Publications by authors named "Abdallah Al-Salameh"

38 Publications

Pituitary apoplexy in the aftermath of a SARS-CoV-2 infection: a case series from Amiens University Hospital.

Eur J Endocrinol 2022 Sep 19;187(3):K19-K25. Epub 2022 Jul 19.

Department of Endocrinology, Diabetes Mellitus and Nutrition.

Objective: Since the outbreak of the COVID-19 pandemic, several cases of pituitary apoplexy (PA) following a SARS-CoV-2 infection have been described in several countries. Here, we describe a case series of PA occurring in the aftermath of a SARS-CoV-2 infection to alert physicians about possible neuro-endocrinological damage caused by the virus that can lead to visual sequelae and hypopituitarism.

Design And Methods: We retrospectively identified all the adult patients treated at Amiens University Hospital between March 2020 and May 2021 for PA confirmed by cerebral imaging and following an RT-PCR-confirmed SARS-CoV-2 infection.

Results: Eight cases (six women, two men) occurred between March 2020 and May 2021 and were reviewed in this study. The mean age at diagnosis was 67.5 ± 9.8 years. Only one patient had a 'known' non-functional pituitary macroadenoma. The most common symptom of PA was a sudden headache. Brain imaging was typical in all cases. Only two patients required decompression surgery, whereas the others were managed conservatively. The clinical outcome was favorable for all patients but without recovery of their pituitary deficiencies. There was no diabetes insipidus.

Conclusion: This case series, the largest in the literature, reinforces the strength, consistency, and coherence of the association between SARS-CoV-2 infection and PA. Our study provides support for the hypothesis that SARS-CoV-2 may be a new precipitating factor for PA. It is essential that practitioners be alerted about possible pituitary disease due to the virus so that such patients are recognized and appropriately managed, hence improving their prognosis.
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http://dx.doi.org/10.1530/EJE-22-0056DOI Listing
September 2022

Smoking and diabetes interplay: A comprehensive review and joint statement.

Diabetes Metab 2022 Jun 29;48(6):101370. Epub 2022 Jun 29.

Outpatient Addiction Center, Georges Pompidou European Hospital, AP-HP, Sorbonne Paris Cité, Paris, France.

Evidence shows that smoking increases the risk of pre-diabetes and diabetes in the general population. Among persons with diabetes, smoking has been found to increase the risk of all-cause mortality and aggravate chronic diabetic complications and glycemic control. The current paper, which is a joint position statement by the French-Speaking Society on Tobacco (Société Francophone de Tabacologie) and the French-Speaking Society of Diabetes (Société Francophone du Diabète), summarizes the data available on the association between smoking and diabetes and on the impact of smoking and smoking cessation among individuals with type 1, type 2, and gestational diabetes mellitus. It also provides evidence-based information about the pharmacological and behavioral strategies for smoking cessation in these patients.
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http://dx.doi.org/10.1016/j.diabet.2022.101370DOI Listing
June 2022

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.

Diabetes Metab 2022 07 31;48(4):101359. Epub 2022 May 31.

Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France; PériTox/UMR-I 01, University of Picardie Jules Verne, Amiens, France. Electronic address:

Since the outbreak of Covid-19, several observational studies on diabetes and Covid-19 have reported a favourable association between metformin and Covid-19-related outcomes in patients with type 2 diabetes mellitus (T2DM). This is not surprising since metformin affects many of the pathophysiological mechanisms implicated in SARS-CoV-2 immune response, systemic spread and sequelae. A comparison of the multifactorial pathophysiological mechanisms of Covid-19 progression with metformin's well-known pleiotropic properties suggests that the treatment of patients with this drug might be particularly beneficial. Indeed, metformin could alleviate the cytokine storm, diminish virus entry into cells, protect against microvascular damage as well as prevent secondary fibrosis. Although our in-depth analysis covers many potential metformin mechanisms of action, we want to highlight more particularly its unique microcirculatory protective effects since worsening of Covid-19 disease clearly appears as largely due to severe defects in the structure and functioning of microvessels. Overall, these observations confirm that metformin is a unique, pleiotropic drug that targets many of Covid-19's pathophysiology processes in a diabetes-independent manner.
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http://dx.doi.org/10.1016/j.diabet.2022.101359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154087PMC
July 2022

Screening for sleep-disordered breathing in people with type 1 diabetes by combining polysomnography with glucose variability assessment.

