Nutritional Interpretation of Hospital Diets for Elderly Patients With Chronic Diseases and Analysis of Factors Influencing Actual Intakes.

Background: The provision of hospital meals is considered a therapeutic intervention, and a therapeutic diet consisting of a post-discharge meal sample is provided. For elderly patients who require long-term care, it is important to determine the significance of nutrition by taking into account hospital meals, including therapeutic meals for conditions such as diabetes. Therefore, it is important to identify the factors that influence this judgment. This study aimed to investigate the difference between the expected nutritional intake via nutritional interpretation and actual nutritional intake. Methods: The study included 51 geriatric patients (77.7 ± 9.5 years; 36 males and 15 females) who could eat meals independently. The participants completed a dietary survey to determine the perceived nutritional intake obtained from hospital meal contents. Additionally, we investigated the amount of hospital meal leftovers from the medical records and the amount of nutrients from the menus to calculate the actual nutritional intake. We calculated the amount of calories, protein concentration, and non-protein/nitrogen ratio from the perceived and actual nutritional intake values. We then calculated the cosine similarity and conducted a qualitative analysis of factorial units to examine similarities between perceived and actual intake. Results: Among factors that constituted the large cosine similarity group (gender, age, etc.), gender was found as a particularly significant factor, with a high number of female patients (P = 0.014). Conclusions: Gender was found to influence the appropriate interpretation of the significance of hospital meals. The perception of such meals as samples for post-discharge dietary practice was more significant among female patients. This demonstrated that in elderly patients, it is important to consider gender differences when providing diet and convalescence guidance.

Positive Correlation Between Changes in Serum Albumin Levels and Breakfast Non-Protein Calorie/Nitrogen Ratio in Geriatric Patients.

Background: Differences in nutrition intake by meal intake time of geriatric patients may affect albumin (Alb) synthesis ability. Methods: We included 36 geriatric patients (81.7 ± 7.7 years; 20 males and 16 females) as subjects. We calculated their dietary patterns (DPs) by computing intake by breakfast, lunch, and dinner, as well as by nutrient, for a weight of 1 kg/day for 4 weeks after hospitalization. We confirmed the relationship between "DP with a positive correlation with breakfast protein" and the change rate of albumin (Alb-RC). Then, we performed linear regression analysis to explore factors influencing Alb-RC and compared non-protein calorie/nitrogen ratio (NPC/N) between the upper and lower Alb-RC groups. Results: It was observed that Alb-RC was negatively correlated with "DP with a positive correlation with breakfast protein" (B = -0.055, P = 0.038) and positively correlated with breakfast NPC/N (B = 0.043, P = 0.029). Breakfast NPC/N tended to be higher in the upper group than in the lower group (P = 0.058). Conclusion: The study revealed that there was a positive correlation between Alb-RC levels and breakfast NPC/N in geriatric patients at the care mix institution.

Nutritional Intake by Meal Time Zone in Geriatric Patients Is Related to Nutritional Assessment Index.

BACKGROUND: The blood metabolome profiles depend on the meal intake time zone regardless of having the same meal. The serum albumin (Alb) level, which is important in managing geriatric patients with chronic diseases, is included in the metabolome analysis. In this study, we aimed to examine the relationship between Alb and the nutritional value of hospital meals consumed at breakfast, lunch, and dinner among geriatric patients. Chrononutrition was considered while drawing inferences. METHODS: We retrospectively surveyed 52 geriatric patients with chronic diseases (aged 79.7 ± 8.7 years) admitted at a small-scale hospital providing combined healthcare measures and oral nutritional support. The dietary intake per kilogram of body weight of nutritional components for breakfast, lunch, and dinner was individually expressed as the ratio to the whole daily food intake. The dietary pattern was determined by principal component analysis. We also conducted linear regression analysis, with Alb as the dependent variable, and age, sex, and grade assigned in this study as well as the first, second, and third principal components of the dietary patterns as the independent variables. RESULTS: Three principal components with an eigenvalue of > 1 were extracted. The second principal component was a significantly negative determinant factor for Alb (B = -0.108, P = 0.016). In patients with high Alb levels, the energy, protein, and fat ratios at lunch were positively correlated, while the energy and carbohydrate ratios at dinner were negatively correlated. Mealtimes were fixed. CONCLUSIONS: The results of this study showed that the dietary pattern predominantly observed in patients with high Alb levels may be positively associated with Alb synthesis.

