Use of diabetes medications in adults with T2D and CVD in Japan: secondary analysis of the CAPTURE study.

Introduction: The CAPTURE study estimated the global prevalence of established cardiovascular disease (CVD) and characterized the usage of glucose-lowering agents (GLAs) in adults with type 2 diabetes (T2D) across 13 countries. The purpose of this secondary analysis of data from the Japanese sites within CAPTURE (NCT03786406, NCT03811288) was to provide data about medication usage stratified by CVD status among Japanese participants with T2D. Materials and methods: Data on GLA usage (including those with proven cardiovascular [CV] benefits) in Japanese participants with T2D managed in clinics or hospitals were collected and stratified by CVD subgroups. Results: There were 800 Japanese participants in the CAPTURE study (n = 502 [no CVD group], n = 298 [CVD group], n = 268 [atherosclerotic CVD subgroup]). Oral antidiabetic agents and insulin were used by 88.5% and 23.4%, respectively, of participants overall. Among participants with established CVD, dipeptidyl peptidase-4 inhibitors (65.1%) were most frequently used, followed by biguanides (50.7%) and insulins (26.2%). The pattern was similar among participants with atherosclerotic CVD. A lower proportion of participants in the CVD group used glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) with proven CV benefits versus the no CVD group (GLP-1 RAs: 7.0% vs. 8.6%; SGLT-2is: 13.4% vs. 19.1%). Conclusion: This analysis of the CAPTURE study provided a comprehensive overview of prescription patterns for the treatment of T2D in Japan. Use of GLAs with proven CV benefit was low, even in participants with established CVD, which was comparable to the findings from the global cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00638-w.

Treatment Burden on Once-Weekly Omarigliptin Versus Daily Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes: Randomized Controlled Trial (ONWARD-DPP4 Study).

INTRODUCTION: Preference for quality of life is important in deciding the treatment strategy for patients with type 2 diabetes mellitus. This study aimed to assess the effect of omarigliptin on patients' psychological attitudes and responses compared with daily dipeptidyl peptidase-4 inhibitors (DPP4is) by measuring the burden of pharmacotherapy using the Diabetic Treatment Burden Questionnaire (DTBQ). METHODS: Patients with type 2 diabetes mellitus who were taking daily DPP-4is were enrolled and randomized to a group that switched to omarigliptin or a group that continued daily DPP4is and were monitored for 12 weeks. The primary endpoint was the change in the DTBQ score from baseline to week 12. The secondary endpoints included changes in blood test results, medication preferences and medication adherence. RESULTS: The DTBQ total score significantly decreased from baseline to week 12 in both groups; however, no significant intergroup differences were observed. The DTBQ subscale, implementation and flexibility burden scores significantly decreased in the group that switched to omarigliptin, although no significant intergroup difference in the change was observed. DTBQ scores and medication preferences were associated with improvements in the DTBQ scores. CONCLUSION: Although this study failed to demonstrate the improvement of DTBQ total score by switching from daily DPP4is to omarigliptin compared with continuing the daily DPP4is, the DTBQ subscale score implementation and flexibility burden score were significantly improved only in the group that switched to omarigliptin, suggesting the possibility of switching from daily DPP4is to omarigliptin to decrease the patients' medication burden. TRIAL REGISTRATION: jRCTs031200437.

Efficacy and Safety of 5-Aminolevulinic Acid Combined with Iron on Skeletal Muscle Mass Index and Physical Performance of Patients with Sarcopenia: A Multicenter, Double-Blinded, Randomized-Controlled Trial (ALADDIN Study).

