Effect of concomitant use of yokukansan on steady-state blood concentrations of donepezil and risperidone in real-world clinical practice.

AIM: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting. METHODS: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan. RESULTS: The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan. CONCLUSIONS: The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.

Reduced Number of Remaining or Healthy Teeth in Patients with Type 2 Diabetes Mellitus: A Cross-sectional Study Assessed by Dentists or Dental Hygienists in Japan.

Objective This study assessed the relationships between oral health (number of remaining and healthy teeth and periodontal disease) and type 2 diabetes mellitus (T2DM) to contribute to improved patient care. Patients We conducted a cross-sectional cohort study of consecutive patients being regularly treated for chronic diseases (T2DM, hypertension, and dyslipidemia). A dentist or dental hygienist accurately evaluated the oral environment. Patients with fewer than 20 teeth were classified as having reduced remaining teeth (RRT). Results A total of 267 patients were enrolled, including 153 patients (57%) with T2DM and 114 without (43%). Patients with T2DM had 3 fewer remaining teeth on average than those without DM [median: 22 (interquartile range (IQR): 11-27) vs. median: 25 (IQR: 17.3-28), p=0.02]. In addition, patients with T2DM had 4 fewer healthy teeth on average than those without DM [median: 8 (IQR: 2.8-15) vs. median: 12 (IQR: 6-16), p=0.02]. The frequency of RRT was higher in the T2DM group (n=63; 41%) than in the non-DM group (n=31; 27%, p=0.02). Multivariable logistic regression for the presence of RRT in the T2DM group found that age [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.03-1.13; p<0.01] and regular dental consultations (OR, 0.28; 95% CI, 0.10-0.76; p=0.01) were independently and significantly associated. Conclusion The number of remaining or healthy teeth was significantly lower in patients with T2DM than in those without T2DM in current Japanese clinical practice. Regular dental consultation is recommended to preserve remaining teeth in patients with T2DM.

Predictive Ability of Visit-to-Visit Variability of HbA1c Measurements for the Development of Diabetic Kidney Disease: A Retrospective Longitudinal Observational Study.

AIMS: This study is aimed at clarifying the relationship between visit-to-visit variability of glycated hemoglobin (HbA1c) and the risk of diabetic kidney disease (DKD) and to identifying the most useful index of visit-to-visit variability of HbA1c. METHODS: This clinic-based retrospective longitudinal study included 699 Japanese type 2 diabetes mellitus patients. Visit-to-visit variability of HbA1c was calculated as the internal standard deviation of HbA1c (HbA1c-SD), the coefficient of variation of HbA1c (HbA1c-CV), the HbA1c change score (HbA1c-HVS), and the area under the HbA1c curve (HbA1c-AUC) with 3-year serial HbA1c measurement data, and the associations between these indices and the development/progression of DKD were examined. RESULTS: Cox proportional hazards models showed that the HbA1c-SD and HbA1c-AUC were associated with the incidence of microalbuminuria, independently of the HbA1c level. These results were verified and replicated in propensity score (PS) matching and bootstrap analyses. Moreover, the HbA1c-SD and HbA1c-AUC were also associated with oxidized human serum albumin (HSA), an oxidative stress marker. CONCLUSIONS: Visit-to-visit variability of HbA1c was an independent risk factor of microalbuminuria in association with oxidative stress among type 2 diabetes mellitus patients. HbA1c-AUC, a novel index of HbA1c variability, may be a potent prognostic indicator in predicting the risk of microalbuminuria.

Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus.

AIMS: Obesity and ectopic fat accumulation are important conditions of type 2 diabetes mellitus (T2DM). Our aim was to determine whether bioelectrical impedance body composition analysis combined with blood test results could estimate liver ectopic fat accumulation in patients with treatment-naïve T2DM. METHODS: Subjects were 119 untreated T2DM patients. Computed tomography scans were performed to calculate the liver to spleen attenuation ratio (L/S ratio) as a measure of liver fat accumulation, with excess liver fat accumulation defined as an L/S ratio <1.0. Elementary body composition was measured by bioelectrical impedance analysis using InBody770. RESULTS: The Nagelkerke R2 test showed that the muscle mass/fat mass ratio (muscle/fat ratio) was the most suitable variable among anthropometric factors and body component indexes for estimating liver fat accumulation. The muscle/fat ratio was significantly correlated with the L/S ratio (ρ = 0.4386, P < 0.0001). Multivariable logistic regression analysis showed that the muscle/fat ratio (odds ratio 0.40, 95% confidence interval 0.22-0.73, P < 0.01) and alanine aminotransferase (odds ratio 1.06, 95% confidence interval 1.02-1.10, P < 0.01) were independently and significantly associated with liver fat accumulation. In receiver operating characteristic curve analysis, the cutoff value of the muscle/fat ratio for excess liver fat accumulation was 2.34. CONCLUSION: In patients with treatment-naïve T2DM, the muscle/fat ratio and ALT are useful for estimating the presence of excess liver fat accumulation in daily clinical practice.

Clinical Factors Associated with Initial Decrease in Body-Fat Percentage Induced by Add-on Sodium-Glucose Co-transporter 2 Inhibitors in Patient with Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE: Obesity is globally recognized as an important clinical problem and sodium-glucose co-transporter 2 (SGLT2) inhibitors are considered a suitable therapy for obese patients with type 2 diabetes mellitus (T2DM). We examined the clinical factors associated with initial decrease in body-fat percentage (Fat %) induced by SGLT2 inhibitors in patients with T2DM. METHODS: We retrospectively enrolled patients newly treated with SGLT2 inhibitors in addition to ongoing medications at Jinnouchi Hospital between April 2014 and December 2015. We examined the SGLT2 inhibitor-induced change in body composition by using a bioelectrical impedance analyzer (InBody770®) before SGLT2 inhibitor administration and after 4 weeks' treatment. RESULTS: A total of 175 patients with T2DM were enrolled and we analyzed 148 patients. Add-on SGLT2 inhibitor treatment significantly reduced body weight (- 1.04 ± 1.18 kg, p < 0.01), total fat quantity (- 0.62 ± 1.19 kg, p < 0.01), and Fat % (- 0.4 ± 1.4%, p < 0.01). Pretreatment levels of glycated hemoglobin (HbA1c) [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.15-2.25, p < 0.01] and smoking (OR, 2.65; 95% CI, 1.14-6.15, p = 0.02) were significantly associated factors for greater fat-reduction defined as more than 0.4% (median) decrease in Fat % in multivariate logistic regression analysis. In receiver operator characteristic analysis, the cut-off value of pretreatment levels of HbA1c for a greater Fat % decrease was 7.7% (sensitivity 53% and specificity 69%, p < 0.01). CONCLUSION: Additional treatment with SGLT2 inhibitors effectively decreased Fat % in T2DM patients with high HbA1c levels before SGLT2 inhibitor administration. Our results suggest a greater initial response in Fat % reduction to SGLT2 inhibitor therapy in diabetic patients with pretreatment HbA1c levels ≥ 7.7%.