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論文 - 池ノ上　学

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Association between supraclavicular brown adipose tissue composition at birth and adiposity gain from birth to 6 months age

Entringer, S., Rasmussen, J., Cooper, D. M., Ikenoue, S., Waffarn, F., Potkin, S. G., Wadhwa, P. D. and Buss, C.

Pediatr Res 2017年07月

ISSN 0031-3998

BACKGROUND: Brown Adipose Tissue (BAT) is associated with higher energy expenditure and lower adiposity in adults. However, the relationship between BAT composition and adiposity in early life is unknown. The objective of this study was to test the hypothesis that brown fat composition at birth is prospectively associated with adiposity gain during the first six months of postnatal life. METHODS: N=35 healthy infants were followed prospectively from intrauterine life and birth through 6 months age. Dixon MRI scans were conducted during the neonatal period to characterize supraclavicular BAT composition. Dual-energy X-ray absorptiometry to assess total body composition was performed within the first month of life and at 6 months age. RESULTS: After adjusting for potential confounding factors, a more brown-like composition (smaller fat fraction) of the supraclavicular BAT depot was associated with a smaller increase in percent body fat over the first six months of postnatal life. CONCLUSIONS: A more brown-like BAT composition at birth appears to be protective against excess adiposity gain in early life. Newborn BAT tissue may constitute a target for prevention strategies against the subsequent development of obesity.Pediatric Research accepted article preview online, 19 July 2017. doi:10.1038/pr.2017.159.

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Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis

Kasuga Y., Miyakoshi K., Nishio H., Akiba Y., Otani T., Fukutake M., Ikenoue S., Ochiai D., Matsumoto T., Tanaka K., Minegishi K., Kuji N., Roberts R., Aoki D., Tanaka M.

BJOG: An International Journal of Obstetrics and Gynaecology （BJOG: An International Journal of Obstetrics and Gynaecology） 124 （ 11 ） 1729 - 1735 2017年04月

ISSN 1471-0528

© 2017 Royal College of Obstetricians and Gynaecologists Objective: To investigate the association between mid-trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT). Design: Retrospective cohort study. Setting: University hospital. Population: A total of 33 deliveries after 22 weeks’ gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016. Methods: The association between mid-trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver–operating characteristics (ROC) curve analysis was performed to estimate the optimal cut-off values of the mid-trimester residual CL for the prediction of preterm birth. Main outcome measures: Preterm birth before 34 weeks’ gestation. Results: Mid-trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75). Conclusions: Mid-trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT. Tweetable abstract: Mid-trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.

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Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy

Kasuga Y., Miyakoshi K., Nishio H., Akiba Y., Otani T., Fukutake M., Ikenoue S., Ochiai D., Matsumoto T., Tanaka K., Minegishi K., Kuji N., Roberts R., Aoki D., Tanaka M.

BJOG: An International Journal of Obstetrics and Gynaecology 2017年

ISSN 1470-0328

Objective: To investigate the association between mid-trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT). Design: Retrospective cohort study. Setting: University hospital. Population: A total of 33 deliveries after 22 weeks' gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016. Methods: The association between mid-trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver-operating characteristics (ROC) curve analysis was performed to estimate the optimal cut-off values of the mid-trimester residual CL for the prediction of preterm birth. Main outcome measures: Preterm birth before 34 weeks' gestation. Results: Mid-trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75). Conclusions: Mid-trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT. Tweetable abstract: Mid-trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.

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Clinical impact of women with gestational diabetes mellitus by the new consensus criteria

Ikenoue Satoru, Miyakoshi Kei, Saisho Yoshifumi, Sakai Kensuke, Kasuga Yoshifumi, Fukutake Marie, Izumi Yoko, Matsumoto Tadashi, Minegishi Kazuhiro, Yoshimura Yasunori

Endocrine Journal 61 （ 4 ） 353 - 358 2014年

ISSN 0918-8959

There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values (2/3-AV) needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P<0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists.

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Clinical impact of women with gestational diabetes mellitus by the new consensus criteria: Two year experience in a single institution in Japan

Ikenoue S., Miyakoshi K., Saisho Y., Sakai K., Kasuga Y., Fukutake M., Izumi Y., Matsumoto T., Minegishi K., Yoshimura Y.

Endocrine Journal （Endocrine Journal） 61 （ 4 ） 353 - 8 2014年

ISSN 0918-8959

There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values (2/3-AV) needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P<0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists. © The Japan Endocrine Society.

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Complete chorion-amnion separation presenting as a stuck fetus

Kasuga Yoshifumi, Miyakoshi Kei, Ikenoue Satoru, Kadohira Ikuko, Matsumoto Tadashi, Minegishi Kazuhiro, Yoshimura Yasunori

Acta Obstetricia et Gynecologica Scandinavica 92 （ 8 ） 990 - 991 2013年08月

ISSN 0001-6349

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Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women

Saisho Y., Miyakoshi K., Ikenoue S., Kasuga Y., Matsumoto T., Minegishi K., Yoshimura Y., Itoh H.

