Benefits of Long-Term Continuation of Low-Dose Methimazole Therapy in the Prevention of Recurrent Hyperthyroidism in Graves' Hyperthyroid Patients: A Randomized Prospective Controlled Study.

Background: The long-term continuation of the low-dose antithyroid drug (ATD) beyond the standard duration of ATD therapy of 12-18 months to prevent recurrent hyperthyroidism (RH) is recommended with low quality of evidence. Objectives: To examine whether long-term continuation of low-dose ATD beyond the recommended duration of treatment would provide a benefit in the prevention of RH in patients with Graves' hyperthyroidism (GH) who achieved euthyroid status with a standard course of ATD therapy. Methods: A 36-month prospective randomized controlled study was conducted in 184 patients who had first diagnosed GH and were treated with a standard regimen of ATD therapy using methimazole (MMI) until achieving euthyroidism that was stably maintained for at least 6 months with a low-dose of (2.5-5 mg/day) MMI. All patients had neither a history of adverse effects from MMI, recurrent GH, severe and active ophthalmopathy nor conditions known to affect thyroid function before randomization. The patients were randomized into 2 groups: one group (92 cases) was assigned to discontinue (DISCONT-MMI) and the other (92 cases) was assigned to continue low-dose MMI (CONT-MMI) that was taken at the time of enrollment. The patients in both groups were followed up at 3, 6, 12, 18, 24, 30, and 36 months. The rate of RH was compared between both groups, and the adverse effects and risk factors of RH were also studied. Results: At the end of the 36-month study, 83 cases in CONT-MMI and 90 cases in DISCONT-MMI were eligible for analysis. The cumulative rates of RH in CONT-MMI were significantly lower than those in DISCONT-MMI at every follow-up time point (1.2% vs. 11.2%, 6.8% vs. 18.4%, 11.0% vs. 27.2%, 11.0% vs. 35.0%, and 11.0% vs. 41.2% at 6, 12, 18, 24, and 36 months, respectively; p < 0.01). Cox proportional hazard multivariate analysis showed that there were 2 factors independently associated with the risk of RH, including continuation of low-dose MMI therapy, which decreased the risk of RH by 3.8 times (HR = 0.26, p = 0.007, 95% CI = 0.10-0.70) and age onset of hyperthyroidism before 40 years, which increased the risk of RH by 2.9 times (HR = 2.9, p = 0.015, 95% CI = 1.23-6.88). Neither minor nor major adverse effects of low-dose MMI therapy were observed during the study period. Conclusions: In Graves' hyperthyroid patients with no or nonsevere ophthalmopathy who have completed a standard course of methimazole therapy without an adverse effect and have achieved an euthyroid status that is stably maintained with low-dose methimazole, a long-term continuation of the low-dose methimazole of 2.5-5 mg daily is effective and safe in the prevention of recurrent hyperthyroidism or maintenance of euthyroid status as long as the low-dose methimazole is continued. (TCTR20170705002).

Darker Skin Color Measured by Von Luschan Chromatic Scale and Increased Sunlight Exposure Time Are Independently Associated with Decreased Odds of Vitamin D Deficiency in Thai Ambulatory Patients.

BACKGROUND: Little is known about the association among skin color, sunlight exposure. and vitamin D status in Southeast Asian population. OBJECTIVE: To investigate the association between skin color measured by von Luschan chromatic scale (VLCS) and vitamin D status in Thai medical ambulatory patients. METHODS: Medical ambulatory patients were enrolled. The eligibility criteria were as follows: aged >18 years, stable medical conditions, and no conditions directly affecting vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels were assessed. Skin color at the outer forearm was assessed using VLCS which grades skin color from the lightest score of 1 to the darkest score of 36. Patients were systematically interviewed to estimate daily sunlight exposure time. RESULTS: A total of 334 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 25.21 ± 10.06 ng/mL. There were 17 (5.1%), 217 (65.0%), and 100 (29.9%) patients who had light brown (VLCS score 18-20), medium brown (VLCS score 21-24), and dark brown (VLCS score 25-27) skin colors, respectively. The mean serum 25(OH)D level was higher in patients with dark brown skin than in patients with medium brown and light brown skin (28.31 ± 10.34 vs. 24.28 ± 9.57 and 19.43 ± 9.92 ng/mL, respectively, both p < 0.05). Multivariate analysis showed that darker skin color and increased sunlight exposure time were independently associated with decreased odds of vitamin D deficiency (dark brown vs. light brown: odds ratio, 0.263, 95% CI: 0.081-0.851, p=0.026; medium brown vs. light brown: odds ratio, 0.369, 95% CI: 0.987-1.003, p=0.067; sunlight exposure time odds ratio per 1 minute/day increase 0.955, 95% CI: 0.991-1.000, p=0.037), after adjusting for possible confounders. CONCLUSIONS: We found that darker skin color at sunlight exposure area and increased sunlight exposure time were independently associated with decreased odds of vitamin D deficiency in Thai medical ambulatory patients.

