Evaluation of the Intestinal Permeability of Rosmarinic Acid from Thunbergia laurifolia Leaf Water Extract in a Caco-2 Cell Model.

Thunbergia laurifolia (TL) has been traditionally used as an antidote and an antipyretic drug by folk healers for centuries in Thailand. Rosmarinic acid (RA) is major compound in TL extract and has attracted great interest due to its potential broad pharmacological effects. Herein, the permeability of RA was investigated in TL extract and as a pure compound in a Caco-2 cell model by using high-performance liquid chromatography with a photodiode array detector (HPLC-PDA). The results reveal that the apparent permeability coefficient (Papp) values of RA in TL extracts and pure RA significantly increased after deconjugation by ß-glucuronidase/sulfatase enzymes. Our findings exhibit possible saturable biotransformation of RA and/or membrane transport while penetrated through Caco-2 cells. The cumulative amounts of RA as pure compounds and in TL extracts increased with the exposure time, and the efflux ratio (ER) was 0.27-1.14. RA in the TL extract has a similar absorption in the conjugated form and in the pure compound. The intestinal absorption of them is through passive diffusion. Therefore, our findings conclude that the intestinal transport of RA in TL extracts was mainly penetrated as conjugated forms with glucuronic acid and/or sulfate across Caco-2 cells and transported via passive diffusion.

An impact of relative adrenal insufficiency on short-term outcomes in non-critically ill cirrhotic patients: A prospective cohort study.

BACKGROUND: Relative adrenal insufficiency (RAI) is frequently found in patients with liver cirrhosis, especially in critically ill conditions. However, the prognostic impact of RAI in non-critically ill cirrhosis remains controversial. The aim of the present study was to assess the prevalence of RAI and its prognostic implication in non-critically ill cirrhotic patients. METHODS: From December 2015 to November 2017, hospitalised non-critically ill cirrhotic patients admitted with hepatic decompensation were prospectively enrolled in this study. Within 24 hours after admission, 250 mcg ACTH stimulation test was performed. RAI was defined as an increase in serum cortisol <9 mcg/dL in patients with basal serum cortisol <35 mcg/dL. Clinical outcomes were evaluated during admission and at 30-, 90-day visits. RESULTS: One hundred and fifteen patients were included (66% male, mean age 59.9 ± 16 years, mean MELD 16.1 ± 6.8, Child A/B/C 15.7%/53.9%/30.4%). The main indications for admission were bacterial infection (44.6%) and portal hypertension-related bleeding (19.1%). RAI was detected in 35 patients (30.4%). Patients with RAI had higher Child-Pugh score (9.4 ± 1.9 vs 8.0 ± 1.7, P < .01), and MELD scores (18.3 ± 5.9 vs 15.1 ± 6.9, P = .02). The in-hospital, 30-, and 90-day mortality rates were 9.6%, 20.9%, and 26.1%, respectively. There was no significant difference in the incidence of nosocomial infection, severe sepsis, septic shock, HRS, and mortality rates between patients with and without RAI. By multivariate analysis, bacterial infection on admission (HR 3.13, P < .01) and acute-on-chronic liver failure (HR 4.98, P < .001) were independent predictors of 90-day survival. CONCLUSIONS: RAI is found in about one-third of hospitalised non-critically ill cirrhotic patients and is associated with the severity of cirrhosis. However, the presence of RAI has no influence on short-term outcomes.

Improved participants' understanding of research information in real settings using the SIDCER informed consent form: a randomized-controlled informed consent study nested with eight clinical trials.

PURPOSE: This study aimed to test the applicability and effectiveness of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) across multiple clinical trials involving Thai research participants with various conditions. METHODS: A single-center, randomized-controlled study nested with eight clinical trials was conducted at Thammasat University Hospital, Thailand. A total of 258 participants from any of the eight clinical trials were enrolled and randomly assigned to read either the SIDCER ICF (n = 130) or the conventional ICF (n = 128) of the respective trial. Their understanding of necessary information was assessed using the post-test questionnaire; they were allowed to consult a given ICF while completing the questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥80%, and the secondary endpoint was the total score of the post-test. RESULTS: The proportion of the participants in the SIDCER ICF group who achieved the primary endpoint was significantly higher than that of the conventional ICF group (60.8 vs. 41.4%, p = 0.002). The total score of the post-test was also significantly higher among the participants who read the SIDCER ICF than those who read the conventional ICF (83.3 vs. 76.0%, p < 0.001). CONCLUSIONS: The present study demonstrated that the SIDCER ICF was applicable and effective to improve Thai research participants' understanding of research information in diverse clinical trials. Using the SIDCER ICF methodology, clinical researchers can improve the quality of ICFs for their trials.

