Enhanced prediction of renal function decline by replacing waist circumference with "A Body Shape Index (ABSI)" in diagnosing metabolic syndrome: a retrospective cohort study in Japan.

BACKGROUND: Abdominal obesity as a risk factor for diagnosing metabolic syndrome (MetS) is conventionally evaluated using waist circumference (WC), although WC does not necessarily reflect visceral adiposity. OBJECTIVE: To examine whether replacing WC with "A Body Shape Index (ABSI)", an abdominal obesity index calculated by dividing WC by an allometric regression of weight and height, in MetS diagnosis is useful for predicting renal function decline. SUBJECTS/METHODS: In total, 5438 Japanese urban residents (median age 48 years) who participated in a public health screening program for 4 consecutive years were enrolled. Systemic arterial stiffness was assessed by cardio-ankle vascular index (CAVI). The predictability of the new-onset renal function decline (eGFR < 60 mL/min/1.73 m2) by replacing high WC with high ABSI (ABSI ≥ 0.080) was examined using three sets of MetS diagnostic criteria: Japanese, IDF and NCEP-ATPIII. RESULTS: In Japanese and NCEP-ATPIII criteria, MetS diagnosed using ABSI (ABSI-MetS) was associated with significantly higher age-adjusted CAVI compared to non-MetS, whereas MetS diagnosed using WC (WC-MetS) showed no association. Kaplan-Meier analysis of the rate of new-onset renal function decline over 4 years (total 8.7%) showed remarkable higher rate in subjects with ABSI-MetS than in those without (log-rank test p < 0.001), but almost no difference between subjects with and without WC-MetS (p = 0.014-0.617). In gender-specific Cox-proportional hazards analyses including age, proteinuria, and treatments of metabolic disorders as confounders, ABSI-MetS (Japanese criteria for both sexes, IDF criteria for men) contributed independently to the new-onset renal function decline. Of these, the contribution of IDF ABSI-MetS disappeared after adjustment by high CAVI in the subsequent analysis. CONCLUSION: In this study, replacing WC with ABSI in MetS diagnostic criteria more efficiently predicted subjects at risk of renal function decline and arterial stiffening.

In situ AFM Observation of the Movements of Isolated Isotactic Poly(methyl methacrylate) Chains in a Precursor Film of an Oligo(methyl methacrylate) Droplet Spreading on Mica.

Atomic force microscopy (AFM) is a powerful tool to observe polymer chains at the molecular level. In this study, we show that the movements of isolated linear polymer chains in a precursor film of a droplet of an oligomer spreading on a substrate could be visualized in situ at the molecular level by AFM for the first time. The system was an isotactic poly(methyl methacrylate) (it-PMMA) solubilized in an oligo(MMA) matrix (it-PMMA/oligo(MMA) = 1/10,000 w/w) spreading on mica under high humidity. Because of the limited resolution of the AFM instrument, condensed linear polymer chains could not be visualized, but a small amount of it-PMMA chains that were solubilized as isolated chains in the oligo(MMA) matrix could be visualized in the precursor film, the contrast of which came from a large difference in glass transition temperature (Tg) of it-PMMA and oligo(MMA). The it-PMMA chains in the precursor film spread in the radial direction of the droplet with vigorously changing chain conformations. The spreading rate of it-PMMA chains under 72% relative humidity was ∼1/30 of the spreading rate of the oligo(MMA) matrix, which was estimated based on the decrease in the volume of the macroscopic droplet. The spreading of the it-PMMA chains and droplet strongly depended on humidity and was suppressed with the decrease in humidity, most likely because of the increase in friction with the substrate. The difference in the spreading rate of it-PMMA and oligo(MMA) further increased under low humidity. The dynamic molecular information of a precursor film by AFM should help to elucidate the wetting dynamics on a substrate.

Structural Origin of Additional Infrared Transparency and Enhanced Glass-Forming Ability in Rare-Earth-Rich Borate Glasses without B-O Networks.

