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).

Clinical Characteristics, Glycemic Control, and Microvascular Complications Compared Between Young-Onset Type 1 and Type 2 Diabetes Patients at Siriraj Hospital - A Tertiary Referral Center.

Purpose: This study aimed to investigate the clinical characteristics, glycemic control, and microvascular complications compared between young-onset type 1 (T1DM) and type 2 diabetes (T2DM) patients at Siriraj Hospital. Patients and Methods: We collected demographic, clinical, glycemic control, and microvascular complication data of young-onset (onset <30 years of age) T1DM and T2DM patients at our center using February 2019-December 2020 data from the Thai Type 1 Diabetes and Diabetes diagnosed Age before 30 years Registry, Care and Network (T1DDAR CN). Results: Of 396 patients, 76% had T1DM and 24% had T2DM. At diagnosis, T1DM were significantly younger (9.7±5.4 vs 16.9±6.4 years, p<0.001), had a lower body mass index (17.2±4.1 vs 30.8±7.9 kg/m2, p<0.001), higher prevalence of diabetic ketoacidosis (DKA) (66.1% vs 13.7%, p<0.001), and higher HbA1c level (12.8±2.6% vs 10.9±3.1%, p=0.002) compared to T2DM. Regarding glycemic control, the mean HbA1c at registry enrollment did not differ between groups (T1DM 8.3±1.8% vs T2DM 8.1±2.2%, p=0.303), but T1DM achieved HbA1c <7% significantly less than T2DM (19.3% vs 47.8%, p<0.001). T1DM showed deterioration of glycemic control during 10-20 years of age, and gradually improved during 20-30 years of age, whereas patients with T2DM showed progressive worsening of glycemic control over time. Concerning microvascular complications, the prevalence of diabetic retinopathy (10.6% vs 9%, p=0.92) and diabetic neuropathy (3.4% vs 5.5%, p=0.514) between T1DM and T2DM was not significantly different. However, T2DM had a significantly higher prevalence of diabetic nephropathy (T1DM 10.1% vs T2DM 40.2%, p<0.001) that developed within a significantly shorter duration of diabetes (T1DM 11.0±6.8 vs T2DM 4.3±5.1 years, p<0.001) compared to T1DM. Conclusion: T1DM had a significantly high prevalence of DKA at presentation, and most T1DM did not achieve the glycemic target, especially during adolescence. T2DM had a significantly higher prevalence of diabetic nephropathy that developed within a shorter duration of diabetes compared to T1DM.

Young-onset diabetes patients in Thailand: Data from Thai Type 1 Diabetes and Diabetes diagnosed Age before 30 years Registry, Care and Network (T1DDAR CN).

AIMS/INTRODUCTION: There is a lack of current information regarding young-onset diabetes in Thailand. Thus, the objectives of this study were to describe the types of diabetes, the clinical characteristics, the treatment regimens and achievement of glycemic control in Thai patients with young-onset diabetes. MATERIALS AND METHODS: Data of 2,844 patients with diabetes onset before 30 years-of-age were retrospectively reviewed from a diabetes registry comprising 31 hospitals in Thailand. Gestational diabetes was excluded. RESULTS: Based on clinical criteria, type 1 diabetes was identified in 62.6% of patients, type 2 diabetes in 30.7%, neonatal diabetes in 0.8%, other monogenic diabetes in 1.7%, secondary diabetes in 3.0%, genetic syndromes associated with diabetes in 0.9% and other types of diabetes in 0.4%. Type 1 diabetes accounted for 72.3% of patients with age of onset <20 years. The proportion of type 2 diabetes was 61.0% of patients with age of onset from 20 to <30 years. Intensive insulin treatment was prescribed to 55.2% of type 1 diabetes patients. Oral antidiabetic agent alone was used in 50.8% of type 2 diabetes patients, whereas 44.1% received insulin treatment. Most monogenic diabetes, secondary diabetes and genetic syndromes associated with diabetes required insulin treatment. Achievement of glycemic control was identified in 12.4% of type 1 diabetes patients, 30% of type 2 diabetes patients, 36.4% of neonatal diabetes patients, 28.3% of other monogenic diabetes patients, 45.6% of secondary diabetes patients and 28% of genetic syndromes associated with diabetes patients. CONCLUSION: In this registry, type 1 diabetes remains the most common type and the prevalence of type 2 diabetes increases with age. The majority of patients did not achieve the glycemic target, especially type 1 diabetes patients.

Prevalence of and Factors Associated with Diabetic Retinopathy in Patients with Diabetes Mellitus at Siriraj Hospital - Thailand's Largest National Tertiary Referral Center.