Metabolic Syndrome in Thai Women Previously Diagnosed with Gestational Diabetes.

Background: The study of metabolic syndrome after delivery and its relationship to gestational diabetes (GDM) in Thai is lacking. Objective: To compare the prevalence and risk factors of metabolic syndrome after delivery in GDM and normal pregnant Thai women. Material and Method: A case-control study was performed at Thammasat University Hospital. Women with previous history of GDM (n = 56) and normal pregnant women (n = 51) delivered during 2007-2013 were enrolled. All of them underwent metabolic profile evaluation and 75 gm oral glucose tolerance test in 2013-2014. Risk factors of metabolic syndrome were assessed by logistic regression model. Results: Women were recruited a mean of 2.97±)1.15 years after delivery. Compared to the control group, the mean current age, median body mass index (BMI) before pregnant, current BMI, waist/height ratio and systolic blood pressure were significantly higher in GDM group. Metabolic syndrome was more in the GDM group (26.8% (15/56) vs. 7.8% (4/51), OR 4.3, 95% CI: 1.32-13.99). Only a BMI ≥25 kg/m2 before index pregnancy was a significant independent factor for this condition (OR 7.18, 95% CI 1.79-28.80; p = 0.005). After delivery, GDM group had more insulin resistance, assessed by HOMA-IR, less insulin sensitivity assessed by Masuda index and QUICKI score and less insulin secretion assessed by HOMA-B, comparing to control group without metabolic syndrome. Conclusion: Previously diagnosed GDM women have higher prevalence of metabolic syndrome after delivery. Obesity before pregnant is a strong independent risk factor for this condition.

Glucose-Lowering Efficacy of Water Extract of Malvastrum coromandelianum in Type 2 Diabetes Subjects: A Double Blind, Randomized Controlled Trial.

BACKGROUND: Water extract from Malvastrum coromandelianum (Linn.) Garcke (MC) has been shown to have glucose lowering effect, short- and long-term safety in animal studies. A preliminary study in human reveals safety and its potential use as an adjunctive treatment to antihyperglycemic medications. OBJECTIVE: To investigate the glycemic-lowering efficacy ofMC in type 2 diabetes subjects. MATERIAL AND METHOD: A multicenter randomized, double-blind, placebo-controlled trial was conducted. Seventy-one diabetes subjects, who were treated with either diet control or single oral anti-diabetic drug (sulphonylurea or biguanide) with HbA1C between 6.5-9%, were recruited. Subjects were randomized to take MC tablets in a total dose of 1,200 mg/day or placebo for 12 weeks. Clinical parameters, glycemic control, HOMA-IR and HOMA-ß were assessed. RESULTS: Both MC (n = 34) and placebo (n = 37) groups had comparable baseline characteristics with a mean baseline HbA1C of 7.6 ± 0.82 vs. 7.5 ± 0.8%, respectively. During the study, HbA1C did not differ statistically after 4, 8 and 12 weeks of treatment (7.7 ± 0.97 vs. 7.6 ± 1.0, 7.9 ± 1.09 vs. 7.8 ± 1.03 and 7.8 ± 1.1 vs. 7.6 ± 1.1%, respectively). The body weight, insulin resistance and insulin secretion were also similar between groups (p > 0.05). No episode of hypoglycemia was reported. CONCLUSION: MC in a dosage of 1,200 mg/day does not have glucose lowering efficacy in type 2 diabetes.

The needs of patients with diabetes for the prevention and treatment of foot complications in Thailand: A qualitative descriptive study.

