論文 - 上野 浩晶
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Ueno H., Mizuta M., Shiiya T., Tsuchimochi W., Noma K., Nakashima N., Fujihara M., Nakazato M.
Diabetes Care 37 ( 7 ) 2024 - 2027 2014年7月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diabetes Care
OBJECTIVE: This study aimed to assess the efficacy and safety of our newly developed nasal glucagon-like peptide-1 (GLP-1) compound and injector. RESEARCH DESIGN AND METHODS: Twenty-six patients with type 2 diabetes were enrolled in this double-blind placebo-controlled study. The nasal compound containing 1.2 mg of human GLP-1 (7-36) amide or placebo was administered immediately before every meal for 2 weeks. RESULTS: The plasma peak concentration of active GLP-1 was 47.2 pmol/L, and its Tmax was 8.1 min. The early phase of insulin and glucagon secretion were recovered and suppressed, respectively, in the GLP-1 group. Glycoalbumin levels became significantly lower and 1,5-anhydroglucitol levels significantly higher after GLP-1 administration. No marked adverse events were observed after using nasal GLP-1. CONCLUSIONS: The newly developed nasal GLP-1 compound may be a potential treatment for type 2 diabetes. The long-term application of the drug should be evaluated in future trials. © 2014 by the American Diabetes Association.
DOI： 10.2337/dc13-0690
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GLP-1受容体作動薬による視床下部を介する体重減少効果 招待あり
上野浩晶
脳神経内科 102 344 - 350 2025年3月
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers 査読あり
Kameda T., Utsunomiya A., Otsuka N., Kubuki Y., Uchida T., Shide K., Kamiunten A., Nakano N., Tokunaga M., Miyazono T., Ito Y., Yonekura K., Kawakita T., Akizuki K., Tahira Y., Karasawa M., Hidaka T., Konagata A., Taniguchi N., Nagatomo Y., Kogo F., Shimizu K., Ueno H., Ishizaki J., Takahashi N., Ikei Y., Hidaka M., Yamaguchi H., Shimoda K.
BMC Infectious Diseases 24 ( 1 ) 96 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Infectious Diseases
Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown. Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors. Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers. Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.
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Islam M.N., Nabekura H., Ueno H., Nishida T., Nanashima A., Sakoda H., Zhang W., Nakazato M.
Scientific Reports 14 ( 1 ) 24782 2024年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Liver-expressed antimicrobial peptide 2 (LEAP2) is a peptide that counteracts the hunger hormone ghrelin-induced functions. Recently, we showed that vertical sleeve gastrectomy (VSG) did not alter the serum LEAP2 concentration in individuals with obesity. Here, we investigated the effects of VSG in both chow diet (CD)-fed and high-fat diet (HFD)-fed mice. In CD-fed mice, VSG increased plasma LEAP2 levels and hepatic Leap2 mRNA levels while decreasing body weight, blood glucose levels, and ghrelin levels. Intraperitoneal (ip) administration of ghrelin reversed these changes. These effects were found in both male and female mice. In contrast, VSG or weight loss in HFD-induced obese mice decreased LEAP2 levels. After fasting, the plasma LEAP2 concentration was in the following order: hepatic vein > abdominal aorta > portal vein. A high glucose concentration robustly increased the plasma LEAP2 concentration in the hepatic vein and abdominal aorta but not in the portal vein. In addition, corn oil or palmitate increased LEAP2 expression and secretion. The increase in LEAP2 levels after the meal tolerance test was delayed in the human subjects with diabetes. Our data suggest that various factors (metabolic, hormonal, and nutritional) regulate LEAP2, and the liver is the predominant site for the production and secretion of LEAP2. Furthermore, the interaction between ghrelin and LEAP2 is involved in the pathogenesis of obesity and diabetes.
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Mitsutome E., Yanagi S., Uchida T., Horiguchi T., Tsubouchi H., Sumiyoshi M., Kitamura A., Oda Y., Ueno H., Yamaguchi H., Miyazaki T.
