Comparisons of in-hospital fee and surgical outcomes between robot-assisted, laparoscopic, and open radical cystectomy: a Japanese nationwide study.

OBJECTIVE: To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database. METHODS: All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score-matched comparisons were performed to assess the differences between RARC and ORC. RESULTS: During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score-matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees. CONCLUSIONS: RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society.

Relationship between dietary fiber to carbohydrate ratio and mortality risk in US adults: NHANES 2007-2018.

BACKGROUND AND AIMS: The evidence is inconsistent regarding associations between relative proportions of macronutrient intake and disease risk, potentially due to limitations in accounting for differential effects of simple sugars and dietary fiber, grouped as "carbohydrates." We examined the association between the ratio of dietary fiber to carbohydrate intake (FC-R) measure, the relative proportion of macronutrients, and mortality risk in a nationally representative sample of U.S. adults. METHODS AND RESULTS: We performed a retrospective cohort study, using data from the National Health and Nutrition Examination Survey in 2007-2018 and linked mortality data among 15,789 adults aged ≥40 years. We categorized participants into three groups by tertile cutpoints of FC-R, and by percent calories from carbohydrate (<45 %, 45-65 %, and >65 %). Cox proportional hazards regression was performed to estimate hazard ratios (HR) for all-cause mortality with 95 % confidence intervals (95 % CI), adjusting for demographic, health history, and lifestyle factors. During a median follow-up of 6.5 years, 2044 deaths were observed. Compared to the low FC-R group, higher FC-R groups showed a reduction in mortality risk after adjusting for potential confounders (high vs low: HR = 0.71, 95 % CI = 0.62-0.83). The association persisted in those consuming 45-65 % and >65 % of calories from carbohydrate, while the association was attenuated in those with <45 % of calories from carbohydrate. Percent calories from carbohydrate showed no association with mortality risk. CONCLUSION: Higher FC-R was associated with lower all-cause mortality risk in adults with moderate to high levels of percent calories from carbohydrate. Mechanisms of the association warrant further investigation.

Relationship between the cholesterol and triglyceride content of lipoprotein subclasses and carotid intima-media thickness: A cross-sectional population-based study.

BACKGROUND: The association between lipoprotein subclasses and carotid intima-media thickness (cIMT) progression has yet to be fully evaluated. We assessed which lipoprotein subclasses were associated with maximum cIMT levels in the general population. METHODS: In this study, cholesterol and triglyceride content of 20 lipoprotein subclasses were analyzed using gel permeation high-performance liquid chromatography (GP-HPLC) in 864 Japanese women and men (mean age 57 y, free of chronic liver or kidney diseases and off lipid-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses and univariate and partial correlation analyses were performed to examine the relationships between lipoprotein subclasses and maximum cIMT levels. RESULTS: After adjusting for age, sex, systolic blood pressure, smoking, diabetes, and anti-hypertensive agents, elevated low-density lipoprotein (LDL)-2 and -3 cholesterol (particle diameter 25.5 nm and 23.0 nm, respectively; medium and small LDL) were associated with higher maximum cIMT levels in both women and men (all p for trend < 0.05). These associations were significant even after participants taking anti-diabetic or anti-hypertensive agents were excluded. No significant associations were found between any triglyceride subclasses and maximum cIMT levels. CONCLUSIONS: Smaller LDL particle cholesterol values are the most atherogenic lipoprotein parameter.

Surgical outcomes of robot-assisted radical cystectomy in octogenarian or older patients: A Japanese nationwide study.

OBJECTIVE: To evaluate the surgical outcomes of robot-assisted radical cystectomy (RARC) in octogenarian or older patients based on a Japanese nationwide database. METHODS: The diagnosis procedure combination database was used to extract the data on radical cystectomy cases. Surgical outcomes of RARC in octogenarian or older patients (older group) were initially compared to those of patients younger than 80 years (younger group). Then, the surgical outcomes of RARC in the older group were compared to those of open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) in the same age group. RESULTS: Between 2018 and 2021, 478 RARC cases in the older group and 2257 RARC cases in the younger group were identified. In the older group, ileal conduit, neobladder, and other urinary diversions were carried out in 352 (73.6%), 22 (4.6%), and 104 (21.8%) patients, respectively. In the older group, when compared with the younger group, the complication rate (24.9%), blood transfusion rate (41.4%), and in-hospital mortality (1.4%) were equivalent, while significantly shorter anesthesia time and longer length of stay were observed in the older group (521.0 ± 140.4 min vs. 595.1 ± 141.71 min, p < 0.01, and 32.9 ± 16.8 days vs. 30.6 ± 17.8 days, p = 0.01, respectively). In the comparison of the surgical outcomes of older patients receiving RARC to those receiving ORC (n = 746) and LRC (n = 375), the RARC group had the lowest complication rate and the shortest length of stay, while the shortest anesthesia time was noted in the ORC group. CONCLUSION: The feasibility of RARC for octogenarian or older patients was demonstrated by the nationwide database study.

