Publications by authors named "Pierre-Jean Saulnier"

74 Publications

Do diabetic complications influence cancer-related events in people with type 2 diabetes? A cohort approach.

Diabetes Metab 2021 Oct 10:101289. Epub 2021 Oct 10.

Institut du thorax, INSERM, CNRS, Université de Nantes, CHU Nantes, Nantes, France.

Aim: To investigate whether diabetic micro- and macrovascular complications (mMVC) influence cancer-related events in people with type 2 diabetes.

Methods: People with type 2 diabetes from the SURDIAGENE cohort were characterized (duration of diabetes, HbA1c, mMVC, history of cancer) and prospectively followed-up for death and cancer-related events (occurrence, dissemination and cancer-related death).

Results: Between 2002 and 2012, 1468 participants (58% men, mean age 64.8 ± 10.7 years, mean duration of diabetes 14.5 ± 9.9 years at baseline) were enrolled. At baseline, 119 (8%) had a personal history of cancer. Incident cancer occurred in 207 (14%) patients during a mean follow-up of 7.3 ± 3.7 years and was associated with older age, smoking status and personal history of cancer. mMVC were not associated with cancer-related events, considering cancer occurrence, node/metastasis dissemination and cancer-specific death. Risk of all-cause mortality was increased in diabetic patients cumulating cancer history and mMVC (HR 1.73, 95%CI 1.25-2.38) compared to those with neither cancer nor mMVC. In our cohort, cancer-related death was not associated with mMVC (HR 1.05, 95%CI 0.67-1.64), but conversely history of cancer was significantly associated with cardiovascular-related death (HR 2.41, 95%CI 1.36-4.26).

Conclusion: In our cohort, mMVC were not associated with cancer-related events, while history of cancer was significantly associated with cardiovascular death.
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http://dx.doi.org/10.1016/j.diabet.2021.101289DOI Listing
October 2021

Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of ESKD in Diabetes.

J Am Soc Nephrol 2021 Sep 17;32(9):2331-2351. Epub 2021 Jun 17.

Research Division, Joslin Diabetes Center, Boston, Massachusetts.

Background: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood.

Methods: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins.

Results: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both.

Conclusions: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.
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http://dx.doi.org/10.1681/ASN.2021010105DOI Listing
September 2021

Correlates of premature pap test screening, under 25 years old: analysis of data from the CONSTANCES cohort study.

BMC Public Health 2021 03 25;21(1):595. Epub 2021 Mar 25.

Clinical Research Centree CIC1402, INSERM, Department of Obstetrics, Gynecology, and Reproductive Medicine Poitiers University Hospital Centre, University of Poitiers, Poitiers, France.

Background: Many countries currently recommend that screening for cervical cancer begin at the age of 25 years. Premature screening (before that age) could lead to unnecessary follow-up examinations and procedures that turn out to be useless. Our objective is to ascertain if the use of particular contraceptive methods are associated with premature screening.

Methods: This cross-sectional study based on the CONSTANCES cohort enabled us to include 4297 women younger than 25 years. The factors associated with premature screening were modeled by logistic regression. Missing data were handled by multiple imputations. The multivariate analyses were adjusted for sex life, social and demographic characteristics, and health status.

Results: Nearly half (48.5%) the women younger than 25 years had already undergone premature screening. Women not using contraceptives (aOR 0.3, 95% CI 0.3-0.5) and those using nonmedicalized contraceptives (condom, spermicide, etc.) (aOR 0.5, 95% CI 0.4-0.6) had premature screening less often than women using birth control pills. Higher risks of premature screening were observed in 20-year-old women (aOR 2.7, 95% CI 2.2-3.3) and in those with more than 5 lifetime partners (aOR 2.5, 95% CI 2.0-3.1), compared respectively with women who were younger and those with 5 or fewer lifetime partners.

Conclusion: Young women using contraceptives that require a doctor's prescription are exposed to premature screening more often than those not using contraception and those with nonmedicalized contraceptives.
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http://dx.doi.org/10.1186/s12889-021-10603-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993455PMC
March 2021

Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study.