Background: Inadequate diabetes self-management leads to foot infections and lower extremity amputations. Effective self-care, supported by nurse-provided information, is crucial, particularly in foot care. However, the current approach in Thailand focuses more on what nurses want patients to know rather than addressing patients' actual needs. Consequently, nurses might misunderstand their patients' perspectives. Hence, nurses need to grasp patients' needs for successful foot care behavior. Objective: This study aimed to explore the needs of patients with diabetes regarding the prevention and treatment of foot complications. Methods: The study employed a qualitative descriptive design. Thirty participants classified as high risk for foot ulcers were purposively selected from Thailand's university hospitals. Focus group discussions were used for data collection between June and July 2021. Verbatim transcription and content analysis were carried out for data analysis. Results: Four emergent themes highlighted patients' needs: 1) information-giving, 2) proactive foot screening with foot-care affirmation, 3) foot care services, and 4) relieving foot burdens and limb loss. Conclusion: Nurses should change their mindset to care for and continually understand patients' needs. This involves adapting educational strategies like the teach-back method and coaching while providing skill training. Offering diverse service platforms, both online and onsite education programs and counseling, is essential. Additionally, ensuring accessibility and affordability, such as establishing after-hours clinics and supplying foot care toolkits, remains crucial.

Validation of an electrochemical sensor based on gold nanoparticles as a point-of-care test for quantitative determination of glycated hemoglobin.

Monitoring the level of glycated hemoglobin (HbA1c) has become the gold standard measure for diabetes mellitus (DM) diagnosis and control, used in conjunction with fasting blood glucose (FBG) and oral glucose tolerance test. This study aimed to investigate the applicability of a newly developed nanoparticle-based electrochemical sensor-multiwalled nanotubes incorporated with gold nanoparticles (POCT-HbA1cMWCNTs/AuNPs)-used as a routine point-of-care test (POCT) for detection of HbA1c for the diagnosis of DM. Finger-prick and venous blood samples were collected from 108 DM and 98 non-DM subjects to determine HbA1c and total hemoglobin by POCT-HbA1cMWCNTs/AuNPs compared with the standard HPLC method. The performance of the POCT-HbA1cMWCNTs/AuNPs was evaluated using the standard cut-off HbA1c level of >6.5%. The test's sensitivity, specificity, positive predictive value, and negative predictive value were 100.00%, 90.32%, 87.23%, and 100.00%, respectively. The probability of DM diagnosis in a subject with HbA1c >6.5% (positive predictive value) was 87.23% (82/94). The accuracy of the POCT-HbA1cMWCNTs/AuNPs was 94.18%, with a %DMV (deviation from the mean value) of 0.25%. The results indicate satisfactory assay performance and applicability of the POCT-HbA1cMWCNTs/AuNPs for diagnosis of DM using the cut-off criteria of HbA1c >6.5.

Effects of the Consumption of Low to Medium Glycemic Index-based Rice on the Rate of Insulin Initiation in Patients with Gestational Diabetes: A Triple-blind, Randomized, Controlled Trial.

INTRODUCTION: Medical nutritional therapy is vital in patients with diabetes. A low glycemic index (GI) is generally advised in the management of women with gestational diabetes mellitus (GDM). However, the efficacy of this advice has not been systematically examined. The purpose of this study was to determine whether recommending a low to moderate GI rice (RD43 rice; GI = 56.9) in women with GDM would reduce the number of women requiring insulin, compared with rice of high GI (Thai Hom Mali [THM] rice; GI = 80.1). METHODS: Ninety-six participants with GDM were randomly assigned to receive either RD43 rice or THM rice. RESULTS: The mean ± SD ages in the RD43 and THM groups were 33.1 ± 13.1 and 33.6 ± 4.1 years, respectively. The mean gestational ages at the sampling in the RD43 and THM groups were 23.3 ± 5.9 and 23.5 ± 5.4 weeks. Both groups had comparable baseline characteristics, including age, gestational age, body mass index prior to pregnancy and at enrollment, baseline postprandial (oral glucose tolerance test) plasma glucose level, and hemoglobin A1c. Of the 48 women assigned to the RD43 group, 3 (6.3%) required insulin; in the THM group, 11 (22.9%) met the criteria for insulin therapy (P = 0.017). However, 10 of these 11 women were able to avoid insulin use by changing to the low to moderate GI rice. CONCLUSION: Using a low to moderate GI rice in GDM effectively reduced the number of patients requiring insulin therapy. Thai Clinical Trials Registry ID: TCTR20210524007.

