scholarly journals A16 FIBER SUPPLEMENTATION DIFFERENTIALLY MODULATES RESPONSES TO FECAL MICROBIAL TRANSPLANTATION IN PATIENTS WITH METABOLIC SYNDROME AND SEVERE OBESITY: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT TRIAL

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 20-21
Author(s):  
V Mocanu ◽  
Z Zhang ◽  
E Deehan ◽  
K Samarasinghe ◽  
N Hotte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Dietary Intake ◽  
Primary Outcome ◽  
Linear Mixed Model ◽  
Severe Obesity ◽  
Pilot Trial ◽  
Model Assessment ◽  
Double Blind

Abstract Background Fecal microbial transplantation (FMT) from lean donors to obese patients with metabolic syndrome (MS) has been associated with promising yet short-term metabolic improvements. The concept of using dietary or fiber supplementation to enhance effects induced by FMT has been much discussed in the literature, but to date no human trials have examined this concept. Aims The aim of this study was to determine if fiber supplementation following FMT was able to enhance or sustain FMT-mediated metabolic benefits. Methods We performed a 12-wk double-blind randomized placebo-controlled trial in patients with severe obesity and MS recruited from Edmonton’s Bariatric Clinic from 2018 to 2019. Patients were stratified by sex and block randomized 1:1:1:1 amongst one of four groups: (1) Placebo FMT and a non-fermentable fiber (NF) (2) Placebo FMT and fermentable fiber (FF); (3) FMT and non-fermentable fiber (FMT-NF); and (4) FMT and fermentable fiber (FMT-FF). Patients received a single dose of FMT (50g donor stool) with 20 oral capsules followed by a 6-wk period of daily fiber. The primary outcome was evaluating mean differences (MD) in insulin sensitivity from baseline to 6-wks using the homeostatic model assessment of insulin resistance (HOMA2-IR). Results Sixty-eight patients were randomized with 61 completing the primary outcome (NF = 17; FF = 15; FMT-NF = 14; FMT-FF = 15) and evaluated using a modified intent-to-treat analysis. Baseline characteristics were similar with a mean BMI 45 ± 7 kg/m2, a female predominance (83.6%), and a HOMA2-IR of 3.43 ± 2.2. There were no baseline differences in clinical characteristics, metabolic parameters, medications, or dietary intake. FMT-NF had improvements in HOMA2-IR (MD -24.0% ± 12.0%; p=0.02), insulin sensitivity (MD 27.6% ± 12.3%; p=0.02), and insulinemia (MD -25.4% ± 12.3%; p=0.02) from baseline to 6-wks (Figure 1). These benefits were associated with increased microbial richness and improvements in GLP-1 metabolism. Linear mixed model regression revealed that select bacterial taxa including Phascolarctobacterium, Ruminococcaeceae, and B. stercoris correlated with increased insulin sensitivity. Findings occurred in the absence of changes in anthropometric parameters, dietary intake, medication regimen and were not observed in groups receiving fermentable fiber or in any group following cessation of fiber. Conclusions This proof-of-concept trial provides evidence that a single FMT dose combined with daily non-fermentable fiber supplementation can successfully improve insulin resistance in patients with metabolic syndrome and severe obesity on optimized medical therapy. Funding Agencies W. Garfield Weston Foundation

scholarly journals A Possible Role for Pioglitazone in the Management of Depressive Symptoms in Metabolic Syndrome Patients (EPICAMP Study): A Double Blind, Randomized Clinical Trial

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hamidreza Roohafza ◽  
Pedram Shokouh ◽  
Masoumeh Sadeghi ◽  
Zahra Alikhassy ◽  
Nizal Sarrafzadegan
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
General Health Questionnaire ◽  
Depression Scale ◽  
Depression Score ◽  
Model Assessment ◽  
Double Blind ◽  
Resistance Level ◽  
Insulin Resistant ◽  
Present Trial