Vitamin D and parathyroid hormone status in community-dwelling elderly patients with mild-to-moderate kidney impairment.

INTRODUCTION: Evidence on vitamin D and parathyroid hormone (PTH) status in patients with early kidney impairment is limited. We aimed to determine the associations among kidney function, vitamin D, and PTH status in community-dwelling elderly patients with mild-to-moderate kidney impairment. METHODS: Community-dwelling elderly patients were enrolled in this Institutional Review Board approved cross-sectional study. The eligibility criteria were as follows: age > 60 years, no recent hospitalization within the past 12 months, no conditions that affect vitamin D status including vitamin D supplementation, and eGFR > 30 mL/min/1.73 m2. Serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels were assessed. RESULTS: A total of 226 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 26.61 ± 10.44 ng/mL and the mean serum PTH was 50.67 ± 22.67 pg/mL. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] and secondary hyperparathyroidism [PTH > 65 pg/mL] were 25.3% and 18.1%, respectively. Patients with eGFR 30- < 60 mL/min/1.73m2 had significantly higher prevalence of 25(OH)D < 20 ng/mL (33.7% versus 19.4%, p < 0.05) than patients with eGFR ≥ 60 mL/min/1.73 m2. Multiple regression analysis showed independent negative association of serum PTH level with eGFR (mL/min/1.73 m2, ß: - 0.261, 95% CI [- 0.408, - 0.114]) and serum 25(OH)D (ng/mL, ß: - 0.499, 95% CI [- 0.775, - 0.223], adjusted for possible confounders). CONCLUSIONS: The prevalence of vitamin D deficiency was higher in patients with eGFR 30 - < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. Both decreased serum 25(OH)D levels and decreased eGFR were independently associated with increased serum PTH levels among these patients.

Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes.

BACKGROUND: High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. MATERIALS AND METHODS: T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of ß-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. RESULTS: Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was -0.1% and +0.1% (p=0.03) at 6 weeks, and -0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. CONCLUSION: Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Efficacy and Safety of Switching from Low-Dose Statin to High-Intensity Statin for Primary Prevention in Type 2 Diabetes: A Randomized Controlled Trial.

INTRODUCTION: Statin intensification is required in patients who have high-risk for cardiovascular events. However, it is unclear if this is needed in whom plasma LDL-C target was achieved with low-dose statin for primary prevention. We investigated the efficacy and safety of switching from low-dose statin to high-intensity statin among type 2 diabetes (T2D) who had achieved plasma LDL-C <100 mg/dl with low-dose statin treatment. METHODS: T2D patients with no atherosclerotic cardiovascular disease who had plasma LDL-C level <100 mg/dl while taking simvastatin ≤20 mg/day were randomized to continue using the same dosage of simvastatin (low-dose statin group; LS) for 12 weeks, or to switch to atorvastatin 40 mg/day for 6 weeks, and then, if tolerated, to atorvastatin 80 mg/day for 6 weeks (high-intensity statin group; HS). Biochemical test and adverse events were evaluated at baseline, 6 weeks, and 12 weeks. RESULTS: One hundred and fifty patients (76 LS, 74 HS, mean age 58.9±8.9 years, 72% female) were included. The mean baseline plasma LDL-C level on statin was slightly higher in the HS group (71.9±13.6 vs. 68.1±14.2 mg/dl, p=0.09). The HS group had a significantly lower plasma LDL-C level at both 6 and 12 weeks (both p<0.001). Plasma LDL-C <40 mg/dl was found more frequently in the HS group (23.0% vs. 3.9%, p<0.001). Discontinuation of statin due to adverse effects was more frequent in the HS group (5.4% vs. 1.3%, p=0.38 for atorvastatin 40 mg/day, 12.2% vs. 1.3%, p=0.03 for atorvastatin 80 mg/day). No serious adverse events were observed in either group. CONCLUSION: Switching from low-dose statins to high-intensity statins resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period.