Journal of Infection and Chemotherapy 31 ( 1 ) 102482 2024年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
Most cases of nontuberculous mycobacterial pulmonary disease (NTM-PD) have a progressive clinical course, and initiation of treatment is recommended rather than watchful waiting. The NTM-PD medications are frequently associated with adverse reactions, occasionally serious. Optimization of the methods for monitoring and managing adverse events in NTM-PD treatment is thus an important medical issue. Here we report a first case of postprandial hypoglycemia caused by the combination of clarithromycin (CAM) and rifampicin (RFP) in a patient with NTM-PD. A 73-year-old Japanese woman with NTM-PD was hospitalized for treatment with a combination of oral CAM, RFP, and ethambutol. She took the first doses of antibiotics before breakfast, and 3 h later went into a hypoglycemic state. Postprandial hypoglycemia occurred with high reproducibility and was accompanied by relative insulin excess. Continuous glucose monitoring with or without food and in combination with various patterns of medication revealed that the combination of CAM and RFP specifically induced postprandial hypoglycemia. Shifting the timing of administration of the CAM and RFP combination from morning to before sleep corrected the hypoglycemia and enabled continuation of the antimicrobial treatment. In conclusion, our report suggests the importance of introducing NTM-PD medication under inpatient management in order to closely monitor and early detect postprandial hypoglycemia and other serious adverse events.
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Uchida T., Ueno H., Sekishima A., Sekishima H., Konagata A., Nakamura T., Kogo F., Nabekura H., Tanaka Y., Shimizu K., Yamaguchi H., Shimoda K.
Diabetology International 2024年
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diabetology International
Aim: Education on insulin self-injection techniques is important for good glycemic control, but its effectiveness in some elderly patients is limited due to loss of cognitive function and impaired activities of daily living. We hypothesized that classification using the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) would help identify elderly patients with diabetes who effectively learn self-injection techniques. Methods: Diabetes patients aged ≥ 65 years who used a self-injection insulin pen were administered the DASC-8 and a questionnaire to evaluate insulin self-injection techniques, and then received technical education. The questionnaire was administered again 4 months later, and patients were classified into the education-effective and education-ineffective groups. The achievement of HbA1c targets defined for each patient according to guidelines based on DASC-8 category was examined over 12 months. Results: 76 Japanese patients (median age 72.0 years and 53.9% female) with DASC-8 categories I (n = 55), II (n = 13), and III (n = 8) were enrolled. In the education-effective group, the percentage of patients in category I was significantly higher than that of patients in category II or III (92.0% to 23.8%, P < 0.001). Category I was independently associated with education effectiveness (odds ratio 14.50, 95% confidence interval: 2.110–100.0, P = 0.007). Category I patients in the education-effective group showed significantly improved achievement of target HbA1c from baseline to the 12th month (from 27.6% to 62.1%, P = 0.008). Conclusions: The DASC-8 was a useful indicator for identifying elderly patients who would benefit from education on self-injection techniques.
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Impact of the lipase inhibitor orlistat on the human gut microbiota 査読あり
Uehira Y., Ueno H., Miyamoto J., Kimura I., Ishizawa Y., Iijima H., Muroga S., Fujita T., Sakai S., Samukawa Y., Tanaka Y., Murayama S., Sakoda H., Nakazato M.