Sarcopenia is a geriatric syndrome characterized by decreased physical performance, muscle mass, and strength. Since the intake of 5-aminolevulinic acid (ALA) with iron can increase muscle mass and mitochondria in mice and elevate physical exercise performance in humans, the beneficial effects of ALA in patients with sarcopenia are expected, but this remains unexplored in the literature. This study aimed to assess the efficacy and dose dependency of ALA combined with iron in sarcopenia by measuring skeletal muscle mass index (SMI). Subjects with sarcopenia were enrolled and randomized into the ALA and sodium ferrous citrate (SFC) intake groups (ALA50/SFC29, ALA100/SFC29, ALA150/SFC29, ALA 100/SFC57, and ALA0/SFC29 placebo) and ingested the assigned study food for 12 weeks. The primary endpoint, the change in SMI from baseline to week 12, did not differ significantly between the groups. Hand grip significantly increased or tended to increase from baseline after 12 weeks with all doses of ALA or SFC compared with the placebo group. No consistent changes were observed in the other endpoints, including calf circumference, physical function, or quality of life (QOL). Although this study suggests safe administration and the possibility of ALA improving hand grip strength in patients with sarcopenia, further investigation is required.

Cardiovascular disease prevalence in adults with type 2 diabetes in Japan: results from the Japanese centers in the CAPTURE study.

Introduction: CAPTURE was a cross-sectional, non-interventional study (NCT03786406, NCT03811288) investigating the prevalence and characteristics of cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) across 13 countries worldwide. Here we present the findings for Japan. Materials and methods: Data were collected from adults aged ≥ 20 years (aged ≥ 18 years in countries outside Japan) with T2D who were managed in clinics or hospitals in 2019. Standardized methodology was used for all countries. The prevalence of CVD and its subtypes was estimated, weighted by care setting (clinics versus hospitals). Results: Among participants from Japan (total: 800; clinics: 440; hospitals: 360), mean (standard deviation) age was 65.6 (11.2) years and glycated hemoglobin 7.2% (0.9). Sixty-seven percent of participants were male, 57.8% had diabetes duration > 10 years, 49.8% had body mass index ≥ 25 kg/m2 and 63.1% had hypertension. The weighted prevalences (95% confidence interval [CI]) of CVD and atherosclerotic CVD were 37.3% (34.2;40.3) and 33.5% (30.6;36.4), respectively. The prevalence (95% CI) of the most common subtypes of CVD was: carotid artery disease 20.5% (18.2;22.8), coronary heart disease 11.9% (9.7;14.1) and cerebrovascular disease 10.4% (8.3;12.5). Conclusions: These contemporary data from the CAPTURE study on CVD prevalence in adults with T2D in Japan show that approximately one in three adults with T2D had established CVD, which is comparable to the prevalence in the global study cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00612-y.

Efficacy and Safety of Luseogliflozin in Patients with Type 2 Diabetes Complicated by Hepatic Dysfunction: A Single-Site, Single-Arm, Open-Label, Exploratory Trial.

INTRODUCTION: Improvements in glycemic control and hepatic function are clinically important goals in the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by hepatic dysfunction. The favorable effects of the sodium-glucose co-transporter inhibitor luseogliflozin on hepatic dysfunction were anticipated for humans. Nevertheless, few clinical studies have confirmed its real-world efficacy on hepatic dysfunction. This trial assessed the efficacy and safety of luseogliflozin in patients with T2DM complicated by hepatic dysfunction. METHODS: This prospective, single-site, single-arm, open-label, exploratory trial included 55 subjects with T2DM complicated by hepatic dysfunction. Subjects were administered luseogliflozin and observed for 52 weeks. The primary endpoints were the change in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), and hemoglobin A1c (HbA1c) from baseline to week 52. The secondary endpoints included body weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), homeostatic model assessment beta (HOMA-ß), homeostatic model assessment of insulin resistance (HOMA-IR), ferritin, Mac-2 binding protein (M2-BP), fatty liver index (FLI), fibrosis-4 (FIB-4) index, type IV collagen 7S domain, nonalcoholic fatty liver disease (NAFLD) fibrosis score, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). RESULTS: AST, ALT, γ-GTP, and HbA1c significantly decreased from baseline to week 52. Body weight, BMI, waist circumference, and FPG also significantly decreased. HOMA-IR significantly decreased but HOMA-ß was unchanged. FLI, ferritin, M2-BP, and NAFLD fibrosis scores significantly decreased whereas the FIB-4 index and type IV collagen 7S domain did not significantly change. The hs-CRP and IL-6 levels did not significantly change. CONCLUSION: Luseogliflozin administration in patients with T2DM complicated by hepatic dysfunction was well tolerated, did not worsen the hepatic condition, and might even be beneficial to improve hepatic function, reduce liver fat, and attenuate liver injury and fibrosis. TRIAL REGISTRATION: This study was registered under the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (No. UMIN000025808) and the Japan Registry of Clinical Trials (jRCT) (No. jRCTs021180017).

