Greater Efficacy and Improved Endothelial Dysfunction in Untreated Type 2 Diabetes with Liraglutide versus Sitagliptin

Objective:The incretin hormone glucagon-like peptide 1 (GLP-1) and its analogs, including the glucagonlike peptide 1 receptor agonist liraglutide, use a simple once-daily regimen and can be easily introduced in the outpatient setting. We compared treatment with liraglutide monotherapy and dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy in patients with untreated type 2 diabetes( T2DM).Methods:This study included 40 outpatients with untreated T2DM who were randomized to receive liraglutide (0.9 mg/day, n=24) or DPP-4 inhibitors (n=16:sitagliptin, 50 mg/day) as initial treatment for 6 months. Glycemic control, urinalysis, blood pressure, body weight, lipid levels, vascular endothelial function, and inflammatory factors were assessed before and after treatment.Results:Significant improvement was observed in HbA1c and fasting blood glucose levels after treatment in both groups;improvements in the liraglutide group were significantly better than in the sitagliptin group. Only the liraglutide group demonstrated significant improvements in blood pressure, low-density lipoprotein cholesterol levels, urinary albumin excretion, flow-mediated dilatation, and high-sensitivity C-reactive protein levels. Linear regression analysis demonstrated a significant negative relation between change in flow-mediated dilatation and high-sensitivity C-reactive protein levels.Conclusion:Liraglutide provided significant glycemic control and improved blood pressure, lipid levels, endothelial function, and inflammatory factors in untreated T2DM. In addition to its impact on blood glucose levels, liraglutide may have beneficial effects on the cardiovascular system in patients with T2DM

Effect of Poly (ADP-ribose) Polymerase Inhibitors on Hypoadiponectinemia Caused by Chronic Blockade of Nitric Oxide Synthesis in Rats

Oxidant stress-induced activation of poly (ADP-ribose) polymerase (PARP) contributes to the pathogenesis of various cardiovascular diseases. Adiponectin is an adipocyte-derived anti-atherogenic protein. In the present study, we investigated the role of PARP in the development of hypoadiponectinemia caused by chronic blockade of nitric oxide synthesis with N^ω-nitro-L-arginine methyl ester (L-NAME) in rats. Decreased production of NO and increased production of O_2^- were observed in aortas from L-NAME-treated rats. Plasma adiponectin levels and adiponectin mRNA levels within adipose tissue were markedly decreased in L-NAME-treated rats. Concurrent administration of potent PARP inhibitors, INO-1001 or PJ34, with L-NAME did not restore plasma adiponectin levels or fat adiponectin mRNA levels. Thus, the cardiovascular protective effects of PARP inhibitors are not associated with adiponectin levels. Therefore, drugs which increase adiponectin levels may be beneficial alongside PARP inhibitors in the treatment of cardiovascular disease

HMG-CoA Reductase Inhibitors Suppress High Glucose-induced Excessive O2⁻ production in J-774 Cells

Statins (HMG-CoA reductase inhibitors) have so-called pleiotropic effects, which directly reduce neoinitial inflammation of atherosclerosis, and one possible mechanism is the attenuation of oxidative stress. Although an increase in oxidant stress is suggested to cause and aggravate arteriosclerosis in diabetes, the origin of oxidant stress and effects of statins on the oxidant stress in diabetes are not clearly delineated. We evaluated in this study the effect of high glucose on superoxide anion (O_2^-) production in the J-774 macrophage-like cell line, and the effect of various statins (cerivastatin, fluvastatin, and nisvastatin) on it. The basal and 12-O-tetradecanoylphor-bol 13-acetate (TPA)-stimulated O_2^- productions were measured by chemiluminescence (CL) amplified with a Cypridina luciferin analog. Both basal CL and TPA-stimulated CL (TPA-CL) in J-774 cells cultured with high glucose were apparently increased in dose and time dependent manners, and the increments were clearly suppressed by a NADPH oxidase inhibitor (diphenyleneiodonium chloride) or a protein kinase C inhibitor (GF-109803 X). Three statins significantly inhibited the high glucose-induced excessive O_2^- production in a dose dependent manner. Furthermore, co-incubation with mevalonic acid and the metabolites, geranylgeranyl pyrophosphate and farnesyl pyrophosphate, partially prevented the statin-induced suppression of TPA-CL. These data suggest that in J-774 cells high glucose causes excessive O_2^- production through NADPH oxidase and protein kinase C pathways, and statins suppress the excessive O_2^- generation. This effect of statins could be, in part, dependent on the inhibition of synthesis of isoprenoid intermediates. Statins may be useful as a drug to prevent arteriosclerosis by inhibiting oxidative stress in poorly controlled diabetic patients