Diabetes insipidus and panhypopituitarism as a first presentation of silent adenocarcinoma of lung: a case report and literature review.

BACKGROUND: Pituitary metastasis is a rare condition with a poor prognosis. Very few patients with pituitary metastasis are symptomatic. It is often associated with presence of co-existing metastases to other organs. Isolated pituitary metastasis as the first presentation of primary malignancy is uncommon. CASE PRESENTATION: A 72-year-old woman presented with a 2-month history of polyuria, increasing thirst and unexplained weight loss. Esophagogastroduodenoscopy (EGD) was scheduled as part of the investigation. She was kept nil per os for 10 h prior to EGD, after which she developed alteration of consciousness. Further investigation revealed hypernatremia with sodium level of 161 mmol/L and low urine osmolality of 62 mOsm/kg. Her urine output was 300 mL per hour. Diabetes insipidus (DI) was diagnosed based on evidence of polyuria, hypernatremia, and low urine osmolality. Her urine output decreased and urine osmolality increased to 570 mOsm/kg in response to subcutaneous desmopressin acetate, confirming central DI. Pituitary magnetic resonance imaging showed a heterogeneous gadolinium enhancing lesion at the sellar and suprasellar regions, measuring 2.4 × 2.6 × 3.9 cm compressing both the hypothalamus bilaterally and the inferior aspect of optic chiasm as well as displacing the residual pituitary gland anteriorly. The posterior pituitary bright spot was absent. These MRI findings suggested pituitary macroadenoma. There were also multiple small gadolinium-enhancing lesions up to 0.7 cm in size with adjacent vasogenic brain edema at the subcortical and subpial regions of the left frontal and parietal areas, raising the concern of brain metastases. Pituitary hormonal evaluation was consistent with panhypopituitarism. Histopathological and immunohistochemical studies of the pituitary tissue revealed an adenocarcinoma, originating from the lung. Computed tomography of the chest and abdomen was subsequently performed, showing a 2.2-cm soft tissue mass at the proximal part of right bronchus. There was no evidence of distant metastases elsewhere. The final diagnosis was adenocarcinoma of the lung with pituitary metastasis manifesting as panhypopituitarism and central DI. Palliative care along with hormonal replacement therapy was offered to the patient. She died 4 months after diagnosis. CONCLUSION: Diagnosis of pituitary metastasis is challenging, especially in patients with previously undiagnosed primary cancer. It should be considered in the elderly patients presenting with new-onset central DI with or without anterior pituitary dysfunction.

Beta-cell function in type 2 diabetic patients who failed to maintain good glycemic status with a combination of maximum dosages of metformin and sulfonylurea.

