Renal Protective Effects of Combination of Diltiazem and ACEI/ARB on the Progression of Diabetic Nephropathy: Randomized Controlled Trial.

Background: Strict control of blood sugar and maintenance of normal blood pressure levels are the standard treatments shown to delay the progression of diabetic nephropathy in type 2 diabetic patients. The recommended antihypertensive medications for diabetic nephropathy are angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Previous studies have shown that a non-dihydropyridine calcium channel blocker (diltiazem) could reduce urinary protein excretion in type 2 diabetic patients. Objective: To evaluate the effects of the combinations of diltiazem and ACEI/ARB treatment compared with ACEI/ARB alone in type 2 diabetic patients with diabetic nephropathy. Material and Method: A prospective, randomized, double-blind, placebo-controlled multicenter trial was conducted at the out-patient departments of Rajavithi Hospital (Bangkok) and Ban-phaeo Hospital (Samut Sakhon). A total of 106 type 2 diabetic patients with hypertension and urine protein/creatinine (UPCr) >0.3 gm/gm who had received ACE/ARB were randomized into two groups: a diltiazem group (ACEI/ARB + sustained-release diltiazem 120 mg daily) (50 cases) and a placebo group (ACEI/ARB + placebo) (56 cases). Intention-to-treat analysis was utilized with the data of patients who withdrew from the study before its completion date. Results: 39 cases in the diltiazem group (78.0%) and 38 in the placebo group (67.9%) completed the 1-year treatment. The diltiazem group achieved better preservation of glomerular filtration rate and had lower proteinuria than the placebo group (p<0.05), whereas blood pressure was similar in the two groups. Four patients in the diltiazem group and one patient in the placebo group developed severe pedal edema and discontinue treatment. Conclusion: A combination of diltiazem and ACE/ARB could reduce proteinuria and preserve kidney function in type 2 diabetic patients with diabetic nephropathy.

Prevalence of Diabetic Foot Ulcers and Risk Classifications in Type 2 Diabetes Mellitus Patients at Rajavithi Hospital.

BACKGROUND: Diabetic foot ulcers are a major cause of non-traumatic lower limb amputation in patients with type 2 diabetes. In 2014, the Diabetes Association of Thailand issued new guidelines for classifying type 2 diabetes patients' levels of risk of developing foot ulcers, but no research on the prevalence of type 2 diabetes using these new classification criteria had been performed prior to the current study. OBJECTIVE: To study the prevalence of diabetic foot ulcers overall and in different risk groups in type 2 diabetes mellitus patients in Rajavithi Hospital, and to evaluate risk factors of these groups and correlations with ankle brachial index (ABI) and cardio-ankle vascular index (CAVI). MATERIAL AND METHOD: 593 type 2 diabetes patients at Rajavithi Hospital were studied and classified into risk groups based on the classification criteria issued by the Thailand Diabetes Association in 2014. ABI measurements were taken from 132 patients, and measurements of CAVI were taken from 101 patients. RESULTS: The prevalence of foot ulcers was 3.4% and 2.2% of patients had a history of amputation. The percentages of patients at low, intermediate and high risk of developing foot ulcers were 55.8%, 33.6% and 10.6%, respectively. Age, duration of diabetes, estimated glomerular filtration rate (eGFR), history of hypertension, dyslipidemia, nephropathy, cardiovascular disease (CVA), deformity of foot, numbness, abnormal protective sensation, pulse deficit, ulcer, and amputation were factors significantly associated with a high risk of foot ulcers (p < 0.05), but fasting plasma glucose (FPG) and HbA1c were not significant factors. There was an association between cerebrovascular accident and abnormal ABI. CONCLUSION: Nearly half of these type 2 diabetes patients were in the groups with an intermediate or high risk of developing foot ulcers. Screening of patients at risk of foot ulceration is necessary in order to classify patients into risk groups and provide appropriate education, as well as proper monitoring and management.

Somatic HRPT2 Mutation (Arg234X) of Parathyroid Carcinoma Associated with Slipped Capital Femoral Epiphysis: A First Case Report.

A 14-year-old boy was admitted to the orthopedic clinic of Rajavithi Hospital complaining of pain in the left hip. A year earlier, pain had developed in his left joint and had gradually increased in intensity in both hips. A month before he was referred, radiographs obtained at another hospital showed bilateral slipped capital femoral epiphysis (SCFE). The patient's biochemical laboratory data showed hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone (iPTH) compatible with primary hyperparathyroidism. HRPT2 gene analysis found heterozygosity for c. 700 C > T mutation (Arg234X) of HRPT2 gene at exon 7. This is the first report in the literature about somatic mutation of the HRPT2 gene of parathyroid carcinoma associated with slipped capital femoral epiphysis.