Obesity Research and Clinical Practice 17 ( 5 ) 411 - 420 2023年9月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Obesity Research and Clinical Practice
Orlistat, an anti-obesity agent, inhibits the metabolism and absorption of dietary fat by inactivating pancreatic lipase in the gut. The effect of orlistat on the gut microbiota of Japanese individuals with obesity is unknown. This study aimed to explore the effects of orlistat on the gut microbiota and fatty acid metabolism of Japanese individuals with obesity. Fourteen subjects with visceral fat obesity (waist circumference ≥85 cm) took orlistat orally at a dose of 60 mg, 3 times a day for 8 weeks. Body weight; waist circumference; visceral fat area; levels of short-chain fatty acids, gut microbiota, fatty acid metabolites in the feces, and gastrointestinal hormones; and adverse events were evaluated. Body weight, waist circumference, and blood leptin concentrations were significantly lower after orlistat treatment (mean ± standard deviation, 77.8 ± 9.1 kg; 91.9 ± 8.7 cm; and 4546 ± 3211 pg/mL, respectively) compared with before treatment (79.4 ± 9.0 kg; 94.4 ± 8.0 cm; and 5881 ± 3526 pg/mL, respectively). Significant increases in fecal levels of fatty acid metabolites (10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid, and 10-oxo-trans-11-octadecenoic acid) were detected. Meanwhile, no significant changes were found in abdominal computed tomography parameters, blood marker levels, or short-chain fatty acid levels in the feces. Gut microbiota analysis revealed that some study subjects had decreased abundance of Firmicutes, increased abundance of Bacteroidetes, and increased α-diversity indices (Chao1 and ACE) after 8 weeks of treatment. The levels of Lactobacillus genus and Lactobacillus gasseri were significantly higher after 8 weeks of treatment. None of the subjects discontinued treatment or experienced severe adverse events. This study suggested that orlistat might alter gut microbiota composition and affect the body through fatty acid metabolites produced by the modified gut bacteria.
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Association between personality traits and glycemic control after inpatient diabetes education. 査読あり
Uchida T, Ueno H, Konagata A, Nakamura T, Taniguchi N, Nabekura H, Kogo F, Nagatomo Y, Tanaka Y, Shimizu K, Shiiya T, Yamaguchi H, Shimoda K
Metabolism open 18 100244 2023年6月
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Uchida T., Ueno H., Konagata A., Taniguchi N., Kogo F., Nagatomo Y., Shimizu K., Yamaguchi H., Shimoda K.
Diabetes Therapy 14 ( 6 ) 1075 - 1076 2023年6月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diabetes Therapy
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Association of Serum Levels of Cholesterol Absorption and Synthesis Markers with the Presence of Cardiovascular Disease: The CACHE Study CVD Analysis. 査読あり
Katsuki S, Matoba T, Akiyama Y, Yoshida H, Kotani K, Fujii H, Harada-Shiba M, Ishibashi Y, Ishida T, Ishigaki Y, Kabata D, Kihara Y, Kurisu S, Masuda D, Matsuki K, Matsumura T, Mori K, Nakagami T, Nakazato M, Taniuchi S, Ueno H, Yamashita S, Yoshida H, Tsutsui H, Shoji T
Journal of atherosclerosis and thrombosis 2023年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b>Aim: </b>Serum levels of cholesterol absorption and synthesis markers have been associated with cardiovascular risk in the United States and European countries. In this study, we examined the relevance of these biomarkers and the presence of cardiovascular disease (CVD) in Japanese individuals.<b> </b><b>Methods: </b>The CACHE consortium, comprising of 13 research groups in Japan possessing data on campesterol, an absorption marker, and lathosterol, a synthesis marker measured by gas chromatography, compiled the clinical data using the REDCap system.<b> </b><b>Results: </b>Among the 2,944 individuals in the CACHE population, those with missing campesterol or lathosterol data were excluded. This cross-sectional study was able to analyze data from 2,895 individuals, including 339 coronary artery disease (CAD) patients, 108 cerebrovascular disease (CeVD) patients, and 88 peripheral artery disease (PAD) patients. The median age was 57 years, 43% were female, and the median low-density lipoprotein cholesterol and triglyceride levels were 118 mg/dL and 98 mg/dL, respectively. We assessed the associations of campesterol, lathosterol, and the ratio of campesterol to lathosterol (Campe/Latho ratio) with the odds of CVD using multivariable-adjusted nonlinear regression models. The prevalence of CVD, especially CAD, showed positive, inverse, and positive associations with campesterol, lathosterol, and the Campe/Latho ratio, respectively. These associations remained significant even after excluding individuals using statins and/or ezetimibe. The associations of the cholesterol biomarkers with PAD were determined weaker than those with CAD. Contrarily, no significant association was noted between cholesterol metabolism biomarkers and CeVD.<b> </b><b>Conclusion: </b>This study showed that both high cholesterol absorption and low cholesterol synthesis biomarker levels were associated with high odds of CVD, especially CAD.