Analysis of Dietary Factors Affecting Body Mass Index in Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Body mass index (BMI) is correlated with the outcomes of various metabolic and pathological conditions. To elucidate the factors affecting BMI in elderly persons, we studied elderly persons with and without diabetes mellitus for BMI management target values using receiver operating characteristic (ROC) analysis. METHODS: We conducted a dietary survey targeting 60 elderly outpatients with type 2 diabetes mellitus (diabetes group, 70.1 ± 7.8 years) and 66 elderly persons who participated in a health class offered by the municipality (health class group, 72.5 ± 5.7 years). RESULTS: In the diabetes group, positive correlations were observed between BMI and several variables including blood glucose levels (all P < 0.05), whereas BMI had negative correlations with the third principal component (positive weight for oils and fats). In addition, BMI was negatively correlated with the intake of oils and fats. In the health class group, BMI was positively correlated (all P < 0.05) with grip strength/sixth principal component (positive weight for sweets)/condiments. An analysis of dietary patterns revealed that dietary factors correlated with BMI in each group. The cutoff value of BMI was suggested to be near the normal upper limit or slightly higher in the subject group. CONCLUSION: We considered that BMI management was useful as an indicator for maintaining grip and muscle strength in elderly persons and as an indicator for diabetes care management. From the present study, we may propose the utility of a careful dietary survey as one of the approaches for these aims.

Relationship between Food-Intake Trends and Estimated Glomerular Filtration Rate in Elderly Patients with Type 2 Diabetes Mellitus.

The aim of this study is to investigate how vegetable and fruit intake trends affect the estimated glomerular filtration rate (eGFR) by analyzing therapeutic diet status in elderly type 2 diabetes mellitus patients. The study included 59 elderly patients with type 2 diabetes mellitus (mean age: 70.1±7.8 y) who had previously received therapeutic education for type 2 diabetes mellitus from a clinical team and were subsequently receiving outpatient treatment. Blood examination data were retrospectively collected from medical records and diet status was investigated using a simplified self-administered diet history questionnaire. Dietary patterns were extracted using principal component analysis, and the relationships with each blood examination data were investigated. Linear regression analysis was then used to examine the intake food groups related to eGFR. Energy intake was 27±9 kcal/kg. Overall, these results were in line with the Guidelines for the Treatment of Diabetes in Japan 2016. As a result of principal component analysis, seven dietary patterns were extracted, and the cumulative contribution ratio of the seven components was 74.0%. Among the dietary patterns, the 6th factor (positive weighting with fruit) for eGFR was a negative prognostic factor (p=0.010). Analysis of food group intake and eGFR indicated that green and yellow vegetables were positive prognostic factors, whereas fruits were negative prognostic factors (both p<0.05). The dietary patterns dependent on green and yellow vegetables and fruit intake appeared to influence eGFR positively and negatively, respectively.

Weekly glucagon-like peptide-1 receptor agonist albiglutide as monotherapy improves glycemic parameters in Japanese patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled study.