Diabetes Res Clin Pract 2022 Mar 17;185:109786. Epub 2022 Feb 17.

Department of Endocrinology-Diabetes Mellitus-Nutrition, Amiens University Hospital, Amiens, France; PériTox, UMR-I 01, University of Picardie Jules Verne, Amiens, France. Electronic address:

Aims: There are few published data on sleep-disordered breathing (SDB) in type 1 diabetes (T1DM). Here, we used a combination of polysomnography and glucose variability assessment to screen for SDB.

Methods: In a prospective, single-centre study, adults with T1DM underwent polysomnography and continuous glucose monitoring during a single night. We measured high glucose variability and the occurrence of a low or very low glucose level. Mild and moderate-to-severe SDB were defined as an apnoea-hypopnoea index above 5/h and 15/h, respectively.

Results: We studied 46 patients (25 men; median age: 42 [35-54]; diabetes duration: 18 years [13-29]; body mass index (BMI): 24.8 kg/m [23.0-28.9]). SDB was present in 17 patients (37.0%) overall (mild SDB: n = 9; moderate-to-severe SDB; n = 8). When compared with the absence of SDB or mild SDB, moderate-to-severe SDB was associated with a higher BMI (29.8 kg/m [27.8-31.1]) and a longer diabetes duration (26 years [18-31]) but not with above-target glucose variability or more sleep disorder symptoms. Conversely, sleep disorder symptoms were not more frequent in patients with above-target glucose variability.

Conclusion: SDB was highly prevalent and associated with obesity. According to the methods used here, sleep disorders were not associated with above-target glucose variability or low glucose values.
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http://dx.doi.org/10.1016/j.diabres.2022.109786DOI Listing
March 2022

The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation.

Diabetes Metab 2021 11 23;47(6):101297. Epub 2021 Oct 23.

Department of Endocrinology- Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France; PériTox, UMR_I 01, University of Picardie Jules Verne, Amiens, France. Electronic address:

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http://dx.doi.org/10.1016/j.diabet.2021.101297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536836PMC
November 2021

Pharmacodynamics and pharmacokinetics of extended-release metformin in patients with type 2 diabetes and chronic kidney disease stage 3B.

Diabetes Obes Metab 2022 01 4;24(1):166-170. Epub 2021 Oct 4.

PériTox, UMR_I 01, University of Picardie Jules Verne, Amiens, France.

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http://dx.doi.org/10.1111/dom.14554DOI Listing
January 2022

Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study.

Eur J Endocrinol 2021 Jul 5;185(2):299-311. Epub 2021 Jul 5.

Department of Endocrinology, Diabetology and Nutrition, Strasbourg University Hospitals, Strasbourg, France.

Objective: Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19.

Methods: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736).

Results: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only.

Conclusions: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.
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http://dx.doi.org/10.1530/EJE-21-0068DOI Listing
July 2021

Clinical aspects of multiple endocrine neoplasia type 1.

Nat Rev Endocrinol 2021 04 9;17(4):207-224. Epub 2021 Feb 9.

Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, France.

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours (NETs) and/or pituitary adenomas. MEN1 can predispose patients to other endocrine and non-endocrine tumours, such as cutaneous tumours, central nervous system tumours and breast cancer. Endocrine tumours in patients with MEN1 differ from sporadic tumours in that they have a younger age at onset, present as multiple tumours in the same organ and have a different clinical course. Therefore, patients with overt MEN1 and those who carry a MEN1 mutation should be offered tailored biochemical and imaging screening to detect tumours and evaluate their progression over time. Fortunately, over the past 10 years, knowledge about the clinical phenotype of these tumours has markedly progressed, thanks to the implementation of national registries, particularly in France and the Netherlands. This Review provides an update on the clinical management of MEN1-related tumours. Epidemiology, the clinical picture, diagnostic work-up and the main lines of treatment for MEN1-related tumours are summarized. Controversial therapeutic aspects and issues that still need to be addressed are also discussed. Moreover, special attention is given to MEN1 manifestations in children and adolescents.
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http://dx.doi.org/10.1038/s41574-021-00468-3DOI Listing
April 2021

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.

Diabetes Metab 2021 09 10;47(5):101216. Epub 2020 Dec 10.

Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, 80054 Amiens, France; PériTox = UMR_I 01, University of Picardie Jules Verne, Amiens, France.