DOI： 10.5551/jat.64119
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Uchida T., Ueno H., Konagata A., Taniguchi N., Kogo F., Nagatomo Y., Shimizu K., Yamaguchi H., Shimoda K.
Diabetes Therapy 14 ( 3 ) 569 - 579 2023年3月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diabetes Therapy
Introduction: Endothelial dysfunction is a risk factor for cardiovascular disease in patients with diabetes. We hypothesized that imeglimin, a novel oral hypoglycemic agent, would improve endothelial function. Methods: In this study, imeglimin was administered to patients with type 2 diabetes and HbA1c ≥ 6.5% who were not receiving insulin therapy. A meal tolerance test (592 kcal, glucose 75.0 g, fat 28.5 g) was performed before and 3 months after administration, and endothelial function, blood glucose, insulin, glucagon, and triglycerides were evaluated. Endothelial function was assessed by flow-mediated dilation (FMD). Results: Twelve patients (50% male) with a median age of 55.5 years old (interquartile range [IQR] 51.3–66.0) were enrolled. Fasting FMD did not differ before or 3 months after imeglimin administration (from 6.1 [3.9–8.5] to 6.6 [3.9–9.0], p = 0.092), but 2 h postprandial FMD was significantly improved 3 months after imeglimin administration (from 2.3 [1.9–3.4] to 2.9 [2.4–4.7], p = 0.013). In terms of the glucose profile, imeglimin administration significantly improved HbA1c (from 7.2 ± 0.6% to 6.9 ± 0.6%, p = 0.007), fasting glucose (from 138 ± 19 mg/dL to 128 ± 20 mg/dL, p = 0.020), and 2 h postprandial glucose (from 251 ± 47 mg/dL to 215 ± 68 mg/dL, p = 0.035). The change in 2 h postprandial FMD between before and 3 months after imeglimin administration (Δ2 h postprandial FMD) was negatively correlated with Δ2 h postprandial glucose (r = − 0.653, p = 0.021) in a univariate correlation coefficient analysis. Both patients with and without decreased postprandial glucose 3 months after imeglimin administration had improved postprandial FMD. Conclusion: In this small study, imeglimin administration improved 2 h postprandial FMD. Both glycemic control-dependent and -independent mechanisms might contribute to improved endothelial function. Trial Registration: This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000046311).
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Serum Values of Cholesterol Absorption and Synthesis Biomarkers in Japanese Healthy Subjects: The CACHE Study HEALTHY Analysis. 査読あり
Ishibashi Y, Yoshida H, Kotani K, Akiyama Y, Fujii H, Harada-Shiba M, Ishida T, Ishigaki Y, Kabata D, Kihara Y, Kurisu S, Masuda D, Matoba T, Matsuki K, Matsumura T, Mori K, Nakagami T, Nakazato M, Taniuchi S, Ueno H, Yamashita S, Yano S, Yoshida H, Tetsuo S
Journal of atherosclerosis and thrombosis 2023年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b>Aim: </b>Blood cholesterol absorption and synthesis biomarkers predict cardiovascular risk. This study aimed to determine the values of serum non-cholesterol sterol markers [lathosterol (Latho), campesterol (Campe), and sitosterol (Sito)] in healthy individuals and factors affecting these markers.<b> </b><b>Methods: </b>The CACHE Consortium compiled clinical data, including serum Latho (cholesterol synthesis marker), and Campe and Sito (cholesterol absorption markers), by a gas chromatography method in 2944 individuals. Healthy subjects were selected by excluding those with prior cardiovascular disease, diabetes mellitus, hypertension, chronic kidney disease, familial hypercholesterolemia, sitosterolemia, current smokers, those with low ( ＜17 kg/m <sup>2 </sup>) or high (≥ 30 kg/m <sup>2</sup>) body mass index (BMI), and those with treatment for dyslipidemia or hyperuricemia. Nonlinear regression stratified by sex was used to examine the associations of cholesterol metabolism markers with age, BMI, and serum lipid levels.<b> </b><b>Results: </b>Of 479 individuals selected, 59.4% were female; the median age was 48 years in females and 50 years in males. The three markers showed positively skewed distributions, and sex differences were present. Age was associated positively with Latho, inversely with Campe, but not significantly with Sito. BMI was associated positively with Latho, but not significantly with Campe or Sito. High-density lipoprotein cholesterol (HDL-C) was positively associated with Campe and Sito, but not significantly with Latho. Non-HDL-C was positively associated with the three markers.<b> </b><b>Conclusion: </b>Our study results in the healthy subjects help to interpret the non-cholesterol sterol markers for cardiovascular risk assessment in patients with cardiovascular risk factors.