AIMS/INTRODUCTION: The present phase 3, randomized, double-blind 24-week study with extension to 1 year assessed the efficacy and safety of albiglutide compared with placebo in Japanese patients with type 2 diabetes mellitus inadequately controlled by diet and exercise with or without a single oral antidiabetic drug. MATERIALS AND METHODS: Patients received weekly albiglutide 30 mg (n = 160), albiglutide 50 mg (n = 150) or a placebo switched to albiglutide 30 mg after 24 weeks (n = 77). Open-label daily liraglutide 0.9 mg (n = 103) was included as a reference. Oral antidiabetic drug use was discontinued before baseline. The primary end-point was 24-week change from baseline in glycated hemoglobin (HbA1c). Secondary end-points included fasting plasma glucose, bodyweight and adverse events. RESULTS: At 24 weeks, mean HbA1c changes from baseline were -1.10, -1.30, and 0.25% for albiglutide 30, 50 mg and placebo, respectively (P vs placebo <0.0001 for both albiglutide doses), -1.19% for liraglutide. Decreases in HbA1c with albiglutide were sustained through the study. Mean fasting plasma glucose decreased by ≥20 mg/dL, and the mean change in bodyweight was ≤0.5 kg through 1 year across groups. Most commonly reported adverse events were nasopharyngitis, constipation and nausea. The incidence of adverse events was higher in active treatment groups than in the placebo group. Few hypoglycemia events were reported; no patient withdrew as a result of hypoglycemia. No new safety signals were detected. CONCLUSIONS: Albiglutide monotherapy achieved clinically significant decreases in HbA1c and fasting plasma glucose with good tolerability in Japanese patients with type 2 diabetes mellitus inadequately controlled by diet and exercise with or without a single oral antidiabetic drug.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients.

BACKGROUND: Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. METHODS: Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. RESULTS: A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. CONCLUSION: We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects.

BACKGROUND: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD). The effect of daprodustat in Japanese CKD patients with anemia has not been previously investigated. METHODS: We evaluated the relationship between daprodustat dose and hemoglobin response in Japanese patients on hemodialysis (HD) with anemia in a 4-week, phase II, double-blind, placebo-controlled study. After interrupting their erythropoiesis-stimulating agent for between 2 and 8 weeks, subjects with hemoglobin 8.5-10.5 g/dL were randomized to placebo or daprodustat 4, 6, 8, or 10 mg orally once daily. Hemoglobin, erythropoietin (EPO), and vascular endothelial growth factor (VEGF) levels during therapy were evaluated. RESULTS: Eighty-six of 97 randomized subjects completed the study. Mean baseline hemoglobin ranged from 9.68 to 9.92 g/dL across groups. After 4-week administration, mean hemoglobin changes were -0.28, -0.01, 0.54, and 0.97 g/dL in the 4, 6, 8, and 10 mg groups, respectively, as compared to -1.41 g/dL for placebo. Dose-dependent increase in plasma EPO concentration were observed up to 8 mg, with the 10 mg dose responses being similar to 8 mg. Plasma VEGF concentrations were minimally changed, even though 5 subjects treated with 6-10 mg reached EPO >500 mIU/mL. CONCLUSION: Daprodustat 4-10 mg once-daily produced dose-dependent increase in hemoglobin relative to placebo in Japanese HD subjects. The doses evaluated in the study have moderately increased endogenous EPO without changes in circulating VEGF levels.

Albiglutide, a weekly GLP-1 receptor agonist, improves glycemic parameters in Japanese patients with type 2 diabetes over 1 year when added to single oral antidiabetic drugs.

OBJECTIVE: To evaluate the safety and efficacy of once weekly albiglutide added to a single oral antidiabetic drug (OAD) in Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In this phase 3, 1 year study (NCT01777282), patients (N = 374) received albiglutide 30 mg plus a single OAD (sulfonylurea [n = 120], biguanide [n = 67)], glinide [n = 65], thiazolidinedione [n = 61], or α-glucosidase inhibitor [n = 61]). Albiglutide could be increased to 50 mg after Week 4, based on glycemic criteria. Primary endpoints were the incidence of adverse events (AEs) and hypoglycemia; secondary endpoints were changes from baseline at Week 52 in HbA1c and fasting plasma glucose (FPG), proportion of patients achieving HbA1c ≤7.0%, and withdrawals due to hyperglycemia. RESULTS: On-therapy AEs occurred in 78.6% of patients and serious AEs in 2.1%. Common AEs were nasopharyngitis (32.6%), constipation (7.2%), and diabetic retinopathy (5.3%). No serious AEs occurred more than once or were reported in >1 patient. Hypoglycemia occurred in 6.4% of patients, mostly in the albiglutide + sulfonylurea (14.2%) and the albiglutide + glinide (6.2%) groups. Albiglutide was uptitrated in 53.2% of patients. Mean baseline HbA1c was 8.1%. Mean decreases from baseline in HbA1c were observed with the addition of albiglutide to thiazolidinediones (-1.42%), α-glucosidase inhibitors (-1.39%), sulfonylureas (-1.04%), glinides (-0.95%), and biguanides (-0.94%). HbA1c of <7% in >50% of patients and mean reductions in FPG were achieved in all groups. Mean changes from baseline in body weight ranged from +0.52 kg (albiglutide + thiazolidinedione) to -0.33 kg (albiglutide + biguanide). Limitations of the study included open label treatment that was not randomized. CONCLUSIONS: When combined with a single OAD in Japanese patients with inadequately controlled T2DM, albiglutide led to favorable changes in all glycemic parameters, with minor changes in body weight depending on the background OAD. No new safety concerns were noted.

