Faculty Profiles - SAITO Akihiko

Circulating FABP4 is eliminated by the kidney via glomerular filtration followed by megalin-mediated reabsorption Reviewed International journal

Shrestha S, Sunada S, Hanaoka H, Yamaguchi A, Kuwahara S, Umbarawan Y, Nakajima K, Machida T, Murakami M, Saito A, Tsushima Y, Kurabayashi M, Iso T

Scientific Reports (2018) 8 ( 16451 ) 16451 - 16451 2018.11

Language：English Publishing type：Research paper (scientific journal)

Circulating fatty acid binding protein 4 (FABP4), secreted from adipocytes, is a potential biomarker for metabolic and cardiovascular diseases. Circulating FABP4 levels are positively associated with adiposity and adrenergic stimulation, but negatively with renal function. In this study, we addressed the issue of how the kidney regulates clearance of circulating FABP4. Tracing study revealed remarkable accumulation of 125I-labeled FABP4 in the kidney. Exogenous FABP4 was exclusively detected in the apical membrane of proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in marked elevation of circulating FABP4 levels. Accelerated lipolysis by β-3 adrenergic stimulation led to a marked elevation in circulating FABP4 in mice with severe renal dysfunction. Megalin, an endocytic receptor expressed in PTECs, plays a major role in reabsorption of proteins filtered through glomeruli. Quartz-crystal microbalance study revealed that FABP4 binds to megalin. In kidney-specific megalin knockout mice, a large amount of FABP4 was excreted in urine while circulating FABP4 levels were significantly reduced. Our data suggest that circulating FABP4 is processed by the kidney via the glomerular filtration followed by megalin-mediated reabsorption. Thus, it is likely that circulating FABP4 levels are determined mainly by balance between secretion rate of FABP4 from adipocytes and clearance rate of the kidney.

DOI： 10.1038/s41598-018-34902-w

週1回のGLP-1受容体作動薬エキセナチド使用中に腸管気腫症の増悪を来した1例

石川友美, 細島康宏, 佐藤健, 塩谷基, 蒲澤秀門, 忰田亮平, 中枝武司, 和田庸子, 鈴木芳樹, 斎藤亮彦, 成田一衛

糖尿病 61 ( 9 ) 624 - 624 2018.9

Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey Reviewed

K. Tabeta, M. Hosojima, M. Nakajima, S. Miyauchi, H. Miyazawa, N. Takahashi, Y. Matsuda, N. Sugita, Y. Komatsu, K. Sato, T. Ishikawa, K. Akiishi, K. Yamazaki, K. Kato, A. Saito, H. Yoshie

Journal of Periodontal Research 53 ( 3 ) 446 - 456 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Blackwell Munksgaard

Background and Objectives: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. Material and Methods: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI). Results: The concentrations of PCSK9 and hs-CRP were increased (P =.001 and.042, respectively), and the concentration of TBIL was decreased (P =.046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P =.038,.007,.002, and.049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β =.243, P =.040
standardized β = −.443, P =.0002
respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. Conclusion: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.

DOI： 10.1111/jre.12533

Scopus

幼少期における米(胚乳)タンパク質の摂取が成熟期の高脂肪食負荷による肥満および肥満関連腎症に及ぼす影響

樋口裕樹, 細島康宏, 蒲澤秀門, 桑原頌治, 忰田亮平, 成田一衛, 斎藤亮彦

糖尿病 61 ( Suppl.1 ) S - 241 2018.4

Bardoxolone methylによる腎近位尿細管のメガリン調節機構の検討

吉澤優太, 桑原頌治, 細島康宏, 蒲澤秀門, 忰田亮平, 宇賀村大亮, 後藤佐和子, 飯田倫理, 鈴木芳樹, 成田一衛, 斎藤亮彦

糖尿病 61 ( Suppl.1 ) S - 383 2018.4

SGLT2阻害薬ダパグリフロジンの腎近位尿細管細胞における血糖値非依存的なメガリン発現抑制作用

飯田倫理, 桑原頌治, 細島康宏, 石川友美, 後藤佐和子, 蒲澤秀門, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

糖尿病 61 ( Suppl.1 ) S - 382 2018.4

Urinary C-megalin for screening of renal scarring in children after febrile urinary tract infection Reviewed

Sohsaku Yamanouchi, Takahisa Kimata, Jiro Kino, Tetsuya Kitao, Chikushi Suruda, Shoji Tsuji, Hiroyuki Kurosawa, Yoshiaki Hirayama, Akihiko Saito, Kazunari Kaneko

Pediatric Research 83 ( 3 ) 662 - 668 2018.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Publishing Group