Diabetes Obes Metab 2021 05 16;23(5):1162-1172. Epub 2021 Feb 16.

Département d'Endocrinologie, Diabétologie et Maladies Métaboliques, CHU de Rouen, Université de Rouen, Rouen, France.

Aim: To investigate the association between routine use of dipeptidyl peptidase-4 (DPP-4) inhibitors and the severity of coronavirus disease 2019 (COVID-19) infection in patient with type 2 diabetes in a large multicentric study.

Materials And Methods: This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID-19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP-4 inhibitors users vs. non-users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW).

Results: Five hundred and ninety-six participants were under DPP-4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non-users of DPP-4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW-adjusted models showed no significant association between the use of DPP-4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77-1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78-1.17]). Similar neutral findings were found between use of DPP-4 inhibitors and the risk of tracheal intubation and death.

Conclusions: These data support the safety of DPP-4 inhibitors for diabetes management during the COVID-19 pandemic and they should not be discontinued.
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http://dx.doi.org/10.1111/dom.14324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013481PMC
May 2021

Plasma concentrations of lipoproteins and risk of lower-limb peripheral artery disease in people with type 2 diabetes: the SURDIAGENE study.

Diabetologia 2021 Mar 6;64(3):668-680. Epub 2021 Jan 6.

Département d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, Bordeaux, France.

Aims/hypothesis: The lipid profile has not been fully investigated in individuals with peripheral artery disease (PAD). We aimed to evaluate the relationship between plasma concentrations of lipoproteins and the prevalence of lower-limb PAD at baseline and its incidence during follow-up in people with type 2 diabetes.

Methods: Plasma concentrations of total cholesterol, HDL-cholesterol, triacylglycerol and apolipoprotein (Apo) A-I, ApoA-II, ApoB-100 and Apo(a) were measured at baseline using colorimetric or MS methods in the SURDIAGENE cohort. Total cholesterol/HDL-cholesterol ratio, non-HDL-cholesterol and LDL-cholesterol were estimated using computation formulas. Logistic and Cox proportional hazard regression models were fitted to estimate OR or HR, with related 95% CI, for baseline prevalence or incidence of major PAD (lower-limb amputation or requirement of revascularisation) during follow-up by increasing lipoprotein tertiles, after adjustment for key confounders.

Results: Among 1468 participants (women 42%, mean ± SD age 65 ± 11 years, duration of diabetes 14 ± 10 years at baseline), 129 (8.8%) had a baseline history of major PAD. Major PAD was less prevalent at baseline in the highest (vs lowest) tertile of HDL-cholesterol (OR 0.42 [95% CI 0.26, 0.71], p = 0.001) and ApoA-I (OR 0.39 [95% CI 0.23, 0.67], p = 0.0007), and more frequent in the highest tertile of total cholesterol/HDL-cholesterol ratio (OR 1.95 [95% CI 1.18, 3.24], p = 0.01). Among 1339 participants without a history of PAD at baseline, incident PAD occurred in 97 (7.2%) during a median (25th-75th percentile) duration of follow-up of 7.1 (4.4-10.7) years, corresponding to 9685 person-years and an incidence rate of 9.8 (95% CI 8.0, 12.0) per 1000 person-years. The risk of incident PAD was lower in the top (vs bottom) tertile of HDL-cholesterol (HR 0.54 [95% CI 0.30, 0.95], p = 0.03) or ApoA-I (HR 0.50 [95% CI 0.28, 0.86], p = 0.01) and higher in the top tertile of total cholesterol/HDL-cholesterol ratio (HR 2.81 [95% CI 1.61, 5.04], p = 0.0002) and non-HDL-cholesterol (HR 1.80 [95% CI 1.06, 3.12], p = 0.03).