R2O3-B2O3 binary glasses (R denotes rare-earth elements or Y) were fabricated in a very wide composition region using a levitation technique. The maximum R2O3 content of light rare-earth compounds reached 63 mol % and decreased with a decrease in the ionic radius of R3+. The thermal, optical, vibrational, and structural properties were investigated, particularly for 50R2O3-50B2O3 glasses. The glass transition temperature increased with a decrease in the ionic radius of R3+, while the thermal stability was not affected by the glass composition. The packing density increased with a decrease in the ionic radius of R3+ due to lanthanoid contraction. Raman scattering and Fourier transform infrared spectra revealed that, in the rare-earth-rich glasses, no conventional three-dimensional networks consisting of corner-sharing BOn (n = 3 or 4) units existed because all B atoms were formed as isolated BO3 units. The simple environment around B atoms in the glasses led to additional IR transmittance regions, irrespective of the kinds of R. The total correlation functions obtained from high-energy X-ray diffraction measurements were analyzed using the pair-function method and compared with those of various RBO3 crystalline phases. It was suggested that the local structure around R resembles the ν-NdBO3-type crystal structure, and the O coordination number of R ranged from 6.5 to 7.7, smaller than that of the crystalline phase. The glass-forming ability depending on R was discussed based on the structural similarities between the melt, glass, and crystalline phases.

JPH203, a newly developed anti-cancer drug, shows a preincubation inhibitory effect on L-type amino acid transporter 1 function.

JPH203 is a novel anti-cancer drug targeting L-type amino acid transporter 1 (LAT1), which plays a primary role in the uptake of essential amino acids in tumor cells. Although a co-incubation inhibitory effect of JPH203 has been shown in a conventional uptake assay, its preincubation inhibitory effects have remained undetermined. Therefore, we aimed to characterize the preincubation inhibitory effects of JPH203 on LAT1 function using leucine uptake assays in LAT1-positive human colon cancer HT-29 cells. Preincubation of the cells with JPH203 (0.3 µM for 120 min) decreased the activity level to 30% of that in dimethylsulfoxide-treated cells. Similarly, in time-dependency analysis, preincubation of HT-29 cells with 10 µM JPH203 for 30, 60, and 120 min decreased the leucine uptake activity (42%, 32%, and 28% of that in control cells, respectively). Furthermore, the IC50 value of the combination of preincubation and co-incubation effects was lower than that of co-incubation inhibition alone (34.2 ± 3.6 nM vs. 99.2 ± 11.0 nM). In conclusion, we revealed that JPH203 has the capability to inhibit LAT1 function through preincubation effects. Moreover, preincubation synergistically enhances the co-incubation inhibitory effects. These findings provide a novel insight into the anti-cancer effects of JPH203 in cancer therapy.

Influence of modifier cations on the local environment of aluminum in La2O3-Al2O3 and Y2O3-Al2O3 binary glasses.

The local environment of aluminum in xLa2O3-(100 -x)Al2O3 (LA) and yY2O3-(100 -y)Al2O3 (YA) glasses is investigated using 27Al MAS NMR and Raman scattering spectroscopy in the glass forming range, i.e., 27 ≤x≤ 50 and 26 ≤y≤ 37.5, respectively. The results suggest that four-fold Al ([4]Al) is predominant in both glasses, with a content of approximately 90% in LA glasses and 60% in YA glasses; the remaining percentages are made up of five- ([5]Al) and six-fold ([6]Al) Al. In LA glasses, the fraction of [4]Al increases slightly with an increase in the La2O3 content, whereas, in YA glasses, the distribution of Al species does not change. Raman scattering spectroscopy reveals that, in LA glasses, the amount of non-bridging oxygen increases with an increase in x; moreover, [5]Al and [6]Al both increase with a decrease in x for x≤ 40. Comparing with alkali earth aluminate glasses, we discuss the relationship between the fundamental structure of the AlO4 network and two parameters (the ratio of the number of oxygen atoms to that of Al and field strength).

