HbA1c variability is associated with microalbuminuria development in type 2 diabetes: a 7-year prospective cohort study.

AIMS/HYPOTHESIS: HbA(1c) variability has been shown to be an independent risk factor for nephropathy in patients with type 1 diabetes. In this study, we aimed to explore the association between HbA(1c) variability and microalbuminuria development in patients with type 2 diabetes. We also intended to test the applicability of serially measured HbA(1c) over 2 years for this risk assessment. METHODS: Between 2003 and 2005, we recruited 821 middle-aged normoalbuminuric individuals with type 2 diabetes and followed them through to the end of 2010. The average follow-up time was 6.2 years. We defined microalbuminuria as a urine albumin to creatinine ratio of 30 mg/g (3.4 mg/mmol) or higher. HbA(1c) variability was calculated by the SD of serially measured HbA(1c). The Cox proportional hazards model was used to evaluate the association between HbA(1c) SD quartile and development of microalbuminuria. RESULTS: The incidence of microalbuminuria for the overall population was 58.4, 58.6, 60.8 and 91.9 per 1,000 person-years for Q1- to Q4-adjusted HbA(1c) SD, respectively (p for trend = 0.042). Compared with patients in Q1, those in Q4 were about 37% more likely to develop microalbuminuria. The HR derived from a series of 2 year HbA(1c) measurements was similar to that from data collection for longer than 4 years. CONCLUSIONS/INTERPRETATION: In addition to mean HbA(1c) values, HbA(1c) variability, even measured as early as 2 years, is independently associated with the development of microalbuminuria in patients with type 2 diabetes.

The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese women with bone loss: a 2-year randomized double-blind placebo-controlled study.

UNLABELLED: The treatment of 300-mg/day isoflavones (aglycone equivalents) (172.5 mg genistein + 127.5 mg daidzein) for 2 years failed to prevent lumbar spine and total proximal femur bone mineral density (BMD) from declining as compared with the placebo group in a randomized, double-blind, two-arm designed study enrolling 431 postmenopausal women 45-65 years old. INTRODUCTION: This study evaluated the effects of soy isoflavones on bone metabolism in postmenopausal women. METHODS: Four hundred and thirty-one women, aged 45-65 years, orally consumed 300-mg/day isoflavones (aglycone equivalents) or a placebo for 2 years in a parallel group, randomized, double-blind, two-arm study. Each participant also ingested 600 mg of calcium and 125 IU of vitamin D(3) per day. The BMD of the lumbar spine and total proximal femur were measured using dual-energy X-ray absorptiometry at baseline and every half-year thereafter. Serum bone-specific alkaline phosphatase, urinary N-telopeptide of type 1 collagen/creatinine, and other safety assessments were examined regularly. RESULTS: Two hundred out of 217 subjects in the isoflavone group and 199 out of 214 cases in placebo group completed the treatment. Serum concentrations of isoflavone metabolites, genistein and daidzein, of the intervention group were remarkably elevated following intake of isoflavones (p < 0.001). However, differences in the mean percentage changes of BMD throughout the treatment period were not statistically significant (lumbar spine, p = 0.42; total femur, p = 0.39) between the isoflavone and placebo groups, according to the generalized estimating equation (GEE) method. A significant time trend of bone loss was observed at both sites as assessed by the GEE method following repeated measurement of BMD (p < 0.001). Differences in bone marker levels were not significant between the two treatment groups. CONCLUSION: Treatment with 300-mg/day isoflavones (aglycone equivalents) failed to prevent a decline in BMD in the lumbar spine or total femur compared with the placebo group.

Cigarette smoking and proteinuria in Taiwanese men with Type 2 diabetes mellitus.