Aims: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19.

Methods: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach.

Results: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P =  0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P <  0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively.

Conclusion: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.
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http://dx.doi.org/10.1016/j.diabet.2020.101216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832745PMC
September 2021

The association between body mass index class and coronavirus disease 2019 outcomes.

Int J Obes (Lond) 2021 03 21;45(3):700-705. Epub 2020 Nov 21.

Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France.

Background/objectives: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19.

Subjects/methods: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis.

Results: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment.

Conclusions: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.
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http://dx.doi.org/10.1038/s41366-020-00721-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679236PMC
March 2021

Management of diabetes in patients with COVID-19.

Lancet Diabetes Endocrinol 2020 08;8(8):666-667

Department of Endocrinology-Diabetology-Nutrition, Amiens University Hospital, Amiens, France.

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http://dx.doi.org/10.1016/S2213-8587(20)30231-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373379PMC
August 2020

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

Diabetes Metab Res Rev 2021 03 18;37(3):e3388. Epub 2020 Aug 18.

Department of Endocrinology, Diabetes Mellitus and Nutrition, Amiens University Hospital, Amiens, France.

Background: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes.

Methods: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model.

Results: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death.

Conclusions: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.
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http://dx.doi.org/10.1002/dmrr.3388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404605PMC
March 2021

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

Diabetologia 2020 08 29;63(8):1500-1515. Epub 2020 May 29.

Département Diabète et Endocrinologie, Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris, Paris, France.

Aims/hypothesis: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.

Methods: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation.

Results: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7.

Conclusions/interpretations: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.

Trial Registration: clinicaltrials.gov NCT04324736.
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http://dx.doi.org/10.1007/s00125-020-05180-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256180PMC
August 2020

Association between rs4149056 variant in and early discontinuation of statin after acute myocardial infarction.

Pharmacogenomics 2020 02;21(3):163-172

FACT (French Alliance for Cardiovascular Trials), an F-CRIN Network, Paris, France.

Data from two French surveys were used to analyze the association between in-hospital statin discontinuation and polymorphism (rs4149056) in patients with acute myocardial infarction. Using TaqMan allelic discrimination assay, 1674 and 1708 patients were genotyped for in 2005 and 2010, respectively. The association with in-hospital statin discontinuation was assessed after adjusting for confounding factors. In 2005, homozygosity for the reduced-function allele was associated with an increased risk of in-hospital statin discontinuation (OR: 3.68; p = 0.004) compared with the wild-type allele but this association disappeared in 2010. However, statin type and intensity-dose differed significantly between the surveys. polymorphism (rs4149056) does not seem to be a major determinant of early 'in-hospital' statin discontinuation after acute myocardial infarction.
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http://dx.doi.org/10.2217/pgs-2019-0109DOI Listing
February 2020

Cardiovascular Disease in Type 2 Diabetes: A Review of Sex-Related Differences in Predisposition and Prevention.

Mayo Clin Proc 2019 02;94(2):287-308

Centre de recherche en Epidémiologie et Santé des Populations (CESP), Université Paris-Sud, Université Paris-Saclay, INSERM, Villejuif, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Centre de Recherche Clinique Paris-Sud, Le Kremlin-Bicêtre, France; Pharmacology Department, Paris-Sud Faculty of Medicine, Paris-Sud University, Le Kremlin-Bicêtre, France.

Type 2 diabetes mellitus is a major risk factor for cardiovascular disease. However, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to sex. In recent years, large meta-analyses have confirmed that women with type 2 diabetes have a higher relative risk of incident coronary heart disease, fatal coronary heart disease, and stroke compared with their male counterparts. The reasons for these disparities are not completely elucidated. A greater burden of cardiometabolic risk in women was proposed as a partial explanation. Indeed, several studies suggest that women experience a larger deterioration in major cardiovascular risk factors and put on more weight than do men during their transition from normoglycemia to overt type 2 diabetes. This excess weight is associated with higher levels of biomarkers of endothelial dysfunction, inflammation, and procoagulant state. Moreover, sex differences in the prescription and use of some cardiovascular drugs may compound an "existing" disparity. We searched PubMed for articles published in English and French, by using the following terms: ("cardiovascular diseases") AND ("diabetes mellitus") AND ("sex disparity" OR "sex differences" OR "sex related differences" OR "sex-related differences" OR "sex disparities"). In this article, we review the available literature on the sex aspects of primary and secondary prevention of cardiovascular disease in people with type 2 diabetes, in the predisposition to cardiovascular disease in those people, and in the control of diabetes and associated cardiovascular risk factors.
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http://dx.doi.org/10.1016/j.mayocp.2018.08.007DOI Listing
February 2019

Sex Differences in the Occurrence of Major Clinical Events in Elderly People with Type 2 Diabetes Mellitus Followed up in the General Practice.