BackgroundFebrile urinary tract infection (fUTI) in children may cause renal scarring. This study aimed to investigate the usefulness of urinary biomarkers for diagnosing renal scarring after fUTI.MethodsThirty-seven children (median age: 1.36 years, range: 0.52-12.17 years, 25 boys) with a history of fUTI, who underwent renal scintigraphy for 4 months or longer after the last episode of fUTI, were analyzed. A spot urine sample was obtained on the day of renal scintigraphy to measure levels of total protein, N-acetyl-β-D-glucosaminidase (NAG), β 2 -microglobulin (BMG), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and C-megalin (full-length megalin). Results were corrected for urinary creatinine (Cr) and compared between the group with renal scarring (n=23) and that without scarring (n=14). Urinary levels of C-megalin were also measured in healthy control subjects.ResultsNo significant differences in total protein, NGAL, L-FABP, NAG, and BMG levels were found between the groups. However, C-megalin levels were significantly higher in the renal scarring group than in the non-renal scarring group and healthy controls (P&lt
0.001). A cutoff value of 6.5 pmol/nmol of urinary C-megalin/Cr yielded 73.9% of specificity and 92.9% of sensitivity.ConclusionUrinary C-megalin is useful for diagnosing renal scarring caused by fUTI.

DOI： 10.1038/pr.2017.276

Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. Reviewed International journal

Tomohiro Udagawa, Yutaka Harita, Kenichiro Miura, Jun Mitsui, Koji L Ode, Shinichi Morishita, Seiya Urae, Shoichiro Kanda, Yuko Kajiho, Haruko Tsurumi, Hiroki R Ueda, Shoji Tsuji, Akihiko Saito, Akira Oka

Scientific reports 8 ( 1 ) 2351 - 2351 2018.2

Language：English Publishing type：Research paper (scientific journal)

Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria. Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless. We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients. A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin. The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS. Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression. Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting. These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.

DOI： 10.1038/s41598-018-20731-4

Urinary Iron Excretion is Associated with Urinary Full-Length Megalin and Renal Oxidative Stress in Chronic Kidney Disease. Reviewed

Nakatani S, Nakatani A, Ishimura E, Toi N, Tsuda A, Mori K, Emoto M, Hirayama Y, Saito A, Inaba M

Kidney & blood pressure research 43 ( 2 ) 458 - 470 2018

[Exosomal biomarkers for kidney disease.] Reviewed

Hosojima M, Kabasawa H, Kuwahara S, Saito A

Clinical calcium 28 ( 2 ) 252 - 259 2018

A Randomized, Double-Blind, Crossover Pilot Trial of Rice Endosperm Protein Supplementation in Maintenance Hemodialysis Patients Reviewed

Michihiro Hosojima, Hisaki Shimada, Yoshitsugu Obi, Shoji Kuwahara, Ryohei Kaseda, Hideyuki Kabasawa, Hazuki Kondo, Mikio Fujii, Reiko Watanabe, Yoshiki Suzuki, Motoni Kadowaki, Shigeru Miyazaki, Akihiko Saito

SCIENTIFIC REPORTS 7 ( 1 ) 18003 2017.12

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

In maintenance hemodialysis (MHD) patients, low protein intake is associated with protein-energy wasting, a risk factor that affects outcome. However, increased protein intake may lead to hyperphosphatemia and hyperkalemia, which are also mortality risk factors. Here, we evaluated the safety and effects of purified rice endosperm protein (REP), which contains less phosphorus and potassium than soy and casein proteins, as a supplemental protein source for MHD patients. This randomized, double-blind, placebo-controlled, crossover pilot study of REP supplementation (5 g/day x 4 weeks) was carried out in 50 Japanese adult MHD patients (1 dropped out); the primary outcome was the change in the urea kinetic-based normalized protein catabolic rate (nPCR), an indicator of protein intake in MHD patients. Intention-to-treat analyses of 24 patients in the REP-first group and 25 in the placebo-first group showed that REP supplementation increased nPCR significantly by 0.07 g/kg/day (95% confidence interval, 0.03-0.11), whereas changes in serum phosphorus and potassium concentrations were not different from the placebo. REP supplementation did not show a significant effect on other nutritional or metabolic parameters and no specific complications. In conclusion, purified REP with efficient bioavailability may be safe and useful for dietary supplementation in MHD patients.

DOI： 10.1038/s41598-017-18340-8

Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity Reviewed

Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 28 ( 6 ) 1783 - 1791 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC NEPHROLOGY

Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I-mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.