AIMS: Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose-response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. METHODS: Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was > or = 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. RESULTS: Compared with non-smokers, those who had smoked 15-30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34-5.76, P < 0.01) and 3.20 (95% CI 1.74-5.86, P < 0.001) times more likely to develop proteinuria. The dose-response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects (P = 0.001) and in subgroups with relatively short duration of diabetes mellitus (P < 0.001), good blood pressure control (P = 0.001) and those of young age (P = 0.007). CONCLUSIONS: The current study shows a clear dose-response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control.

Risk factors for hip fracture in older adults: a case-control study in Taiwan.

UNLABELLED: We conducted a matched case-control study of hip fracture in older adults. Our findings suggest that hip fracture risk was determined by multiple factors. Older women characterized by low consumption of milk, peak flow rate, grip strength, and bone mineral density (BMD) had increased risk of hip fracture. Older men with impaired cognitive function and low BMD were also at higher risk of hip fracture. INTRODUCTION: Multiple factors contribute to low-trauma hip fracture in older adults. The aim of this study was to determine important characteristics of hip fracture in older population. METHODS: A total of 228 patients with first low-trauma hip fracture were matched with 497 controls. All 77 potential risk factors of hip fracture organized into 13 groups were analyzed using conditional logistic regression. RESULTS: Low milk intake, peak flow rate, hand grip strength, and bone mineral density in women and low mini-mental state examination score and bone mineral density in men were further identified to be independently associated with elevated hip fracture risk. CONCLUSIONS: The factors found in our study may help understand the etiology of hip fracture and be further adopted to evaluate the risk of hip fracture in community and clinical setting.

Secular trend for mortality from breast cancer and the association between diabetes and breast cancer in Taiwan between 1995 and 2006.

AIMS/HYPOTHESIS: Studies have identified an association between diabetes and breast cancer in postmenopausal women in Western countries. Such an association needs to be confirmed in an Asian population. The aim of this study was to evaluate the secular trend for breast cancer mortality in Taiwanese women in the general population and the mortality rate ratios between diabetic patients and the general population. METHODS: Age-specific mortality rates for the general population, categorised into groups aged 25-54, 55-64, 65-74 and > or =75 years, were calculated for the years between 1995 and 2006 (inclusive) from vital statistics published by the Taiwanese government. Linear regression was used to test the trends. A total of 131,573 diabetic women aged > or =25 years from a national cohort recruited between 1995 and 1998 (inclusive) were followed prospectively for vital status, determined from the National Register of Deaths. Mortality rates and mortality rate ratios (mortality rate in diabetic women vs the average and highest mortality rates for the general population) were calculated. RESULTS: A total of 14,230 women aged > or =25 years in the general population died of breast cancer between 1995 and 2006. A trend for an increase in the annual rate was observed for all age groups. A total of 482 diabetic women died of breast cancer, with a crude mortality rate of 45.7 per 100,000 person-years. Compared with the general population the relative risk of mortality for those with diabetes ranged from 1.37 (for the group aged 55-64 years) to 2.43 (for the group aged 25-54 years). CONCLUSIONS/INTERPRETATION: We identified a secular trend of an increase in the rate of breast cancer mortality in the Taiwanese general population. Our data suggest a higher risk of breast cancer mortality in diabetic patients in all age groups.

Increasing incidence of diagnosed type 2 diabetes in Taiwan: analysis of data from a national cohort.