Reduction in X-ray Retake Rate Using the Token Economy Method.

Excessive retakes of X-ray images increase labor and material costs, as well as result in excess radiation exposure for patients and a long waiting time. In this study, we evaluated the effectiveness of the token economy method as a management method for reducing X-ray retake rate among radiology technicians. The results showed a 2.5% reduction in retake rate, indicating the effectiveness of our method. In addition, we suggest that the token-economy-based approach can be applied to other hospital management problems.

Small Dense Low-Density Lipoprotein Cholesterol Levels in Breakfast Skippers and Staple Foods Skippers.

AIMS: Skipping breakfast is known as a cardiovascular disease (CVD) risk. Recently, eating and dietary patterns have been varied in many countries, however, the mechanisms of promoting CVD are still unclear. Our goal was to assess the effects of eating and dietary patterns on CVD risk factors, with a focus on lipid parameters including serum concentration of small dense low-density lipoprotein cholesterol (sdLDL-C). METHODS: Subjects consisted of 27,997 Japanese men and women, who had medical check-up. Lipid parameters including sdLDL-C levels in breakfast skippers were compared with those in breakfast eaters. Lipid parameters in staple foods skippers were also compared with those in staple foods eaters. RESULTS: Breakfast skippers had significantly (p＜0.01) higher serum levels of median sdLDL-C than breakfast eaters in both genders (34.7 versus 32.0 mg/dL in men, 25.4 versus 24.9 mg/dL in women, respectively), and the same was true for sdLDL-C/LDL-C ratio (0.276 versus 0.260 in men, 0.218 versus 0.209 in women, respectively). Similarly, staple foods skippers had significantly higher sdLDL-C level than staple foods eaters in both genders (34.1 versus 31.6 mg/dL in men, 25.8 versus 24.7 mg/dL in women), and the same went for sdLDL-C/LDL-C ratio (0.278 versus 0.256 in men, 0.215 versus 0.208 mg/dL in women, respectively). CONCLUSION: Our data indicate that both skipping breakfast and having meals without staple foods increase serum sdLDL-C concentration and cause unfavorable lipid profiles, and then may promote CVD. These finding provide evidence for the importance of having breakfast and meals with staple foods for preventing CVD.

Trends of radical cystectomy and comparisons of surgical outcomes among surgical approaches focusing on robot-assisted radical cystectomy: A Japanese nationwide database study.

OBJECTIVE: To clarify the trends in radical cystectomy and to compare surgical outcomes among surgical approaches focusing on robot-assisted radical cystectomy based on a Japanese nationwide database. METHODS: The Diagnosis Procedure Combination database was used to extract data on radical cystectomy cases. Trends in open radical cystectomy, laparoscopic radical cystectomy, minimum incision endoscopic radical cystectomy, and robot-assisted radical cystectomy between April 2012 and March 2021 were evaluated. Basic characteristics and peri-operative indicators were compared among the four groups. Propensity score matching was applied to assess the differences between open radical cystectomy and robot-assisted radical cystectomy. RESULTS: During the study period, a decreasing number of open radical cystectomies and an increasing number of minimally invasive radical cystectomies were shown in the total cohort of 28 345 cases. The number of robot-assisted radical cystectomies rapidly increased after government approval in 2018. Minimally invasive radical cystectomies, including robot-assisted radical cystectomies, had a significantly lower complication rate, a shorter length of stay, and a lower blood transfusion rate, but a longer anesthesia time than open radical cystectomies. In the propensity score matching analysis comparing the surgical outcomes of robot-assisted radical cystectomy and open radical cystectomy, similar results were demonstrated, and blood transfusion rates were equivalent. CONCLUSION: For the past decade, the number of minimally invasive radical cystectomies has steadily increased without compromised surgical outcomes, except for anesthesia time. Robot-assisted radical cystectomies in particular rapidly became widespread in Japan after government approval in 2018 and became a standard surgery within the first 3 years.