DOI： 10.1681/ASN.2016060606

Differences in the adsorption of nafamostat mesilate between polyester-polymer alloy and polysulfone membranes Reviewed

Sawako Goto, Susumu Ookawara, Akihiko Saito

JOURNAL OF ARTIFICIAL ORGANS 20 ( 2 ) 138 - 144 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

We previously experienced severe clot formation in a polyester-polymer alloy (PEPA) dialyzer and hemodialysis (HD) circuit with nafamostat mesilate (NM) as an anticoagulant. The possibility of NM adsorption to the PEPA membrane was taken into consideration, but there was not enough information. In the present study, we evaluated differences in the adsorption of NM between a PEPA membrane (FDX-120 GW, Nikkiso, Tokyo, Japan) and two different polysulfone membranes (FX-140, Fresenius Medical Care, Tokyo, Japan; NV-15U, Toray Medical, Tokyo, Japan). We calculated the NM concentration by measuring absorbance at 241 nm using a spectrometer. NM adsorption was evaluated in three ways. First, we evaluated NM adsorption to hollow fibers. Then, we passed an NM solution through dialyzers and evaluated its adsorption in a single-pass examination. Finally, we circulated an NM solution in an HD circuit using a blood pump and evaluated NM adsorption. In all the experiments, NM adsorption to the PEPA membrane was greater than that to the polysulfone membranes examined. In the blood pump experiment, the estimated adsorption quantities of NM to the PEPA membrane and the FX-140 and NV-15U polysulfone membranes were 12.0 +/- 0.1, 1.0 +/- 0.1, and 4.1 +/- 0.4 mg/m(2), respectively. NM adsorption was confirmed, especially in the early phase, and the PEPA membrane adsorbed greater amounts of NM than the polysulfone membranes. We should pay attention to the choice of dialyzer as well as the appropriate dose of NM administration during the preparation of HD circuits.

DOI： 10.1007/s10047-016-0937-2

Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy Reviewed

Shankhajit De, Shoji Kuwahara, Michihiro Hosojima, Tomomi Ishikawa, Ryohei Kaseda, Piyali Sarkar, Yusuke Yoshioka, Hideyuki Kabasawa, Tomomichi Iida, Sawako Goto, Koji Toba, Yuki Higuchi, Yoshiki Suzuki, Masanori Hara, Hiroyuki Kurosawa, Ichiei Narita, Yoshiaki Hirayama, Takahiro Ochiya, Akihiko Saito

DIABETES 66 ( 5 ) 1391 - 1404 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER DIABETES ASSOC

Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using ELISA, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in patients with type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with T2DM. Cultured immortalized rat proximal tubule cells (IRPTCs) treated with fatty acid-free BSA or advanced glycation end product-modified BSA (AGE-BSA), endocytic ligands of megalin, increased EV excretion, and their C-megalin content. C-megalin excretion from IRPTCs via extracellular vesicles was significantly blocked by an exosome-specific inhibitor, GW4869, indicating that this excretion is mainly exocytosis-mediated. AGE-BSA treatment of IRPTCs caused apparent lysosomal dysfunction, which stimulated multivesicular body formation, resulting in increased exosomal C-megalin excretion. In a high-fat diet-induced, megalin-mediated kidney injury model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of DN in patients with T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules, and hence it could be a candidate biomarker linked with DN pathogenesis.

DOI： 10.2337/db16-1031

Decreased urinary excretion of the ectodomain form of megalin (A-megalin) in children with OCRL gene mutations Reviewed

Chikushi Suruda, Shoji Tsuji, Sohsaku Yamanouchi, Takahisa Kimata, Nguyen Thanh Huan, Hiroyuki Kurosawa, Yoshiaki Hirayama, Hiroyasu Tsukaguchi, Akihiko Saito, Kazunari Kaneko

PEDIATRIC NEPHROLOGY 32 ( 4 ) 621 - 625 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

The oculocerebrorenal syndrome of Lowe gene (OCRL) is located on chromosome Xq25-26 and encodes an inositol polyphosphate-5-phosphatase (OCRL-1). Mutations in this gene cause Lowe syndrome (LS) or type 2 Dent disease, of which low-molecular-weight (LMW) proteinuria is a characteristic feature. Megalin is considered to play an important role in the development of renal tubular proteinuria. Two forms of megalin are excreted into the urine: full-length megalin (C-megalin) and megalin ectodomain (A-megalin). We have explored the role of megalin in the development of LMW proteinuria in patients with OCRL mutations by determining urinary megalin fractions.
We measured A- and C-megalin in spot urine samples from five male patients with OCRL mutations (median age 9 years), using sandwich enzyme-linked immunosorbent assays, and adjusted the obtained values for excreted creatinine. The results were compared with those of 50 control subjects and one patient with type 1 Dent disease (T1D).
All patients demonstrated normal levels of urinary C-megalin. However, patients with OCRL mutations or T1D showed abnormally low levels of urinary A-megalin, with the exception of one 5-year-old boy with LS, who was the youngest patient enrolled in the study.
Decreased excretion of urinary A-megalin in four out of five patients with OCRL mutations suggests that LMW proteinuria may be caused by impaired megalin recycling within the proximal tubular cells. Homologous enzymes, similar to inositol polyphosphate-5-phosphatase B in mice, may help to compensate for defective OCRL-1 function during early childhood.