AIMS/HYPOTHESIS: Epidemiological evidence shows an increasing prevalence of type 2 diabetes in Taiwan. The aim of this study was to assess the yearly incidence for this country during 1992-1996. SUBJECTS AND METHODS: Data obtained by telephone interviews of 93,484 diagnosed diabetic patients enrolled in Taiwan's National Health Insurance programme formed the basis of this study. A total of 36,153 incident cases of type 2 diabetes (17,097 men and 19,056 women) were identified and incidence rates calculated. The trends of obesity and parental diabetes were also evaluated. RESULTS: The overall 5-year incidences for men and women were 187.1 and 218.4 per 100,000 population, respectively. The trends from 1992-1996 were increased for all age groups in men and for most age groups in women. A 2.8-fold increase in incidence was observed for the youngest age group (<35 years), in which the increase in incidence was higher than in the older age groups. Men showed a higher fold increase in incidence than did women (3.5 vs 2.1). Obesity at interview increased from 39.2% in 1992 to 47.6% in 1996 (p<0.001) and was significant for all ages. Parental diabetes showed no yearly change when all patients were analysed together, but there was a trend towards a decrease in the youngest age group (<35 years) and a trend towards an increase in the oldest age groups (>/=55 years). CONCLUSIONS/INTERPRETATION: An increasing incidence of diagnosed type 2 diabetes was observed for each sex in most age groups in Taiwan, but was most marked in the youngest age group. A parallel increase in obesity was observed with the increasing incidence of diabetes.

Betel nut chewing and other risk factors associated with obesity among Taiwanese male adults.

OBJECTIVE: The research aimed at examining betel nut chewing and other risk factors associated with obesity among Taiwanese male adults. DESIGN: The research analyzed the data obtained by the 2001 National Health Interview Survey in Taiwan that covered all the administrative divisions in Taiwan. Multistage stratified systematic sampling design was adopted for survey. All members of a sampled household received the interview. SUBJECTS: The research analyzed questionnaires answered by nonaboriginal male respondents aged between 20 and 59 years old, and the total number of samples analyzed read 6126. Since very few female subjects chewed betel nut, they were excluded from the analysis. MEASUREMENTS: Criteria of obesity was defined as body mass index > or = 27 kg/m2. The variables incorporated for analysis included the respondents' status of betel nut chewing, age, educational background, presence of hypertension and diabetes mellitus, drinking and smoking status, exercise status, and demand for physical strength at job. Generalized estimating equations model was employed to estimate the odd ratios (with 95% CI) of obesity of each independent variable. RESULTS: Approximately 16.2% of respondents were obese. The distribution of betel nut chewing was current chewers 15.9%, ex-chewers 4.3%, and nonchewers 79.8%. After controlling above-mentioned independent variables, hypertension, diabetes mellitus, betel nut chewing, never exercising, and sedentary jobs were closely associated with obesity. CONCLUSION: The research found that betel nut chewing closely associated with obesity. The increased appetite of betel nut chewers is speculated as the underlying cause. The prospective study is needed to clarify this issue. In addition to increasing the risk of developing oral cancer, betel nut chewing seemed to be related with another health hazard: obesity.

An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study.

AIM/HYPOTHESIS: Microalbuminuria represents the earliest clinical evidence of diabetic nephropathy and is a marker of increased cardiovascular morbidity and mortality. Its early detection allows the implementation of individualised and aggressive intervention programmes to reduce cardiovascular risk factors. There is limited information on the prevalence of microalbuminuria among hypertensive type 2 diabetic patients in Asia. METHODS: This cross-sectional epidemiological study aimed to assess the prevalence of microalbuminuria and macroalbuminuria among consecutively screened hypertensive type 2 diabetic adult patients in 103 centres in 10 Asian countries or regions. Predictive factors for microalbuminuria and macroalbuminuria were characterised using a stepwise logistic regression model. RESULTS: A total of 6,801 patients were enrolled and 5,549 patients constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). The prevalence of microalbuminuria was 39.8% (39.2-40.5; 95% CI) and the prevalence of macroalbuminuria was 18.8% (18.2-19.3; 95% CI). Only 11.6% of the patients had systolic and diastolic blood pressure below the 130/80 mm Hg target. In the multivariate analyses, the predictive factors for the presence of microalbuminuria were age, BMI, systolic blood pressure and ethnic origin. The highlighted predictive factors for the presence of macroalbuminuria were age, sex, ethnic origin, BMI, duration of diabetes, presence of diabetic complications, intake of diuretics, intake of calcium channel blockers, diastolic and systolic blood pressure. CONCLUSIONS/INTERPRETATION: The high prevalence (58.6%) of micro or macroalbuminuria observed in these patients is alarming and indicates an impending pandemic of diabetic cardiovascular and renal diseases in Asia with its potential economic consequences.