PURPOSE: We aimed to determine the prevalence of and factors associated with diabetic retinopathy (DR) in patients with diabetes mellitus (DM) and to evaluate the relationship between significant factors and severity of DR. PATIENTS AND METHODS: A retrospective cross-sectional study of 1130 diabetic patients (mean age: 60 years, 62.7% female, 91% type 2 diabetes) was conducted in the diabetes clinic of Siriraj Hospital (Bangkok, Thailand) during January 2012 to June 2015. DR was graded as absent, mild, moderate, or severe non-proliferative DR, or proliferative DR. Multivariate logistic regression analysis was used to identify independent risk factors for DR in DM patients. RESULTS: The overall prevalence of DR was 34.78%. Multivariate analysis revealed duration of diabetes, glycated hemoglobin level (HbA1c), presence of albuminuria, and abnormal protective sensation to be independent risk factors for DR. The prevalence of DR increased with longer duration of diabetes (p < 0.001), deterioration of glucose control (p = 0.006 for HbA1c), presence of significant albuminuria (p = 0.010), and loss of protective sensation (p = 0.001). CONCLUSION: In this study, one-third of DM were found to have DR. The independent predictors of DR were duration of diabetes, HbA1c level, presence of significant albuminuria, and impaired protective sensation. Heightened awareness of these risk factors will decrease the prevalence and severity of DR, and will improve early diagnosis and treatment of DR.

Type 1 diabetes management and outcomes: A multicenter study in Thailand.

AIMS/INTRODUCTION: The Thai Type 1 Diabetes and Diabetes Diagnosed Before Age 30 Years Registry, Care and Network was established in 2014 and involved 31 hospitals. The objective of the registry was to evaluate glycemic control and complications of patients with type 1 diabetes. MATERIALS AND METHODS: Patients' demographics, clinical data, frequencies of daily self-monitoring of blood glucose (SMBG), glycemic control and complications were collected. RESULTS: Among the 1,907 type 1 diabetes patients, the mean age was 21.2 ± 11.3 years. The mean glycated hemoglobin level was 9.35 ± 2.41%, with significant variations among age groups (P < 0.001). Conventional insulin treatment and intensive insulin treatment were used in 43 and 57% of patients, respectively. Mean glycated hemoglobin levels were significantly higher in patients treated with conventional insulin treatment compared to those treated with intensive insulin treatment (9.63 ± 2.34 vs 9.17 ± 2.46%, P = 0.002). Compared to the conventional insulin treatment group, significantly more patients in the intensive insulin treatment group achieved good glycemic control (P < 0.001), and fewer had diabetic retinopathy (P = 0.031). The prevalence of microvascular complications increased significantly with age (P < 0.001). Multivariate analysis showed good glycemic control to be associated with age 25 to <45 years, intensive insulin treatment with SMBG three or more times daily and diabetes duration of 1 to <5 years. CONCLUSIONS: Most Thai type 1 diabetes patients were not meeting the recommended glycemic target. As a result of this study, the national program to improve the quality of diabetes treatment and education has been implemented, and the results are ongoing.

Prediction of type 2 diabetes mellitus using fasting plasma glucose and HbA1c levels among individuals with impaired fasting plasma glucose: a cross-sectional study in Thailand.

OBJECTIVES: About 11%-30% of individuals with impaired fasting plasma glucose (IFG) have type 2 diabetes mellitus (T2DM), diagnosed by the 75 g oral glucose tolerance test (75 g OGTT). This study investigated (1) the prevalence and cut-off levels for fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) in IFG individuals that most effectively predict the presence of T2DM diagnosed by a 75 g OGTT; (2) the predictors associated with T2DM; and (3) the pathophysiological characteristics of patients with IFG. MATERIALS AND METHODS: A single-centre, cross-sectional study was conducted in a primary care setting. A standard 75 g OGTT was performed on 123 subjects with IFG. Their beta-cell function and insulin resistance were calculated through plasma glucose and insulin levels monitored during the 75 g OGTT. RESULTS: In the IFG subjects, the prevalence of T2DM using the 2-hour postload plasma glucose (2hPG) criterion was 28.5%. Pre-diabetes and normal glucose metabolism were found in 48.7% and 22.8%, respectively, by 75 g OGTT. An HbA1c level ≥6.0% or FPG ≥5.9 mmol/L were the optimal cut-off thresholds for the prediction of the presence of T2DM. HbA1c had a sensitivity of 76.7% and specificity of 55.7% (95% CI 57.7% to 90.1% and 95% CI 43.3% to 67.6%, respectively), while FPG had a sensitivity of 85.7% and specificity of 23.9% (95% CI 69.7% to 95.2% and 95% CI 15.4% to 34.1%, respectively). The presence of metabolic syndrome, a higher HbA1c and higher FPG levels were associated with the risk of T2DM in the Thai IFG population. CONCLUSIONS: Almost one-third of the people with IFG had T2DM diagnosed by the 2hPG criterion. HbA1c was more effective than FPG in predicting the presence of T2DM in the IFG subjects. IFG individuals with HbA1c≥6.0% or FPG≥5.9 mmol/L should be advised to undergo a 75 g OGTT to detect T2DM earlier than otherwise.