Circadian Rhythm of Subspecies of Low-Density Lipoprotein-Cholesterol and High-Density Lipoprotein-Cholesterol in Healthy Subjects and Patients with Type 2 Diabetes.

AIMS: We established automated assay kits for quantifying small dense low-density lipoprotein (sdLDL)-cholesterol (C), LDL-triglyceride (TG), and high-density lipoprotein (HDL)3-C, and apolipoprotein (apo)E-rich HDL-C, and these have been recognized as sensitive biomarkers for predicting coronary artery disease. We investigated the circadian rhythms of these novel lipids to determine if fasting is required to determine basal levels. METHODS: Forty-eight inpatients with type 2 diabetes and 19 healthy volunteers were studied. Blood samples were collected at seven time points, which were obtained after an overnight fast, before and 2 h after each meal, and before the next breakfast. sdLDL-C, LDL-TG, remnant-like particle (RLP)-C, TG-rich lipoprotein (TRL-C), HDL3-C, and apoE-rich HDL-C were measured by the homogeneous methods. NonHDL-C, large buoyant (lb)LDL-C and HDL2-C were calculated by subtracting sdLDL-C from LDL-C or HDL3-C from HDL-C, respectively. RESULTS: Serum TG levels were significantly increased after meals in both healthy participants and patients with diabetes. RLP-C and TRL-C were also increased postprandially. LDL-TG, LDL-C, nonHDL-C, HDL2,3-C, and apoE-rich HDL-C did not exhibit significant fluctuation during the day in healthy participants and patients with diabetes. sdLDL-C was slightly increased postprandially in subjects with diabetes (1-2 mg/dl, 3%-9%), though its increase was not significant compared to the baseline (fasting) level. Significant postprandial reduction was observed with LDL-C and lbLDL-C. There was no influence of statin therapy or oral anti-diabetes drugs on the circadian rhythm of LDL-C subspecies. CONCLUSIONS: Subtle postprandial increase in sdLDL-C is considered a negligible level in general clinical practice. Fasting is not mandatory to measure basal concentrations of LDL and HDL subspecies.

Development of internal standard for lipoprotein subclass analysis using dual detection gel-permeation high-performance liquid chromatography system.

The LipoSEARCH® System is an innovative lipoprotein class analysis method based on gel-permeation high-performance liquid chromatography (HPLC). This system uses a gel permeation column to separate the major lipoprotein subclasses (chylomicron, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein) in serum according to particle size and splits them into two pathways to measure total cholesterol (TC; esterified + unesterified cholesterol) and triglyceride (TG) concentrations simultaneously to obtain chromatograms for each. These chromatograms were analyzed based on the results of the calibration serum by fitting Gaussian curves to profile the 20 lipoprotein subclasses defined in detail. An important assumption of this HPLC system is its simultaneous detection of two pathways to guarantee the accuracy of each analysis. Therefore, in the present study, we investigated the development of an internal standard that can guarantee the simultaneous detection of this system by adding a pigment to the serum. We focused on quinone pigments with absorption at 550 nm, which is the wavelength used for the enzymatic assay of TC and TG concentrations in the system. As a result, we succeeded in producing overlapping pigment peaks that appeared after the analytical chromatograms in two pathways. It is also suggested that the pigment solution as an internal standard is stable in freezing storage and has little effect on the analysis. The developed internal standard is expected to contribute to the accuracy assurance of lipoprotein analysis by this dual-detection HPLC system.

Reference interval for serum concentration of small dense low-density lipoprotein cholesterol in the healthy Japanese population.