Smart Industrial Metabolism: a literature review and future directions

Corporate and academic interest in the concept of industrial metabolism has risen considerably in recent years. This can be observed in the number of papers published. In order to go deep into current and future trends in this field, the paper objective is multiple. Firstly, the purpose of this paper is to carry out a literature review on industrial metabolism. Secondly, this paper offers a summary of the research in this field, performing a descriptive analysis based on identifying temporal distribution of publications, journals in which papers are published and classifying different applications of industrial metabolism concept. Thus, this paper seeks to provide a review of the main approaches to industrial metabolism. Finally, an overview of immense opportunities for the implementation of industrial metabolism based on Industry 4.0 is presented

コウジョウセン クリーゼ 20レイ ノ チリョウ ト ヨゴ : コウジョウセン クリーゼ シンダン キジュン オ モチイタ ケントウ

日本甲状腺学会から甲状腺クリーゼの診断基準が2008 年に発表された.2004 年4 月から2009 年3月に当院で臨床的に甲状腺クリーゼと診断,治療した20 症例を,その診断基準にあてはめ,治療と予後等について解析した.基礎疾患は全例バセドウ病だった.誘因として服用不規則や中断が9 例,感染症6 例,糖尿病性ケトアシドーシス3 例,情動ストレス2 例,脳血管障害1 例,外傷1 例だった.診断基準で確定診断例が15例,疑い例が1 例,除外症例が4 例だった.症状では中枢神経症状が疑い・確定診断例では11 例,脈拍130/分以上は12 例認められたが,除外例では認められなかった.治療としてはチアマゾールが全症例に使用されていた.ヨードは13 例,b ブロッカーは17 例,ステロイドは12 例の症例で使用されており全例救命できた.服用不規則や中断,感染症が誘引となりやすく,症状では中枢神経症状・脈拍が特にクリーゼの診断には重要と考えられた.後遺症を残す重症例は6 例で全て新診断基準によって確定診断された症例であり,新診断基準は予後への有用性も期待できると考えられた.The Japan Thyroid Association established diagnosticcriteria for thyroid crisis in 2008. Using these criteria, weanalyzed 20 cases clinically diagnosed as thyroid crisis andtreated in our hospital from April 2004 to March 2009. Allpatients had Basedow\u27s disease at the basal disease. Thecauses were irregular compliance or interruption of treatment(9 cases), infection (6 cases), diabetic ketoacidosis (3cases), emotional stress( 2 cases), stroke( 1 case), and trauma(1 case). Fifteen cases were confirmed as thyroid crisis,1 case was suspected as thyroid crisis, and 4 cases were rejectedas thyroid crisis according to the diagnostic criteria.Central nervous symptoms were observed in 11 cases, andtachycardia (over 130 beats/min) in 12 cases in the definitiveand suspicious cases, although there were no centralnervous symptoms or tachycardia in the excluded cases.Thiamazole was administered to all patients. In addition, iodine(13 cases), b -blocker (17 cases), and corticosteroids(12 cases) were administered. All patients were recovered.Irregular internal use, stopping treatment, and infectionwere likely to induce thyroid crisis. In paticular, centralnervous symptoms and tachycardia were important factorsfor diagnosis. As 6 serious cases with aftereffect were diagnosedas definitive cases of thyroid crisis according to thenew criteria, these new criteria may be useful to predictthe prognosis

コウレイシャ 2 ガタ トウニョウビョウ カンジャ ニ オケル ニンチ キノウ チョウサ ト ソノ カンレン インシ ニ ツ イテ

目的:2型糖尿病は,認知症発症との関連が報告されている.そこで実際の高齢者2型糖尿病患者において,認知機能が低下している患者の頻度を調査し,また認知機能に影響を与える因子を検討した.方法:2014年2月?4月の間に,入院加療を行った糖尿病多発合併症や心血管病の既往がない2型糖尿病患者64名のうち,60歳以上の高齢者で,臨床研究に同意した35名(男性:23名,女性:12名)を対象とし,Mini-Mental State Examination(MMSE)にて認知機能を評価した.認知機能(MMSE score)と年齢,血糖コントロール(HbA1c),血圧,脂質,喫煙歴,糖尿病罹患歴,動脈硬化の指標として,Cardio Ankle Vascular Index(CAVI)に対する相関を検討した.結果:高齢者糖尿病のうち31.4%に認知機能の低下が疑われた.またそれは,年齢,糖尿病罹患歴,CAVI値にMMSE値は単相関を認め,重回帰分析では,糖尿病罹患歴とCAVI値が有意な影響を与えている因子であった.結論:高齢者2型糖尿病における認知機能は,罹患歴や動脈硬化が影響を与える事が示唆され,中年期からの糖尿病管理や動脈硬化抑制が老年期の認知機能障害の発生と関連する可能性が示唆された.Objective:Type 2 diabetes is reportedly associated with the risk of developing dementia. Hence, we surveyed elderly patients with type 2 diabetes to investigate the actual level of cognitive function decline and examine factors that affect cognitive function. Methods:From among 64 patients with type 2 diabetes who underwent inpatient treatment in the Department of Endocrinology and Metabolism of Dokkyo Medical University between February and April 2014, we selected as study subjects 35 patients aged ? 60 years(23 men and 12 women)who had no history of multiple diabetic complications or cardiovascular disease. The Mini-Mental State Examination(MMSE)was used to assess cognitive function. The correlations of cognitive function(MMSE score) with age, glycemic control(HbA1c), blood pressure, fat, smoking, diabetes history, and cardio-ankle vascular index (CAVI)as an index of arteriosclerosis were investigated. Results:Cognitive function decline was suspected in 31.4% of the elderly patients with diabetes. Simple correlations were found between MMSE score and age, diabetes history, and CAVI score. In particular, diabetes history and CAVI score were identified as significant risk factors in a multivariate analysis. Conclusion:Our results suggest that disease history and arteriosclerosis may affect the cognitive function of elderly patients with type 2 diabetes, and that diabetes management and arteriosclerosis control from middle age may be associated with cognitive function in old age