Incidences and outcomes of hyperglycemic crises: a 5-year study in a tertiary care center in Thailand.

OBJECTIVE: To assess the incidences and outcomes of hyperglycemic crises. MATERIAL AND METHOD: A retrospective study of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in adults with type 1 or type 2 diabetes mellitus (DM) admitted to Thammasat Hospital between 2006 and 2010 was performed. Incidences, precipitating causes, clinical and laboratory characteristics, and treatment outcomes of hyperglycemic crises were obtained via medical record review Multivariate logistic regression analysis was used to determine predictors for mortality. RESULTS: Eighty-three patients were eligible and included. The mean age was 54.9 +/- 17.7 years old. Most subjects had type 2 DM (86.7%). The 5-year incidence of hyperglycemic crises was 7.46%. Diabetic ketoacidosis occurred more frequently than HHS (4.67% vs. 1.71%). During the hyperglycemic episodes, the mean plasma glucose level on admission was 741.3 +/- 320.8 mg/dL. Infections were the most common precipitating factor [61/83 (73.5%)], followed by non-compliance with treatments [35/83 (42.2%)]. Treatment complications included recurrent hyperglycemia (69.9%), hypokalemia (48.2%), hypernatremia (21.7%), and hypoglycemia (15.7%). The overall mortality rate of hyperglycemic crises was 8.4% (5.8% in DKA, 15.8% in HHS and 8.3% in the overlap of both conditions). The most common causes of death were infections [5/7 (71.4%)]. By multivariate analysis, serum sodium level on admission was independently associated with mortality (adjusted odds ratio 1.08, 95% CI 1.01-1.16, p = 0.03). CONCLUSION: Hyperglycemic crises were common in the authors' setting. Diabetic ketoacidosis occurred more frequently but had a lower mortality rate than HHS. Complications from hyperglycemic crisis treatment could be prevented by close monitoring, while high serum sodium level on admission was a predictor for mortality. Strategies to prevent infections and improve treatment compliance are needed to reduce the incidence of hyperglycemic crises among patients with DM.

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.

Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.

BACKGROUND: The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. METHODS: A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. RESULTS: A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. CONCLUSION: Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.

Phase I clinical trial to evaluate the safety and pharmacokinetics of capsule formulation of the standardized extract of Atractylodes lancea.

BACKGROUND AND AIM: Atractylodes lancea (AL) has been demonstrated in a series of studies to be a potential candidate for the treatment of cholangiocarcinoma. The aim of the current study was to evaluate the safety and pharmacokinetics of the capsule formulation of the standardized AL extract in healthy Thai participants. EXPERIMENTAL PROCEDURE: Forty-eight healthy Thai participants who fulfilled the inclusion and had none of the exclusion criteria were allocated to two study groups. The group 1 participants were randomized to receive a single oral dose of 1,000 mg of AL or placebo (20:4 participants). The group 2 participants were randomized to receive daily oral doses of 1,000 mg AL or placebo daily for 21 days (20:4 participants). Safety and tolerability of the two AL regimens were monitored. Blood samples were collected for measurement of atractylodin concentrations by HPLC and pharmacokinetic analysis was performed using model-dependent and model-independent analysis. RESULTS AND CONCLUSION: The AL extract was well tolerated in both groups. Atractylodin was rapidly absorbed but with low systemic exposure and residence time. There was no difference in the pharmacokinetic parameters of atractylodin following a single or multiple dosing, suggesting the absence of accumulation and dose-dependency in human plasma after continuous dosing for 21 days. The information on human pharmacokinetics of AL, when given as capsule formulation of the standardized extract, would assist in further dose optimization in cholangiocarcinoma patients with the defined pharmacokinetic-pharmacodynamic relationship.

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.

Lipid lowering efficacy between morning and evening simvastatin treatment: a randomized double-blind study.