Exp Clin Endocrinol Diabetes 2020 May 22;128(5):311-318. Epub 2018 Aug 22.

Centre de recherche en Epidémiologie et Santé des Populations (CESP), Faculté de Médecine - Université Paris-Sud, INSERM, Université Paris-Saclay, 94805, Villejuif, France.

Aims: The main aim of the present work was to assess if sex influences the occurrence of major clinical events in elderly people with type 2 diabetes followed up in the primary care.

Methods: 983 subjects aged ≥65years with type 2 diabetes were included by 213 general practitioners and followed up prospectively for three years. Major clinical events were recorded every six month. The first endpoint was a composite of all-cause death and major vascular events (acute coronary syndrome, non-fatal stroke or transient ischemic attack, or revascularization for peripheral artery disease). The second endpoint was all-cause hospitalization. The occurrence of each endpoint was analyzed in order to estimate the role of sex and determine other predictors of major clinical events.

Results: At baseline, women were older than men but they had a lower prevalence of coexisting diseases (cardiovascular disease and cancer) and equivalent diabetes control (Glycated hemoglobin A1C: 6.9%±0.9 vs. 7.0%±1.1). Over the follow-up period, women were at lower risk to develop the composite endpoint (HR 0.60, 95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases, functional ability and concomitant medications emerged as significant predictors of both endpoints.

Conclusions: Elderly women with well-controlled type 2 diabetes were less likely to experience major clinical events than their male counterparts. More studies are needed to determine the reasons for the higher hospitalization rate in men.
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http://dx.doi.org/10.1055/a-0662-5923DOI Listing
May 2020

Could Sleep Apnea Paradoxically Protect Myocardium After Acute Coronary Syndrome?

Chest 2018 08;154(2):452-453

Centre de Recherche Clinique Paris Sud, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2018.02.039DOI Listing
August 2018

Update on multiple endocrine neoplasia Type 1 and 2.

Presse Med 2018 Sep 13;47(9):722-731. Epub 2018 Jun 13.

Centre hospitalier de Saint-Denis, service d'endocrinologie, 2, rue du Docteur-Delafontaine, BP 279, 93205 Saint-Denis cedex, France. Electronic address:

Multiple endocrine neoplasia type 1 is a rare genetic syndrome, characterized by the co-occurrence, in the same individual or in related individuals of the same family, of hyperparathyroidism, duodenopancraetic neuroendocrine tumors, pituitary adenomas, adrenocortical tumors, and neuroendocrine tumors (carcinoids) in the thymus, the bronchi, or the stomach. Multiple endocrine neoplastic type 2 is a rare genetic syndrome, characterized by the familial occurrence of medullary thyroid carcinoma either isolated or associated with pheochromocytoma, primary hyperparathyroidism, or typical features (Marfanoid habitus, mucosal neuromas). Subjects with clinical MEN1 and those who carry a mutation in the MEN1 gene should be offered biochemical and imaging screening in order to detect tumors and evaluate their progression over time. Children with mutation in the RET gene should have prophylactic total thyroidectomy according to the category of aggressiveness of the detected mutation whereas those with clinical MEN2 should be operated on upon diagnosis. In MEN1 patients, special attention should be paid to evaluate the progression duodenopancraetic neuroendocrine tumors because of their malignant potential. Also, thymic neuroendocrine tumors should be detected as soon as possible because they represent the most lethal tumor. In MEN2, calcitonin and carcinoembryonic antigen (CEA) serve as excellent tumor markers for medullary thyroid carcinoma. Their preoperative levels are correlated with tumor size and predict postoperative cure. Moreover, calcitonin or CEA doubling time has important prognostic value. In both MEN syndromes, multidisciplinary approaches are very important in the care of affected patients. Moreover, those patients should be comprehensively informed and enabled to participate in the decision-making procedure. In addition to multidisciplinary approaches, every effort should be made to follow the recommendations and guidelines issued by national (the French Group of Endocrine Tumors) and international groups.
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http://dx.doi.org/10.1016/j.lpm.2018.03.005DOI Listing
September 2018

Looking younger, dying later: General practitioners' intuitive clinical impression predicts mortality.