New index of abdominal obesity, a body shape index, is BMI-independently associated with systemic arterial stiffness in real-world Japanese population.

OBJECTIVE: To clarify that the new index of abdominal obesity, a body shape index (ABSI), is associated with obesity-related metabolic disorders and arterial stiffness. MATERIALS: We analyzed the cross-sectional data from 62,514 Japanese subjects (mean age 44.4 years, mean body mass index (BMI) 22.2 kg/m2) without a past history of cardiovascular disease, stroke, or treatment for obesity-related metabolic disorders. METHODS: Various body adiposity indices including BMI, waist circumference (WC), and ABSI were evaluated for abilities to indicate metabolic disorders and arterial stiffness assessed by cardio-ankle vascular index (CAVI). RESULTS: WC, WC/height ratio, and WC/BMI ratio correlated with BMI regardless of gender or obesity, whereas ABSI hardly correlated with BMI. ROC analyses demonstrated that ABSI had the highest discriminatory power in predicting high CAVI (≥ 90th percentile) compared to other body adiposity indices, and the cut-off value was 0.080. Increases in ABSI as well as BMI reflected severity of metabolic disorders. After adjusting for confounders identified by multiple regression analysis, adjusted CAVI correlated positively with ABSI, whereas an inverted relationship was observed between adjusted CAVI and BMI. Additionally, the contribution of high ABSI (≥ 0.080) for high CAVI was independent of gender, age, obesity, and obesity-related metabolic disorders in the multivariate logistic regression model. CONCLUSION: ABSI is an easily calculated index of abdominal obesity which reflects metabolic disorders and systemic arterial stiffening, and may be useful in primary health screening even without any medical equipment for visceral fat quantification.

Blood management in a patient with anti-Oka antibody who underwent cardiac surgery using cardiopulmonary bypass: a case report.

BACKGROUND: Cardiac surgery under cardiopulmonary bypass (CPB) is often associated with massive bleeding and blood transfusion. For patients requiring specific blood products, meticulous blood management is critical to reduce blood loss, as well as the need for transfusion. Here, we have described the intraoperative blood management in a patient with anti-Oka antibody, who underwent cardiac surgery with CPB. CASE PRESENTATION: A 79-year-old woman was scheduled for open aortic valve replacement and tricuspid valve annuloplasty under hypothermic CPB. Her blood type was A RhD(+) Ok(a-), and anti-Oka, an extremely rare antibody against erythrocyte antigen, was detected. Eight units of Ok(a-) frozen thawed red cells (FTRCs), and six units of red blood cells donated by three Ok(a-) individuals were collected just prior to surgery. Although she was anemic, acute normovolemic hemodilution was conducted after anesthesia induction to preserve the autologous whole blood. Four units of FTRCs were loaded in the CPB priming solution, and modified ultrafiltration was adopted during CPB to prevent further hemodilution. After CPB termination, two units of FTRCs, four units of fresh frozen plasma, and ten units of platelet concentrate were intensively transfused, facilitating surgical hemostasis and stable hemodynamics. The autologous whole blood was returned to the patient in the intensive care unit. Since the hemoglobin and hematocrit levels were maintained postoperatively, no additional transfusion was required throughout her hospital stay. CONCLUSIONS: Multidisciplinary intraoperative blood management in a patient with anti-Oka antibody facilitated successful cardiac surgery using CPB, along with effective use of limited blood products.

Tetanus toxin fragments and Bcl-2 fusion proteins: cytoprotection and retrograde axonal migration.