Background: The aim of this study was to investigate beta-cell function and examine whether sulfonylureas (SUs) are still useful in patients with type 2 diabetes (T2DM) who failed to maintain optimal glycemic control with a combination of maximum dosages of metformin and SU. Method: T2DM who had HbA1c >8% during treatment with a combination of maximum dosages of metformin and SU were studied. After enrollment, the patients were assigned to continue maximum dosages of SU and metformin for 2 weeks and then underwent the first oral glucose tolerance test (OGTT), the Max-SU OGTT. After the Max-SU OGTT, SUs were discontinued for 4 weeks and the second OGTT, the Discont-SU OGTT, was performed. After the Discont-SU OGTT, the same SU was restarted at 25% of the maximum dosage (25%Max-SU). After taking 25%Max-SU for 4 weeks, the third OGTT, the 25%Max-SU OGTT, was performed. Metformin at the same dosage was continued throughout the study. Normal OGTT (NGT) subjects, matched for age and body mass index (BMI), were also studied. Results: There were 25 T2DM and 28 NGT subjects. There was no difference in age and BMI between the two groups. The beta-cell function during Max-SU was 0.1, which was higher than 0.06 during Discont-SU (p<0.001) and also higher than 0.09 during 25%Max-SU (p=0.269). The beta-cell function during 25%Max-SU was higher than during Discont-SU (p<0.001). The beta-cell function of the NGT group was 0.34 and higher than during Max-SU (p<0.001). Fasting capillary blood glucose (FCBG) levels during Discont-SU (14.2±3.7 mmol/L) were higher than during 25%Max-SU (12.3±3.4 mmol/L) and during Max-SU (10.3±2.4 mmol/L) (p<0.05). In addition, the FCBG during Discont-SU was higher than that during 25%Max-SU (p<0.05). Conclusion: In T2DM patients who failed to achieve glycemic control with a combination of maximum dosages of metformin and SU, the beta-cell function declined compared to NGT subjects. However, the beta-cells were still responsive to SUs, which play a significant role in glycemic control.

Relationship between vitamin D and chronic spontaneous urticaria: a systematic review.

BACKGROUND: Vitamin D has been reported to be associated with many allergic diseases. There are a limited number of the studies of vitamin D supplementation in patients with chronic spontaneous urticaria (CSU). This study aims to study the relationship between vitamin D and CSU in terms of serum vitamin D levels, and the outcomes of vitamin D supplementation. METHODS: A literature search of electronic databases for all relevant articles published between 1966 and 2018 was performed. The systematic literature review was done following Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations. RESULTS: Seventeen eligible studies were included. Fourteen (1321 CSU cases and 6100 controls) were concerned with serum vitamin D levels in CSU patients. Twelve studies showed statistically significant lower serum vitamin D levels in CSU patients than the controls. Vitamin D deficiency was reported more commonly for CSU patients (34.3-89.7%) than controls (0.0-68.9%) in 6 studies. Seven studies concerned with vitamin D supplementation in CSU patients showed disease improvement after high-dosages of vitamin D supplementation. CONCLUSION: CSU patients had significantly lower serum vitamin D levels than the controls in most studies. However, the results did not prove causation, and the mechanisms were not clearly explained. Despite the scarcity of available studies, this systematic review showed that a high dosage of vitamin D supplementation for 4-12 weeks might help to decrease the disease activity in some CSU patients. Well-designed randomized placebo-controlled studies are needed to determine the cut-off levels of vitamin D for supplementation and treatment outcomes.

High prevalence of diabetes and abnormal glucose tolerance in Thai women with previous gestational diabetes mellitus.

AIM: To determine the prevalence of and risk factors for abnormal glucose tolerance (AGT) in previous gestational diabetes mellitus (pGDM) women. METHODS: 100 pGDM women randomly selected from the database of the Department of Obstetrics/Gynecology. 75 g-OGTT were performed in subjects without known diabetes. AGT was diagnosed using the American Diabetes Association criteria. RESULTS: The mean age, pre-gestational BMI, and time since delivery were 38 ± 5 years, 24.5 ± 5.7 kg/m2, and 46 ± 26 months. Overall, 81% of the subjects had AGT, including IGT (38%), IGT + IFG (5%), T2DM (38%). Plasma glucose (PG) at 1 h after a 50 g-glucose challenge test (GCT), PG at 1 h after 100 g-OGTT, HbA1c, and HOMA-IR were significantly greater in women with AGT than normal glucose tolerance (NGT) women. The proportion of women with ≥3 abnormal PG values during 100 g-OGTT was greater in AGT than NGT group (50.7% vs. 15.8%). Multivariate analysis showed that PG ≥ 150 mg/dl at 1 h after a 50 g-GCT and ≥3 abnormal PG values in 100 g-OGTTs were risk factors for developing AGT. CONCLUSIONS: Eighty-one percent of pGDM women developed AGT within 4 years after delivery. Risk factors for AGT were PG ≥ 150 mg/dl at 1 h after a 50 g-GCT and ≥3 abnormal PG values in a 100 g-OGTT.

