Clinical characteristics and treatment outcomes in acromegaly, a retrospective single-center case series from Thailand.

INTRODUCTION: acromegaly, an overproduction of growth hormone (GH), is associated with high rate of morbidity and mortality particularly in case of delayed in diagnosis and treatment. A wide variation of clinical presentations, treatment outcomes and morbidities have been reported. METHODS: a retrospective study was conducted to review clinical characteristics and treatment outcomes of patients with acromegaly treated in King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 2006 and 2018. RESULTS: eighty-four patients (31 males and 53 females) were reviewed, mean age at diagnosis was 45.7 ± 12.6 years (±SD), mean time of disease onset was 7.6 ± 6.4 years and mean follow-up period was 7.8 ± 5.3 years. The most common presenting symptoms were maxillofacial change (96.8%) and acral enlargement (94.7%). Hypertension (39.3%), diabetes mellitus (28.6%) and dyslipidemia (23.8%) were prevalent co-existing conditions. Four patients were identified having cancer at presentation; however, no additional malignancy was reported during the follow up. Most patients harbored macroadenomas, only 10 were found to have microadenomas. The outcomes of treatment were controlled disease in 70% of microadenoma and 64.9% of macroadenoma. Permanent loss of pituitary function was found in about 21.3% and there was one case reported of mortality. The logistic regression analysis for controlled disease outcome showed the IGF-I index after surgery was associated with controlled disease outcome with statistically significant result (P-value=0.006). CONCLUSION: our study offers descriptive clinical data of case series of acromegalic patients, which had favorable outcomes comparable with previous reports. In addition, IGF-I index after surgery is a predictive parameter for outcome of treatment.

Real-world Evaluation of glycemic control and hypoglycemic Events among type 2 Diabetes mellitus study (REEDS): a multicentre, cross-sectional study in Thailand.

OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) often experience hypoglycaemia and weight gain due to treatment side effects. Sulfonylureas (SU) and the combination of SU and metformin (SU+MET) were the most common monotherapy and combination therapies used in Thailand tertiary care hospitals. This study aimed to assess the glycaemic goal attainment rates, hypoglycaemic episodes, weight gain and treatment compliance among patients with T2DM receiving SU or SU+MET. RESEARCH DESIGN AND METHODS: A multicentre cross-sectional survey and retrospective review was conducted in five tertiary care hospitals, Thailand. Patients with T2DM aged ≥30 years were included consecutively during a 12-month period. Glycaemic control, experiences of hypoglycaemia, weight gain and compliance were evaluated. Glycaemic goal attainment was defined by HbA1c level less than 7%. RESULTS: Out of the 659 patients (mean age (±SD)), 65.5 (10.0) years and median duration of T2DM (IQR), 10 (5-15) years), 313 (47.5%) achieved the glycaemic goal. HbA1c levels in the patients with goal attainment was significantly lower compared with those without (6.3%±0.5% vs 8.1%±1.2%, p<0.001). Goal attainment was significantly lower among patients treated with SU+MET than those treated with SU alone (43.5% vs 63.0%; OR 0.45, 95% CI 0.31, 0.66, p<0.001). A third of patients reported experiencing hypoglycaemia (30.7%) and weight gain (35.4%). Weight gain in the SU+MET group was lower than those receiving SU alone (33.1% vs 44.6%, p=0.015), but there was no difference in hypoglycaemic events. Major events in the previous 12 months were experienced by 68 patients, most commonly congestive heart failure and ischaemic heart disease. Approximately half of the patients (52.2%) reported not always taking their medication as prescribed. CONCLUSIONS: Among patients with T2DM receiving SU or SU+MET, only about half of the patients achieved glycaemic goal and compliance with the treatment. Hypoglycaemia and weight gain posed a significant burden with risk of weight gain higher in the SU group.

Efficacy and safety of gemigliptin as add-on therapy to insulin, with or without metformin, in patients with type 2 diabetes mellitus (ZEUS II study).

