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

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

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