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.

Older Subjects With ß-Cell Dysfunction Have an Accentuated Incretin Release.

Objective: Insulin secretion (IS) declines with age, which increases the risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is lower in older adults and that this decline is associated with ß-cell dysfunction. Research Design: A total of 40 young (25 ± 3 years) and 53 older (74 ± 7 years) lean nondiabetic subjects underwent a 2-hour oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with IGT (O-IGT; n = 21). Main Outcome Measures: Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of ß-cell glucose sensitivity. Results: Matsuda index, early phase ISR (0 to 30 minutes), and parameters of ß-cell function were lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 concentrations were elevated in both older groups [GLP-1 area under the curve (AUC)0-120 was 2.8 ± 0.1 in Y-NGT, 3.8 ± 0.5 in O-NGT, and 3.7 ± 0.4 nmol/L∙120 minutes in O-IGT subjects; P < 0.05], whereas GIP secretion was higher in O-NGT than in Y-NGT subjects (GIP AUC0-120 was 4.7 ± 0.3 in Y-NGT, 6.0 ± 0.4 in O-NGT, and 4.8 ± 0.3 nmol/L∙120 minutes in O-IGT subjects; P < 0.05). Conclusions: Aging is associated with an exaggerated GLP-1 secretory response. However, it was not sufficient to increase insulin first-phase release in O-IGT and overcome insulin resistance.

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.

Rare Cause of Recurrent Hypoglycemia: Insulin Autoimmune Syndrome.

We report a case of insulin autoimmune syndrome associated with several autoantibodies, presenting with recurrent hypoglycemia, predominantly in the postprandial period, which improved by dietary management and spontaneously resolved within two months. Differentiation from other causes of hyperinsulinemic hypoglycemia, such as insulinoma, is important to avoid unnecessary invasive procedures or surgical interventions. The 75-gram oral glucose tolerance test (OGTT) and mixed meal test showed a typical pattern, which may be useful indirect evidence of insulin autoimmune syndrome.

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.

Prevalence, Risk Factors, and Type of Organism in Fungal Foot Infection and Toenail Onychomycosis in Thai Diabetic Patients.

Background: Diabetes mellitus (DM) is a known and important predisposing factor for toenail onychomycosis and fungal foot infection. DM also increases the risk of patient developing secondary bacterial infection if fungal infection goes unrecognized and untreated. Objective: To assess the prevalence and risk factors of toenail onychomycosis and fungal foot infection in Thai diabetic patients. Material and Method: This single center cross-sectional observational study recruited type 1 and type 2 diabetic patients older than 18 years who attended Siriraj Hospital between October 1, 2012 and November 30, 2013. Patient demographic data, clinical data, and medical history were collected by questionnaire and assessed. Diagnosis of fungal infection was confirmed by potassium hydroxide investigation and fungal culture was performed to identify the type of organism. Results: One hundred forty four diabetes outpatients were enrolled and 38.9% were men. The mean (±SD) age was 59.6±12.7 years. Fungal infection was diagnosed 46 cases (31.9%). There were 28 cases (61%) with only toenail onychomycosis, two cases (4%) with only fungal foot infection, and 16 cases (35%) with co-infection (fungal foot infection and toenail onychomychosis). The organisms identified as causing fungal foot infection and toenail onychomycosis were dermatophytes (44.4% and 34.1%, respectively), non-dermatophytes (44.5% and 47.7%, respectively), and Candida species (5.6% and 4.5%, respectively). Risk factors found to be significantly correlated with toenail onychomycosis and fungal foot infection were male gender (p = 0.001), age older than 60 years (p = 0.006), agriculture-related activities (p = 0.006), family history of dermatophytosis (p = 0.034), and co-morbidity coronary heart disease (p = 0.044). No significant association was found for BMI, duration of DM, HbA1c, and diabetes related complications. Conclusion: Prevalence of fungal foot and toenail infection in Thai diabetes patient was 31.9%. We found higher prevalence of non-dermatophyte organisms as the cause of dermatomycosis and toenail onychomycosis. Accordingly, clinical diagnosis without proper culture identification may result in treatment failure.