BACKGROUND: Tetanus neurotoxin (TeNT) is taken up at nerve terminals and undergoes retrograde migration. The toxic properties of TeNT reside in the toxin light chain (L), but like complete TeNT, the TeNT heavy chain (TTH) and the C-terminal domain (TTC) alone can bind and enter into neurons. Here, we explored whether atoxic fragments of TeNT could act as drug delivery vehicles in neurons. In this study, we used Bcl-2, a protein known to have anti-apoptotic properties in vivo and in vitro, as a parcel to couple to TeNT fragments. RESULTS: We expressed Bcl-2 and the TTC fragments alone, and also attempted to express fusion proteins with the Bcl-2 coupled at the N-terminus of TTH (Bcl2-TTH) and the N- and C-terminus of TTC (TTC-Bcl2 and Bcl2-TTC) in mammalian (Cos7 cells) and Escherichia coli systems. TTC and Bcl-2 were efficiently expressed in E. coli and Cos7 cells, respectively, but Bcl-2 and the fusion proteins did not express well in E. coli. The fusion proteins were also not expressed in Cos7 cells. To improve the yield and purity of the fusion protein, we genetically deleted the N-terminal half of TTC from the Bcl2-TTC fusion to yield Bcl2-hTTC. Purified Bcl2-hTTC exhibited neuronal binding and prevented cell death of neuronal PC12 cells induced by serum and NGF deprivation, as evidenced by the inhibition of cytochrome C release from the mitochondria. For in vivo assays, Bcl2-hTTC was injected into the tongues of mice and was seen to selectively migrate to hypoglossal nuclei mouse brain stems via retrograde axonal transport. CONCLUSIONS: These results indicate that Bcl2-hTTC retains both Bcl-2 and TTC functions and therefore could be a potent therapeutic agent for various neurological conditions.

7-Ketocholesterol induces ROS-mediated mRNA expression of 12-lipoxygenase, cyclooxygenase-2 and pro-inflammatory cytokines in human mesangial cells: Potential role in diabetic nephropathy.

7-Ketocholesterol (7-KCHO) is a highly proinflammatory oxysterol and plays an important role in the pathophysiology of diabetic nephropathy (DN). Lipoxygenases (LOXs) and cyclooxygenases (COXs) are also involved in the development of DN. The aim of this study was to clarify the effects of 7-KCHO on mRNA expression of LOXs and COXs as well as pro-inflammatory cytokines in human mesangial cells (HMC). We evaluated cell viability by WST-8 assay and measured mRNA expression by reverse transcription-polymerase chain reaction. Intracellular reactive oxygen species (ROS) production was evaluated by flow cytometry. Although 7-KCHO did not affect cell viability of HMC, 7-KCHO stimulated significant increases in mRNA expression of 12-LOX, COX-2 and pro-inflammatory cytokines. 7-KCHO also induced an increase in ROS production, while N-acetylcysteine partially suppressed the increase. The 12-LOX and COX-2 inhibitors also suppressed mRNA expression of cytokines. These findings may contribute to the elucidation of the molecular mechanism of the pathophysiology of DN.

Electrophysiological analyses of transgenic mice overexpressing KCNJ8 with S422L mutation in cardiomyocytes.

Genetic analysis of KCNJ8 has pointed a mutation (S422L) as a susceptible link to J wave syndrome (JWS). In vitro expression study indicated that the ATP-sensitive K+ (KATP) channel with the S422L mutation has the gain-of-function with reduced sensitivity to ATP. However, the electrophysiological impact of KCNJ8 has not been elucidated in vivo. Transgenic mouse strains overexpressing KCNJ8 S422L variant (TGmt) or WT (TGWT) in cardiomyocytes have been created to investigate the influence of KCNJ8 in cardiomyocytes and the JWS-related feature of the S422L variant on the cardiac electrophysiology. These TG strains demonstrated distinct changes in the J-ST segment of ECG with marked QT prolongation, which might be ascribed to the action potential prolongation resulting from the reduction of voltage-dependent K+ currents in ventricular cells. The pinacidil-induced KATP current was decreased in these TG myocytes and no obvious difference between TG and non-TG (WT) myocytes in the ATP sensitivity of the KATP channel was observed although the open probability of the KATP channels was significantly lower in TG myocytes than WT. These transgenic mouse strains with distinct ECG changes suggested that the S422L mutation in KCNJ8 gene is not a direct cause of JWS.