バセドウ ビョウ ト ハカイセイ コウジョウセン エン ノ ショシンジ ニオケル ジンソク カンベツホウ

[目的]バセドウ病 (GD) と破壊性甲状腺炎 (DT) の迅速鑑別法にはTSHレセプター抗体の有無,甲状腺エコー検査,遊離T3/T4 (FT3/FT4),総T3/T4比 (T3/T4),総ALP (T-ALP),甲状腺血流が有用とされている.そのうち最も鋭敏な指標となりうる項目を検討した.[方法]2007年から未治療で当科を受診したGD:15名,無痛性甲状腺炎(PT):8名,亜急性甲状腺炎( SAT):10名( DT:18名) を対象として,FT3/FT4,T3/T4,T-ALP,上甲状腺動脈平均血流速度( mean velocity STA) を測定した.[結果]年齢:GD51.2± 18.8歳,DT49.3±21.0歳,FT3/FT4:GD3.3±1.0,DT2.9±1.9,T3/T4:GD15.9±4.7,DT15.2± 3.3,T-ALP( U/l):GD431.3 ±196.6,DT299.1±163.2,mean velocitySTA( cm/s):GD65.0±8.7,DT41.0± 7.0,(P < 0.0001).[結論]今回の検討ではmean velocity STA がGD とDT の鑑別に最も有用であった.It is important to make a rapid differentialdiagnosis of Graves\u27Diseases (GD) and Destructive Thyroiditis(DT). However, it is often difficult to make a distinctionwithout measurement of radioactive iodine uptake(RAIU). Instead of measurement of RAIU, measuringFreeT3/FT4ratio (FT3/FT4), totalT3/T4ratio (T3/T4),total alkaline phosp hatase activity( T-ALP), blood flow inthe thyroid, is useful for differential diagnosis. We searchedfor the parameters is most sensitive parameter for rapiddifferential diagnosis.Patients and Methods:We investigated on 33 patientswith untreated hyperthyroidism (15 with GD and 18 withDT). When 33 patients were first seen in our hospital, wemeasured FT3/FT4, T3/T4, T-ALP, and mean velocity inthe superior thyroid arteries( STA).Results:In comparison between GD and DT, mean velocitySTA was significantly increased in patients with GD.In the group of GD, FT3/FT4 and T-ALP tend to be higherin patients with GD but without statistical significance.Conclusion:Mean velocity STA might be the most sensitiveparameter for rapid differential diagnosis of GD andDT

トウイン ニオケル コウ カルシウム ケッショウ ノ ビョウイン・ビョウタイ ノ カイセキ ト チリョウ : コウ カルシウム ケッショウ クリーゼ モ フクメテ