Evaluation of D-Dimer in Screening Deep Vein Thrombosis in Hospitalized Japanese Patients with Acute Medical Diseases/Episodes.

Objective: To investigate the usefulness of D-dimer as a screening method as well as to explore potent predictors of deep vein thrombosis (DVT) in hospitalized Japanese patients with acute medical diseases/episodes. Methods and Subjects: This study was a multi-center, prospective, observational study. The inclusion criteria were hospitalized patients at high risk of developing venous thromboembolism with; (1) congestive heart failure, acute exacerbation of chronic obstructive pulmonary disease, infectious diseases, or inflammatory diseases, (2) bed rest ≥4 days, and (3) ≥60 years old. D-dimer was measured on the same day as ultrasonography. Multivariate logistic regression analysis was performed to investigate predictors associated with the presence of DVT. Results: Sixty-nine patients were enrolled. The prevalence of DVT was 33.3% (23/69; 95% C.I., 19.4% to 47.3%). D-dimer was measured in 42 patients and the sensitivity and negative predictive value reached 100%, while the specificity (13.3%) and positive predictive value (31.6%) were low (cut-off value: 0.9 or 1.0 µg/mL). Statistically significant predictor was not assigned. Conclusion: As the sensitivity and negative predictive value of D-dimer reached 100%, D-dimer have a role in excluding patients who might otherwise undergo diagnostic imaging for DVT in hospitalized Japanese patients with acute medical diseases/episodes.

Evaluation of a Novel Glucose Area Under the Curve (AUC) Monitoring System: Comparison with the AUC by Continuous Glucose Monitoring.

BACKGROUND: Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. METHODS: Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. RESULTS: AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. CONCLUSION: Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.

Glucose area under the curve during oral glucose tolerance test as an index of glucose intolerance.

HbA1c and fasting plasma glucose (FPG) levels are commonly recognized as diagnostic indices for diabetes and glucose intolerance. However, they are not sufficient for clear detection of glucose intolerance in the early stage unless an oral glucose tolerance test (OGTT) is performed. Moreover, even in case of an OGTT, 2-h postprandial plasma glucose (PG) levels, a criterion for glucose intolerance in OGTTs, may not provide complete information regarding glucose tolerance. Whole glucose excursion after OGTT is considered to represent glucose tolerance well, and the glucose area under the curve (AUC) can be an index of glucose excursion. However, few studies have investigated measurement of the glucose AUC in glucose intolerance screening. In the present study, data from 520 OGTTs were analyzed to define the cutoff value for the glucose AUC for glucose intolerance screening. Our results showed that a cutoff value of 290 mg h/dl for the glucose AUC was highly sensitive and specific (90 and 93 %, respectively) for detecting diabetes, impaired glucose tolerance (IGT), and group at increased risk of diabetes (normal glucose tolerance with 1-h PG levels of ≥180 mg/dl after glucose load) and showed a better concordance rate than the use of HbA1c, FPG, or 2-h PG levels. Moreover, the cutoff value for the glucose AUC calculated using the diagnostic criteria in the OGTT (305 mg h/dl) was consistent with the value determined from OGTT analysis. These data suggest a possibility that glucose intolerance screening using a glucose AUC cutoff value of 290 mg h/dl could be useful.