The objective of this study was to evaluate the efficacy and safety of gemigliptin added to a stable dose of insulin alone or of insulin in combination with metformin in patients with type 2 diabetes mellitus. After a two-week run-in period, patients were randomized 2:1 to receive gemigliptin 50 mg or placebo once daily as add-on to background therapy with insulin or insulin plus metformin for 24 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline at Week 24. Baseline characteristics were similar between the gemigliptin (n = 188) and placebo (n = 95) groups in terms of HbA1c (8.1%). At Week 24, the gemigliptin group showed a statistically significant reduction in mean HbA1c from baseline as compared with placebo (between-group mean difference, -0.7% [95% CI, -0.9% to -0.4%]; P-value < 0.0001). The incidence of overall adverse events and the number of hypoglycaemic adverse events were similar between the study groups. Gemigliptin added to insulin alone or to insulin in combination with metformin resulted in superior glycaemic control compared to that in the placebo group and was well tolerated for 24 weeks in patients with type 2 diabetes mellitus, without causing weight gain or increasing the incidence of hypoglycaemia.

Impact of Hypoglycemia on Health-Related Quality of Life among Type 2 Diabetes: A Cross-Sectional Study in Thailand.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases. Patients are generally advised lifestyle changes with antihyperglycemic agents prescribed. The major drawback of prescribing antihyperglycemic agents is the risk of hypoglycemia which subsequently impacts on health-related quality of life (HRQoL). This study is aimed at examining association between previous history of hypoglycemia and HRQoL. The study was a multicenter cross-sectional study, conducted from February 2013 to March 2015 at 5 tertiary care hospitals in Thailand (Srinagarind, Phramongkutklao, Ramathibodi, King Chulalongkorn Memorial, and Siriraj hospitals). The study population were males or females diagnosed with type 2 DM according to ADA criteria, 30 years of age or older, who had been treated with sulfonylurea (SU) monotherapy or SU and metformin combination for at least 6 months. Prespecified medical factors were extracted from medical records 12 months prior to patients' enrolment. The experience of hypoglycemia questionnaire was used to collect and measure severity of hypoglycemia experienced during the previous 6 months. HRQoL was assessed using the 3-level version of EuroQol-5-dimension (EQ-5D-3L) and visual analogue scale (EQ-VAS) questionnaires. Of 659 eligible patients surveyed, 202 patients (30.65%) had experienced symptoms of hypoglycemia. HRQoL was significantly lower among patients reporting at least one of hypoglycemic symptoms, measured by EQ-VAS scores (mean ± SD; 73.66 ± 13.18, 73.56 ± 15.10, or 68.93 ± 14.76 vs. 77.01 ± 13.02, one-way ANOVA; p = 0.006) and EQ-5D-3L index scores (0.62 ± 0.47, 0.68 ± 0.38, or 0.58 ± 0.51 vs. 0.79 ± 0.31, one-way ANOVA; p < 0.001) for mild, moderate, or severe/very severe hypoglycemic patients compared with patients without hypoglycemic symptoms. After adjusting for confounding factors in a multiple linear regression model, patients with hypoglycemic symptoms either mild, moderate, or severe/very severe demonstrated significantly higher impairment for EQ-VAS and EQ-5D indexes than those who did not experience hypoglycemic symptoms. In conclusion, our study showed decreased HRQoL determined by EQ-5D and EQ-VAS in patients reporting symptoms of hypoglycemia compared with patients not reporting hypoglycemic symptoms, relative to severity of hypoglycemia.

Painful and non-painful diabetic polyneuropathy: Clinical characteristics and diagnostic issues.

Diabetic neuropathy (DN) is a common complication of diabetes and can be either painful or non-painful. It is challenging to diagnose this complication, as no biomarker or clear consensus on the clinical definition of either painful or non-painful DN exists. Hence, a hierarchical classification has been developed categorizing the probability of the diagnosis into: possible, probable or definite, based on the clinical presentation of symptoms and signs. Pain is a warning signal of tissue damage, and non-painful DN therefore represents a clinical and diagnostic challenge because it often goes unnoticed until irreversible nerve damage has occurred. Simple clinical tests seem to be the best for evaluation of DN in the general care for diabetes. Screening programs at regular intervals might be the most optimal strategy for early detection and interventions to possibly prevent further neuronal damage and to lower the economic burden of this complication.