Prev Med 2018 06 21;111:28-34. Epub 2018 Feb 21.

CESP, INSERM U1018, INED, Université Paris-Saclay, Université Parie-Sud, UVSQ, Villejuif, France.

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http://dx.doi.org/10.1016/j.ypmed.2018.02.022DOI Listing
June 2018

A Somewhat Bizarre Case of Graves Disease Due to Vitamin Treatment.

J Endocr Soc 2017 May 23;1(5):431-435. Epub 2017 Mar 23.

Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, F-94275, France.

Context: Accurate measurements of circulating hormones is essential for the practice of endocrinology. Immunometric assays employing the streptavidin-biotin system are widely used to measure hormones. However, these assays are susceptible to interference in patients taking biotin supplementations. This interference could mimic a coherent hormone profile, leading to misdiagnosis and unnecessary treatment.

Case Description: The patient, a 32-year-old man with X-linked adrenomyeloneuropathy recently diagnosed with Graves disease, was referred to our department to evaluate his response to antithyroid drugs. His thyroid function tests were still consistent with hyperthyroidism while he had been receiving carbimazole 40 mg/d for 6 weeks. We found no signs of thyrotoxicosis on physical examination despite the "frank and severe" biochemical hyperthyroidism. Noticing that all the patient's assays had been done at the same laboratory, we suspected assay interference. We therefore repeated the thyroid function tests at our hospital laboratory, which uses a different assay platform. Surprisingly, all the results were normal, confirming assay interference. The patient was taking an investigational "vitamin" therapy, which turned out to be biotin, prescribed at a dose of 100 mg tid as part of a trial of high-dose biotin in X-linked adrenomyeloneuropathy.

Conclusions: This case should encourage physicians to ask their patients about possible biotin intake, especially when laboratory results are not compatible with clinical findings. If biotin interference is suspected, we propose either using a different assay not based on the streptavidin-biotin system or repeating the analyses after stopping biotin supplementation for one week.
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http://dx.doi.org/10.1210/js.2017-00054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686664PMC
May 2017

Gender-Related Differences in the Control of Cardiovascular Risk Factors in Primary Care for Elderly Patients With Type 2 Diabetes: A Cohort Study.

Can J Diabetes 2018 Aug 13;42(4):365-371.e2. Epub 2017 Oct 13.

Pharmacology Department, Paris-Sud Faculty of Medicine, Paris-Sud University, UMR 1184, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Inserm Center for Immunology of Viral Infections and Autoimmune Diseases, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France.

Objective: The aim of this study was to estimate the association between gender and control of diabetes and other cardiovascular risk factors in elderly patients with type 2 diabetes mellitus.

Methods: The sujets âgés cohort is an observational study whose main objective was to describe the real-life management of elderly patients with type 2 diabetes mellitus in France. Nine hundred eighty-three patients with diabetes (517 men and 466 women) were recruited by 213 general practitioners and were followed up prospectively every 6 months for 3 years. Diabetes, hypertension and dyslipidemia were considered controlled if the glycated hemoglobin (A1C) was ≤7%, blood pressure was <140/90 mm Hg and low-density lipoprotein (LDL) cholesterol was ≤100 mg/dL. A1C levels and blood pressure measurements were recorded every 6 months for all patients. LDL cholesterol levels were optionally sampled every year.

Results: Women were older than men (77.3±5.72 vs. 76.1±6.01 years), more likely to be alone, less likely to be smokers/ex-smokers and less likely to have cardiovascular disease at baseline. Mean A1C levels of female patients (6.98%±1.03%) did not differ from those of male patients (6.91%±0.96%). Mean blood pressure measurements during follow up were not different between male and female patients. In contrast, female patients had significantly higher LDL cholesterol levels than male counterparts (105.2±32.6 vs. 94.9±29.1 mg/dL), regardless of statin therapy.

Conclusion: Our results suggest no difference in the management of cardiovascular risk factors between elderly female patients with type 2 diabetes mellitus and their male counterparts, except for LDL cholesterol, which is significantly higher in women.
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http://dx.doi.org/10.1016/j.jcjd.2017.08.248DOI Listing
August 2018

The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

PLoS One 2017 9;12(3):e0173615. Epub 2017 Mar 9.