Occurrence of Deep Vein Thrombosis among Hospitalized Non-Surgical Japanese Patients.

OBJECTIVE: To estimate the frequency of deep vein thrombosis (DVT) among non-surgical inpatients, and to evaluate the D-dimer assay as a screening tool for DVT. METHODS: Subjects were non-surgical inpatients aged 20 years or older who had been bedridden for at least 24 hours and had moderate-to-high risk factors for DVT. We assessed the presence of DVT by venous ultrasonography. Patients who received a diagnosis of venous thromboembolism (VTE) before admission, who had symptoms or findings of VTE at admission, or who had surgery or trauma within the past 3 months before admission were excluded. RESULTS: DVT was confirmed in 96 of 525 patients (18.3%). In a logistic regression analysis, longer duration of hospitalization, higher D-dimer value, and history of cancer surgery were significantly associated with the occurrence of DVT. The D-dimer assay showed high sensitivity (96.1%) and high negative predictive value (97.6%). CONCLUSION: Non-surgical inpatients with a long-term hospitalization or history of cancer surgery have a risk for DVT, and need to be considered for added DVT preventive measures as recommended in the prevention guidelines. In addition, the D-dimer assay is beneficial for the screening of DVT in medical practice.

Frequency of deep vein thrombosis among hospitalized non-surgical Japanese patients with congestive heart failure.

PURPOSE: Congestive heart failure (CHF) is one of the risk factors for deep vein thrombosis (DVT) according to the Japanese guidelines for DVT treatment and prevention. The purpose of this study is to estimate the frequency of DVT among hospitalized CHF patients, since there have been only limited DVT data in Japanese CHF patients. METHODS: Patients enrolled in the study were with risk factors for DVT listed in the guidelines as well as with acute exacerbation of CHF, bed rest for at least 4 days, and aged 60 or above. Patients treated by physical prophylaxis or anti-platelet medication were included, while patients treated by any anticoagulant medicines were excluded. Patients with surgery or injury within 3 months before the hospitalization or diagnosed clinically or with obvious past history as having DVT at hospitalization were excluded. The presence of DVT in the eligible patients was determined by ultrasonography and the images were evaluated by an independent central evaluation committee. RESULTS: Forty-four patients were enrolled in the study including 19 males and 25 females. The mean age was 79.0±10.6 years, and the mean duration of bed rest was 8.9±3.2 days. Out of these 44 patients, DVT was detected in 15 (34%) patients. Eight patients were on treatment with physical prophylaxis but DVT was still detected in two patients. Furthermore, 12 out of the rest of the patients were treated by anti-platelet agents and were still with DVT in 3 patients. CONCLUSION: When evaluated ultrasonographically, the frequency of DVT in hospitalized non-surgical Japanese patients with CHF was approximately 35%. DVT occurred in 25% of patients treated by physical prophylaxis or anti-platelet agents. The results suggest that Japanese hospitalized patients with CHF have a high risk of DVT and thus can be recognized to have potential benefit by preventing and treating DVT according to the guidelines.

