differ from controls in total cholesterol levels (5.04+/-0.08 vs. 5.16+/-0.05 mmol/l, respectively) but had lower serum HDL cholesterol (0.98+/-0.03 vs. 1.12+/-0.02 mmol/l, P<0.001), higher serum triglyceride (2.38+/-0.16 vs. 1.80+/-0.08 mmol/l, P<0.001), lower LDL(1) and LDL(2) and higher LDL(3) concentration. An LDL(3) concentration exceeding 100 mg/dl was found in 59.1% of diabetics and 39.1% of non-diabetics (P<0.001). Diabetic subjects also had higher body mass index, waist to hip ratio and insulin resistance (HOMA). Difference in LDL subfraction between groups disappeared after adjustments were made for either triglyceride or HDL cholesterol. CONCLUSION: Well controlled Type 2 diabetes mellitus subjects exhibit an increased cardiovascular burden through low HDL cholesterol and predominance of small, dense LDL particles.

Benefits of micronised Fenofibrate in type 2 diabetes mellitus subjects with good glycemic control.

AIMS: To determine the effects of micronised fenofibrate on lipids and low density lipoprotein (LDL) subfraction in well-controlled diabetic subjects with mild elevations in cholesterol levels. METHODS: Thirty-five male type 2 diabetic subjects with LDL(3) greater than 100 mg/dl and good glycemic control (mean HbA1c 6.7%) were treated with micronised fenofibrate in an open labeled study for 6 months. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A-I and B, and LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h, at the beginning and end of the 6 months treatment period. RESULTS: The blood pressure, waist to hip ratio, body mass index and glycemic control remained unchanged throughout the 6 months study period. Mean serum triglyceride fell from 2.49 to 1.72 mmol/l (33%) whilst HDL cholesterol increased from 0.88 to 0.96 mmol/l (10.8%). There were no significant changes in total or LDL cholesterol. Both LDL(1) and LDL(2) rose significantly whilst the dense LDL(3) fell from a mean of 148 to 85 mg/dl (43% reduction). Fenofibrate changed the LDL subfraction distribution from dense LDL(3) particles towards buoyant LDL(1) and LDL(2) particles in 63% of the subjects. No subjects had elevations in transaminases greater than three-fold or creatine kinase greater than ten-fold from pre-treatment levels. CONCLUSION: Diabetic subjects with mild hypercholesterolemia and good glycemic control may benefit from therapy with micronised fenofibrate because of the reduction in serum triglyceride, elevation in HDL cholesterol and a shift in LDL subfraction towards a non-atherogenic form.

Anti-oxidant ebselen causes the resolution of experimentally induced hepatic fibrosis in rats.

BACKGROUND: Hepatic fibrosis occurs because of injury to the liver parenchyma and biliary system. We have investigated the effect of an organic selenium anti-oxidant, ebselen, in the resolution of experimentally induced hepatic fibrosis, and evaluated its effect on various paradigms involved in hepatic fibrosis. METHODS: Following pretreatment with phenobarbitone, liver fibrosis was induced in male Fischer 344 rats by using carbon tetrachloride treatment for 10 weeks. Carbon tetrachloride-treated rats were randomly assigned into two groups: (i) no ebselen; and (ii) ebselen administered for 3 weeks following a 10-week carbon tetrachloride treatment period. Normal controls were: (i) neither carbon tetrachloride nor ebselen treated; or (ii) ebselen treated for 13 weeks. Liver sections were stained with hematoxylin and eosin, Masson trichrome and stained for reticulin by using silver impregnation. Reverse transcription-polymerase chain reaction was used to analyze the steady-state levels of gene(s) involved in: (i) hepatic fibrosis, namely, transforming growth factor-beta1, procollagen I and III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-13; (ii) oxidative stress, namely, cytochrome P4502E1; and (iii) preneoplastic liver foci, namely, the placental form of glutathione-S-transferase. RESULTS: Histological staining showed that ebselen resolves carbon tetrachloride-induced hepatic fibrosis. Treatment with ebselen reduced steady-state levels of transforming growth factor-beta1, procollagen I and III, tissue inhibitor of metalloproteinase-1, cytochrome P4502E1 and placental form glutathione-S-transferase transcripts, and increased transcripts of matrix metalloproteinase-13. CONCLUSION: These findings provide evidence that ebselen significantly causes the resolution of carbon tetrachloride-induced hepatic fibrosis in rats.

Screening for diabetes mellitus--a two-step approach in individuals with impaired fasting glucose improves detection of those at risk of complications.

AIMS: To compare the new American Diabetes Association (ADA) fasting plasma glucose (FPG) criteria to the 1985 World Health Organization (WHO) 2-h post glucose (2hPG) criteria when used for screening of those with no prior history of diabetes mellitus. METHODS: The study included 3,407 subjects without a history of diabetes in whom both FPG and 2hPG were available from the 1992 Singapore National Health Survey. The agreement (kappa) between FPG and 2hPG for the diagnosis of DM was assessed. The optimal cut-off of FPG for the detection of individuals with 2hPG > or = 11.1 mmol/l was determined by receiver-operating characteristics analysis. RESULTS: The prevalence of diabetes diagnosed by FPG alone was 7.3% compared to 8.4% diagnosed by 2hPG. The prevalence of impaired fasting glucose was 8.0%. FPG and 2hPG showed moderate agreement (kappa = 0.646, 95% confidence interval 0.584-0.708). Age, ethnic group and obesity did not affect the degree of agreement. Of those with 2hPG > or = 11.1 mmol/l, 40.8% had FPG in the non-diabetic range while 24.8% of those with FG > or = 7.0 mmol/l had 2hPG in the non-diabetic range. The optimal FPG for the detection of 2hPG > or =11.1 mmol/l was 6.1 mmol/l. Oral glucose tolerance tests (OGTT) in those with 6.0 mmol/ < FPG < 7.0 mmol/l resulted in the diagnosis of diabetes in 90.7% of individuals at risk of microvascular complications. CONCLUSIONS: FPG provides a simple screening test for diabetes, which shows moderate agreement with the 2hPG. A two-step strategy of OGTT in those with impaired fasting glucose improves the detection of at-risk individuals. However, diabetes should not be diagnosed on a single test. The test should be repeated on another day if an individual tests positive for diabetes.