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-β), 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-β 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).
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/m
2
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.
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.
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.
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.
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.
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.
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%,
< 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg,
< 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,
< 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's
= - 0.17,
= 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's
= - 0.19,
= 0.011).
Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.
UMIN-CTR: UMIN000016304.
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 individuals with type 2 diabetes.
Materials and Methods
A nationwide survey was carried out including 12,811 individuals with type 2 diabetes. Participants 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 participants 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 one drug, 42.5% on two drugs, 47.2% on three drugs and 56.8% on four or more drugs, respectively. The most prescribed drugs were renin–angiotensin system inhibitors, followed by calcium channel blockers, diuretics and beta‐blockers. The multiple logistic regression analysis showed 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 glycosylated hemoglobin A1c and lipids, and less retinopathy.
Conclusions
In type 2 diabetes, hypertension is common, and just 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 this clustering to be a serious problem.
A nationwide large‐scale survey was performed to investigate the current status of achieved blood pressure levels in association with the number of antihypertensive drugs. The percentages achieving a blood pressure of <130/80 or 140/90 mmHg were 52.0% and 86.1%, respectively. A difficulty in blood pressure lowering was correlated with difficulties in glycemic and lipid management, obesity, and vascular complications, implying these clustering to be a serious problem.
Dosing accuracy of two insulin pre-filled pens Asakura, Toshinari; Seino, Hiroaki; Kageyama, Miho ...
Current medical research and opinion,
05/2008, Letnik:
24, Številka:
5
Journal Article
Recenzirano
ABSTRACT
Objective: This study was designed to determine the dose accuracy of two commonly available insulin pre-filled pens for use in diabetes - FlexPen* (Novo Nordisk A/S, Bagsværd, Denmark) (FP) ...and SoloStar† (Sanofi-Aventis, Paris, France) (SS).
Research design and methods: Dosing accuracy was tested at 5 U, 10 U and 30 U doses - three previously unused pens of both pre-filled pens were used for each dose. At the 5 U dose each pen was tested 42 times, at the 10 U dose each pen was tested 25 times and at the 30 U dose each pen was tested 9 times. The pre-filled pens were used strictly according to manufacturers' instructions and measurements were made on a sensitive balance and corrected for the specific density of the insulin formulations used. Specified limits were based on ISO standards (±1 U for the 5 U and 10 U doses and ±1.5 U for the 30 U dose).
Results: FP was more accurate for injecting 5 U, 10 U and 30 U doses (absolute mean 4.95 ± 0.19 U, 9.61 ± 0.27 U and 29.70 ± 0.34 U, respectively) than SS (absolute mean 4.86 ± 0.39 U, 9.27 ± 0.52 U and 28.73 ± 0.47 U, respectively). No doses were outside specified limits for 5 U and 30 U with FP and 1.3% of doses were outside these limits at the 10 U dose. For SS; 1.6%, 29.3% and 33.3% of doses were below the pre-specified threshold for the 5 U, 10 U and 30 U doses, respectively.
Conclusions: This non-blinded comparison indicates that FP is a more accurate insulin pre-filled pen than SS at three different insulin doses. In this single-user study, FP delivered consistent and accurate doses of insulin but SS had a high frequency of under dosing. No assessment was made of user variability in this study.
Abstract 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.
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