A randomized dose-finding study demonstrating the efficacy and tolerability of albiglutide in Japanese patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the optimal dosage/regimen and to evaluate the efficacy and safety of albiglutide in Japanese patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-ranging, superiority study in Japanese patients with type 2 diabetes mellitus. Patients (n = 215) who were treatment naive or washed out of one oral antidiabetic drug were randomized to placebo or albiglutide 15 mg weekly, 30 mg weekly, or 30 mg every other week (biweekly). CLINICAL TRIAL REGISTRATION: NCT01098461. MAIN OUTCOME MEASURES: The primary end point was the change from baseline in HbA1c at week 16, measured using the Japan Diabetes Society standardization scheme and presented here using the National Glycohemoglobin Standardization Program equivalents. Other measures of efficacy as well as safety and population pharmacokinetics and pharmacokinetics/pharmacodynamics of albiglutide were assessed. RESULTS: Baseline HbA1c was 8.53%. There was a statistically significant difference between each albiglutide treatment group and placebo for change from baseline in HbA1c at week 16, with treatment effects of -0.89% for 15 mg weekly, -1.55% for 30 mg weekly, and -1.10% for 30 mg biweekly (P < 0.0001 for all groups vs placebo). By week 16, 63.0% and 33.3% of patients in the 30 mg weekly albiglutide group compared with 6.0% and 0% of patients in the placebo group achieved HbA1c <7.4% and <6.9%, respectively. No serious adverse events were related to study therapy; no deaths occurred. Nasopharyngitis was the most frequently reported adverse event in all treatment groups (n = 43 [20.3%]). CONCLUSIONS: Albiglutide exhibited therapeutic hypoglycemic effects with good tolerability among Japanese patients with type 2 diabetes mellitus; the 30 mg weekly dose was the most efficacious in this study. The 16 week duration of the study prevents generalizing these conclusions to longer treatment periods.

Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement.

AIMS: We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs). MATERIALS AND METHODS: Fifty diabetes mellitus inpatients and 10 healthy subjects undergoing the 75 g OGTT were included. Two sites on the forearm were pretreated with microneedle arrays, then hydrogels for interstitial fluid extraction were placed on the treated sites. Simultaneously, hydrogels for sweat monitoring were placed on untreated sites near the treated sites. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference AUC values. Using MIET, IG AUC was calculated from extracted glucose and sodium ion levels after attachment of the hydrogel for 2 h. RESULTS: Good correlation between IG AUC measurements using MIET and reference AUCs measured using PG levels was confirmed over a wide AUC range (202-610 mg/h/dl) after correction for the sweat-induced error detected by the hydrogel patches on the nonpretreated skin. Strong correlation between IG AUC and peak glucose levels indicates that glucose spikes can be easily detected by this system. CONCLUSION: We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice.

Effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity in Japanese dyslipidemic patients, with exploratory analysis of a PLA2G7 gene polymorphism of Val279Phe.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is being evaluated as a therapeutic target for treatment of atherosclerosis. This is the first study to examine the effects of darapladib, a novel selective Lp-PLA2 inhibitor, on Lp-PLA2 activity in Japanese dyslipidemic patients with/without the Val279Phe (V279F) single-nucleotide polymorphism (SNP) of the PLA2G7 gene. Exploratory analysis to examine the effects of V279F on Lp-PLA2 inhibition of darapladib was also performed. METHODS AND RESULTS: This was a 4-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging trial of darapladib in 107 Japanese patients with dyslipidemia receiving statins. Patients were randomized to placebo (n=25), darapladib 40 mg (n=28), 80 mg (n=28), or 16 0mg (n=26). All darapladib doses produced sustained dose-dependent inhibition of Lp-PLA2 activity of approximately 49%, 58%, and 67%, respectively (P<0.001 for all comparisons). The inhibitory effect achieved a plateau by 1 week. Patients with the V279F homogenous mutation who have no circulating levels of Lp-PLA2, were excluded from the study. The Lp-PLA2 activity was inhibited in both homozygous wild-type and heterozygote genotypes of the V279F polymorphism subjects to a similar extent, although the heterogeneous mutation has almost half the level of Lp-PLA2 activity compared with that of wild-type in Japanese people. The most common adverse events were odor related. No major safety concerns were noted. CONCLUSIONS: Darapladib produced sustained inhibition of Lp-PLA2 activity in Japanese dyslipidemic patients with/without the V279F SNP of Lp-PLA2.

Usefulness of a novel system for measuring glucose area under the curve while screening for glucose intolerance in outpatients.