DIFFERENCES IN MORTALITY BY EDUCATION LEVEL AMONG PATIENTS IN DIABETIC REGISTRY FOR THAILAND.

This study was conducted in order to determine the impact of education on mortality due cardiovascular, infectious and renal disease, and cancer among Thai diabetics using data from the Thailand diabetes registry cohort prospected and conducted between April 2003 and February 2006. The study population consisted of 9,370 registered diabetic patients attending ten diabetes clinics at tertiary medical centers in Bangkok and major provinces. The population was classified by education level: those who had not yet attained a bachelor's degree classified as having "lower education" (7,684: 82%) and those with a bachelor's degree or higher classified as having "higher education" (1,686:18%). The overall mortality rate among those in the higher education group was lower than those in the lower education group (8.9 vs 20.5 per 1,000 patient-years, respectively) with a hazard ratio (HR) of 0.43 (0.31-0.61). The higher education group also had lower mortality rates due to infectious disease [HR 0.10 (0.02-0.41)], renal disease [HR 0.24 (0.06-0.99)] and cardiovascular disease [HR 0.42 (0.22-0.80)]. There was no difference in cancer mortality between the two groups [HR 1.25 (0.74-2.11)].

Practical approaches for self-monitoring of blood glucose: an Asia-Pacific perspective.

Comprehensive glycemic control is necessary to improve outcomes and avoid complications in individuals with diabetes. Self-monitoring of blood glucose (SMBG) is a key enabler of glycemic assessment, providing real-time information that complements HbA1c monitoring and supports treatment optimization. However, SMBG is under-utilized by patients and physicians within the Asia-Pacific region, because of barriers such as the cost of monitoring supplies, lack of diabetes self-management skills, or concerns about the reliability of blood glucose readings. Practice recommendations in international and regional guidelines vary widely, and may not be detailed or specific enough to guide SMBG use effectively. This contributes to uncertainty among patients and physicians about how best to utilize this tool: when and how often to test, and what action(s) to take in response to high or low readings. In developing a practical SMBG regimen, the first step is to determine the recommended SMBG frequency and intensity needed to support the chosen treatment regimen. If there are practical obstacles to monitoring, such as affordability or access, physicians should identify the most important aspects of glycemic control to target for individual patients, and modify monitoring patterns accordingly. This consensus paper proposes a selection of structured, flexible SMBG patterns that can be tailored to the clinical, educational, behavioral, and financial requirements of individuals with diabetes.

Smoking and death in Thai diabetic patients: the Thailand Diabetic Registry cohort.

OBJECTIVE: To determine the impact of smoking and quit smoking on mortality rate. MATERIAL AND METHOD: This prospective cohort was a three-year follow-up of Thai Diabetes Registry project that registered 9,370 diabetic patients from 10 diabetic clinics in tertiary medical centers in Bangkok and major provinces between April 2003 and February 2006. RESULTS: The groups of 7,487 (80%), 1,315 (14%), and 568 (6%) patients were classified as non-smokers, ex-smokers, and current smokers. The crude death rate of ex-smokers (Hazard Ratio (HR) 1.52 (95% CI 1.19-1.95)) and current smokers (HR 1.55 (1.10-2.19)) were higher than death rate of non-smokers. After control for covariates, the HR comparing ex-smokers with non-smokers was not different (1.10 (0.81-1.50)), while the HR comparing current smokers with non-smokers remained statistical significant (1.74 (1.17-2.61)). CONCLUSION: Smoking increases mortality rate in diabetic patients by about 74%. Quitting smoking decreased mortality rate to the same rate as of diabetic non-smokers.

NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients.