Comparison of tofogliflozin versus glimepiride as the third oral agent added to metformin plus a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes: A randomized, 24-week, open-label, controlled trial (STOP-OB).

Metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i) is the most common therapy for Japanese patients with type 2 diabetes. This 24-week, multicentre, open-label, parallel-group trial randomized patients on dual therapy to add-on tofogliflozin (20 mg/day, n = 33) or glimepiride (0.5 mg/day, n = 31). The primary outcome was change in body fat percentage. The secondary outcomes included changes in HbA1c, fat mass, fat-free mass, liver function variables and uric acid. Tofogliflozin and glimepiride reduced HbA1c to a similar extent. Body fat percentage did not change from baseline in either group. Fat mass was reduced by tofogliflozin but was increased by glimepiride (by -2.0 ± 1.7 kg and +1.6 ± 1.6 kg, P = .002). Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by -1.3 ± 1.3 kg and +0.9 ± 2.0 kg, P < .001). Alanine aminotransferase and uric acid levels were reduced by tofogliflozin (P = .006 and P < .001, respectively). These data provide novel information useful for selecting the third oral agent for patients whose diabetes is inadequately controlled with metformin plus DPP-4i dual therapy.

Rationale and Design of the STOP-OB Study for Evaluating the Effects of Tofogliflozin and Glimepiride on Fat Deposition in Type 2 Diabetes Patients Treated with Metformin/DPP-4 Inhibitor Dual Therapy.

BACKGROUND: The global pandemic of type 2 diabetes mellitus (T2DM) is an enormous clinical and socioeconomic burden. Biguanides and DPP-4 inhibitors (DPP-4i) are the most commonly used therapies in Japanese T2DM patients. When glycemic control is not adequate despite combination of these drugs, there is no consensus on the next step drug. Systematic reviews and meta-analyses of previous trials have indicated that glycemic control with triple combination therapies yields similar results. Thus, beneficial effects on cardiovascular risk factors may be important. The present study was designed to evaluate body fat percentage and several insulin resistance parameters after addition of tofogliflozin or glimepiride to the regimens of patients being treated with metformin and a DPP-4 inhibitor but failing to attain adequate blood glucose control. METHODS: Sodium glucose cotransporter-2 inhibitor, tofogliflozin versus glimepiride, comparative trial in patients with type 2 diabetes on body composition is an ongoing, multicenter, prospective, randomized, open-label, parallel-group trial. T2DM patients treated with metformin/DPP-4 inhibitor dual therapy have been recruited and randomly assigned to 20 mg/day tofogliflozin (n = 32) or 0.5 mg/day glimepiride (n = 32) groups, with either of these drugs being added to pre-existing regimens for 24 weeks. PLANNED OUTCOMES: The primary endpoint is the change in body fat percentage from baseline to 24 weeks. The secondary outcomes are changes in body composition other than fat percentage, body weight, parameters related to glycemic control and ß-cell function, parameters related to lipids and arteriosclerosis, parameters related to liver function, parameters related to diabetic nephropathy, and uric acid levels. Safety parameters will also be analyzed. This is the first trial comparing the effects and safety of adding an SGLT2i and a sulfonylurea as the third-line oral agent to metformin/DPP-4i dual therapy. The results will provide valuable information for choosing third-line oral agents. TRIAL REGISTRATION: UMIN000026161. FUNDING: Kowa Co. Ltd. and Kowa Pharmaceutical Co. Ltd., Tokyo, Japan.