A case of anterior mediastinum paraganglioma presented with pericardial effusion two years before symptoms of catecholamine excess: first case report in Thailand.

Pheochromocytoma (PCC) and paraganglioma (PGL) are uncommon tumors. Clinical manifestations are mass effect or hormone secretion. The initial manifestation with pericardial effusion is rare. The author presented a case of anterior mediastinum paraganglioma presenting with pericardial effusion two years before symptoms of catecholamine excess. This is the first case reported in Thailand. A 34 year-old female patient presented with dyspnea. There was pericardial effusion from echocardiography was diagnosed with no definite causes of pericardial effusion. After treatment with ibuprofen, pericardial effusion was absolutely resolved from repeated echocardiography. Two years later she had headache and hypertension. Chest X-ray, there was an anterior mediastinal mass. Her 24 hours urine metanephrine was very high. By imaging, an anterior mediastinal mass was observed from CT chest without adrenal mass from CT abdomen. The result of metaiodobenzylguanidine (MIBG) scan was compatible with paraganglioma. Symptoms of headache and hypertension disappeared after surgical removal of the mass. Pericardial effusion may be the first manifestation of paraganglioma especially if the patient had hypertension or could not find the etiology. Thus, pericardial effusion should be investigated for paraganglioma. Due to long term follow-up, this indolent growing tumor may respond to NSAIDs or regress spontaneously.

A prospective, longitudinal, multicenter, observational study to assess insulin treatment patterns in diabetic patients in Thailand: results from the TITAN Study.

OBJECTIVE: To assess usage patterns, effectiveness, andsafety of newly prescribed insulin treatment in patients with diabetes in Thailand MATERIAL AND METHOD: Type 1 or type 2 diabetes mellitus patients who failed achievement of HbA1c <7%, and were about to start or switch to a new insulin treatment were enrolled into this prospective, longitudinal, multicenter observational study. Data regarding insulin usage pattern, HbA1c, fasting plasma glucose (FPG), and hypoglycemia were collected at enrollment, three and six-month. RESULTS: Between July 2008 and February 2010, 751 patients were recruited Mean (SD) age was 57.0 (12.8) years. Mean BMI was 26.1 (5.0) kg/m2. At enrollment, 269 (35.8%), 241 (32.1%), 206 (27.4%), and 35 (4.7%) patients were prescribed neutral protamine Hagedorn (NPH) insulin, long-acting insulin analogues (LAA), premixed insulin (Premixed), and insulin combinations, respectively. Significant HbA1c and FPG reductions were noted at six-month (-1.4% and -56.2 mg/dl, respectively, p<0.01). After stratifying patients into three subgroups according to insulin, the patients could continue throughout six months (588 patients, 211 NPH-group, 201 LAA-group, and 176 Premixed-group). Patients in LAA-group attained higher rate of achievement HbA1c <7% without any hypoglycemia (18.9%) than NPH-group (7.1%) and Premixed-group (6.3%; p<0. 001). Mild-to-moderate hypoglycemic events were reported at 638 events (1.9 events/patient-year) while severe hypoglycemia was reported at 10 events (3.0 event/l00 patient-year). CONCLUSION: In this observational study of real-life clinical practice in Thailand, most common newly prescribed insulin for patients having inadequate glycemic control was NPH, followed by LAA and premixed insulin. More patients on LAA achieved target HbA1c without hypoglycemic events than those on NPH and premixed insulin.

Association between hs-CRP and Hba1c in overweight type 2 diabetic female patients.

BACKGROUND AND OBJECTIVE: High-sensitive C-reactive protein (hs-CRP) is associated with atherosclerosis. Previous studies have shown that hs-CRP is associated with insulin resistance, type 2 diabetes and higher HbA1c levels. As type 2 diabetes is often found in overweight women, the present study investigated the relationship between hs-CRP and HbA1c levels in such patients. MATERIAL AND METHOD: This was a retrospective study of type 2 diabetic patients in Rajavithi Hospital from January 2009 until June 2011. All the subjects were females aged 40 years or more who had body mass index (BMI) of more than 25 kilograms per square metre. The patients were examined and blood was collected in order to check hs-CRP and HbA1c levels. RESULTS: Data from 75 cases, classified the patients into 2 groups by their levels of hs-CRP and risk of coronary artery disease. Of the 75 patients, 35 had hs-CRP levels less than 1 mg/L, and the remaining 40 patients had hs-CRP levels of 1 mg/ L or more, representing 46.67% and 53.33% respectively, and it was found that hs-CRP values correlated with HbA1c levels. The group with hs-CRP of less than 1 milligram per liter had a mean HbA1c of 7.36 +/- 1.23%, while the group with hs-CRP of 1 mg/L or more had a mean HbA1c of 8.77 +/- 1.78%, with statistical significance at p-value < 0.001. CONCLUSION: In the present study of patients with type 2 diabetes, the authors found that hs-CRP levels correlated with HbA1c levels. Mean HbA1c levels were significantly higher in patients who had hs-CRP levels of 1 mg/L or more (p-value < 0.001). Other factors such as age, blood pressure, BMI, LDL-C, serum creatinine were not correlated with hs-CRP level.

