Liraglutide in polycystic ovary syndrome:a randomized trial, investigating effects on thrombogenic potential

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulinresistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0–7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32–31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01–0.25, P < 0.05) and 0.38 min (95% CI 0.09–0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies

Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity

BACKGROUND: Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). RESULTS: A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or to a control group that was offered diet-related counselling. N-terminal proBNP (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body composition using dual-energy x-ray absorptiometry (DEXA) scanning were determined at baseline and after 52 weeks. Comparisons between groups were analysed using t-tests. Changes from the baseline within the groups were analysed with paired tests. Changes in the variables, delta (∆), were calculated as 52 weeks minus the baseline. In the intervention group, BMI decreased by almost 20% (31.6 ± 6.2 vs. 37.1 ± 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5 ± 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased (from 55 ± 31 to 97 ± 55 pg/ml; P < 0.001, and from 59 ± 21 to 74 ± 26 pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 ± 153 to 534 ± 173 pmol/L; P <0.001). Changes (Δ) in MR-proANP correlated with Δfat mass (r = −0.359; P = 0.011) and Δglucose (r = −0.495; P <0.001), while increases in NT-proBNP were primarily associated with reduced plasma glucose (r = −0.462; P <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the control group with no changes in plasma concentrations of NT-proBNP or MR-proANP, and a minor change in MR-proADM. CONCLUSIONS: Plasma NT-proBNP and MR-proANP concentrations increase and MR-proADM concentration decreases during weight loss, underlining the dynamic impact of BMI, body composition and glucose metabolism on these cardiovascular biomarkers

Evaluation of ICD-10 algorithms to identify hypopituitary patients in the Danish National Patient Registry

OBJECTIVE: Routinely collected health data may be valuable sources for conducting research. This study aimed to evaluate the validity of algorithms detecting hypopituitary patients in the Danish National Patient Registry (DNPR) using medical records as reference standard. STUDY DESIGN AND SETTING: Patients with International Classification of Diseases (10th edition [ICD-10]) diagnoses of hypopituitarism, or other diagnoses of pituitary disorders assumed to be associated with an increased risk of hypopituitarism, recorded in the DNPR during 2000–2012 were identified. Medical records were reviewed to confirm or disprove hypopituitarism. RESULTS: Hypopituitarism was confirmed in 911 patients. In a candidate population of 1,661, this yielded an overall positive predictive value (PPV) of 54.8% (95% confidence interval [CI]: 52.4–57.3). Using algorithms searching for patients recorded at least one, three or five times with a diagnosis of hypopituitarism (E23.0x) and/or at least once with a diagnosis of postprocedural hypopituitarism (E89.3x), PPVs gradually increased from 73.3% (95% CI: 70.6–75.8) to 83.3% (95% CI: 80.7–85.7). Completeness for the same algorithms, however, decreased from 90.8% (95% CI: 88.7–92.6) to 82.9% (95% CI: 80.3–85.3) respectively. Including data of hormone replacement in the same algorithms PPVs increased from 73.2% (95% CI: 70.6–75.7) to 82.6% (95% CI: 80.1–84.9) and completeness decreased from 94.3% (95% CI: 92.6–95.7) to 89.7% (95% CI: 87.5–91.6) with increasing records of E23.0x. CONCLUSION: The DNPR is a valuable data source to identify hypopituitary patients using a search criteria of at least five records of E23.0x and/or at least one record of E89.3x. Completeness is increased when including hormone replacement data in the algorithm. The consequences of misclassification must, however, always be considered

Galectin-3 and fibulin-1 in systolic heart failure:relation to glucose metabolism and left ventricular contractile reserve

Abstract Background Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserve in these patients. Methods A total of 155 patients with HF with reduced ejection fraction underwent a low-dose dobutamine echocardiography and blood sampling for biomarker measurements. Patients were classified according to history of DM and an oral glucose tolerance test (OGTT) as: normal glucose tolerance (NGT) ( n \u2009=\u200970), impaired glucose tolerance (IGT) ( n \u2009=\u200925) and DM ( n \u2009=\u200960). Results Galectin-3 levels were elevated in DM patients as compared to non-diabetic patients ( P \u2009=\u20090.02), while higher fibulin-1 levels were observed in HF patients with IGF and DM ( P \u2009=\u20090.07). Reduced LV contractile reserve was associated with increasing Gal-3 levels (\u3b2\u2009=\u2009\u22120.19, P \u2009=\u20090.03) although, this association was attenuated after adjustment for estimated glomerular filtration rate ( P \u2009=\u20090.66). Fibulin-1 was not associated with LV contractile reserve ( P \u2009=\u20090.71). Conclusions Galectin-3 and fibulin-1 levels were elevated in HF patients with impaired glucose metabolism. However, reduced LV contractile reserve among HF patients with DM does not to have an independent impact on plasma Gal-3 and fibulin-1 levels

Participation in introductory APIB training at the Colorado NIDCAP Center-Report on the training and its applicability to future studies-

本研修の目的は,新生児・早産児行動評価(Assessment of Term and Preterm Infant Behavior:APIB 1))を研究に活用するため,その具体的な方法を学ぶことであった.今回,国際NIDCAP®連盟(Newborn Individualized Developmental Care and Assessment Program FederationInternational:NFI)が認定する公式のトレーニング施設,Colorado NIDCAPセンターにおいて,2013年9月7日～8日の2日間,APIBの導入研修に参加する機会を得た.NFIは米国マサチューセッツ州ボストンに本部を置き,北米,南米,ヨーロッパに20のトレーニング施設を認定し,包括的で質の高いトレーニングとコンサルテーションの機会を提供している.APIBは,正期産児を対象とする新生児行動評価(Neonatal Behavioral Assessment Scale:NBAS 2))を,早産児と発達上のリスクを持つ新生児に適合するように開発された評価法であり,新生児と観察者の相互作用を通して,中枢神経系の組織化の状態と受け入れられる刺激を評価し,発達の評価や発達支援の方策を考案するために用いられている.APIBを研究に活用する際は,評価者としての認定が必要であり,トレーニングは「準備の段階」「導入トレーニング」「自主トレーニングおよび指導者との調整(中間評価)」「信頼性の評価」の4段階からなる.今回参加した導入研修では,APIBの基盤となる理論と実際の評価法を学び,評価の進め方とスコア化の基準を理解するとともに,早産児の現在の状態と受け入れられる刺激を評価することの重要性を知ることができた.本稿では,研修内容および今後の研究への活用性について報告する