Anthocyanin suppresses the toxicity of Aß deposits through diversion of molecular forms in in vitro and in vivo models of Alzheimer's disease.

OBJECTIVES: The pathogenesis of Alzheimer's disease (AD) is strongly correlated with the aggregation and deposition of the amyloid beta (Aß1-42) peptide in fibrillar form, and many studies have shown that plant-derived polyphenols are capable of attenuating AD progression in various disease models. In this study, we set out to correlate the effects of anthocyanoside extracts (Vaccinium myrtillus anthocyanoside (VMA)) obtained from bilberry on the in vitro progression of Aß fibril formation with the in vivo effects of this compound on AD pathogenesis. METHODS: Thioflavin T fluorescence assays and atomic force microscopy were used to monitor Aß amyloid formation in in vitro assays. Effects of Aß amyloids on cellular viability were assayed using cultured Neuro2a cells. Cognitive effects were probed using mice that simultaneously expressed mutant human Aß precursor and mutant presenilin-2. RESULTS: Addition of VMA inhibited the in vitro formation of Aß peptide fibrils and also reduced the toxicity of these aggregates toward Neuro2a cells. A diet containing 1% VMA prevented the cognitive degeneration in AD mice. Curiously, this diet-derived retention of cognitive ability was not accompanied by a reduction in aggregate deposition in brains; rather, an increase in insoluble deposits was observed compared with mice raised on a control diet. DISCUSSION: The paradoxical increase in insoluble deposits caused by VMA suggests that these polyphenols divert Aß aggregation to an alternate, non-toxic form. This finding underscores the complex effects that polyphenol compounds may exert on amyloid deposition in vivo.

Network topology for the formation of solvated electrons in binary CaO-Al2O3 composition glasses.

Glass formation in the CaO-Al2O3 system represents an important phenomenon because it does not contain typical network-forming cations. We have produced structural models of CaO-Al2O3 glasses using combined density functional theory-reverse Monte Carlo simulations and obtained structures that reproduce experiments (X-ray and neutron diffraction, extended X-ray absorption fine structure) and result in cohesive energies close to the crystalline ground states. The O-Ca and O-Al coordination numbers are similar in the eutectic 64 mol % CaO (64CaO) glass [comparable to 12CaO·7Al2O3 (C12A7)], and the glass structure comprises a topologically disordered cage network with large-sized rings. This topologically disordered network is the signature of the high glass-forming ability of 64CaO glass and high viscosity in the melt. Analysis of the electronic structure reveals that the atomic charges for Al are comparable to those for Ca, and the bond strength of Al-O is stronger than that of Ca-O, indicating that oxygen is more weakly bound by cations in CaO-rich glass. The analysis shows that the lowest unoccupied molecular orbitals occurs in cavity sites, suggesting that the C12A7 electride glass [Kim SW, Shimoyama T, Hosono H (2011) Science 333(6038):71-74] synthesized from a strongly reduced high-temperature melt can host solvated electrons and bipolarons. Calculations of 64CaO glass structures with few subtracted oxygen atoms (additional electrons) confirm this observation. The comparable atomic charges and coordination of the cations promote more efficient elemental mixing, and this is the origin of the extended cage structure and hosted solvated (trapped) electrons in the C12A7 glass.

Stimulation of 5-HT4 receptor enhances differentiation of mouse induced pluripotent stem cells into neural progenitor cells.