DOI： 10.5551/jat.63943
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Matsuki K, Harada-Shiba M, Hori M, Ogura M, Akiyama Y, Fujii H, Ishibashi Y, Ishida T, Ishigaki Y, Kabata D, Kihara Y, Kotani K, Kurisu S, Masuda D, Matoba T, Matsumura T, Mori K, Nakagami T, Nakazato M, Taniuchi S, Ueno H, Yamashita S, Yoshida H, Yoshida H, Shoji T
Journal of atherosclerosis and thrombosis advpub ( 0 ) 1152 - 1164 2023年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b>Aim: </b>Serum levels of cholesterol absorption and synthesis markers are known to be associated with cardiovascular risk. Familial hypercholesterolemia (FH) is a well-known inherited disorder presenting elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels and premature coronary disease. In this study, we aim to examine the differences in terms of serum markers of cholesterol metabolism between FH and non-FH individuals and to examine their associations with serum lipid levels.<b> </b><b>Methods: </b>In this study, we utilized data on serum markers of cholesterol metabolism, namely, lathosterol (Latho, synthesis marker), campesterol (Campe, absorption marker), and sitosterol (Sito, absorption marker) measured by gas chromatography of the CACHE consortium, which comprised of 13 research groups in Japan. Clinical data were compiled using REDCap system. Among the 2944 individuals in the CACHE population, we selected individuals without lipid-lowering medications and hemodialysis patients for this CACHE study FH analysis. Multivariable adjustment was performed to assess the associations.<b>Results: </b>In this study, we analyzed data from 51 FH patients and 1924 non-FH individuals. After adjustment for possible confounders, the FH group was shown to have significantly higher Campe and Sito concentrations and insignificantly higher Latho concentrations than the non-FH group. These marker concentrations showed nonlinear associations with TC in the FH group. Campe/Latho and Sito/Latho ratios were significantly higher in the FH group than in the non-FH group.<b>Conclusion: </b>FH group had significantly elevated serum Campe and Sito concentrations and insignificantly elevated Latho concentrations; thus, intestinal cholesterol absorption relative to hepatic cholesterol synthesis was suggested to be elevated in patients with FH. Serum Latho, Campe, and Sito concentrations showed nonlinear associations with TC in the FH group.
DOI： 10.5551/jat.63899
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今月の臨床 女性医学から読み解くメタボリック症候群-専門医のための必須知識 最新治療編 肥満に対する最新治療-抗肥満薬の現状と未来 招待あり
上野 浩晶
臨床婦人科産科 76 ( 10 ) 1028 - 1034 2022年10月
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Relationship between Diabetes Mellitus and Serum Lathosterol and Campesterol Levels: The CACHE Study DM Analysis. 査読あり
Matsumura T, Ishigaki Y, Nakagami T, Akiyama Y, Ishibashi Y, Ishida T, Fujii H, Harada-Shiba M, Kabata D, Kihara Y, Kotani K, Kurisu S, Masuda D, Matoba T, Matsuki K, Mori K, Nakazato M, Taniuchi S, Ueno H, Yamashita S, Yoshida H, Yoshida H, Shoji T
Journal of atherosclerosis and thrombosis advpub ( 0 ) 2022年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b>Aim: </b>Risk of cardiovascular disease is increased in patients with diabetes mellitus (DM). Cholesterol metabolism (hepatic synthesis and intestinal absorption) is known to be associated with cardiovascular risk. Next, we examined the association of DM with cholesterol absorption/synthesis.<b> </b><b>Methods: </b>The CACHE Consortium, which is comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured by gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were used for several analyses including this study.<b> </b><b>Results: </b>This study analyzed data from eligible 2182 individuals including 830 patients with DM; 42.2% were female, median age was 59 years, and median HbA1c of patients with DM was 7.0%. There was no difference in Latho between DM and non-DM individuals. Campe and Campe/Latho ratio were significantly lower in DM individuals than in non-DM individuals. When the associations of glycemic control markers with these markers were analyzed with multivariable-adjusted regression model using restricted cubic splines, Campe and Campe/Latho ratio showed inverse associations with glucose levels and HbA1c. However, Latho showed an inverted U-shaped association with plasma glucose, whereas Latho showed a U-shaped association with HbA1c. These associations remained even after excluding statin and/or ezetimibe users.<b> </b><b>Conclusion: </b>We demonstrated that DM and hyperglycemia were independent factors for lower cholesterol absorption marker levels regardless of statin/ezetimibe use.