Efficacy of low- and moderate-intensity statins for achieving low- density lipoprotein cholesterol targets in Thai type 2 diabetic patients.

BACKGROUND: Low dose statins are commonly used among Asians, because plasma low-density lipoprotein cholesterol (LDL-C) reductions similar to those observed in Westerners are achieved at lower doses. We aimed to assess the efficacy of low- and moderate-intensity statins for achieving plasma lipid targets in Thai type2 diabetes (T2D) and to evaluate factors associated with greater LDL-C reduction by statins. METHODS: T2D patients who were treated with low- and moderate-intensity statins at the Siriraj Diabetes Clinic during the January 2013 to December 2014 study period were eligible for inclusion(n = 978), 400 patients were randomly recruited. Patients were classified into 1 of the following 2 groups according to their plasma LDL-C reductions by statins (N = 393); very favorable response (LDL-C reduction ≥50%) or less favorable response (LDL-C reduction <50%). RESULTS: Of the 400 patients, 41.3% were low-intensity statin users. Mean age was 64.4 ± 12.7 years, 64% were female. Median duration of diabetes was 13.3 years and mean HbA1C was 8.1 ± 1.9%. Plasma LDL-C goal of <100 mg/dl and <70 mg/dl was achieved in 84.3% and 38.0% respectively, with no significant difference between the low- and moderate-intensity statin users. LDL-C reductions ≥50% can be achieved in 38.4%. Factors associated with very favorable responses from statins were age, hypertension, patients with stable or reduced weight, and better glycemic control. CONCLUSION: Low- and moderate-intensity statins achieved plasma LDL-C goal of <100 mg/dl and <70 mg/dl in 84.3%, and 38.4% of the patients respectively. Due to the improved response to lower doses observed in Asians, a titration dosage strategy should be considered.

Efficacy of Once Daily versus Divided Daily Administration of Low Daily Dosage (15 mg/Day) of Methimazole in the Induction of Euthyroidism in Graves' Hyperthyroidism: A Randomized Controlled Study.

BACKGROUND: Previous studies used unequal or high daily dosages of methimazole (MMI) to compare the efficacy of once daily dose regimen (OD-MMI) with that of divided daily doses regimen (DD-MMI) in inducing euthyroidism. OBJECTIVES: To compare the efficacy of OD-MMI to that of DD-MMI using low daily dosage of MMI in inducing euthyroidism. METHODS: Fifty patients with clinically nonsevere Graves' hyperthyroidism were randomized to be treated with 15 mg/day OD-MMI or 15 mg/day DD-MMI. RESULTS: 21 cases (84%) in OD-MMI and 23 cases (92%) in DD-MMI were eligible for analyses. During the treatment, there was no difference in baseline characteristics, serum FT3 and FT4 reductions, and cumulative rate of achieving euthyroidism (4.8% versus 4.3%, 28.6% versus 34.8%, 71.4% versus 82.6%, and 85.7% versus 87.0% at 2, 4, 8, and 12 weeks, resp.) between both regimens. Hypothyroidism developed in DD-MMI significantly more than in OD-MMI (17.4% versus 0%, p < 0.05). CONCLUSIONS: Treatment with MMI at a low daily dosage of 15 mg/day OD-MMI is as effective as DD-MMI in the reduction of serum thyroid hormone levels and induction of euthyroidism. The OD-MMI regimen is preferable to the DD-MMI regimen in the treatment of clinically nonsevere Graves' hyperthyroidism. This trial is registered with Thai Clinical Trials Registry: TCTR20170529001.

Withdrawal of sulfonylureas from patients with type 2 diabetes receiving long-term sulfonylurea and insulin combination therapy results in deterioration of glycemic control: a randomized controlled trial.