Maternal 25 hydroxyvitamin D level and its correlation in Thai gestational diabetes patients.

OBJECTIVE: To identify 25 hydroxyvitamin D (250HD) levels in Thai pregnant women with gestational diabetes and nongestational diabetes. MATERIAL AND METHOD: This prospective study was conducted on 197 pregnant women at Rajavithi Hospital, a tertiary care medical center in Bangkok from October 2010 to July 2011. Plasma 25 hydroxyvitamin D concentration and HbA1c level during the 75 g OGTT in gestational diabetes mellitus (GDM) and non-GDM were evaluated. The recommendations of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) were used for diagnosis of GDM in the present study. RESULTS: In the selected 197 Thai pregnant women aged from 18 to 49 years, the mean age was 32.1 years, and the mean plasma 250OHD level was 34.3 ng/dl. The percentages of patients classified as having 25OHD deficiency (< 20 ng/dl), 25OHD insufficiency and normal 25OHD were 3.1%, 22.3% and 74.6%, respectively. Among the 197 women, 70 patients (34.8%) had GDM. In the GDM group, 29 patients (41.4%) had abnormal 25OHD level of which 5.7% had 25OHD deficiency and 35.7% had 25OHD insufficiency. Among those with GDM, plasma 25OHD concentration was significantly lower than in the non-GDM subjects (32.3 +/- 10.3 vs. 35.5 +/- 6.7 ng/dl, p = 0.001). Fasting blood glucose and HbA1C independently predicted low 25OHD levels in Thai GDM subjects after applying regression model and adjusting for age, BMI, trimester and family history of DM (p = 0.031, p = 0.014 respectively). Higher pre-pregnancy BMI was associated with GDM and lower 25OHD level. CONCLUSION: Thai pregnant women with GDM had lower levels of 25OHD compared to those without GDM. Only fasting plasma glucose independently predicted low 25OHD levels in GDM subjects.

Novel COL1A1 gene mutation (R1026X) of type I osteogenesis imperfecta: A first case report.

A 22-year-old Thai man with blue sclera, normal height and absence of deformity sustained an open fracture at the right talus and talo-navicular dislocation while playing in a volleyball match. The patient had a history of several fractures of his elbows, wrists and ankles from minor impacts. Novel COL1A1 nonsense mutation (c. 3202 C-->T), a C to T transition at position 3,203, resulting in arginine to stop codon at codon 1026 (R102 6X) mutation in exon 42 was found, and this is the first case reported in the literature.

Fulminant type I diabetes: the first case report in Thailand.

Type 1 diabetes is classified as either autoimmune (type IA) or idiopathic (type IB) diabetes. Fulminant type 1 diabetes is a recently-discovered subtype of idiopathic type 1 diabetes. It is defined as diabetes with complete abrupt onset of beta cell destruction and progression to hyperglycemia and ketoacidosis within a short period of time, but with a near-normal HbA1c level. The patients often have flu-like or abdominal symptoms at onset and elevated levels of pancreatic exocrine enzymes. Their diabetes-related autoantibodies are usually negative. In the present report, the authors present a case of fulminant type 1 diabetes in a 43-year-old Thai woman who presented with sudden onset of flu-like symptoms and abdominal pain. Findings on admission included a high blood glucose level and ketoacidosis, but a prediabetes range ofHbA1c level. Autoantibodies to glutamic acid decarboxylase (GAD) were negative. This subtype of type 1 diabetes was first identified in 2000 and there have been case reports from Japan, Korea, the Philippines and the Netherlands. Nonetheless, no case had been reported in Thailand until the present study. Here the authors report the first case of fulminant type 1 diabetes in Bangkok, Thailand.

Abnormal liver function test in Graves' disease: a prospective study of comparison between the hyperthyroid state and the euthyroid state.

BACKGROUND: Abnormal liver function test is sometimes seen in hyperthyroidism but no study had been carried out to compare liver function test in the hyperthyroid state and the euthyroid state. OBJECTIVE: This study aimed to find the prevalence of abnormal liver function test in Graves' disease and compare liver function test result in the hyperthyroid state with the euthyroid state. MATERIAL AND METHOD: This is a prospective study of 112 patients who had Graves' disease. These patients were new cases or recurrent cases of Graves' disease whose medication had been discontinue for more than 3 months. We followed-up 86 patients received treatment with antithyroid drugs up to the euthyroid state and compared liver function test at diagnosis and in the euthyroid state. RESULTS: An abnormal level of serum globulin was the most abnormal liver function test results in Graves' disease at 30.4%, followed by an abnormal level of serum alkaline phosphatase of 25.0% and gamma-glutamyl transpeptidase (GGT) of 23.3%. The trend of GGT levels returned to normal but there was an increased in serum alkaline phosphatase after treatment until the euthyroid state in the follow-up group. CONCLUSION: Abnormal liver function tests in Graves' disease are common, after treatment until the euthyroid state, experienced an improvement in GGT level but also an increase in serum alkaline phosphatase level.