DOI： 10.5551/jat.63725
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Regulation of feeding and therapeutic application of bioactive peptides 査読あり
Ueno H., Zhang W., Nakazato M.
Pharmacology and Therapeutics 239 108187 - 108187 2022年8月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pharmacology and Therapeutics
Obesity and obesity-related diseases, such as diabetes mellitus and dyslipidemia, are worldwide pandemics; therefore, studies have been conducted energetically to elucidate the mechanism of obesity and develop anti-obesity drugs. Robust progress in the peptide chemistry and molecular biology has identified many peptides that regulate appetite and energy metabolism over the past dozen years. Several drugs, such as analogs or receptor agonists of anorectic peptides, have been developed. Overall, peptide-related drugs have powerful anti-obesity effects with fewer adverse effects than previous anti-obesity drugs. Liraglutide, a glucagon-like peptide-1 receptor agonist, was first used as an antidiabetic drug, and then high-dose liraglutide was used as an anti-obesity drug. Several candidates have been developed to explore their anti-obesity effects. Additionally, hybrid peptides consisting of two or more peptide sequences with strong anorectic effects have been designed. Here, we review peptides that are important for feeding regulation in terms of their mechanisms of action, interactions, and clinical application as anti-obesity drugs.
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Uehira Y., Ueno H., Ebihara E., Uchida T., Nabekura H., Sakoda H., Yonekawa T., Yamaguchi H., Nakazato M.
Journal of Diabetes Investigation 13 ( 6 ) 1011 - 1020 2022年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Diabetes Investigation
Aims/Introduction: The Japanese diabetes treatment guidelines do not specify the first choice of hypoglycemic agents, unlike those of Western countries. Furthermore, the current situation in diabetes treatment is that the choice of hypoglycemic agents is determined by each physician. Therefore, we aimed to determine the current situation in Miyazaki Prefecture, Japan, in this context. For this, we carried out a questionnaire survey among physicians twice regarding the target value of glycated hemoglobin and the choice of hypoglycemic agents in various cases. Materials and Methods: We administered an unsigned questionnaire to physicians in Miyazaki Prefecture, Japan, in July 2016 and March 2020. We divided responses into those of diabetologists and those of non-diabetologists, and analyzed each response. We then compared the results between both years. Results: In total, 18 diabetologists and 142 non-diabetologists responded in 2016, and 21 diabetologists and 134 non-diabetologists responded in 2020. Many diabetologists chose biguanide as the first-line drug for obese type 2 diabetes patients. In addition, the rate of choice of sodium–glucose cotransporter 2 inhibitor (SGLT2i) among physicians almost increased in 2020. Some non-diabetologists, and even a few diabetologists, inappropriately chose SGLT2i and biguanide for patients with severe renal dysfunction. Conclusions: Because SGLT2i became available in 2016 and a few years have passed, both diabetologists and non-diabetologists seemed to refrain from prescribing SGLT2i. However, with the emergence of various lines of firm evidence regarding the use of SGLT2i, physicians started to prescribe it. However, some diabetologists and non-diabetologists chose hypoglycemic agents inadequately; therefore, there is a need for novel and precise information.