BACKGROUND: The benefit of sulfonylureas (SUs) to patients with type 2 diabetes mellitus receiving long-term insulin treatment is unclear. This study evaluated glycemic control and beta-cell function after SU withdrawal in these patients. METHODS: In this 8-week randomized controlled study, patients with type 2 diabetes who had been treated with insulin for at least 3 years plus moderate to high doses of SUs were randomly assigned to withdrawal (n=16) or continuation (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events, and insulin secretion, including homeostasis model assessment of beta-cell function (HOMA-B) score, C-peptide concentration, and Matsuda index, were evaluated at baseline and after 2 and 8 weeks. RESULTS: Thirty patients (16 in the SU withdrawal group and 14 in the SU continuation group) completed the study. Median duration of diabetes was 17 (range 5-40) years. Baseline clinical characteristics, glycemic control, and HOMA-B were similar in the two groups, but the mean fasting C-peptide concentration was higher in the SU withdrawal group. After 8 weeks, the SU withdrawal group showed a significant increase in mean glycosylated hemoglobin levels from 7.8%±0.5% (62±5 mmol/mol) to 8.6%±1.2% (71±13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight but not significant increase from 7.7%±0.5% (61±5 mmol/mol) to 7.9%±1.2% (63±13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA-B, decreased by 18% and 36%, respectively, in the SU withdrawal group. Hypoglycemic events were significantly more frequent in the SU continuation group whereas body weight did not change significantly in either group. CONCLUSION: Withdrawal of SU from patients with type 2 diabetes receiving long-term combination treatment with SU and insulin resulted in deterioration of glycemic control and insulin secretion.

Blood glucose patterns in type 2 diabetic patients with optimal fasting plasma glucose but high HbA1c.

BACKGROUND: Achieving fasting plasma glucose (FPG) target may not reflect hemoglobin A1c (HbA1c) target achievement. OBJECTIVE: Illustrate the blood glucose patterns contributing to HbA1c > 7% in patients whose FPG was < 130 mg/dl and correlation between HbA1c and plasma glucose at various times. The contribution of caloric intake, carbohydrate consumption and glycemic index of food to plasma glucose were determined. MATERIAL AND METHOD: Patients with type 2 diabetes, attended out-patient clinics at Siriraj Hospital, who had FPG of < 130 mg/dl but HbA1c level of > 7% were invited to participate in this 4-week study. They were treated with single or combined oral hypoglycemic agents except for alpha glucosidase inhibitors and glinide. Each patient performed self monitoring of capillary plasma glucose (CPG) before and 2 hours after each meal and before retiring to bed on the most convenient day in the first and fourth weeks and monitored two CPG before breakfast and before dinner weekly. Daily food intake was recorded in the logbooks. RESULTS: The observed patterns of CPG in 60 cases were postprandial hyperglycemia with FPG of < 130 mg/dl in 21.7%, a high pre-meal and post-meal CPG with FPG of < 130 mg/dl in 36.7% and elevated all fasting, pre-meal and post-meal CPG in 41.7% of the patients. The correlation coefficients between HbA1c at the end of the present study and CPG were 0.345, 0.40 and 0.337 at pre-breakfast, pre-lunch and pre-dinner, respectively (p = 0.01). The correlation coefficients between HbA1c and 2 hours CPG post-lunch, post-dinner and bed time were 0.402, 0.412 and 0.472, respectively (p = 0.01). The correlation between CPG and caloric intake, carbohydrate consumption or glycemic index of food were not observed. CONCLUSION: Elevated blood glucose at all times was the commonest finding in type 2 diabetic patients whose FPG < 130 mg/ dl but HbA1c level > 7%. A sole measurement of FPG should not be used to assure optimal glycemic control. Significant correlations between HbA1c and pre- or post- meal CPG indicated that frequent monitoring of pre- and post- meal could be used in assessing overall glycemic control.

A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

OBJECTIVE: To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. MATERIAL AND METHOD: One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. RESULTS: At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). CONCLUSION: A high dose regimen of radioactive iodine treatment is more effective than the low dose regimen. The successful outcome of a high dose regimen occurred significantly earlier than that of the low dose regimen. For the persistent hyperthyroid patients, the average total cost in the low dose group was significantly higher than that of the high dose group.

Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

OBJECTIVE: Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. PATIENTS AND METHODS: Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. RESULTS: We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. CONCLUSIONS: Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

Hypercalcemia of malignancy: a study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide.