The present trial aimed to evaluate the effects of pioglitazone on the mental status of nondiabetic metabolic syndrome patients. From 145 patients screened, 104 eligible volunteers (57% female; age 20–70 years) were enrolled and randomly assigned to receive either pioglitazone (uptitrated to 30 mg/day; P=53) or matching placebo (P=51) for 24 weeks. Depression and anxiety were quantified using the hospital anxiety and depression scale and stress level using the general health questionnaire 12 at baseline, week 12, and endpoint. Homeostasis model assessment was used to estimate insulin resistance. At week 24, pioglitazone was superior in mitigating depression score (P=0.011). In trend analysis, the effect of time (P<0.001) and group (P=0.023) as well as the time by group interaction (P=0.032) on the mean depression score was considerable. In contrast, significant decrements in anxiety and stress levels (P<0.001 and P=0.012, resp.) were comparable between two groups. With respect to our findings, alterations in depression severity were not correlated with changes in insulin resistance level (P=0.145). In conclusion, our findings suggest that pioglitazone might be able to improve mood in nondiabetic insulin resistant patients. (Registered at Australian New Zealand Clinical Trials Registry; ACTRN12611000351910.)

Long-term Effect of Glimepiride and Rosiglitazone on Non-conventional Cardiovascular Risk Factors in Metformin-treated Patients Affected by Metabolic Syndrome: A Randomized, Double-blind Clinical Trial

2005 ◽  
Vol 33 (3) ◽  
pp. 284-294 ◽  
Author(s):  
G Derosa ◽  
AV Gaddi ◽  
L Ciccarelli ◽  
E Fogari ◽  
M Ghelfi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Cardiovascular Risk ◽  
Plasma Glucose ◽  
Double Blind Study ◽  
Model Assessment ◽  
Rapid Improvement ◽  
Double Blind

We evaluated the effect of glimepiride plus metformin and rosiglitazone plus metformin on glucose, and on cardiovascular risk parameters such as lipoprotein(a) (Lp[a]) and homocysteine (HCT) in patients with type 2 diabetes and metabolic syndrome. Ninety-nine patients in the multicentre, randomized, double-blind study took metformin (1500 mg/day) plus glimepiride (2 mg/day) or rosiglitazone (4 mg/day) for 12 months. Changes in body mass index, glycosylated haemoglobin (HbA1c), Lp(a) and HCT were primary efficacy variables. Fasting plasma glucose (FPG), post-prandial plasma glucose (PPG) and homeostasis model assessment index were also used to assess efficacy. On average, HbA1c decreased by 9.1% and 8.1%, FPG decreased by 7.3% and 10.9%, and PPG decreased by 7.6% and 10.5%, respectively, in the glimepiride and rosiglitazone groups after 12 months. Patients receiving rosiglitazone experienced more rapid improvement in glycaemic control than those on glimepiride, and showed a significant improvement in insulin resistance-related parameters. There was a statistically significant decrease in basal homocysteinaemia in glimepiride-treated patients (−27.3%), but not in rosiglitazone-treated patients. Rosiglitazone plus metformin significantly improved long-term control of insulin resistance-related parameters compared with glimepiride plus metformin, although glimepiride treatment was associated with a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients, and with significant improvements in non-traditional risk factors for cardiovascular disease, such as basal homocysteinaemia and plasma Lp(a) levels.

scholarly journals Effect of Hedan tablets on body weight and insulin resistance in patients with metabolic syndrome

Obesity Facts ◽  
2021 ◽  
Author(s):  
Lian-Yong Liu ◽  
Lin Zhou ◽  
Xing-Zhen Liu ◽  
Da-Jin Zou
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Treatment Group ◽  
Lipid Level ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Control Group ◽  
Model Assessment ◽  
Double Blind