AIM: To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease (NAFLD) fibrosis score can predict all-cause mortality, cardiac complications, and/or liver complications of patients with NAFLD over long-term follow-up. METHODS: A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project. The NAFLD fibrosis score (NFS) was used to separate NAFLD patients with and without advanced liver fibrosis. We used the NFS score to classify the probability of fibrosis as < -1.5 for low probability, > -1.5 to < 0.67 for intermediate probability, and > 0.67 for high probability. Primary endpoints included all-cause death and cardiovascular- and/or liver-related mortality. From the 479 patients with NAFLD assessed, 302 patients (63%) greater than 18 years old were included. All patients were followed, and medical charts were reviewed until August 31, 2009 or the date when the first primary endpoint occurred. By using a standardized case record form, we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period. RESULTS: A total of 302/479 (63%) NAFLD patients (mean age: 47 ± 13 year) were included with a follow-up period of 12.0 ± 3.9 year. A low probability of advanced fibrosis (NFS < -1.5 at baseline) was found in 181 patients (60%), while an intermediate or high probability of advanced fibrosis (NSF > -1.5) was found in 121 patients (40%). At the end of the follow-up period, 55 patients (18%) developed primary endpoints. A total of 39 patients (13%) died during the follow-up. The leading causes of death were non-hepatic malignancy (n = 13/39; 33.3%), coronary heart disease (CHD) (n = 8/39; 20.5%), and liver-related mortality (n = 5/39; 12.8%). Thirty patients had new-onset CHD, whereas 8 of 30 patients (27%) died from CHD-related causes during the follow-up. In a multivariate analysis, a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of death (OR = 2.6 and 9.2, respectively; P < 0.0001). Our study showed a significant, graded relationship between the NFS, as classified into 3 subgroups (low, intermediate and high probability of liver fibrosis), and the occurrence of primary endpoints. The use of metformin or simvastatin for at least 3 mo during the follow-up was associated with fewer deaths in patients with NAFLD (OR = 0.2 and 0.03, respectively; P < 0.05). Additionally, the rate of annual NFS change in patients with an intermediate or high probability of advanced liver fibrosis was significantly lower than those patients with a low probability of advanced liver fibrosis (0.06 vs 0.09, P = 0.004). The annual NFS change in patients who died was significantly higher than those in patients who survived (0.14 vs 0.07, P = 0.03). At the end of the follow-up, we classified the patients into 3 subgroups according to the progression pattern of liver fibrosis by comparing the NFS at baseline to the NFS at the end of the follow-up period. Most patients were in the stable-fibrosis (60%) and progressive-fibrosis (37%) groups, whereas only 3% were in the regressive fibrosis. CONCLUSION: A higher NAFLD fibrosis score at baseline and a new onset of CHD were significantly predictive of death in patients with NAFLD.

Challenges in achieving optimal glycemic control in type 2 diabetes patients with declining renal function: The Southeast Asia perspective.

It is well recognised that Asia is at the epicenter of the global type 2 diabetes epidemic. Driven by socioeconomic changes involving industrialization, urbanization and adoption of Western lifestyles, the unprecedented increases in the prevalence of diabetes are particularly evident in Southeast Asia. The impact of diabetes is immense, and despite evidence of the benefit of optimal glucose control in reducing the risk of disease progression and development of macrovascular and microvascular complications, many individuals in this region remain poorly controlled. Chronic kidney disease (CKD) is an increasingly common diabetes-associated complication in Asian patients. Furthermore, Southeast Asia has one of the highest rates of end-stage renal disease (ESRD) in the world. Consequently, CKD in diabetes is associated with considerable morbidity and cardiovascular-related mortality, highlighting the need to screen and assess patients early in the course of the disease. The management of type 2 diabetes patients with declining renal function represents a significant challenge. Many of the older antidiabetic agents, such as metformin and sulfonylureas, are limited in their utility in CKD as a result of contraindications or hypoglycemic episodes. In contrast, dipeptidyl-peptidase IV inhibitors have provided a welcome addition to the therapeutic armamentarium for achieving glycemic control in these special populations. With comparable efficacy to and more favorable pharmacokinetic and side-effect profiles than traditional therapies, agents in this drug class, such as linagliptin, offer a more tailored approach to disease control in type 2 diabetes patients with declining renal function.