Dapagliflozin improves treatment satisfaction in overweight patients with type 2 diabetes mellitus: a patient reported outcome study (PRO study).

BACKGROUND: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. METHODS: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. RESULTS: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). CONCLUSIONS: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.

Correction to: Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study.

Unfortunately, in Table-5 of the original article, the parameter in the 5th row was published incorrectly as "LDL-C (mg/dL)". The correct parameter should read as "HDL-C (mg/dL)".

Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study.

Atherosclerosis, a chronic inflammatory disease in arterial blood vessels, is one of the major causes of death in worldwide. Meanwhile, periodontal disease is a chronic inflammatory disease caused by infection with periodontal pathogens such as P. gingivalis (Porphyromonas gingivalis). Several studies have reported association between periodontal infection and atherosclerosis, but direct investigation about the effects of periodontal treatment on atherosclerosis has not been reported. We have planned Japanese local clinics to determine the relationship between periodontal disease and atherosclerosis under collaborative with medical and dental care. A prospective, multicentre, observational study was conducted including 38 medical patients with lifestyle-related diseases in the stable period under consultation at participating medical clinics and 92 periodontal patients not undergoing medical treatment but who were consulting at participating dental clinics. Systemic and periodontal examinations were performed before and after periodontal treatment. At baseline, LDL-C (low-density lipoprotein cholesterol) levels and percentage (%) of mobile teeth were positively related to plasma IgG (immunoglobulin) antibody titer against P. gingivalis with multivariate analysis. Corresponding to improvements in periodontal clinical parameters after treatment, right and left max IMT (maximum intima-media thickness) levels were decreased significantly after treatment (SPT-S: start of supportive periodontal therapy, SPT-1y: at 1 year under SPT, and SPT-3y: at 3 years under SPT). The present study has clarified our previous univariate analysis results, wherein P. gingivalis infection was positively associated with progression of atherosclerosis. Thus, routine screening using plasma IgG antibody titer against P. gingivalis and periodontal treatment under collaborative with medical and dental care may prevent cardiovascular accidents caused by atherosclerosis.

Current status of achieving blood pressure target and its clinical correlates in Japanese type 2 diabetes.

AIMS/INTRODUCTION: To investigate the current status of achieved blood pressure levels in association with the number of antihypertensive drug classes as of 2013, and to explore the clinical correlates with achievement of target blood pressure in a large-scale cohort of Japanese subjects with type 2 diabetes. MATERIALS AND METHODS: A nationwide survey was conducted including 12,811 subjects with type 2 diabetes. Subjects were divided by achieved blood pressure, <130/80 or 140/90 mmHg, and the number of drug classes taken. RESULTS: The percentages achieving a blood pressure of <130/80 or 140/90 mmHg were 52.0% and 86.1%, respectively. The prevalence of hypertension, if defined as ≥130/80 mmHg or treated, became 67.9%. Among subjects taking antihypertensive drugs, a blood pressure of <130/80 or <140/90 mmHg was 46.7% and 83.2%, respectively. The percentages of <130/80 mmHg were 55.9% without drugs, 47.1% on 1, 42.5% on 2, 47.2% on 3, and 56.8% on ≥4 drugs, respectively. The most prescribed drugs were renin-angiotensin system inhibitors, followed by calcium channel blockers, diuretics, and ß-blockers. The multiple logistic regression analysis indicated that a blood pressure <130/80 mmHg was associated with lower values in age, body mass index, albuminuria, and glomerular filtration rate, higher proportions on targets for HbA1C and lipids, and less retinopathy. CONCLUSIONS: In type 2 diabetes, hypertension is common and only 52% achieved <130/80 mmHg, indicating a difficulty in blood pressure lowering. This was correlated with difficulties in glycemic and lipid management, obesity, and vascular complications, implying these clustering to be a serious problem. This article is protected by copyright. All rights reserved.

Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis.