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.

Elevated muscle TLR4 expression and metabolic endotoxemia in human aging.

Aging is associated with alterations in glucose metabolism and sarcopenia that jointly contribute to a higher risk of developing type 2 diabetes. Because aging is considered as a state of low-grade inflammation, in this study we examined whether older, healthy (lean, community-dwelling) participants have altered signaling flux through toll-like receptor 4 (TLR4), a key mediator of innate and adaptive immune responses. We also examined whether a 4-month aerobic exercise program would have an anti-inflammatory effect by reducing TLR4 expression and signaling. At baseline, muscle TLR4, nuclear factor κB p50 and nuclear factor κB p65 protein content, and c-Jun N-terminal kinase phosphorylation were significantly elevated in older versus young participants. The plasma concentration of the TLR4 agonist lipopolysaccharide and its binding protein also were significantly elevated in older participants, indicative of metabolic endotoxemia, which is a recently described phenomenon of increased plasma endotoxin level in metabolic disease. These alterations in older participants were accompanied by decreased insulin sensitivity, quadriceps muscle volume, and muscle strength. The exercise training program increased insulin sensitivity, without affecting quadriceps muscle volume or strength. Muscle TLR4, nuclear factor κB, and c-Jun N-terminal kinase, and plasma lipopolysaccharide and lipopolysaccharide binding protein were not changed by exercise. In conclusion, insulin resistance and sarcopenia of aging are associated with increased TLR4 expression/signaling, which may be secondary to metabolic endotoxemia.

Efficacy of quantitative capillary beta-hydroxybutyrate measurement in the diagnosis of diabetic ketoacidosis: a comparison to quantitative serum ketone measurement by nitroprusside reaction.

OBJECTIVE: To examine the efficacy of using capillary beta-hydroxy butyrate (beta-OHB) levels in comparison with serum ketone levels in distinguishing diabetic ketoacidosis (DKA) from non-DKA states in patients who had severe hyperglycemia and to determine a cut-off level of capillary beta-OHB that is best for the diagnosis of DKA. MATERIAL AND METHOD: Diabetic patients who presented with capillary blood glucose of > or = 400 mg/dL were studied. Capillary beta-OHB levels were measured by using a ketometer (OptiumXceed) at the same time as blood sample collection for biochemical tests and serum ketone measurement using nitroprusside reaction. The American Diabetes Association (ADA) criteria 2012 were used as the gold standard in the diagnosed of DKA. RESULTS: There were 13 cases (34.2%) with DKA (DKA group) and 25 cases (65.8%) without DKA (non-DKA group). There was no difference in plasma glucose levels between both groups. (DKA group = 714.2 +/- 367.6 mg/dl vs. non-DKA group = 589.4 +/- 220.2 mg/dl). The DKA group had significantly higher serum ketone (7.2 +/- 3.6 vs. 0.28 +/- 0.05 mmol/L, p < 0.001) and capillary beta-OHB levels (4.3 +/- 0.7 vs. 1.0 +/- 1.1 mmol/L, p < 0.001) than did the non-DKA group. Capillary beta-OHB levels significantly correlated to serum anion gap values (r = 0.828, p < 0.001), serum bicarbonate (r = 0.715, p < 0.001), and ketone (r = 0.72, p < 0.001) levels. ROC analyses showed that a capillary beta-OHB level of > 3.1 mmol/L was the best cut-off level for the diagnosis of DKA, and yielded a sensitivity of 100% (95% CI = 75.1-100) with a specificity of 96% (95% CI = 79.6-99.3). CONCLUSION: Using a cut-off capillary beta-OHB level of > 3.1 mmol/L is highly effective in the diagnosis of DKA in patients who presented with hyperglycemia. Quantitative measurement of capillary beta-OHB levels using a ketometer offers an immediate result that is useful for a reliable triage of screening for DKA in patients presented with severe hyperglycemia.

Energy expenditure evaluation in humans and non-human primates by SenseWear Armband. Validation of energy expenditure evaluation by SenseWear Armband by direct comparison with indirect calorimetry.