Conclusions/interpretation: We reported independent associations between HDL-cholesterol, ApoA-I, total cholesterol/HDL-cholesterol ratio or non-HDL-cholesterol and the prevalence or the incidence of major PAD in people with type 2 diabetes. Our findings provide a picture of lipoprotein profile in people with type 2 diabetes. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05326-xDOI Listing
March 2021

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

Diabetes Metab 2020 Dec 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
December 2020

Relationship Between Diabetic Retinopathy Stages and Risk of Major Lower-Extremity Arterial Disease in Patients With Type 2 Diabetes.

Diabetes Care 2020 11 2;43(11):2751-2759. Epub 2020 Sep 2.

Hôpital Haut-Lévêque, Département d'Endocrinologie, Diabétologie, Nutrition, Pessac, Bordeaux, France

Objective: We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors to this relationship in a prospective cohort of patients with type 2 diabetes.

Research Design And Methods: Diabetic retinopathy was staged at baseline as absent, nonproliferative, or proliferative. A Cox regression model was fitted in order to compute the hazard ratio (HR) (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. The retinopathy-LEAD association was assessed in subgroups by age, sex, diabetes duration, HbA, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy in stratifying LEAD risk was assessed by using the C statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).

Results: Among 1,320 participants without a history of LEAD at baseline, 94 (7.1%) developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6 per 1,000 person-years [95% CI 7.8-11.7]). The LEAD incidence rate (per 1,000 person-years) increased as retinopathy worsened: it was 5.5 (95% CI 3.9-7.8) in participants in whom retinopathy was absent, 14.6 (11.1-19.3) in those with nonproliferative retinopathy, and 20.1 (11.1-36.3) in those with proliferative retinopathy. Nonproliferative retinopathy (adjusted HR 2.31 [95% CI 1.43-3.81], = 0.0006) and proliferative retinopathy (3.14 [1.40-6.15], = 0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced the C statistic (+0.023 [95% CI 0.003-0.044], = 0.02), IDI (0.209 [0.130-0.321], < 0.001), and NRI (0.562 [0.382-0.799], < 0.001) values for risk of LEAD, beyond traditional risk factors.

Conclusions: An independent dose-response relationship was identified between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for stratifying risk of LEAD, suggesting its usefulness as a predictor of LEAD.
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http://dx.doi.org/10.2337/dc20-1085DOI Listing
November 2020

Relationship between obesity and severe COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study.

Diabetes Obes Metab 2021 02 6;23(2):391-403. Epub 2020 Nov 6.

Département d'Endocrinologie, Diabétologie et Nutrition, L'Institut du Thorax, INSERM, CNRS, University of Nantes, CHU Nantes, Nantes, France.

Aim: To assess the relationship between body mass index (BMI) classes and early COVID-19 prognosis in inpatients with type 2 diabetes (T2D).

Methods: From the CORONAvirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study, we conducted an analysis in patients with T2D categorized by four BMI subgroups according to the World Health Organization classification. Clinical characteristics and COVID-19-related outcomes (i.e. intubation for mechanical ventilation [IMV], death and discharge by day 7 [D7]) were analysed according to BMI status.

Results: Among 1965 patients with T2D, 434 (22.1%) normal weight (18.5-24.9 kg/m , reference group), 726 (36.9%) overweight (25-29.9 kg/m ) and 805 (41.0%) obese subjects were analysed, including 491 (25.0%) with class I obesity (30-34.9 kg/m ) and 314 (16.0%) with class II/III obesity (≥35 kg/m ). In a multivariable-adjusted model, the primary outcome (i.e. IMV and/or death by D7) was significantly associated with overweight (OR 1.65 [1.05-2.59]), class I (OR 1.93 [1.19-3.14]) and class II/III obesity (OR 1.98 [1.11-3.52]). After multivariable adjustment, primary outcome by D7 was significantly associated with obesity in patients aged younger than 75 years, while such an association was no longer found in those aged older than 75 years.

Conclusions: Overweight and obesity are associated with poor early prognosis in patients with T2D hospitalized for COVID-19. Importantly, the deleterious impact of obesity on COVID-19 prognosis was no longer observed in the elderly, highlighting the need for specific management in this population.
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http://dx.doi.org/10.1111/dom.14228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675375PMC
February 2021

Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France.