Interferon-alpha reduces insulin resistance and beta-cell secretion in responders among patients with chronic hepatitis B and C.

This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.

Adiponectin mRNA levels in the abdominal adipose depots of nondiabetic women.

BACKGROUND: The human adiponectin gene has been implicated in the pathophysiology of obesity, type II diabetes mellitus, dyslipidemia and atherosclerosis. Investigation of the physiological functions of the adiponectin gene in humans was mainly conducted at the levels of plasma proteins or DNA polymorphisms. The depot-specific adiponectin mRNA levels also could be relevant to these physiological functions. OBJECTIVES: The relation between the adipose depot-specific adiponectin mRNA expression levels and various metabolic factors, including BMI, fasting plasma glucose, insulin, triglycerides (TGs) and HDL-cholesterol and insulin resistance index by HOMA, was investigated among 66 nondiabetic women using quantitative real-time PCR. RESULTS: The subcutaneous relative adiponectin mRNA levels (SRAmR) correlated significantly with the omental relative adiponectin mRNA levels (ORAmR) (gamma=0.468, P=0.0001). The SRAmR correlated inversely with the fasting plasma glucose with a borderline significance (gamma=-0.35, P=0.058). On the other hand, the ORAmR correlated negatively with serum TG levels with the adjustment for age (gamma=-0.33, P=0.007) or age plus BMI (gamma=-0.27, P=0.027). CONCLUSION: These results indicate that the adiponectin mRNA levels in different adipose depots were at least related to certain phenotypes of metabolic syndrome. The expression levels of adiponectin in the omental adipose depots are related to TG metabolism.

Sagittal abdominal diameter is associated with insulin sensitivity in Chinese hypertensive patients and their siblings.

The purpose of the study is to observe the relation between anthropometric measurements, focusing on sagittal abdominal diameter (SAD), and insulin sensitivity indices in Chinese hypertensive patients and their siblings. In total, 907 participants, 537 hypertensive and 370 nonhypertensive, from 311 Taiwanese families were drawn from the Stanford Asia and Pacific Program for Hypertension and Insulin Resistance for the study. The participants received anthropometric measurements and 75-g oral glucose tolerance tests after an overnight fast. Fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the insulin sensitivity index ISI(0,120) were chosen as surrogate measures of insulin sensitivity. In addition to Pearson and partial correlations, we used generalized estimating equations (GEEs) to examine the association between anthropometric measurements and insulin sensitivity indices. A small deviance in the GEEs indicates the goodness of model fit, irrespective of the independence among variables. The hypertensive patients were older in age, wider in waist circumference (WC), larger in body mass index (BMI) and SAD, and more insulin resistant than the nonhypertensive counterparts. The logarithmic transformation of fasting insulin, HOMA-IR, and ISI(0,120) significantly correlated with SAD, WC, and BMI before and after adjustments for age and sex. The deviances of SAD in the GEEs were similar to those of WC in all subjects, while BMI had smaller deviances than SAD and WC in the hypertensive patients. Our results suggest that the performance of SAD in predicting insulin sensitivity is comparable with WC in Chinese hypertensive patients and their siblings. BMI, however, seems to have better association with insulin sensitivity than SAD and WC in the patients with hypertension.

The Diabcare-Asia 1998 study--outcomes on control and complications in type 1 and type 2 diabetic patients.