Activation of serotonin (5-hydroxytryptamine; 5-HT) receptors plays a role in adult neurogenesis and differentiation of neural progenitor cells (NPC). Herein, we examined the involvement of 5-HT receptors in the differentiation of mouse induced pluripotent stem (iPS) cells into NPC. To induce embryoid body (EB) formation, mouse iPS cells were cultured on ultralow-attachment dishes. All-trans retinoic acid (ATRA; 1 µmol/L) and/or 5-HT (0.03 or 0.1 µmol/L) was added to the EB cultures for 4 days and then EB plated on gelatin-coated plates were cultured for 7 or 14 days. Immunofluorescence staining revealed that mouse iPS cells expressed both 5-HT2A and 5-HT4 receptors and, to a lesser extent, 5-HT1A receptors. Treatment with 5-HT significantly enhanced the ATRA-induced expression of nestin, a specific marker for NPC, and phosphorylation of cAMP response element-binding protein (CREB). Pretreatment of EB cultures with either 1 µmol/L GR113808 (a selective 5-HT4 receptor antagonist) or 1 µmol/L H89 (a protein kinase (PKA) inhibitor) significantly inhibited these effects of 5-HT. These findings suggest that stimulation of 5-HT4 receptors may enhance ATRA-induced neural differentiation of mouse iPS cells through activation of PKA and CREB.

A retrospective study of the prevalence of isolated prolongation of activated partial thromboplastin time in the preoperative setting.

BACKGROUND: Isolated prolongation of activated partial thromboplastin time (APTT) has various causes including inheritable bleeding disorders, and has medical significance as it can lead to the cancelation of surgery. However, even an emergency surgery can be conducted in a patient presenting with severe APTT prolongation, provided careful evaluation and appropriate measures are taken. Hence, the identification of the underlying etiology of the prolonged APTT is crucial. To date, little evidence exists regarding the prevalence of isolated APTT prolongation in Japanese patients undergoing surgery. Herein, we aimed to clarify the prevalence of isolated prolongation of APTT in the preoperative setting and to identify the reasons underlying isolated, severely prolonged APTT. METHODS: Preoperative coagulation data of all elective and emergent patients who presented to the anesthetic department between January 1, 2020, and June 30, 2023, were retrospectively collected. Isolated prolongation of APTT was defined as an APTT ≥ 37 s with an international normalized ratio of prothrombin time < 1.2. The underlying etiology of the patient with isolated, severely prolonged APTT (≥ 46 s) was investigated, and canceled surgical procedures in relation to the isolated APTT prolongation were searched. RESULTS: Overall, 10,684 measurements from 9413 patients were included, of which 725 (6.8%) were identified as having isolated APTT prolongation. The reasons for the severely prolonged APTT (n = 60) were miscellaneous, with the most frequently detected etiology being antiphospholipid antibody positivity. Preoperative isolated APTT prolongation contributed to the cancellation of surgery in elective five cases. CONCLUSIONS: We clarified the prevalence of preoperative isolated prolongation of APTT. The presence of antiphospholipid antibody was the most frequently detected etiology of the patient with isolated, severely prolonged APTT. The present study provides an important dataset regarding the isolated prolongation of APTT in East Asian patients undergoing surgery.

Relationship of Serum Uric Acid with Kidney Function Decline Mediated by Systemic Arterial Stiffness: A Retrospective Cohort Study in Japan.

Hyperuricemia is associated with kidney function decline (KFD), although whether hyperuricemia directly causes nephrotoxicity or is indirectly mediated by systemic arterial stiffening remains unclear. We examined the detailed relationship of serum uric acid (SUA) with KFD and potential mediation by arterial stiffness. Study population was 27,648 urban residents with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 at baseline, and they participated in a median of three consecutive annual health examinations. Arterial stiffness was assessed using cardio-ankle vascular index (CAVI). KFD was defined as a decrease in eGFR to below 60. Multivariate analysis showed an association between baseline SUA and CAVI independent of eGFR. During the study period, 6.6% of participants developed KFD. Stratified analysis revealed a linear relationship between the contribution of CAVI or SUA and KFD. ROC analysis determined a cutoff CAVI of 8.0 (males) or 7.9 (females) and a cutoff SUA of 6.3 (males) or 4.5 mg/dL (females) for predicting KFD. The linkage between SUA and CAVI was associated with a greater increase in the hazard ratio for KFD with an increase in SUA. CAVI showed the mediating effect on the relationship of SUA with KFD after an adjustment for confounders. SUA was associated positively with CAVI-mediated KFD. Further studies should verify whether intensive SUA-lowering treatment prevents KFD via improving vascular function.