Radiology 2021 02 1;298(2):E81-E87. Epub 2020 Sep 1.

From the University Hospital Centre Poitiers, Radiology, 2 rue de la Milétrie, 86000 Poitiers, Vienne, France (G. Herpe.); Laboratoire de Mathématiques et Applications Université de Poitiers, DACTIM-MIS TEAM, Chasseneuil, Nouvelle Aquitaine, France (G. Herpe.); University Hospital of Rennes, Radiology, Rennes, Ille-et-Vilaine, France (M. Lederlin.); University of Rennes, Rennes, Ille-et-Vilaine, France (M. Lederlin.); Université de Poitiers Laboratoire de Mathématiques et Applications, DACTIM-MIS, Chasseneuil, Nouvelle Aquitaine, France (M.N.); University Hospital Centre Poitiers, DACTIM-MIS, Poitiers, France (M.N.); Nouvel Hôpital Civil, Radiology, Strasbourg, Alsace, France (M.O.); APHM, Radiology, Marseille, PACA, France (K.C.); AMU, Marseille, PACA, France (K.C.); Beaujon Hospital Department of Medical Imaging, Radiology, Clichy, France (J.G.); Beaujon University Hospitals Paris Nord Val de Seine, Radiology, Clichy, Hauts-de-Seine, France (V.V.); CHU Nîmes, Nîmes, Gard, France (C.A.F.); Hôpital Saint-Louis, Radiology, Paris, Île-de-France, France (C.D.M.M.); Université de Paris, INSERM U1149-Center for Research on Inflammation, Paris, Île-de-France, France (C.D.M.M.); Centre Hospitalier Universitaire de Nice Hôpital Pasteur, Radiology, Nice, Alpes Maritimes, France (V.F.); Centre Hospitalier Annecy Genevois, Radiology, Epagny Metz-Tessy, Auvergne-Rhône-Alpes, France (M. Ludwig.); CHU Nice, Radiology, Nice, PACA, France (L.M.); European Hospital Group Georges-Pompidou, Radiology, Paris, Île-de-France, France (I.F.); Université de la Méditérranée, Faculté de Médecine de Marseille, Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR CNRS no. 6612, Marseille, BdR, France (A.R.R.J.); Centre Hospitalo Universitaire la Timone, Service de Radiologie Cardiovasculaire, Marseille, France (A.R.R.J.); Centre Hospitalier de la Côte Basque, Bayonne, Nouvelle Aquitaine, France (P.A.); CHRU de Nancy, Radiology, Nancy, Grand Est, France (I.P.); HIA Legouest, Service d'Imagerie Médicale, Metz, France (A.G.); CHU Nancy, Service D'imagerie Guilloz, Nancy, France (A.G.); Hôpital Saint-Joseph, Radiology, Marseille, PACA, France (O.B.); Clinique Emilie de Vialar, IMEV, Radiologie, Rhône, France (A.C.); CH Douai, NORD, Loffre, France (M.M.S.); University Hospital Centre Poitiers, Poitiers, Vienne, France (C.T.); CHRDS, Neuilly-sur-Seine, Neuilly-sur-Seine, France (G. Henry.);, Île de France, France (V.B.); Hôpital d'Instruction des Armées Begin, Radiology, Saint Mande, Île-de-France, France (T.L.T.); Hôpital d'Instruction des Armées Percy, Radiology, Clamart, Île-de-France, France (T.L.T.); CHU Limoges, Radiology, Limoges, Nouvelle Aquitaine, France (M.S.G.); CHU Dupuytren, Radiologie, Limoges, Haute-Vienne, France (P.G.); Military Teaching Hospital Clermont-Tonnerre, Radiology, Brest, Bretagne, France (M.G.); Hôpital Argenteuil, Argenteuil, Île-de-France, France (E.B.); Centre Hospitalier Pierre-le-Damany Lannion Trestel, Kergomar, Lannion, Bretagne, France (C.M.); Institut Bergonie, Bordeaux, Nouvelle Aquitaine, France (B.L.); CH Douai, Radiology, Douai, Nord, France (A.K.); Centre Hospitalier de Vienne Lucien Hussel, Medical Imaging, Vienne, Aura, France (H.K.); Hôpital d'Instruction des Armées Laveran, Radiology, Marseille, Bouches-du-Rhône, France (F.D.); CHU Tivoli, La Louvière, Wallonie, Belgium (B.D.); CHU Poitiers, Clinical Investigation Center CIC1402, Poitiers, Vienne, France (P.J.S.); CHU Poitiers, Radiology, Poitiers, Poitou-Charentes, France (R.G.); La Timone Hospital, Radiology, Marseille, BdR, France (J.M.B.); University Hospital Center of Nîmes, Radiology, Nîmes, Gard, France (J.P.B.); Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, France, France (J.P.T.); and CHU de Poitiers, Service de Radiologie, Poitiers, France, France (J.P.T.) .