Efficacy and safety of generic and original pioglitazone in type 2 diabetes mellitus: a multicenter, a double-blinded, randomized-controlled study.

OBJECTIVE: To compare the efficacy and safety of generic (Utmos) and original (Actos) 30 mg Pioglitazone tablets. STUDY DESIGN: A multicenter, parallel randomized, double-blinded, controlled study. MATERIAL AND METHOD: Type 2 diabetic patients, with glycosylated hemoglobin (HbA,) > or = 7.0%, who received Metformin not less than 1000 mg/day over three months were recruited. Patients were randomized to receive either generic or original Pioglitazone 30 mg/day for 24 weeks. RESULTS: Eighty-five patients were enrolled, forty-four patients received generic Pioglitazone andforty-one received original Pioglitazone. There were no significant differences in baseline characteristics between generic and original Pioglitazone group. There were significantly reduced HbA(1c), fasting plasma glucose (FPG) and significantly increased HDL-cholesterol from baseline (p < 0.0001) without statistically differences between the two groups. Headache and edema were found in both groups at comparable rates (p > 0.05). CONCLUSION: Generic Pioglitazone (Utmos) is effective in controlling blood glucose and has similar effects on lipid profile as the original one. Both generic (Utmos) and original (Actos) 30 mg Pioglitazone tablets were not different in the efficacy and safety profiles.

Thailand Diabetic Registry cohort: predicting death in Thai diabetic patients and causes of death.

INTRODUCTION: The prevalence of type 2 diabetes in Thailand is 9.8 percent which is double the number forecast by World Health Organization. There is inadequate information to statistically represent all Thai diabetic patients for their causes of death. OBJECTIVE: To determine the clinical characteristics that predicted death and causes of death in Thai diabetic patients. MATERIAL AND METHOD: This prospective cohort was a 3-year follow-up study of the Thai Diabetes Registry project done between April, 2003, and February, 2006, which registered 9,419 diabetic patients attending 11 diabetic clinics in tertiary medical centers in Bangkok and major provinces of Thailand. The dead or alive status (99.5%) was determined. The causes of death were defined by reviewing the medical records. RESULTS: Of the 9,370 diabetic patients registered, 425 patients died, 1.84 percent per year. There was an increased risk of death associated with age, type of healthcare plan, lower education, insulin use, smoking, history of coronary artery disease and cerebrovascular disease, serum creatinine and high HbA1c. Lipid-lowering medication and metformin decreased the risk of death. Cardiovascular disease, infection and cancer were the prevalent causes of death. CONCLUSION: The present study showed risk factors that influenced death and causes of death in Thai diabetics.

Normal reference range of serum insulin-like growth factor (IGF)-I in healthy Thai adults.

BACKGROUND: Serum insulin-like growth factor (IGF)-I level is growth hormone (GH) dependent and reflects GH secretion. Analysis of IGF-I is a component in the diagnosis of GH-related disorders and is going to be of interest in determining the risk of many disorders such as cancer or atherosclerosis. The diagnosis value of IGF-I is dependent on the establishment of an accurate reference ranges, which can be affected by parameters such as age, gender, ethnicity, medications, chronic illness, or assay methodologies. OBJECTIVE: To determine reference ranges of IGF-I for healthy Thai adults. MATERIAL AND METHOD: Eight hundred sixteen healthy Thai adults aged between 21-70 years were recruited in the present study. Serum IGF-I was measured by using immunochemiluminescent (ICMA; Roche, USA). Subjects were recorded by their age and gender groups. Data were presented in mean and +/- 2 standard deviation (SD). Correlation analysis between serum IGF-I and physical parameters including sex, age, weight, height, and body mass index (BMI) was also made. RESULTS: The present study demonstrated normal reference range of serum IGF-I by using mean +/- 2 SD value. The well-known age dependency of serum IGF-I levels was also revealed. Levels decreased with increasing age in both genders. The mean value of serum IGF-I was slightly higher in women at the age of 30-40 years compared with men in the same age group, but not statistically insignificant. In addition, serum IGF-I was found to correlate directly with the height and negatively with BMI. However, age-adjusted IGF-I level did not show correlation with these physical parameters. CONCLUSION: This reference range will be beneficial for using IGF-I assay as a tool in the diagnosis of GH function abnormalities in Thai subjects.