Effects of Vildagliptin, a Dipeptidyl Peptidase-4 Inhibitor, on the Parameters of Glucose Metabolism and the Cardio-Ankle Vascular Index in Individuals with Type 2 Diabetes.

DPP-4 inhibitors are frequently used as first-line agents for the treatment of type 2 diabetes in Japan. This study aimed to examine the effects of vildagliptin on glucose metabolism and arterial stiffness. Twenty treatment-naïve patients with type 2 diabetes (8 males and 12 females) received vildagliptin 50 mg twice daily for 6 months. Self-monitored blood glucose measurements and a 75 g OGTT were performed. Arterial stiffness was assessed using the CAVI. After the vildagliptin treatment, a significant decrease in the median HbA1c (from 8.3 to 6.4%) and fasting HOMA-ß (from 26.1 to 34.5%), and a marginally significant decrease in the CAVI (from 8.9 to 8.4, p = 0.087) were observed. The glycemic variability parameters also improved, whereas the insulin sensitivity and oxidative stress remained unchanged. Participants with a lower glycemic variability on the 75 g OGTT after vildagliptin treatment showed a significant decrease in their CAVI. The baseline BMI was significantly higher for the participants with a decreased CAVI than in those with no change in their CAVI (24.5 vs. 20.8 kg/m2). After vildagliptin treatment, a decrease in the CAVI was observed, especially in the individuals with improved glycemic variability on the 75 g OGTT. Vildagliptin may be suitable for vascular protection in individuals with high glycemic variability and/or an elevated BMI.

Once-weekly semaglutide administered after laparoscopic sleeve gastrectomy: Effects on body weight, glycemic control, and measured nutritional metrics in Japanese patients having both obesity and type 2 diabetes.

Background: Glucagon-like peptide (GLP)-1 analogue may be useful for controlling weight recurrence and diabetes relapse after bariatric surgery, but may also adversely affect the measured nutritional metrics. This study aimed to investigate the effect of treatment with once-weekly semaglutide after laparoscopic sleeve gastrectomy (LSG) in patients with type 2 diabetes (T2D). We also examined the effects of combined use with a low-energy, high-protein formula diet (FD). Methods: This study was a single-center retrospective database analysis. We enrolled 29 Japanese patients with T2D who underwent LSG, and more than 12 months later received semaglutide. The patients were divided retrospectively into a FD group (=6) and a conventional diet (CD) group (n = 23). Results: BMI and HbA1c decreased significantly by 10.7 kg/m2 and 1.1 %, respectively, 12 months after LSG, and decreased by an additional 1.6 kg/m2 and 0.6 % after 12-months of treatment with semaglutide. Decreases in serum albumin, vitamin B12 and zinc were observed only after semaglutide administration. A ratio of energy from protein, fat and carbohydrates changed from 13:31:56 before to 19:30:50 after LSG, and from 17:32:51 before to 15:29:56 after semaglutide. Skeletal muscle ratio, which is the ratio of skeletal muscle mass to body weight, increased after LSG, but did not change after semaglutide. FD group showed a significant increase in skeletal muscle mass per 1 % body weight compared to CD group during semaglutide treatment. Conclusion: Semaglutide after LSG in patients with obesity and T2D resulted in additional weight reduction and improved glycemic control, but worsened measured nutritional metrics. Administration of a low-energy, high protein formula diet may ameliorate adverse nutritional effects of semaglutide in patients with T2D after LSG. (Ethics Committee of Toho University Sakura Medical Center approval number S18061).

Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity.

INTRODUCTION: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. RESULTS: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. CONCLUSIONS: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.