OBJECTIVES: To compare lipid-lowering efficacy and high sensitive C-reactive protein (hsCRP) level between morning and evening simvastatin administration in hyperlipidemia subjects. MATERIAL AND METHOD: A randomized double blind controlled trial was conducted in 52 dyslipidemia subjects. A group of twenty five subjects received 10 mg simvastatin in the morning and placebo in the evening. The other group of twenty seven subjects received vice versa. Serum lipid profiles were evaluated every 4 weeks for the total course of 12 weeks. High sensitive CRP was measured at the beginning and the end of the study. RESULTS: Baseline LDL levels were similar in both groups (p = 0.95). The evening simvastatin group had significantly less low density lipoprotein level (LDL) than the morning group at 4 weeks (112 +/- 26.1 mg/dl vs. 136.3 +/- 32 mg/dl, p = 0.001) and 8 weeks after treatment (109.7 +/- 28 mg/dl vs. 129.5 +/- 27 mg/dl, p = 0.006). Difference in LDL after 12th week between two groups was not significant (p = 0.23). Triglyceride and HDL level were not different in both groups. Only evening simvastatin administration could significantly decrease hsCRP (p = 0.03). CONCLUSION: Simvastatin should be taken in the evening. Although lipid profiles were not statistically different in morning and nighttime simvastatin, the inflammatory marker (hsCRP level) is significantly reduced as a result of evening simvastatin administration.

Screening Test on Metabolic Syndrome Using Electro Interstitial Scan Instrument.

BACKGROUND: Metabolic syndrome is diagnosed using clinical and laboratory data. Electro interstitial scan (EIS) is a rapid and noninvasive screening. It measures and calculates the parameters to reflect hypertension, sympathetic activity, stiffness of the arteries, body fat composition, leptin and insulin resistance. Metabolic syndrome will be diagnosed if calculated score ≥10 CU. PURPOSE: To evaluate the accuracy, validity and appropriate cut-off score to diagnose metabolic syndrome. MATERIALS AND METHODS: A cross-sectional study was conducted using the population-based approach. Metabolic syndrome was diagnosed according to the modified National Cholesterol Education Program (NCEP ATP III) and International Diabetes Federation (IDF) criteria. The appropriate cut-off score to diagnose metabolic syndrome by instrument was determined. RESULTS: A total of 253 participants were enrolled with mean age of 40.06±6.33 years, and 64.43% (163/253) were female. Metabolic syndrome was diagnosed among 123 (48.62%) and 104 (41.11%) patients according to the NCEP ATP III and IDF criteria, respectively. The diagnostic indices of metabolic syndrome score ≥10 CU had a sensitivity of 23.6% and 27.9%, a specificity of 100% and area under ROC of 0.62 and 0.64, according to the NCEP ATP III and IDF criteria, respectively. The best cut-off level of metabolic syndrome score was ≥9 CU with a sensitivity of 79.67% (95% CI, 71.5-86.4%) and 88.46% (95% CI, 80.7-93.9%), a specificity of 96.92% (95% CI, 92.3-99.2%) and 93.29% (95% CI, 88.0-96.7%) and area under ROC 0.89 (95% CI, 0.85-0.93) and 0.92 (95% CI, 0.88-0.95), respectively, according to the NCEP ATP III and IDF criteria. CONCLUSION: Screening of metabolic syndrome using ES TECK in a Thai population demonstrated inadequate accuracy when using metabolic syndrome score ≥10 CU. We recommend using a metabolic syndrome score ≥9 CU to provide the best accuracy. This instrument is safe, fast and easy to use for metabolic syndrome screening.

Clinical use of fructosamine in islet transplantation.

Many islet transplant recipients have medical conditions that could interfere with the accuracy of HbA1c measurements (e.g., anemia/dapsone use). Fructosamine is less prone to have clinical interferences and reflects glucose control in a shorter period of time than HbA1c. This study aimed to validate fructosamine use in islet transplant subjects and to evaluate its effectiveness as a predictor for islet graft dysfunction. Thirty-three islet transplant recipients who had concomitant fructosamine and HbA1c data available were retrospectively analyzed. HbA1c, fructosamine, mean capillary blood glucose, and islet graft function (fasting C-peptide/glucose ratio) were assessed. There was a significant and positive association between fructosamine and HbA1c (p < 0.0001). Both variables were also positively associated with mean overall and fasting capillary glucose. Neither fructosamine nor HbA1c was shown by ROC analysis to significantly discriminate between periods with and without subsequent graft dysfunction. HbA1c >6% was predictive of this outcome 1 month in advance (OR 2.95, p = 0.003). However, although significantly associated with graft dysfunction, use of this cutoff as a predictor of dysfunction has poor sensitivity (50%) and specificity (77.6%). Fructosamine above the normal range (>270 mumol/L Quest Diagnostics) was also predictive of ensuing dysfunction (OR 2.47, p = 0.03); however, it had similarly poor sensitivity (62%) and specificity (64%). Fructosamine can be used as an alternative to HbA1c for glycemic assessment in islet transplant recipients in situations with HbA1c assay interference. Neither HbA1c nor fructosamine are good predictors of islet graft dysfunction.