Background The role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020. These dates correspond to the peak of the national COVID-19 epidemic. Radiology departments were selected to reflect the estimated geographic prevalence heterogeneities of the epidemic. All symptomatic patients suspected of having COVID-19 pneumonia who underwent both initial chest CT and at least one RT-PCR test within 48 hours were included. The final discharge diagnosis, based on multiparametric items, was recorded. Data for each center were prospectively collected and gathered each week. Test efficacy was determined by using the Mann-Whitney test, Student test, χ test, and Pearson correlation coefficient. < .05 indicated a significant difference. Results Twenty-six of 26 hospital radiology departments responded to the survey, with 7500 patients entered; 2652 did not have RT-PCR test results or had unknown or excess delay between the RT-PCR test and CT. After exclusions, 4824 patients (mean age, 64 years ± 19 [standard deviation], 2669 male) were included. With final diagnosis as the reference, 2564 of the 4824 patients had COVID-19 (53%). Sensitivity, specificity, negative predictive value, and positive predictive value of chest CT in the diagnosis of COVID-19 were 2319 of 2564 (90%; 95% CI: 89, 91), 2056 of 2260 (91%; 95% CI: 91, 92), 2056 of 2300 (89%; 95% CI: 87, 90), and 2319 of 2524 (92%; 95% CI: 91, 93), respectively. There was no significant difference for chest CT efficacy among the 26 geographically separate sites, each with varying amounts of disease prevalence. Conclusion Use of chest CT for the initial diagnosis and triage of patients suspected of having coronavirus disease 2019 was successful. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2020202568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465292PMC
February 2021

Comprehensive geriatric assessment in older patients with cancer: an external validation of the multidimensional prognostic index in a French prospective cohort study.

BMC Geriatr 2020 08 18;20(1):295. Epub 2020 Aug 18.

Department of Geriatrics, Poitiers University Hospital, Poitiers, France.

Background: Older patients with cancer require specific and individualized management. The 3-group Multidimensional Prognostic Index (MPI) based on the Comprehensive Geriatric Assessment (CGA) has shown a predictive interest in terms of mortality. The objective of our study was to assess the prognostic value of MPI for 1-year mortality in an external prospective French cohort of elderly patients with cancer.

Methods: From March 2015 to March 2017 a prospective single-center cohort study enrolled all patients with cancer, aged 75 years and older referred to the geriatric oncology clinic. We used a proportional hazard model for 1-year mortality adjusted for age, sex, tumor sites and metastatic status. C-statistics were used to assess the incremental predictive value of MPI index to these risk factors.

Results: overall, 433 patients underwent CGA with MPI (women 42%; mean age 82.8 ± 4.8 years). The most common tumor sites were prostate (23%), skin (17%), colorectum (15%) and breast (12%); 29% of patients had a metastatic disease; 231 patients (53%) belonged to the "MPI-1" group, 172 (40%) to the "MPI-2" group and 30 patients were classified in the "MPI-3" group. One-year mortality rate was 32% (23% in MPI-1, 41% in MPI-2 and 53% in MPI-3, p = 0.024). All domains of MPI except cognition and living status were significantly associated with mortality at one-year, as well as tumor sites and metastatic status. Higher MPI was associated with a higher mortality risk (adjusted HR 1.56 [95%CI 1.70-2.09] and 1.72 [1.33-2.22] for MPI groups 2 and 3 compared to 1; p < 0.0001).