BACKGROUND: Small dense low-density lipoprotein a smaller and denser subfraction among whole low density lipoprotein particles is known to be highly atherogenic. The reference interval (RI) is not strictly defined for serum concentration of sdLDL-cholesterol (sdLDL-C) in Japan. The purpose of this study is to set the reference interval for sdLDL-C in healthy subjects. METHODS: The population of this cross-sectional study was consisted of 40,862 individuals who had annual health checkups, and healthy subjects were extracted based on exclusion criteria such as medical history, social history, and blood sampling test results. Their serum sdLDL-C values were statistically analyzed and the RIs were set in men, premenopausal women, and postmenopausal women separately. RESULTS: The mean values of serum sdLDL-C in healthy subjects were 23.9 mg/dL in men, 20.0 mg/dL in premenopausal women and 23.7 mg/dL in postmenopausal women, and the RIs were 12.6-45.3 mg/dL in men, 11.4-35.1 mg/dL in premenopausal women and 14.6-38.6 mg/dL in postmenopausal women. Serum sdLDL-C values were significantly higher in men than in women. Besides, sdLDL-C values were significantly higher in postmenopausal women than in premenopausal women. In both genders, sdLDL-C values tended to increase with age. CONCLUSION: These results suggest that the RIs for sdLDL-C are recommended as follows: 13-45 mg/dL in men, 11-35 mg/dL in premenopausal women, and 15-39 mg/dL in postmenopausal women, respectively. Aside from these RIs, it is also necessary to define clinical cutoff values graded according to individual risk levels for atherosclerotic cardiovascular diseases.

Trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval in Japan: A nationwide database study from 2016 to 2018.

OBJECTIVES: To evaluate the trends and safety of robot-assisted partial nephrectomy during the initial 2-year period after government approval for this type of procedure in April 2016. METHODS: This nationwide retrospective study included 3722 received robot-assisted partial nephrectomy cases carried out from April 2016 to March 2018 in 124 participating institutions. The institutions were divided into lower- and higher-volume institutions according to the median of 19 robot-assisted partial nephrectomy cases during the study period. Surgical outcomes between 616 cases from lower-volume institutions and 3106 cases from higher-volume institutions were compared using propensity score matching. RESULTS: During the study period, both the number of robot-assisted partial nephrectomy surgeries and the number of institutions in which the surgery was carried out steadily increased. Overall, the median anesthesia time was 217 min, the median postoperative length of stay was 9 days, and the proportion of blood transfusions, complications and readmissions were 0.8%, 5.1% and 1.0%, respectively. There were no significant differences in anesthesia time, incidence of blood transfusions, and complication rates between the lower-volume and higher-volume institutions. However, a slightly, but significantly, longer postoperative length of stay and a lower incidence of readmission were observed in lower-volume institutions both before and after propensity score matching. CONCLUSIONS: Robot-assisted partial nephrectomy has become widespread during the initial 2-year period after government approval with an acceptable safety profile, regardless of the institutional caseloads. This technique has become a standard of care for stage 1 renal cancer patients in Japan.

Comparison of the Japan Society of Clinical Chemistry reference method and CDC method for HDL and LDL cholesterol measurements using fresh sera.

OBJECTIVES: In 2009, the Japan Society of Clinical Chemistry (JSCC) recommended a reference method for the measurement of serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. This automated method uses cholesterol esterase-cholesterol dehydrogenase to measure cholesterol levels in fractions obtained after ultracentrifugation and dextran sulfate/magnesium chloride precipitation. In the present study, using fresh samples, we compared the LDL-C and HDL-C levels measured using this method with those measured using the traditional Centers for Disease Control and Prevention (CDC)-beta-quantification (BQ) method. DESIGN: and methods: Using both the JSCC and CDC-BQ methods, LDL-C/HDL-C levels were measured in 47 non-diseased and 126 diseased subjects, whose triglyceride levels were lower than 11.29 â€‹mmol/L (1000 â€‹mg/dL). RESULTS: For LDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.991x + 0.009 â€‹mmol/L; r â€‹= â€‹0.999; and Sy/x â€‹= â€‹0.025 â€‹mmol/L, where x is the mean LDL-C level measured using the CDC-BQ method. Similarly, for HDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.988x + 0.041 â€‹mmol/L, r â€‹= â€‹0.999, and Sy/x â€‹= â€‹0.019 â€‹mmol/L, where x is the mean HDL-C level measured using the CDC-BQ method. CONCLUSIONS: The JSCC method agreed with the CDC-BQ method in cases of both non-diseased and diseased subjects, including those with dyslipidemia.

Relationships between Smoking Status, Cardiovascular Risk Factors, and Lipoproteins in a Large Japanese Population.