Endocrine Journal （Endocrine Journal） 60 （ 4 ） 533 - 539 2013年

ISSN 0918-8959

The aim of this study is to investigate glucose metabolism longitudinally during pregnancy to explore mechanisms underlying gestational diabetes mellitus (GDM). We reviewed a total of 62 pregnant Japanese women who underwent a 75g oral glucose tolerance test (OGTT) twice during pregnancy (median: early, 13; late, 28 weeks' gestation) because of positive GDM screening. All showed normal OGTT results in early pregnancy. Based on late OGTT, 15 had GDM (late- onset GDM) and 47 normal glucose tolerance (NGT). In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [ISOGTT] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUCins/glu] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups. In each group, insulin sensitivity significantly decreased from early to late pregnancy, most in the late-onset GDM group (each p < 0.05). The insulin secretion showed no significant changes with advancing pregnancy in both of the groups, although late-onset GDM showed significantly lower IGI compared with NGT in late OGTT (p < 0.05). When assessed beta cell function by OGTT-derived disposition index (i.e. Insulin Secretion-Sensitivity Index-2 and IGI/fasting insulin), the indices significantly decreased from early to late pregnancy in the both groups (each p < 0.05). Women with late-onset GDM showed significantly lower indices compared with NGT (each p < 0.05). The failure of beta cell to compensate for decreased insulin sensitivity could contribute to the development of the late-onset GDM. © The Japan Endocrine Society.

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroidstimulating hormone receptor antibody after ablative therapy

Matsumoto T., Miyakoshi K., Saisho Y., Ishii T., Ikenoue S., Kasuga Y., Kadohira I., Sato S., Momotani N., Minegishi K., Yoshimura Y.

Endocrine Journal （Endocrine Journal） 60 （ 12 ） 1281 - 1287 2013年

ISSN 0918-8959

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure. ©The Japan Endocrine Society.

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当院における新診断基準導入後の妊娠糖尿病の臨床像に関する検討

池ノ上学, 宮越敬, 税所芳史, 春日義史, 門平育子, 松本直, 峰岸一宏, 吉村泰典

糖尿病と妊娠（(一社)日本糖尿病・妊娠学会） 13 （ 1 ） 80 - 83 2013年

ISSN 1347-9172

既報の新基準妊娠糖尿病(GDM)の臨床像は、旧基準でのデータベース解析をもとに推測されたものが多く、基準改定後の実際の臨床像に関して十分な知見は得られていない。そこでわれわれは、基準改定後に当院にて妊娠初期から周産期管理を行った単胎妊婦853例を対象に、GDMの臨床像について後方視的検討を行った。853例中GDM例は101例(11.8%)、overt diabetesは3例(0.3%)であった。さらに経口糖負荷試験(OGTT)陽性ポイント数に関して、OGTT 1点陽性例は69例(68%)、2点/3点陽性例は32例(2点陽性例:24例、3点陽性例:8例)であった。また101例中55例は妊娠初期スクリーニングにて検出された。分娩までの血糖コントロールに関して、OGTT 1点陽性例に比べてOGTT 2点/3点陽性例のインスリン導入率は有意に高値であった(20%vs.84%、p<0.05)。なお、OGTT 1点陽性例のなかでは、糖尿病家族歴を有する場合にインスリン療法を要する頻度が高率であった。本検討により、OGTT 1点陽性例はGDMの過半数を占めることが示され、糖尿病家族歴を有するOGTT 1点陽性例では、インスリン療法を要する可能性を念頭においた周産期管理が必要と考えられた。(著者抄録)

Beta cell dysfunction and its clinical significance in gestational diabetes

Saisho Yoshifumi, Miyakoshi Kei, Tanaka Mamoru, Shimada Akira, Ikenoue Satoru, Kadohira Ikuko, Yoshimura Yasunori, Itoh Hiroshi

Endocrine Journal （JAPAN ENDOCRINE SOC） 57 （ 11 ） 973 - 980 2010年

ISSN 0918-8959

The aim of this study is to explore beta cell dysfunction and its clinical significance in gestational diabetes mellitus (GDM). We assessed insulin sensitivity and insulin secretion in a total of 277 Japanese women between 24 and 27 weeks of pregnancy who underwent a 2 h, 75 g oral glucose tolerance test (OGTT) because of an abnormal result on a 1 h 50 g oral glucose challenge conducted as part of a standard screening for GDM. Insulin sensitivity was evaluated by an insulin sensitivity index derived from OGTT (IS_OGTT), whereas insulin secretion was calculated as a ratio of the total area under the insulin curve to the total area under the glucose curve (AUC_ins/glu). Beta cell function in relation to insulin sensitivity (i.e. disposition index) was derived from the product of insulin sensitivity and insulin secretion (i.e. AUC_ins/glu × IS_OGTT). In women diagnosed with GDM (n=57), the disposition index was significantly lower than that in those without GDM, irrespective of obesity. The disposition index in women with GDM was significantly correlated with levels of fasting and mean preprandial capillary glucose and HbA1c before initiating insulin therapy (r = -0.45, -0.38, -0.49, respectively). Furthermore, there was a significant correlation between the disposition index and total insulin dosage to achieve glycemic goal (r = -0.41). In conclusion, we demonstrated beta cell dysfunction in Japanese women with GDM irrespective of obesity. The level of beta cell dysfunction in GDM was associated with the severity of glucose intolerance and total insulin dosage required. These findings underpin clinical significance of beta cell dysfunction in GDM.

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