Conclusions: In addition to established risk factors, MPI improves risk prediction of 1-year mortality. This practical prognostic tool may help to optimize management of these vulnerable patients.
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http://dx.doi.org/10.1186/s12877-020-01692-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433061PMC
August 2020

COVID-19 impact assessment on the French radiological centers: a nationwide survey.

Eur Radiol 2020 Dec 3;30(12):6537-6544. Epub 2020 Jul 3.

University Hospital Center of Nîmes, Radiology, Nîmes, Gard, France.

Purpose: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak.

Materials And Methods: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CT) and whole chest CT scan activities (CT) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson's test.

Results: Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CT activity per radiologic structure ranged from 75.8 ± 133 (0-1444) on week 12 to 99.3 ± 138.6 (0-1147) on week 13. Mean ratio of CT on CT varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CT (r = 0.73, p = 3.10) but no link with the number of positive RT-PCR results.

Conclusion: In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients.

Key Points: • Over the 4-week survey period, 117,686 chest CT (CT) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CT). • Across the country, the ratio CT/CT varied from 0.36 to 0.59 and depended significantly on the local epidemic density (p = 0.003). • In clinical practice, in a context of growing epidemic, in France, chest CT was used as a surrogate to RT-PCR for patient triage.
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http://dx.doi.org/10.1007/s00330-020-07035-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333367PMC
December 2020

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

Comparison of a new versus standard removable offloading device in patients with neuropathic diabetic foot ulcers: a French national, multicentre, open-label randomized, controlled trial.

BMJ Open Diabetes Res Care 2020 05;8(1)

Department of Endocrinology, Diabetology and Nutrition, CHU Bordeaux, Haut Lévèque Hospital, Pessac, France.

Introduction: The offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. is a new customized removable knee-high offloading device immobilizing foot and ankle joints, with some specific and innovative features that may improve offloading. We aimed to evaluate the efficiency of in DFU healing.

Research, Design And Methods: The evaluation of Offloading using a new removable ORTHOsis in DIABetic foot study is a French multicenter (13 centers) randomized controlled trial with blinded end points evaluation. Adults with neuropathic DFU were randomly assigned to either ), or any type of conventional (usually used in France) removable offloading devices (control group). The primary outcome was the 3-month proportion of patients with fully healed DFU.

Results: Among 112 randomized patients (men 78%, age 62±10 years), the primary outcome occurred in 19 (33%) participants using conventional device vs 19 (35%) users (p=0.79). Study groups were also comparable in terms of prespecified secondary end points including occurrence of new DFU (25% vs 27% in conventional and experimental groups), ipsilateral lower-limb amputation (4% vs 10%) or infectious complications (14% vs 13%) (p>0.05 for all). Adverse events were comparable between groups, including 4 deaths unrelated to study allocation (1 sudden death, 2 ventricular arrhythmias and 1 pancreatic cancer). Adverse events believed to be related to the device were higher in the group than in the control group (15% vs 4%). was less frequently worn than conventional devices (46% vs 66%, p=0.04).

Conclusions: , a new removable offloading orthosis immobilizing foot and ankle joints did not show superiority compared with conventional removable devices in neuropathic DFU healing and cannot be recommended to heal DFU.

Trial Registration Number: NCT01956162.
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http://dx.doi.org/10.1136/bmjdrc-2019-000954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223015PMC
May 2020

Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes.

J Clin Endocrinol Metab 2020 07;105(7)

CRNH-O, Plateforme Spectrométrie de Masse (PFSM, Mass Spectrometry Core Facility), Nantes, France.

Objective: Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D).

Research Design And Methods: We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D.

Results: The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration [interquartile range], 85 [75] months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P < 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514.