AIMS: Smoking is a major risk factor for cardiovascular disease (CVD), a leading cause of death and disability. Other CVD risk factors include age, gender, hypertension, diabetes, increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Our goal was to assess relationships between smoking status and CVD risk factors, with a focus on direct LDL-C, HDL-C, triglycerides (TG) and small dense LDL-C (sdLDL-C). METHODS: A total of 34,497 Japanese men and women, mean age 51 years, had their CVD risk factors including fasting serum total cholesterol, TG, HDL-C, sdLDL-C, and direct LDL-C assessed. One-way ANOVA and multiple linear regression analyses were carried to assess the interrelationships of these parameters with smoking. RESULTS: In both men and women, current smokers had significantly (p＜0.001) higher median TG (+19.6%, +16.9%) and sdLDL-C levels (+12.7%, +4.2%) levels, and significantly (p＜0.001) lower HDL-C levels (-7.3%, -4.3%) than non-smokers. They were also significantly (p＜0.05) more likely to have TG values ＞150 mg/dL (+56.8%, +116.3%), sdLDL-C ＞40.1 mg/dL (+28.8%, +44.9%), and HDL-C ＜40 mg/dL (+89.8%, +114.3%). Ex-smokers generally had lipid values that were intermediate between non-smokers and current smokers. Multivariate analysis confirmed the significance of these relationships. CONCLUSION: Our data indicate that current cigarette smoking is associated with increased TG and sdLDL-C levels, as well as decreased HDL-C levels. Furthermore, smoking effect on lipid profiles remain after cessation. These data provide further justification for smoking cessation.

Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression.

AIM: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan. METHODS: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression. RESULTS: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C ＜100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population. CONCLUSIONS: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

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.

Direct Versus Calculated LDL Cholesterol and C-Reactive Protein in Cardiovascular Disease Risk Assessment in the Framingham Offspring Study.

BACKGROUND: Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study. METHODS: We used stored frozen plasma samples (-80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods. RESULTS: Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death). CONCLUSIONS: Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C.

Lipoprotein Subfractions and Glucose Homeostasis in Prediabetes and Diabetes in Taiwan.

AIMS: Prediabetes and diabetes are associated with increased insulin resistance and decreased insulin production, dyslipidemia, and increased cardiovascular disease (CVD) risk. Our goals were to assess lipoprotein subfractions using novel assays in such subjects. METHODS: Fasting normal, prediabetic, and diabetic Taiwanese men and women (n=2,049) had their serum glucose, glycosylated hemoglobin, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, apolipoprotein E-HDL-C, direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-TG, and remnant lipoprotein cholesterol (RLP-C) levels measured using novel assays. HDL2-C, LDL-C, and large-buoyant LDL-C (lbLDL-C) were calculated. RESULTS: Prediabetic male and female subjects had significantly higher levels of TG, RLP-C, sdLDL-C, the sdLDL-C/LDL-C ratio, and LDL-TG than normal subjects, and statin treatment abolished this effect in men, but not in women. Diabetic male and female subjects had significantly higher TG and sdLDL-C/LDL-C ratios, and significantly lower levels of HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, as did prediabetic women. Median direct LDL-C levels were ＞100 mg/dL in all groups, even in those receiving statin therapy. Calculated LDL-C significantly underestimated direct LDL-C by ＞10% in diabetic subjects. CONCLUSIONS: Our data indicate that prediabetic subjects were more likely to have significantly elevated RLP-C, sdLDL-C, and LDL-TG, while diabetic subjects were more likely to have significantly decreased HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, and calculated LDL-C significantly underestimated their direct LDL-C. In our view, direct LDL-C and sdLDL-C should be measured and optimized in both diabetic and prediabetic subjects to reduce CVD risk.

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.

Effects of linagliptin versus voglibose on treatment-related quality of life in patients with type 2 diabetes: sub-analysis of the L-STEP study.

Treatment-related quality of life (QOL) is an important aspect of diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet and exercise therapy. Among 366 subjects in the original study, 182 in the linagliptin group and 173 in the voglibose group were included in this analysis. The outcome of this study was change in QOL as assessed by the Diabetes Therapy-Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12. Compared with baseline data, total DTR-QOL17 scores were significantly higher after 12 weeks of linagliptin and voglibose treatment. The change in the total DTR-QOL17 score and the score of one domain, burden on social activities and daily activities, was significantly greater in the linagliptin group than in the voglibose group. In addition, only linagliptin treatment was identified as a factor associated with an increased total DTR-QOL17 score. Linagliptin is superior to voglibose in terms of improving treatment-related QOL in Japanese patients with T2DM.