Introduction: Apart from their recognized lipid-lowering effect, Hedan tablets, a mixture of Chinese herbal medicines, have demonstrated a certain weight-loss effect in clinical practice. The aim of this randomized, double-blind, placebo-controlled study is to verify the effect of Hedan tablets on body weight (BW) and insulin resistance (IR) in patients with metabolic syndrome (MetS). Methods: A total of 62 eligible patients with MetS were divided into two groups: the treatment group (Hedan tablets at 4.38 g/day tid) and the control group (placebo treatment). Both groups attended follow-ups at 8, 16, and 24 weeks during the process. The parameters of the assessment include lipid level, BW, triglyceride (TG) to high-density lipoprotein cholesterol (HDLc) ratio (TG/HDLc), homeostasis model assessment for IR (HOMA-IR) index, and adiponectin. Results: Patients in the treatment group showed a significant decrease in BW compared with the control group (−4.47 vs. 0.06 kg) after 8 weeks of treatment. A significant decrease in body mass index was also observed in the treatment group after 16 weeks of treatment (−1.79 vs. −0.03 kg/m2). In the treatment group, 20 out of 31 (64.5%) patients lost 5–10% BW and 4 out of 31 (12.9%) patients lost over 10% BW after 24 weeks of treatment. Although there were no significant changes in the patients’ HOMA-IR, the treatment group showed a significant reduction in TG/HDLc (−0.98 vs. −0.19) after 8 weeks of treatment and a significant increase in adiponectin (6.87 vs. −0.43) after 16 weeks of treatment. Discussion/Conclusion: The Hedan tablets significantly improve BW, BMI, TG/HDLc, and adiponectin in patients with MetS. Thus, Hedan tablets may be used as an adjunct to existing MetS management methods.

scholarly journals Effect of Ramadan fasting on some indices of insulin resistance and components of the metabolic syndrome in healthy male adults

2008 ◽  
Vol 100 (1) ◽  
pp. 147-151 ◽  
Author(s):  
Z. Vahdat Shariatpanahi ◽  
M. Vahdat Shariatpanahi ◽  
S. Shahbazi ◽  
A. Hossaini ◽  
A. Abadi
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Waist Circumference ◽  
Linear Regression Analysis ◽  
Model Assessment ◽  
Fasting Period ◽  
Ramadan Fasting ◽  
The Metabolic Syndrome ◽  
Before And After

The purpose of the present study was to evaluate the effect of Ramadan fasting on insulin sensitivity in subjects with the metabolic syndrome. Males (n 55; age 34·1 (sd 8·9) years) with the metabolic syndrome were studied. Blood pressure, waist circumference, body weight, HDL-cholesterol (HDL-C), TAG, fasting plasma glucose (FPG), fasting blood insulin and insulin resistance indices (quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and reciprocal index of HOMA-IR (1/HOMA-IR)) were evaluated before and after 30 d of Ramadan fasting (two meals at 12 h intervals). The dietary intake was estimated by 24 h recall before and after fasting. The total daily energy intake was decreased by 234·6 (sd 88·2) kJ/d in the fasting period (P = 0·005). 1/HOMA-IR, QUICKI and HDL-C were significantly increased (P = 0·005, P = 0·001 and P = 0·004) and FPG significantly decreased (P < 0·005) after fasting. Simple linear regression analysis demonstrated that HOMA-IR, 1/HOMA-IR and QUICKI were related to waist circumference after intervention (r 0·458, P < 0·001; r − 0·396, P < 0·05; r − 0·342, P < 0·05). In conclusion, the present study showed that the combined change in the number and timing of meals and portioning of the entire intake into only two meals per d may increase insulin sensitivity in subjects with the metabolic syndrome even when the decrease in energy consumption is minimal.

scholarly journals The Relationship of Metabolic Syndrome Traits with Beta-Cell Function and Insulin Sensitivity by Oral Minimal Model Assessment in South Asian and European Families Residing in the Netherlands

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Thekla Geragotou ◽  
Sjaam Jainandunsing ◽  
Behiye Özcan ◽  
Felix W. M. de Rooij ◽  
Alexander Kokkinos ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
Minimal Model ◽  
South Asians ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Oral Minimal Model

Background. There are different metabolic syndrome traits among patients with different ethnicities.Methods. We investigated this by studying 44 South Asians and 54 Europeans and classified them in three groups according to the occurrence of metabolic syndrome (MetS) and Type 2 Diabetes (T2D). Insulin sensitivity index (ISI), static, dynamic, and total beta-cell responsivity indices (Φ), and disposition indices (DIs) were calculated with the use of oral minimal model (OMM).Results. In both ethnicities, ISI was lower in the subgroup with MetS and T2D as compared to the subgroup without MetS nor T2D (P<0.004). South Asians without MetS were more insulin resistant than Europeans without MetS (P=0.033). In the South Asians, ISI, dynamic DI, and static DI were associated significantly (P<0.006) with high-density lipoprotein cholesterol and triglycerides. In the Europeans, ISI was associated with waist-to-hip ratio (P=0.005) and systolic and diastolic blood pressure (P<0.005), while static DI was related to the systolic blood pressure (P=0.005).Conclusions. MetS was linked with insulin resistance and reduced capacity to handle glucose regardless of ethnicity. ISI and DIs were associated with lipid traits in South Asians and with blood pressure in Europeans suggesting that insulin resistance enhances different metabolic syndrome traits among different ethnicities.