0.075% capsaicin lotion for the treatment of painful diabetic neuropathy: A randomized, double-blind, crossover, placebo-controlled trial.

OBJECTIVE: A randomized, double-blinded, crossover, placebo controlled trial was conducted to evaluate the efficacy and safety of 0.075% capsaicin lotion for treating painful diabetic neuropathy (PDN). PATIENTS AND METHODS: PDN subjects were randomized to receive 0.075% capsaicin/placebo for 8 weeks, then crossing over to the other treatment after a 4-weeks washout period. Primary endpoint was the change in visual analog scale score of pain severity. Secondary outcomes were score changes in Neuropathic Pain Scale, short-form McGill Pain Questionnaires, and proportions of patients with pain score reductions of 30% and 50%, and adverse events. RESULTS: A total of 42 subjects were enrolled, 27 completed at least an 8-week treatment period. Intention-to-treat analysis showed no significant improvement in pain control with capsaicin lotion compared with placebo for all pain measures and proportion of patients who had 30% or 50% pain relief, respectively. Per protocol analysis were consistent. Capsaicin lotion was well tolerated but local skin reactions were common. CONCLUSION: In patients with PDN, the efficacy of 0.075% capsaicin lotion was similar to placebo but was well tolerated. More work is needed to assess different capsaicin formulations.

Nutritional status and behavior in subjects with type 1 diabetes, before and after islet transplantation.

BACKGROUND: To investigate whether changes of nutritional status and behavior are associated with islet transplantation (ITx) and to assess their possible mechanisms. METHODS: In this observational study, 52 subjects with type 1 diabetes, 30 of whom received ITx, underwent nutritional assessments. The study consisted of questionnaires complemented by a dietary intake recording, anthropometric measurements, and body composition analysis. Laboratory tests were also reviewed as part of the follow up. RESULTS: After ITx, significant reductions in body weight (3.7 kg; P<0.0001), body mass index (1.39 kg/m2; P<0.0001), waist circumference (3.96 cm; P=0.006), and fat weight (3.28 kg; P<0.01) were observed. The average consumption of carbohydrate and protein were also lower than pretransplant, together with some micronutrients (vitamins B12 and B6, zinc, and phosphorus). Insulin administration and changes in A1C were not associated with a significant change in anthropometric measurements. Subjects on exenatide after ITx showed significantly lower weight and body mass index than those not taking exenatide. CONCLUSIONS: ITx is associated with modifications in nutritional behavior and status. Drugs and health conditions are likely to be at least in part responsible for these changes, but a voluntary modification of eating habits by the patients also plays a role. Strict monitoring of nutritional parameters, counseling by experts in nutrition, and multivitamin/mineral supplement after ITx could be of benefit to the patients.

Current challenges in islet transplantation.

Allogeneic islet transplantation is becoming a treatment option for patients with unstable type 1 diabetes mellitus (T1DM). Around 80% of the islet recipients achieve insulin independence after one or two islet infusions under "Edmonton-like" immunosuppressive protocol, but only 10% will remain insulin independent over the long term. Islet transplantation leads to glucose stabilization, and severe hypoglycemia is prevented even in patients back on insulin injections. Thus, islet transplantation has achieved the proposed targets in patients with unstable T1DM: normalizing blood glucose and hemoglobin A(1c), preventing severe hypoglycemic episodes, and improving quality of life. The current aims of islet transplantation programs are to maintain the success achieved and to overcome remaining obstacles and limitations.

Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy.

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.