獨協医科大学病院内分泌代謝内科に関連する過去6 年間の入院患者の内,高Ca 血症を呈した91 例について,その病因,病態と治療について検討した.原発性副甲状腺機能亢進症67 例(73.6%),慢性腎不全に伴う三次性副甲状腺機能亢進症10 例(11.0%),腫瘍随伴性高Ca 血症6 例(6.6%),VitD/Ca 過量投与4 例(4.4%),バセドウ病4 例(4.4%)であった.平均年齢は61 歳で,男性27 例に対し女性64 例であった.これら5 群間における血清補正Ca(cCa)値に差はなかったが,血清P 値は慢性腎不全による三次性副甲状腺機能亢進症が最も高く,バセドウ病,VitD/Ca 過量投与,腫瘍随伴性高Ca 血症,原発性副甲状腺機能亢進症の順に低下した.慢性腎不全例を除く4 群において,血清補正Ca(cCa)値あるいはcCaxP 値と血清creatinine(Cr)との間には,有意な正相関が認められた.原発性副甲状腺機能亢進症の内48 例は副甲状腺摘出術を受けたが,19 例は内科的治療や経過観察となった.手術群の方が年齢が若く,血清cCa 値が高く,またintact PTH(iPTH)も高値を示していた.三次性副甲状腺機能亢進症10 例の内3 例は,副甲状腺摘出,自家移植を受けた.腫瘍随伴性高Ca 血症6 例の内PTH-related protein(PTHrP)高値を示すhumoral hypercalcemia of malignancy(HHM)が4 例,local osteolytic hypercalcemia (LOH)が1 例及び両機序による混合型1 例であった.VitD/Ca 過量投与は薬剤中止あるいは減量投与により軽快し,バセドウ病は甲状腺ホルモン低下に伴い正常化した.高Ca 血症91 例中8 例(8.8%)は血清cCa 値が14.5 mg/dl を超える高Ca 血症クリーゼであり,原発性副甲状腺機能亢進症6 例,腫瘍随伴性高Ca 血症1 例,VitD/Ca 過量投与1 例であった.クリーゼに対する緊急的また積極的治療により7 例は軽快したが,原発性副甲状腺機能亢進症の1 例は治療抵抗性で,最終的には心室細動を起こし死亡した.高Ca 血症クリーゼの死亡率は8 例中1 例で12.5%,原発性副甲状腺機能亢進症に起因する例に限れば高Ca 血症クリーゼは67 例中6 例で9.0%,その死亡率は6 例中1 例で16.7%であった.本研究は91 名に及ぶ,高Ca 血症の患者を対象としており,このような報告は本邦では貴重である.さらに各病態において詳細な解析を行っており,今後の高Ca 血症の病態把握や,重症度判定に本研究は極めて有用であると考えられた.高Ca 血症を認めた場合には,その成因,病態について迅速かつ十分な検討を行い,必要に応じた適切な治療を早期に行うことが重要である.The aim of the present study is to investigate the etiology,clinical features and treatment of hypercalcemia and itscrisis among inpatients during 6 years, from May 2005 toApril 2011, admitted to the Department of Endocrinologyand Metabolism in Dokkyo Medical University Hospital.Ninety-one patients were diagnosed with hypercalcemiawhich consisted of 67 cases (72.6 %) with primary hyperparathyroidism,10 cases( 11.0%) with tertiary hyperparathyroidismdue to chronic renal failure, 6 cases (6.6%) ofhypercalcemia associated with malignant tumors, 4 cases(4.4 %) with over dosages of VitD/Ca and 4 cases (4.4 %)with untreated Basedow\u27s disease. The mean age of 91 patientswas 61 years old which consisted of 27 males (29.7%) and 64 females( 70.3%). There were no significant differencein serum corrected Ca (cCa) levels among the 5groups, but serum inorganic phosphate( P) levels were significantlydifferent. The highest values were obtained intertiary hyperparathyroidism and the lowest values were inprimary hyperparathyroidism. Among the 4 groups exceptfor tertiary hyperthyroidism, there are significant correlationbetween serum levels of cCa and creatinine (Cr) andalso between the product of cCa and P (cCa x P) and serumlevels of Cr. These results strongly suggest that thehigher cCa and cCa x P levels may get worse renal dysdysfunction.The number of patients of hypercalcemic crisis showingserum cCa levels over 14.5 mg/dl were 8 (8.8 %) cases in91 hypercalcemic cases, which consisted of 6 with primaryhyperparathyroidism, 1 with tumor-associated hypercalcemiaand 1 with VitD/Ca over dosages. After the early diagnosis,7 patients were relieved according to the intensivetherapy for the crisis such as adequate hydration with normalsaline, administration of furosemide, calcitonin and bisphosphonate.However, 1 patient with primary hyperparathyroidismshowing extremely high iPTH level(3891 pg/ml) was resistant to these therapies and even to hemodialysiswith Ca-free dialysate, and finally died from ventricularfibrillation. The mortality was 12.5 % among 8 patients withcrisis, and 16.0 % among 6 patients with crisis due to primaryhyperparathyroidism.From the present study, it is suggested that the etiologyand severity of hypercalcemia is fully diagnosed and an appropriatemanagement should be performed

Management of acute mesenteric ischaemia: Results of a worldwide survey

Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide. Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected. Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity. Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes

221 Newborn-Screened Neonates with Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency: Findings from the Inborn Errors of Metabolism Collaborative

Introduction: There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods: Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism-Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results: The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcamitine (C8) value on first newborn screen was 11.2 mu mol/L (median 8.6, range 036-43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A\u3eG ACADM gene mutation or compound heterozygous for the c.985A\u3eG mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A\u3eG ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. Conclusions: This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system. (C) 2016 Elsevier Inc. All rights reserved