DOI： 10.1007/s00467-016-3535-x

The Assessment of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Glucocorticoid-induced Diabetes by Continuous Glucose Monitoring Reviewed

Yusuke Yata, Michihiro Hosojima, Hideyuki Kabasawa, Tomomi Ishikawa, Ryohei Kaseda, Noriaki Iino, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita

INTERNAL MEDICINE 56 ( 19 ) 2555 - 2562 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective The administration of glucocorticoids usually causes a mild increase in fasting glucose levels and a greater dose-dependent increase in postprandial values in patients without pre-existing diabetes mellitus. Patients with persistent hyperglycemia due to glucocorticoid therapy sometimes require insulin therapy, which might result in increased weight gain and more episodes of hypoglycemia, some of which are severe. On the other hand, scant evidence is available on the efficacy of oral hypoglycemic agents in treating glucocorticoid-induced diabetes. In this study, we evaluated the efficacy of dipeptidyl peptidase (DPP)-4 inhibitors in patients with glucocorticoid-induced diabetes by continuous glucose monitoring (CGM).
Methods We examined the glycemic profiles using CGM at baseline and 1-4 weeks after initiating DPP-4 inhibitor treatment in patients with newly developed glucocorticoid-induced diabetes.
Results Eleven patients who had been diagnosed with kidney disease or other diseases with renal involvement were recruited for the present retrospective study. After starting DPP-4 inhibitors, the mean and standard deviation (SD) of the glucose level, and the mean amplitude of glycemic excursion (MAGE) were significantly improved in comparison to baseline. Furthermore, the area over the curve (AOC) for the glucose levels <70 mg/dL was not increased in comparison to baseline after the initiation of DPP-4 inhibitor treatment. The results indicate that the treatment of patients with glucocorticoid-induced diabetes using DPP-4 inhibitors can minimize the risk of hypoglycemia and reduce glucose variability.
Conclusion DPP-4 inhibitors are potentially useful for blood glucose control in patients with glucocorticoid-induced diabetes.

DOI： 10.2169/internalmedicine.8296-16

BENEFICIAL EFFECTS OF RICE ENDOSPERM PROTEIN ON CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD) IN ZUCKER DIABETIC FATTY RATS Reviewed

Reiko Watanabe, Masatoshi Kubota, Shogo Sugaki, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Ichiro Sasagawa, Shinobu Fujimura, Motoni Kadowaki

ANNALS OF NUTRITION AND METABOLISM 71 1218 - 1218 2017

Glucose Variability Based on Continuous Glucose Monitoring Assessment Is Associated with Postoperative Complications after Cardiovascular Surgery Reviewed

Hiroki Sato, Michihiro Hosojima, Tomomi Ishikawa, Kenji Aoki, Takeshi Okamoto, Akihiko Saito, Masanori Tsuchida

ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 23 ( 5 ) 239 - 247 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：MEDICAL TRIBUNE INC

Purpose: This purpose of this prospective study was to use a continuous glucose monitoring (CGM) system to evaluate the suitability of our institution's glucose management protocol after cardiovascular surgery and to clarify the impact of glycemic variability on postoperative complications.
Methods: In all, 76 patients who underwent elective cardiovascular surgery and were monitored perioperatively using a CGM system were evaluated. Postoperative glucose management consisted of continuous intravenous insulin infusion (CIII) in the intensive care unit, and subcutaneous insulin injections (SQII) after oral food intake started. CIII and subcutaneous injections were initiated when blood glucose level exceeded 150 mg/dL. CGM data were used to analyze perioperative glycemic variability and association with postoperative complications.
Results: Target glucose levels (71-180 mg/dL) were achieved during 97.1 +/- 5.5% and 86.4 +/- 19.0% of the continuous insulin infusion and subcutaneous injection periods, respectively. Major postoperative complications were surgical site infections, found in 6.6% of total patients, and atrial fibrillation, found in 44% of patients with off-pump coronary artery bypass grafting. High glycemic variability during SQII was associated with increased risk for both complications.
Conclusion: Data analysis revealed that our glucose management protocol during CIII was adequate. However, the management protocol during SQII required improvement.

DOI： 10.5761/atcs.oa.17-00045

Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats Reviewed

Masatoshi Kubota, Reiko Watanabe, Miki Yamaguchi, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Shinobu Fujimura, Motoni Kadowaki

BRITISH JOURNAL OF NUTRITION 116 ( 8 ) 1326 - 1335 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：CAMBRIDGE UNIV PRESS

We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P < 005). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P < 001). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P < 005), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl--d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P < 001). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P < 001). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

DOI： 10.1017/S0007114516003512