scholarly journals Circulating PGRN Is Significantly Associated With Systemic Insulin Sensitivity and Autophagic Activity in Metabolic Syndrome

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3493-3507 ◽  
Author(s):  
Huixia Li ◽  
Bo Zhou ◽  
Lin Xu ◽  
Jiali Liu ◽  
Weijin Zang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Er Stress ◽  
Causative Role ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Chemical Chaperone ◽  
Autophagic Activity

Abstract Progranulin (PGRN) is a secreted protein that has recently emerged as an important regulatory adipokine of glucose metabolism and insulin sensitivity. We report here that serum PGRN concentrations were significantly higher in patients with metabolic syndrome (MS) than in subjects without MS and correlated positively with body mass index, waist circumference, fasting insulin, fasting plasma glucose, glycated hemoglobin A1c, triglyceride, and homeostasis model assessment of insulin resistance, and were inversely related to high-density lipoprotein cholesterol and homeostasis model assessment of β cell function. Subgroup analysis in 32 subjects showed that elevated expression levels of PGRN were positively correlated with increased autophagy markers LC3 and Atg7 proteins in omental adipose tissue of subjects with MS. Consistent with these findings, the enhanced PGRN levels were also observed in multiple insulin-resistant cellular models, whereas PGRN-deficient adipocytes were more susceptible to insulin action and refractory to tunicamycin-induced autophagic disorders. PGRN remarkably attenuated insulin sensitivity, increased autophagic activity, and triggered endoplasmic reticulum (ER) stress in cultured human adipocytes, whereas these effects were nullified by reduction of ER stress with phenylbutyric acid chemical chaperone treatment. In addition, PGRN-induced ER stress and impaired insulin sensitivity were improved in TNFR1−/− cells, indicating a causative role of TNF receptor in the action of PGRN. Collectively, our findings suggest that circulating PGRN is significantly associated with systemic insulin sensitivity and autophagic activity in adipose tissue and support the notion that PGRN functions as a potential link between chronic inflammation and insulin resistance.

Magnesium intake, insulin resistance and markers of endothelial function among women

2021 ◽  
pp. 1-9
Author(s):  
Narges Ghorbani Bavani ◽  
Parvane Saneei ◽  
Ammar Hassanzadeh Keshteli ◽  
Ahmadreza Yazdannik ◽  
Ebrahim Falahi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Intercellular Adhesion Molecule ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Homeostasis Model Assessment

Abstract Objective: We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women. Design: A cross-sectional study. Setting: Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). Participants: Iranian female nurses (n 345) selected by a multistage cluster random sampling method. Results: The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers. Conclusions: Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.

scholarly journals Association of Serum Levels of Zinc, Copper, and Iron with Risk of Metabolic Syndrome

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 548
Author(s):  
Chia-Wen Lu ◽  
Yi-Chen Lee ◽  
Chia-Sheng Kuo ◽  
Chien-Hsieh Chiang ◽  
Hao-Hsiang Chang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Linear Models ◽  
Serum Zinc ◽  
Serum Levels ◽  
Least Square ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Metabolic Factors ◽  
Homeostatic Model Assessment

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 μg/L, 1043.45 ± 306.36 μg/L, and 1246.83 ± 538.13 μg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35–10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25–3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24–3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.

scholarly journals SAT0111 THE RELATIONSHIP BETWEEN THE ADMINISTRATION OF IL-6 INHIBITORS AND INSULIN RESISTANCE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Beneficial Effect ◽  
Disease Activity ◽  
Interleukin 6 ◽  
Normal Weight ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Inflammatory Status

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

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