OBJECTIVE: Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). MATERIAL AND METHOD: Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. RESULTS: The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04). CONCLUSION: The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.

Postprandial leptin response to Thai meals with different macronutrient mixtures.

The objective of this study was to investigate the postprandial response of leptin, an appetite-regulating hormone, to different macronutrient mixtures in Thai meals. A within-subject repeat measurement was performed. Two groups of healthy Thais (10 men and 10 women in each group) received a single meal of equal calories composed either a high carbohydrate, low fat, low protein diet (HC-LFLP, carbohydrate:fat:protein = 70%:15%:15%) or a low carbohydrate, high fat, high protein diet (LC-HFHP, carbohydrate:fat:protein = 20%:50%:30%). Fasting and 30-minute interval postprandial blood levels of leptin, insulin and glucose were measured for a 2-hour period. In comparison to the LC-HFHP meal, the HC-LFLP meal produced a greater increase in glucose and insulin levels, but halted leptin from decreasing. Postprandial leptin levels were suppressed by a LC-HFHP meal but not by a HC-LFLP meal. The reduced leptin in conjunction with lower glucose and insulin levels may encourage overeating in habitual LC-HFHP diet consumers.

Hyperthyroidism induces glucose intolerance by lowering both insulin secretion and peripheral insulin sensitivity.

OBJECTIVE: The objectives of this study were to examine the effects of hyperthyroidism on glucose tolerance, insulin secretion, and insulin sensitivity. MATERIAL AND METHOD: Thirty-eight patients with hyperthyroidism and twenty-six healthy volunteers with matching age and body mass index were included. Patients with conditions known to affect glucose metabolism were excluded. An oral glucose tolerance test was performed after the diagnosis of hyperthyroidism and again when they achieved euthyroid state. Areas under the glucose and insulin curves were used to assess plasma glucose and insulin responses, respectively. Beta-cell function was determined by the corrected insulin response (CIR) and homostatic model assessment model 2 (HOMA2-%B). Peripheral insulin sensitivity was determined by the insulin activity (IA) and HOMA2-%S. RESULT: The prevalence of glucose intolerance in hyperthyroid state was 39.4% [impaired glucose tolerance (IGT) 31.5% and diabetes mellitus (DM) 7.9%]. This was significantly higher than that of 30.7% [IGT 19.2% and DM 11.5%] in healthy volunteers (p < 0.05). Glucose intolerance was associated with higher systolic blood pressure, higher mean arterial pressure, lower CIR, and higher T4 levels but not with the levels of T3. IA and HOMA2-%S significantly improved when achieving a euthyroid state despite the increase in body mass index. CONCLUSION: In conclusion, glucose intolerance is common in hyperthyroidism. Both impaired insulin secretion and decreased peripheral insulin sensitivity are the factors contributing to the development of abnormal glucose tolerance in the hyperthyroid state.

Analysis of the reg1alpha and reg1beta gene transcripts in patients with fibrocalculous pancreatopathy.

Fibrocalculous pancreatopathy is a form of diabetes, associated with tropical chronic calcific pancreatitis, in which islet beta-cell loss and pancreatic stone formation are found. It is likely to be a multifactorial disease with both genetic and environmental components. Regenerating (reg) gene encodes protein that has been involved in pancreatic lithogenesis and the regeneration of islet cells and therefore the abnormality of reg genes could be associated with fibrocalculous pancreatopathy. In this study, regla and reg1beta mRNAs were isolated from peripheral blood lymphocytes obtained from 16 patients with fibrocalculous pancreatopathy, 42 patients with type 1 diabetes, 37 patients with type 2 diabetes, and 22 normal controls. mRNAs were amplified by reverse-transcription polymerase chain reaction (RT-PCR) and analysed by a single strand conformation polymorphism (SSCP) technique. The reg1alpha and reg1beta mRNAs were isolated, indicating the ectopic expression of these genes in peripheral blood lymphocytes; however, variation among mobility patterns was not observed in the SSCP analysis of the RT-PCR products. The results indicated that there was no abnormality of the regla and reg1beta mRNAs obtained from the study groups.