Sensitivity of HRPT2 mutation screening to detect parathyroid carcinoma and atypical parathyroid adenoma of Thai patients.

OBJECTIVE: Detected HRPT2 mutation in parathyroid carcinoma or atypical parathyroid adenoma in sporadic hyperparathyroidism in Thai patients. MATERIAL AND METHOD: Samples of parathyroid carcinoma, typical (atypical) adenoma or hyperplasia were obtained for HRPT2 gene (17 exons) study since September 2001 to August 2010 both somatic and germline by SyBr Green PCR method. RESULTS: Parathyroid carcinomas and atypical parathyroid adenoma from 5 of 26 patients (10 of 32 samples) were tested for HRPT2 mutations. Only somatic HRPT2 mutations were found in tumor from 2 patients but three patients found both somatic and germline HRPT2 mutations. Exon 15 of HRPT2 gene was the best sensitivity (sensitivity 80.0%; p < 0.001, 95% CI 0.75-1.05) followed by exon 2 and exon 11 (sensitivity 60.0%; p = 0.007, 95% CI 0.60-0.99) to detected parathyroid carcinoma or atypical parathyroid adenoma. CONCLUSION: HRPT2 mutations by SyBr Green PCR sensitive method to detected parathyroid carcinoma or atypical adenoma from benign parathyroid tissues. Exon 15 was the best sensitive to detected parathyroid carcinoma or atypical adenoma. Genotyping of such family members for germline mutation would focus implementation of clinical and biochemical monitoring of carriers of these mutations.

Role of loading calcitriol to control hypocalcemia after parathyroidectomy in chronic kidney disease.

OBJECTIVE: To compare the effective calcitriol regimens in hypocalcimic hyperparathyroidism (HPT) patients who were referred to parathyroidectomy. MATERIAL AND METHOD: Retrospective study of fifty patients who underwent parathyroidectomy in Rajavithi Hospital between September 2001 and August 2009 was performed. The authors defined three regimens of calcitriol (A; fixed dose regimen, B; titrated dose regimen and C; loading dose regimen) by reviewing 41 charts of patients with chronic kidney disease. Biochemical factors available within two weeks before and after surgery were recorded and analyzed. RESULTS: Postoperative hypocalcemia was a common complication found in 82.93% (n = 34/41) of patients with chronic kidney disease, 80.61% (n = 25/31) and 90% (n = 9/10) of secondary HPT and tertiary HPT, respectively. In multiple logistic regression analysis; calcium-phosphorus product was the independent predictor of postoperative hypocalcemia requiring intravenous calcium gluconate with statistical significance atp = 0.008, ROC analysis showed calcium phosphorus products more than 53 mg2/dl2 represented the best compromise between sensitivity (0.71) and specificity (0.67) by area under the curve = 0.755). The amount of intravenous calcium gluconate after parathyroidectomy in the loading calcitriol regimen (initial dose 2.25-4 mcg/day) was significantly lower than that in the titrated calcitriol regimen (0.75-1.5 mcg/day) (p = 0.001). CONCLUSION: Loading calcitriol regimen reduced hypocalcemic morbidity in postoperative parathyroidectomy in patients with chronic kidney disease.

Proptosis in normal Thai samples and thyroid patients.

OBJECTIVE: Find normal values of proptosis in Thai population and study proptosis in Graves' disease and Hashimoto's thyroiditis. MATERIAL AND METHOD: Measurement of proptosis was made with Luedde exophthalmometer by one examiner in 277 normal Thai subjects and 591 thyroid patients. RESULTS: The mean proptosis of 168 normal Thai female patients was 11.44 mm. The mean proptosis of 109 normal Thai male patients was 11.84 mm. The value of standard deviation in both groups was 2 mm. The 99% confidence limit for exophthalmoses in Thai males was 16.5 mm and 16.1 mm in Thai females. The maximum value was 17 mm in males and 16 mm in females and the minimum value was 8 mm in males and 7 mm in females. The difference between both eyes was not greater than 2 mm. CONCLUSION: The mean proptosis of normal Thai female is 11.44 mm while the mean proptosis of normal Thai male is 11.84 mm. The distribution in proptosis in Graves' disease patients was greater than the normal population by about 2 mm while in Hashimoto's thyroiditis patients was not different from the normal population.