UNLABELLED: The aim of this study was to describe the glycaemic and metabolic control and diabetes-related complications in type 1 and type 2 Asian patients. METHODS: Data of diabetes patients from 230 diabetes centres in 12 Asian regions were collected on a retrospective-prospective basis through review of medical records, interview and laboratory assessments. Analysis of glycated haemoglobin (HbA1c) was carried out in central laboratories appointed by Bio-Rad. The data collection case record forms were scanned electronically. RESULTS: 22177 patients with valid data made up the analysis population. Among patents with type 1 and type 2 diabetes, there was a higher proportion of women than men (53% vs. 47% for type 1 patients and 56% vs. 44% for type 2 diabetes). Hypertension (61%) and overweight (40% with BMI > or = 25 kg/m2 were common in type 2 patients. Dyslipidaemia was also present in at least half of both types of patients. Control of glycaemia (mean HbA,1c and fasting blood glucose [FBG]) was poor in type 1 (9.9 +/- 2.5%; 10.2 +/- 5.2 mmol/l) and type 2 patients (8.5 +/- 2.0%; 8.9 +/- 3.4 mmol/l). Glycaemia in the majority of both types of patients fell short of those stipulated by various guidelines. In type 2 patients, glycaemia deteriorated (HbA1c > 7.5%, FBG > or = 7.0 mmol/l) with duration of diabetes > 7 years. Both types of diabetes appear to share a similar high prevalence of complications of cataract, retinopathy and neuropathy, although the prevalence of cataract (27%) and neuropathy (35%) was higher in type 2 diabetes. Screening for microalbuminuria was not common. CONCLUSIONS: The Inadequate metabolic and hypertension control, especially in type 2 patients, needs to be addressed.

The status of diabetes control in Asia--a cross-sectional survey of 24 317 patients with diabetes mellitus in 1998.

AIMS: To establish the status of diabetes control in Asia, the Diabcare-Asia 198 study collected data from 230 diabetes centres in Bangladesh, People's Republic of China, India, Indonesia, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan, Thailand and Vietnam from March to December 1998. METHODS: Data were obtained either by patient interview during the enrolment visit or by reviewing medical records for the most recent laboratory assessment and clinical examinations. Blood samples were also collected during patients'. visits for central assessments of HbA1c (normal range 4.7-6.4%). RESULTS: The mean of centrally measured HbA1c was 8.6 +/- 2.0% for 18 211 patients (82% of the analysis population). Of the patients with central HbA1c measurements, the majority (55%) had values exceeding 8%, indicative of poor glycaemic control. The prevalence of retinopathy, microalbuminuria and neuropathy was also higher in the group of patients with higher HbA1c. Based on the findings from central HbA1c measurements and reported local HbA1c assessments, it also appears that more patients with poor glycaemic control did not have access to glycated haemoglobin measurements. Mean HbA1c of thediabetic populations in Bangladesh, Indonesia, Korea, Malaysia and Taiwan were significantly lower (all P = 0.0001, except P = 0.0007 for Malaysia), while that of China, India, Philippines and Vietnam was significantly higher (all P = 0.0001) than the grand mean. CONCLUSIONS: In our study population of the Asian diabetes patients treated at diabetes centres, more than half were not well controlled. The prevalence of diabetic microvascular complications was higher in the group of patients with higher HbA1c. Further therapeutic actions to improve glycaemic control are required to prevent chronic diabetic complications.

Platelet collagen receptor alpha2beta1 integrin and glycoprotein IIIa Pl(A1/A2) polymorphisms are not associated with nephropathy in type 2 diabetes.