INTRODUCTION: The purpose of this study was to compare and validate the use of SenseWear Armband (SWA) placed on the arm (SWA ARM) and on the back (SWA BACK) in healthy humans during resting and a cycle-ergometer exercise and to evaluate the SWA to estimate Resting Energy Expenditure (REE) and Total Energy Expenditure (TEE) in healthy baboons. METHODS: We studied 26 (15F/11M) human subjects wearing SWA in two different anatomical sites (arm and back) during resting and a cycle-ergometer test and directly compared these results with indirect calorimetry evaluation (IC), performed at the same time. We then inserted the SWA in a metabolic jacket for baboons and evaluated the TEE and REE in free living condition for 6 days in 21 (8F/13M) non-human primates. RESULTS: In humans we found a good correlation between SWA place on the ARM and on the BACK with IC during the resting experiment (1.1±0.3 SWAs, 1±0.2 IC kcal/min) and a slight underestimation in the SWAs data compared with IC during the cycle-ergometer exercise (5±1.9 SWA ARM, 4.5±1.5 SWA BACK and 5.4±2.1 IC kcal/min). In the non-human primate (baboons) experiment SWA estimated a TEE of 0.54±0.009 kcal/min during free living and a REE of 0.82±0.06 kcal/min. CONCLUSION: SWA, an extremely simple and inexpensive apparatus, provides quite accurate measurements of energy expenditure in humans and in baboons. Energy expenditure data obtained with SWA are highly correlated with the data obtained with "gold standard", IC, in humans.

Diagnosis and localization of insulinoma in Thai patients: performance of endoscopic ultrasonography compared to computed tomography and magnetic resonance imaging.

BACKGROUND: Endoscopic ultrasonography (EUS) has now been accepted as the most sensitive method to localize insulinoma. However the data in Thai patients is lacking and the diagnostic performances of EUS comparing to computed tomography (CT) and magnetic resonance imaging (MRI) is unknown. MATERIAL AND METHOD: Retrospective analysis of 19 patients with recurrent hypoglycemia suggestive of insulinoma who underwent EUS, CT and MRI for tumor localization during 2007 to 2012. Surgical pathology or long-term follow-up was used as gold standard. RESULTS: There were 14 patients with 15 insulinoma lesions and 5 patients without insulinoma (2 nesidioblastosis and 3 without lesion). EUS, CTand MRI were performed in 19, 11 and 10 patients, respectively. EUS could detect insulinoma with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 93%, 80%, 93% and 80%, respectively. The corresponding performances for CT were 78%, 100%, 100%, 50% and MRI were 71%, 33%, 71%, 33%, respectively. In patients with positive CT subsequent EUS did not change diagnosis. However, EUS was able to detect insulinoma in 50% of patients with negative CT On the other hand, in patients with positive MRI, EUS changed and corrected the diagnosis of MRI in 29% and was able to detect insulinoma in 67% of patients with negative MRI. EUS, CT and MRI correctly localized insulinoma in 87%, 67% and 57%, respectively. The most common incorrect localization was between pancreatic body and tail. CONCLUSION: EUS has the best diagnostic performance in detection and localization of insulinoma. CT is less sensitive but very specific, therefore positive CT may preclude the need of EUS. MRI, however is less sensitive and specific than CT. Either positive or negative MRI may require further EUS.

Reduction in reactive oxygen species production by mitochondria from elderly subjects with normal and impaired glucose tolerance.

OBJECTIVE: Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in subjects with normal glucose tolerance [NGT]) impairs mitochondrial function and how this relates to ROS generation, whether older subjects with IGT have a further worsening of mitochondrial function (lower ATP production and elevated ROS generation), and whether exercise reverses age-related changes in mitochondrial function. RESEARCH DESIGN AND METHODS: Mitochondrial ATP and ROS production were measured in muscle from younger individuals with NGT, older individuals with NGT, and older individuals with IGT. Measurements were performed before and after 16 weeks of aerobic exercise. RESULTS: ATP synthesis was lower in older subjects with NGT and older subjects with IGT versus younger subjects. Notably, mitochondria from older subjects (with NGT and IGT) displayed reduced ROS production versus the younger group. ATP and ROS production were similar between older groups. Exercise increased ATP synthesis in the three groups. Mitochondrial ROS production also increased after training. Proteomic analysis revealed downregulation of several electron transport chain proteins with aging, and this was reversed by exercise. CONCLUSIONS: Old mitochondria from subjects with NGT and IGT display mitochondrial dysfunction as manifested by reduced ATP production but not with respect to increased ROS production. When adjusted to age, the development of IGT in elderly individuals does not involve changes in mitochondrial ATP and ROS production. Lastly, exercise reverses the mitochondrial phenotype (proteome and function) of old mitochondria.