Inserm U1185, Fac Med Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344496PMC
September 2017

Letter by Fysekidis et al Regarding Article, "Development and Validation of a Sudden Cardiac Death Prediction Model for the General Population".

Circulation 2017 03;135(10):e634-e635

From Service d'Endocrinologie, Diabétologie, et Maladies Métaboliques, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France (M.F.); Service d'endocrinologie, Centre Hospitalier de Saint-Denis, Saint-Denis Cedex, France (R.C.); and Centre de Recherche Clinique Paris Sud, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France (A.A.S.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025924DOI Listing
March 2017

Late liver metastasis of medullary thyroid cancer with low calcitonin levels - successfully cured by radiofrequency.

Endokrynol Pol 2016 17;67(3):326-9. Epub 2016 Feb 17.

Hôpital Delafontaine 2 rue du Docteur Delafontaine 93200 Saint Denis.

A 28-year-old female consulted in 1994 for a left thyroid nodule known for two years with documented progression. Left lobe resection was performed initially followed by total thyroidectomy without lymph node dissection in September 1994. Pathological examination concluded on unilateral 10 × 40 mm medullary thyroid carcinoma (MTC). RET mutation was negative. Basal and pentagastrin-stimulated CT levels had been normal from 1994 to 2008 when her CT level was found to be elevated at 33 ng/L and increased subsequently to 111 ng/L in 2010. In accordance with guidelines, cervical ultrasound was performed repeatedly with negative results. After discussion in a multidisciplinary meeting and with patient's consent, an F-Dopa PET scan was proposed in disagreement with guidelines. This scan showed unique uptake in liver segment VI, which was confirmed by MRI. CT levels reached to 253 ng/L when she finally accepted treatment. In February 2013 we performed radiofrequency ablation of the lesion, which allowed normalisation of CT levels. This observation highlights the possibility of late recurrence of MTC. We could propose that for MTC patients with low-calcitonin levels-recurrences F-DOPA-PET/CT is a good diagnostic tool to use in case of repeatedly negative US neck studies. (Endokrynol Pol 2016; 67 (3): 326-329).
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http://dx.doi.org/10.5603/EP.a2016.0038DOI Listing
April 2017

Cardiovascular Drugs and Metformin Drug Dosage According to Renal Function in Non-Institutionalized Elderly Patients.

Basic Clin Pharmacol Toxicol 2016 Jun 28;118(6):468-73. Epub 2015 Dec 28.

Pharmacology Department, Faculty of Medicine Paris-Sud, University Paris-Sud, UMR 1184, CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, INSERM Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique-Hôpitaux de Paris, Hopital Bicêtre, Le Kremlin Bicêtre, France.

Adaptation of drug dosage to kidney function is a common problem in general practice. The aim was to describe adaptation of cardiovascular drugs and metformin according to renal function and its association with mortality with regard to metformin in a cohort of elderly patients. This was an ancillary study to the S.AGES cohort made up of patients over 65 years of age managed by their general practitioner under real-life conditions and followed up prospectively for 3 years. The medications studied were digoxin, spironolactone and metformin. Adaptation of their daily dose according to renal function (eGFR according to CKD/EPI) was compared to that recommended in the summaries of product characteristics (SPCs) or international scientific societies (ISS). A total of 900 patients were included, including 588 on metformin. At baseline, dose adjustment according to renal function was 100% and 87.6% (95% CI: 82.6-92.6) for patients on digoxin and spironolactone respectively. For metformin, only 71.3% (95% CI: 67.6-74.9) or 78.1% (95% CI: 74.7-81.4) of patients had their dosage adapted at inclusion according to their renal function depending on whether the SPCs or ISS recommendations were considered. During the 3-year follow-up period, 42/588 patients died (none from lactic acidosis). At inclusion, a metformin dosage not adapted for renal function according to ISS was not associated with an increase in all-cause mortality (OR 1.7; 95% CI 0.6-5.0, p = 0.32). In conclusion, approximately one-quarter of elderly patients treated with metformin do not have their dosage adapted for renal function according to ISS although there is no increase in mortality after follow-up for 3 years.
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http://dx.doi.org/10.1111/bcpt.12526DOI Listing
June 2016
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