Platelet glycoprotein receptors play a role in the pathogenesis of chronic diabetic complications. Genetic polymorphisms of the alpha2beta1 integrin and glycoprotein IIIa (GPIIIa) have been associated with myocardial infarction, stroke, and diabetic retinopathy. To identify risk factors for their development in a cohort of patients with type 2 diabetes, we evaluated clinical variables and genetic polymorphisms in the alpha2beta1 integrin and GPIIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 patients with and 108 patients without diabetic nephropathy), as well as 217 nondiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, body mass index (BMI), and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), total cholesterol, and triglyceride levels. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. No difference in the Bgl II polymorphism of the alpha2beta1 integrin gene was found between patients with type 2 diabetes with or without nephropathy (11 [8.7%], 47 [37.3%], and 68 patients [54.0%] versus 10 [9.3%], 32 [29.6%], and 66 patients [61.1%] for Bgl II+/+, Bgl II+/-, and Bgl II-/-, respectively; P = 0.271). Multiple logistic regression analyses showed that duration of diabetes, BMI, hypertension, and poor glycemic control were four independent predictors for the development of diabetic nephropathy. No contribution of the Bgl II+ allele of the alpha2beta1 integrin was found for the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.655 to 2.418; P = 0.490). The Pl(A2) allele genotype was not found among our studied subjects. In conclusion, age, duration of diabetes, BMI, and HbA(1c) level are strong predictors for nephropathy in patients with type 2 diabetes. However, the Bgl II polymorphism of the alpha2beta1 integrin gene and the Apa I polymorphism of the platelet GPIIIa gene do not have a major role in the development of diabetic nephropathy in our population.

Sibling-based association study of the PPARgamma2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance.

The peroxisome proliferator activated receptor (PPAR) gamma2 is a transcription factor that has been shown to be involved in adipocyte differentiation, adipogenesis, and insulin sensitivity. To address the role of PPARgamma2 in glucose homeostasis and insulin sensitivity, among many other objectives, we conducted a sibling-controlled association study in a multicenter program - the Stanford Asian-Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe). Approximately 2525 subjects in 734 Chinese and Japanese families have been recruited from six field centers for SAPPHIRe. In total, 1702 subjects including parents and siblings from 449 families have been genotyped for PPARgamma2, of which 328 families were Chinese and 121 Japanese. Only 88 subjects of the 1525 siblings screened for the P12A polymorphism were found to be carriers of the A variant, the most common variant of the PPARgamma2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. A sibling-controlled association study was performed through genetically discordant sibships (i.e., P/P genotype vs. P/A + A/A genotypes). Specifically, we examined whether there were differences in metabolic variables between the discordant siblings within families. In total, 88 subjects carrying either 1 or 2 A alleles had at least one sibling who was discordant for the P12A polymorphism, yielding a total of 180 individuals from 47 families for analyses, among which 92 siblings were homozygous for wild-type P allele. Siblings with the A variant tended to have lower levels of fasting plasma glucose (OG-10), and lower glucose levels at 60 min following oral glucose loading after adjusting for age, gender, and body mass index. Using a mixed model treating family as a random effect, we found that P12A polymorphism of the PPARgamma2 gene contributes significantly to the variance in fasting plasma glucose, glucose level at 60 min, and insulin-resistance homeostasis model assessment. Our results suggest that within families siblings with the A variant in the PPARgamma2 gene may be more likely to have better glucose tolerance and insulin sensitivity independent of obesity in Chinese and Japanese populations.

Direct costs-of-illness of patients with diabetes mellitus in Taiwan.

The purpose of the present study was to examine the characteristics of healthcare costs for diabetic patients in Taiwan. The study analyzed claim data from the Bureau of National Health Insurance for the period from July 1997 to June 1998. There were 536159 documented diabetic patients who were treated within the universal healthcare system in Taiwan during this study period. The annual number of visits of these diabetic patients was 6.2% of the total outpatient visits of all patients due to all causes during the one-year study period. Diabetes-related problems were the causes of 25.2% of outpatient visits among diabetic patients, while 74.8% of visits were for causes unrelated to diabetes. The distribution of treatment for the diabetic patients was by oral hypoglycemic agents 88.3%, insulin only 6.9%, and a combination of insulin and oral agents 4.8%. Diabetic patients accounted for 4,724,711 hospital inpatient days during the study period, which was 22.1% of the total inpatient days in Taiwan. Of the inpatient admissions, 13.9% were for diabetes as the principal cause, 23.4% were for diabetes-related disease, and 62.7% were for causes unrelated to diabetes. The direct costs of healthcare for the documented diabetic patients was 11.5% of the total costs of healthcare in Taiwan, and was 4.3 times higher than the average costs of care for non-diabetic individuals.