AIMS/INTRODUCTION: To realize the effectiveness of a novel system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET), outpatients undergoing oral glucose tolerance tests (OGTT) were investigated for the efficacy of screening for glucose intolerance using this system. MATERIALS AND METHODS: Fifty outpatients scheduled to undergo a 75-g OGTT for medical reasons were recruited to the study. An area of skin on the forearm was pretreated with microneedle arrays before the application of hydrogels for interstitial fluid extraction. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference (actual) AUC. The AUC was predicted by MIET on the basis of glucose extracted by the hydrogel using sodium ion levels as the internal standard. RESULTS: Good correlation between MIET-predicted and reference AUCs obtained using PG levels was confirmed for a wide AUC range. By introducing a threshold level for AUC to separate glucose intolerance with peak glucose ≥180 mg/dL from normal glucose tolerance, the system was demonstrated to provide better screening accuracy compared with conventional methods that use HbA1c and fasting PG levels. The results of a questionnaire-based survey administered to the subjects suggested that this system was readily accepted by the majority as a painless monitoring method. CONCLUSIONS: The findings suggest that our glucose AUC measurement system using MIET would be useful for screening of glucose intolerance. In the future, this system may prove to be a useful aid as a screen for glucose intolerance before performing an OGTT for diagnosis.

Long-term safety and efficacy of ambrisentan in Japanese adults with pulmonary arterial hypertension.

OBJECTIVE: To investigate the safety and efficacy of long-term administration of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). RESEARCH DESIGN AND METHODS: In this open-label extension of a preceding multicenter dose-escalation study, 21 Japanese patients with PAH received treatment with 5 or 10 mg of ambrisentan once daily and were comprehensively evaluated every 12 weeks. The primary endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events. The secondary (efficacy) endpoints were change in exercise capacity (as indicated by 6-minute walk distance), World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, cardiopulmonary hemodynamics, and time to clinical worsening of PAH. CLINICAL TRIAL REGISTRATION: NCT00554619. RESULTS: The mean total duration of treatment (i.e., including the preceding dose-escalation study) was approximately 139 weeks. There were fewer adverse events related to ambrisentan in this study than in the preceding study, and we identified no new safety signals that might preclude the long-term use of ambrisentan among Japanese adults with PAH. Improvements observed in efficacy endpoints in the preceding study were maintained in the present study. LIMITATIONS: This study did not include a control group and lacked the statistical power to reach definite conclusions regarding the efficacy of ambrisentan. CONCLUSION: Our results suggest that long-term administration of ambrisentan is well tolerated and efficacious for Japanese adults with PAH.

A minimally invasive system for glucose area under the curve measurement using interstitial fluid extraction technology: evaluation of the accuracy and usefulness with oral glucose tolerance tests in subjects with and without diabetes.

BACKGROUND: Recent studies have highlighted the importance of managing postprandial hyperglycemia, but adequate monitoring of postprandial glucose remains difficult because of wide variations in levels. We have therefore developed a minimally invasive system to monitor postprandial glucose area under the curve (AUC). This system involves no blood sampling and uses interstitial fluid glucose (IG) AUC (IG-AUC) as a surrogate marker of postprandial glucose. This study aimed to evaluate the usefulness of this system by comparing data with the findings of oral glucose tolerance tests (OGTTs) in subjects with and without diabetes. SUBJECTS AND METHODS: The glucose AUC monitoring system was validated by OGTTs in 37 subjects with and 10 subjects without diabetes. A plastic microneedle array was stamped on the forearm to extract IG. A hydrogel patch was then placed on the pretreated area to accumulate IG. Glucose and sodium ion concentrations in the hydrogel were measured to calculate IG-AUC at 2-h postload glucose. Plasma glucose (PG) levels were measured every 30 min to calculate reference PG-AUC. RESULTS: IG-AUC correlated strongly with reference PG-AUC (r=0.93) over a wide range. The level of correlation between IG-AUC and maximum PG level was also high (r=0.86). The painless nature of the technique was confirmed by the response of patients to questionnaires. CONCLUSIONS: The glucose AUC monitoring system using IG provided good estimates of reference PG-AUC and maximum PG level during OGTTs in subjects with and without diabetes. This system provides easy-to-use monitoring of glucose AUC, which is a good indicator of postprandial glucose.