BACKGROUND: The GetGoal-L-Asia and -S trials were multi-center trials conducted in 4 and 16 countries, respectively including Japan that evaluated the efficacy and safety of lixisenatide add-on treatment vs. placebo among patients with type 2 diabetes. The aims of this study were to determine the efficacy and safety of lixisenatide add-on treatment among Japanese patient groups. METHODS: All Japanese intent-to-treat patients with baseline and endpoint HbA1c measurements were included in the meta-analyses. Subgroup analyses were carried out for patients with low (<8 %) and high (≥8 %) baseline HbA1c levels, low (<25 kg/m(2)) and high (≥25 kg/m(2)) baseline body mass index (BMI), short (<10 years) and long (≥10 years) durations of diabetes, and for those <65 and ≥65 years of age. RESULTS: The overall study population of Japanese type 2 diabetes patients included 143 patients (mean age: 59.0 years; 35 % female) treated with lixisenatide and 136 patients treated with placebo (mean age: 57.8 years; 32 % female). Among the subgroups, lixisenatide treatment vs. placebo was associated with greater change in HbA1c (Low HbA1c -0.80 %, p < 0.0001; High HbA1c -1.19 %, p < 0.0001; low BMI -0.88 %, p < 0.0001; high BMI -1.28 %, p < 0.0001; short diabetes duration -1.28 %, p < 0.0001; long diabetes duration -0.93 %, p < 0.0001; <65 years: -1.00 %, p < 0.0001; ≥65 years -1.24 %, p < 0.0001). Additionally, among the subgroups, lixisenatide treatment vs. placebo was associated with greater change in post-prandial glucose. CONCLUSIONS: For Japanese type 2 diabetes patients lixisenatide may be an efficacious and safe add-on therapy leading to improved glycemic outcomes. GetGoal-L-Asia NCT01169779 GetGoal-S NCT00713830.

Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study.

It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut-off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease.

Assessment of quality of life in patients with type 2 diabetes mellitus before and after starting biphasic insulin aspart 30 (BIAsp 30) therapy: IMPROVE study in Japan.

AIMS: To evaluate treatment satisfaction before and after starting biphasic insulin aspart 30 (BIAsp 30) therapy in patients with type 2 diabetes mellitus (T2D) in the IMPROVE study Japan using the Diabetes Medication Satisfaction (DiabMedSat) questionnaire. METHODS: The DiabMedSat questionnaire assesses overall satisfaction with drug therapy for diabetes treatment in three domains: burden, efficacy and symptoms. Patients previously treated by oral anti-diabetic drugs in the IMPROVE study Japan answered the DiabMedSat questionnaires at baseline (week 0) and week 26 after starting BIAsp 30 treatment. RESULTS: The mean scores for each domain at weeks 0 and 26, respectively, were: burden, 64.5 and 67.5 (p = 0.041); efficacy, 55.0 and 61.5 (p < 0.001); and symptoms, 70.9 and 68.1 (p = 0.049). The overall scores were 63.4 and 65.6, respectively (p = 0.079). With regard to burden, bothersome aspects were significantly improved with BIAsp 30 treatment at week 26, compared with treatment with oral anti-diabetic drugs at week 0. Major hypoglycemic episodes were very rare; most hypoglycemic events were minor and occurred during the daytime. CONCLUSIONS: The study results indicate that BIAsp 30 does not adversely affect QOL in Japanese patients at insulin initiation.

Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes.

Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ-hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7+/- 7.0 % of T cells and 62.7+/- 32.3 % of macrophages (mean+/- SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ-hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.

A comparison of the handling and accuracy of syringe and vial versus prefilled insulin pen (FlexPen).