DOI： 10.1111/jdi.13750
その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdi.13750
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Shoji T, Akiyama Y, Fujii H, Harada-Shiba M, Ishibashi Y, Ishida T, Ishigaki Y, Kabata D, Kihara Y, Kotani K, Kurisu S, Masuda D, Matoba T, Matsuki K, Matsumura T, Mori K, Nakagami T, Nakazato M, Taniuchi S, Ueno H, Yamashita S, Yoshida H, Yoshida H
Journal of atherosclerosis and thrombosis advpub ( 0 ) 1835 - 1848 2022年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b>Aim: </b>Serum levels of cholesterol absorption and synthesis markers are known to be associated with cardiovascular risk. Individuals with reduced kidney function or chronic kidney disease (CKD) are at an increased risk for cardiovascular disease. Hence, we examined the relationship between estimated glomerular filtration rate (eGFR) and serum markers of cholesterol absorption and synthesis.<b> </b><b>Methods: </b>The CACHE (Cholesterol Absorption and Cholesterol synthesis in High-risk patiEnts) Consortium, comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured via gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were utilized for five analyses including this CKD analysis.<b> </b><b>Results: </b>This study analyzed data from 2200 individuals including 522 hemodialysis patients; 42.3% were female, the median age was 58 years, and the median eGFR was 68.9 mL/min/1.73 m<sup>2</sup>. Latho, Campe, and Campe/Latho ratio were significantly different when compared across CKD stages. When the associations of eGFR with these markers were assessed with multivariable nonlinear regression models, Latho, Campe, and Campe/Latho ratio showed positive, inverse, and inverse associations with eGFR. These associations were significantly modified by sex, the presence/absence of diabetes mellitus, and the presence/absence of statin use.<b> </b><b>Conclusion: </b>We showed that individuals with lower eGFR have lower cholesterol synthesis marker levels and higher cholesterol absorption marker levels in this large sample.
DOI： 10.5551/jat.63311
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高度肥満に対する内科的治療が奏功している例とリバウンド例 招待あり
上野浩晶、中里雅光
Medical Practice 38 1096 - 1101 2021年
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Ueno H., Haraguchi N., Azuma M., Shiiya T., Noda T., Ebihara E., Uehira Y., Uchida T., Sasaba K., Nakamura M., Uchimura N., Kita E., Umemura A., Nobe T., Sumoto E., Yano Y., Nakazato M.
Journal of the American College of Nutrition 42 ( 2 ) 1 - 7 2021年
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of the American College of Nutrition
Objective: Konjac is a food mainly consumed in Asian countries with high fiber and low energy. Although glucomannan, a component of konjac, have been used for several clinical studies, there is few reports using konjac itself. This study examined the effects of the active consumption of konjac in patients with type 2 diabetes mellitus (T2DM). Methods: The study included 26 Japanese patients with T2DM. Participants were recommended to take konjac at least once a day using free konjac products (various noodles, rice, and desserts) and plate konjac for 12 weeks. Results: HbA1c and fasting plasma glucose levels significantly decreased from 8.3 ± 0.9% to 8.0 ± 0.8% and from 173.2 ± 44.4 to 152.8 ± 36.7 mg/dL, respectively. No significant changes were observed in body weight and insulin resistance indices, but the index for insulin secretion significantly increased. Serum high molecular weight adiponectin levels significantly increased. Plasma ghrelin, leptin and glucagon-like peptide-1 levels tended to decrease (p = 0.084), decrease (p = 0.057) and increase (p = 0.071), respectively. Actual konjac intake positively correlated with age (r = 0.61, p = 0.001). Body weight and HbA1c significantly decreased in patients aged ≥50 years than in those aged <50 years, and the changes significantly inversely correlated with age. Conclusion: Active consumption of konjac and konjac products seems to be a useful dietary therapy with multifaceted action for T2DM. Further studies with greater sample size and long-term are needed to confirm these findings.