A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined pituitary hormone deficiency.

BACKGROUND: POU1F1 is a pituitary transcription factor that plays a pivotal role in pituitary development and expression of the GH, PRL and TSH beta genes. Therefore, abnormalities of the POU1F1 gene are known to be responsible for a phenotype causing combined pituitary hormone deficiency (CPHD) involving growth hormone, prolactin and thyrotropin. METHODS: We described an 18-year-old Thai man, from a consanguineous family, who presented with short stature and cognitive deficit. He underwent endocrinological and molecular investigations. RESULTS: Hormonal studies showed that the patient had GH deficiency and secondary hypothyroidism, consistent with CPHD. Direct DNA sequencing revealed a novel homozygous mutation at the splice site of exon 4, IVS4+1G>A. It is the first splice site mutation in the POU1F1 gene described to date. Of the 7 other family members studied for this mutation by restriction enzyme digestions, 5 were heterozygous. They were all unaffected, suggesting a recessive pattern of inheritance. CONCLUSIONS: We described a novel POU1F1 splice site mutation, IVS4+1G>A, the first of its kind, in a Thai patient with CPHD. Recessive inheritance is suggested. We also noted preventable morbidities which resulted from delay in diagnosis of concomitant pituitary hormone defects in newborns suspected of CPHD.

Multi-country study on the prevalence and clinical features of peripheral arterial disease in Asian type 2 diabetes patients at high risk of atherosclerosis.

OBJECTIVE: PAD-SEARCH was the first international study to investigate the prevalence of peripheral arterial disease (PAD) in Asian type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD. SUBJECTS AND METHODS: In total 6625 type 2 diabetic patients aged 50 and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in Korea, China, Taiwan, Hong Kong, Indonesia, Thailand and the Philippines. RESULTS: Mean patient age was 63.7+/-8.2 years and mean duration of diabetes was 10.3+/-8.0 years. One thousand one hundred and seventy-two (17.7%) subjects were diagnosed as PAD by ABI (< or =0.9). PAD subjects had a significantly longer duration of diabetes, hypertension, higher HbA1c, and a significantly lower mean BMI than non-PAD subjects. In terms of lipid profiles, triglyceride was the only significant variable. Notably, mean ABI and baPWV in females were significantly poorer than age matched males in subjects with a normal ABI. However, mean ABI and baPWV in males were significantly poorer than in age matched females in subjects with PAD. CONCLUSIONS: These findings suggest that PAD is a common complication in Asian type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for Asian diabetic patients with high risk factors.

A SPINK1 gene mutation in a Thai patient with fibrocalculous pancreatic diabetes.

Fibrocalculous pancreatitis diabetes (FCPD), a late stage of tropical chronic pancreatitis (TCP), is classified as a secondary cause of diabetes mellitus resulting from pancreatic exocrine dysfunction. The distinctive features of FCPD and TCP are young age at onset, presence of large intraductal pancreatic calculi, and reported mainly in tropical developing countries. Their etiology is still obscure, but the autodigestion due to aberrant intraductal activation of zymogens by trypsin is thought to be a primary common event. Recently, mutations in SPINKI gene encoding a pancreatic secretory trypsin inhibitor have been reported in association with an increased risk of pancreatitis. We describe a heterozygous mutation, IVS3+2 T>C, of SPINK1 gene in a young Thai female patient with typical presentation of FCPD. To our knowledge, this is the first report of the SPINK1 gene mutation in a FCPD patient in Southeast Asia.

Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

Pioglitazone reduces urinary protein and urinary transforming growth factor-beta excretion in patients with type 2 diabetes and overt nephropathy.

OBJECTIVE: Increased urinary excretion of protein and transforming growth factor-beta (TGF-beta) are associated with progression of diabetic nephropathy (DN). Thiazolidinediones (TZD) could reduce urinary protein excretion in patients with microalbuminuric DN. There is little data of patients with macroalbuminuric DN. Also, there are no available clinical data regarding the effect of TZD on TGF-beta and type IV collagen in clinical DN. The present study was carried out to evaluate the effect of pioglitazone (PGZ), a member of TZD, on urinary protein, urinary TGF-beta, and urinary type IV collagen excretion in type 2 diabetic patients with macroalbuminuric DN. MATERIAL AND METHOD: Forty patients with type 2 diabetes and overt nephropathy, proteinuria more than 500 mg/day, were randomly assigned to receive PGZ (30 mg/day, n = 24) or placebo (control group, n = 16), for 12 weeks. Blood pressure, plasma glucose, glycated hemoglobin, lipid profile, 24-hour proteinuria, urinary TGF-beta and urinary type IV collagen were determined and compared. RESULTS: Glycemic control and blood pressure in both groups were not significant different. At baseline, the levels of proteinuria, urinary TGF-beta, and type IV collagen were not significant different between both groups. The geometric mean of urinary protein excretion in the PGZ group was progressively reduced from 1.64 to 0.98 gram/day (g/d), or 40.1% decrease which was significantly different (p < 0.05) from the 4.3% increase (from 1.72 to 1.80 g/d) in the control group. Urinary TGF-beta excretion in the PGZ group was decreased by 47.8% which significantly differed from the 59.7% increase in the control group (p < 0.05). Urinary type IV collagen levels in the PGZ group were decreased by 35% which was slightly, but not significantly, different from the 51.6% elevation in the control group (p = 0.06). CONCLUSION: Besides the effectiveness in blood sugar control, pioglitazone could salutarily reduce proteinuria and synthesis of TGF-beta as well as type IV collagen. These beneficial effects of pioglitazone on diabetic nephropathy are comparable to angiotensin converting enzyme inhibitors and angiotensin receptor blockers

Thailand diabetes registry project: type of diabetes, glycemic control and prevalence of microvascular complications in children and adolescents with diabetes.

OBJECTIVE: To determine the etiology, glycemic control and prevalence of microvascular complications in Thai diabetic patients who were diagnosed at the age of less than 18 years and who attended diabetes clinics in university or tertiary care hospitals. MATERIAL AND METHOD: A cross-sectional, multi-center, hospital-based diabetes registry was carried out from diabetes clinics of 11 tertiary centers. Demographic data including laboratory results and microvascular complications were recorded. RESULTS: Two-hundred-and-fifty out of the 9419 (2.66%) diabetic patients were diagnosed before the age of 18 years, 78% had Type 1 diabetes (T1DM), 18.4% had Type2 diabetes (T2DM) and 3.6% had other types of diabetes. Mean +/- SD HbAlc of T1DM was 9.3 +/- 2.5, T2DM was 9.7 +/- 2.6 and other types of diabetes were 8.6 +/- 4%. The majority of patients had poor glycemic control according to ADA and WHO guidelines. The percentage of patients who had diabetes for more than 5 years but had not been screened for nephropathy and retinopathy were 57.7% and 16% in T1DM and were 46.4% and 14.2% in T2DM respectively. A significant correlation between microvacular complications (nephropathy and retinopathy) and duration of disease was found in T1DM (p < 0.001). CONCLUSION: The majority of Thai children and adolescents with diabetes had TIDM and unsatisfactory glycemic control. Screening for microvascular complications was under international standard. The national strategic plan for management of this disease especially in this age group should be urgently implemented.