BACKGROUND: To determine the preferable method for self-injecting insulin, we compared the handling, safety, and dose accuracy of a conventional disposable syringe and vial with FlexPen (Novo Nordisk A/S, Bagsvaerd, Denmark), a prefilled pen. METHODS: Insulin therapy-naive healthcare professionals (HCPs) (n = 30), unfamiliar with insulin delivery, injected 10 U of insulin into a sponge pad using either a syringe and vial or the FlexPen, both with 30-gauge 8-mm needles, on day 1. The following day, they used the alternative method. They evaluated the handling of the two methods on device-specific questionnaires and compared overall preference on a third questionnaire. To evaluate dose accuracy, 30 insulin therapy-experienced HCPs and 20 insulin therapy-naive HCPs were asked to deliver 10 U of insulin using each method, and the amount discharged was weighed. RESULTS: FlexPen was rated easier to use and overall more preferable than the syringe and vial by insulin therapy-naive HCPs (P < 0.001). The pen device was more accurate than the syringe and vial when used by experienced HCPs (mean +/- SD dose delivered, 9.91 +/- 0.11 U vs. 9.82 +/- 0.25 U, respectively; P < 0.001) and by insulin therapy-naive HCPs (9.91 +/- 0.12 U vs. 9.74 +/- 0.85 U; P < 0.001). CONCLUSIONS: Insulin therapy-naive HCPs found FlexPen easier to handle and preferable to use compared to a conventional syringe and vial. Both insulin therapy-experienced and -naive HCPs were able to deliver insulin significantly more accurately with the FlexPen than with a syringe and vial (P < 0.001).

Changes in leukocyte migration during carbonic anhydrase activity inhibition.

Experiment 1 evaluated changes in leukocyte migration during acetazolamide (AZ) inhibition of carbonic anhydrase activity in leukocytes. AZ induced changes in the intracellular calcium concentration, and extracellular calcium is thought to be a factor inducing an increase in leukocyte migration. Next, Experiment 2 determined whether extracellular calcium concentration was a primary factor influencing leukocyte migration in the absence of AZ. The distance of leukocyte migration increased in a dose-dependent manner with AZ despite the presence of IL-8 or LPS in Experiment 1. The extracellular calcium concentration used in the present study had no influence on the distance in leukocyte migration in Experiment 2. The distance of leukocyte migration showed a tendency to increase in a dose-dependent manner with LPS concentration. In conclusion, AZ may stimulate leukocyte migration due to its participation in the regulation of intracellular pH controlled by CA activity without an effect of low extracellular calcium concentration. In addition, AZ was thus suggested to possibly have an anti-inflammatory effect in supporting leukocyte migration during inflammatory reactions.

Intravenous sedation with low-dose dexmedetomidine: its potential for use in dentistry.

This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures.

Patient acceptance and issues of education of two durable insulin pen devices.

BACKGROUND: Insulin pen devices offer patients a more convenient, accurate, and discreet mode of insulin delivery than traditional syringes and vials. This open-label, randomized, comparative crossover study assessed patient preference for two reusable pens: NovoPen 4 (Novo Nordisk A/S, Copenhagen, Denmark) and OptiClik (Sanofi-Aventis, Bridgewater NJ). METHODS: Thirty-five diabetes patients with no previous experience of pen devices (mean age 56.7 years; range 17-80 years; 57% male) used both pens to deliver a 10 unit saline dose into an injection cushion. Half received guidance according to official instruction manuals, and half were given no instructions. Learning times were also measured. Participants completed a detailed questionnaire to determine their preferences. RESULTS: Overall, 32 of 35 participants preferred NovoPen 4 compared with two of 35 for OptiClik (91.4% vs. 5.7% respectively, P<0.001), and one had no preference. NovoPen 4 was significantly favored over OptiClik in almost all questionnaire criteria, including safety (P<0.001), size of pen (P<0.001), appearance (P<0.001), and ease of use (P<0.001). The majority of patients were able to use NovoPen 4 without guidance (94.4%) compared with just over half for for OptiClik (55.6%, P<0.01). Learning time was also significantly faster for NovoPen 4 (62.6 s) than for OptiClik (95.8 s) (P<0.05). CONCLUSIONS: Patients learned how to use both pens quickly (under 2 min), but NovoPen 4 was preferred by participants over OptiClik. Patient acceptance of a pen device may support insulin initiation, particularly in type 2 diabetes.