The current state of diabetes management in Taiwan.

The aim of this study was to provide an overview of diabetes management and complication status in Taiwan. A cohort of 2446 patients (from 25 diabetic centers) with more than 12 months of diabetes management participated and data were collected by interviews and reviewing the medical records. Overall, 97% were diagnosed as type 2 diabetes, with a mean age (+/-S.D.) of 61.6+/-11.3 years, duration of diabetes of 10.3+/-7.3 years and age at onset of diabetes of 51.5+/-11.8 years. Mean BMI was 25.1+/-3.6 kg/m(2) and about 50% had BMI>25 kg/m(2). Majority (75%) were treated with oral hypoglycemic agents (OHAs), 14% with insulin and 10% with combination of insulin and OHA. Mean HbA(1c) was 8.1+/-1.6% and 59% had HbA(1c) >7.4% (1% above the upper limit of normal range, 4.7-6.4%). Mean FBG was 9.0+/-3.3 mmol/l and 59% had FBG>7.8 mmol/l. Of all the patients who had screening for complications, cataract (38%), neuropathy (30%), proteinuria (17%) and stroke (6%) were the most frequently reported eye, feet, kidney and late complications. We conclude that the majority of patients involved in this study had unsatisfactory glycaemic control which may lead to diabetes complications.

Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway.

To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. At a basal glucose concentration of 6 mmol/l, RSG (0.045-4.5 micromol/l) stimulated insulin release in a dose-dependent manner. In addition, 4.5 micromol/l RSG potentiated the glucose (10 mmol/l)-induced insulin secretion. Both the first and second phases of glucose-induced insulin secretion were significantly enhanced by RSG, by 80.7 and 52.4%, respectively. The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In contrast, the glucose-stimulated insulin secretion was not affected by LY294002. The potentiation effect of RSG on glucose-stimulated insulin secretion, in both the first and second phases, was significantly blocked by LY294002. These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. The inability of LY294002 to inhibit glucose-induced insulin secretion suggests that different pathways are responsible for glucose and RSG signaling.

Molecular scanning of the human sorbin and SH3-domain-containing-1 (SORBS1) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes.

In the mouse, the SH3P12 or the c-Cbl-associated protein (CAP) has been shown as an important signaling molecule in insulin-stimulated glucose uptake. The human homolog for the sorbin and SH3-domain-containing-1 gene, termed SORBS1, might play a role in human disorders with insulin resistance. To explore the genetic role of SORBS1 in human obesity and type 2 diabetes, we investigated the nucleotide polymorphisms in the SORBS1 gene with molecular scanning. After scanning for a total of 13,136 bp in each of 40 chromosomes, we have identified 14 single nucleotide polymorphisms (SNPs) in the human SORBS1 gene. Among them, two SNPs affected amino acid coding (R74W and T228A), four occurred within exons but did not affect amino acid coding, and the remaining eight occurred within introns, which were located outside of the consensus region of the splicing mechanism. Further studies in 202 non-obese, 113 obese and 455 subjects with type 2 diabetes revealed that the A-allele of the T228A polymorphism in exon 7 exerted a protective role for both obesity [relative risk 0.466; 95% confidence interval (95% CI) 0.265-0.821] and diabetes (relative risk 0.668; 95% CI 0.472-0.945). Neither allele of the R74W polymorphism was associated with either obesity or diabetes. In conclusion, our results suggest that the A228 allele of the T228A polymorphism of the SORBS1 gene is a protective factor for both obesity and diabetes, and also imply that the SORBS1 gene plays an important role in the pathogenesis of human disorders with insulin resistance.

Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin.

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = -0.5, P = 0.01), waist (r = -0.4, P = 0.04) and hip (r = -0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = -0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (beta = -0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (beta = -0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.