Conclusions: We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.
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http://dx.doi.org/10.1210/clinem/dgaa188DOI Listing
July 2020

Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index.

Environ Int 2020 05 14;138:105622. Epub 2020 Mar 14.

Team of Environmental Epidemiology, IAB, Institute for Advanced Biosciences, Inserm, CNRS, CHU-Grenoble-Alpes, University Grenoble-Alpes, Grenoble, France. Electronic address:

Background: The exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate.

Objectives: We aimed to reduce the dimension of the exposome using information from DNA methylation as a way to more efficiently characterize the relation between exposome and child body mass index (BMI).

Methods: Among 1,173 mother-child pairs from HELIX cohort, 216 exposures ("whole exposome") were characterized. BMI and DNA methylation from immune cells of peripheral blood were assessed in children at age 6-10 years. A priori reduction of the methylome to preselect BMI-relevant CpGs was performed using biological pathways. We then implemented a tailored Meet-in-the-Middle approach to identify from these CpGs candidate mediators in the exposome-BMI association, using univariate linear regression models corrected for multiple testing: this allowed to point out exposures most likely to be associated with BMI ("reduced exposome"). Associations of this reduced exposome with BMI were finally tested. The approach was compared to an agnostic exposome-wide association study (ExWAS) ignoring the methylome.

Results: Among the 2284 preselected CpGs (0.6% of the assessed CpGs), 62 were associated with BMI. Four factors (3 postnatal and 1 prenatal) of the exposome were associated with at least one of these CpGs, among which postnatal blood level of copper and PFOS were directly associated with BMI, with respectively positive and negative estimated effects. The agnostic ExWAS identified 18 additional postnatal exposures, including many persistent pollutants, generally unexpectedly associated with decreased BMI.

Discussion: Our approach incorporating a priori information identified fewer significant associations than an agnostic approach. We hypothesize that this smaller number corresponds to a higher specificity (and possibly lower sensitivity), compared to the agnostic approach. Indeed, the latter cannot distinguish causal relations from reverse causation, e.g. for persistent compounds stored in fat, whose circulating level is influenced by BMI.
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http://dx.doi.org/10.1016/j.envint.2020.105622DOI Listing
May 2020

Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort.

Diabetologia 2020 05 10;63(5):915-923. Epub 2020 Feb 10.

INSERM, Centre d'Investigation Clinique CIC1402, Université de Poitiers, CHU de Poitiers, Poitiers, France.

Aims/hypothesis: Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up.

Methods: We used a prospective, monocentric cohort of consecutive type 2 diabetes participants (the SURDIAGENE [SUivi Rénal, DIAbète de type 2 et GENEtique] cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. We used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors.

Results: We monitored 1321 individuals (58% men, mean age 64 ± 11 years) for a median of 89 months. During follow-up, 442 individuals died and 497 had MACE. Multivariate Cox analysis showed that serum TN-C concentrations were associated with an increased risk of death (HR per 1 SD: 1.27 [95% CI 1.17, 1.38]; p < 0.0001) and MACE (HR per 1 SD: 1.23 [95% CI 1.13, 1.34]; p < 0.0001). Using TN-C concentrations on top of traditional risk factors, prediction of the risk of all-cause death (rIDI: 8.2%; p = 0.0006) and MACE (rIDI: 6.7%; p = 0.0014) improved significantly, but modestly.

Conclusions/interpretation: In individuals with type 2 diabetes, increased serum TN-C concentrations were independently associated with death and MACE. Therefore, including TN-C as a prognostic biomarker could improve risk stratification in these individuals.
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http://dx.doi.org/10.1007/s00125-020-05108-5DOI Listing
May 2020

Frailty and diabetes status in older patients with cancer: impact on mortality in the ANCRAGE cohort.

Aging Clin Exp Res 2020 Sep 2;32(9):1809-1819. Epub 2020 Jan 2.

Department of Geriatrics, CHU Poitiers, 2 rue de la Milétrie, 86021, Poitiers Cedex, France.

Background: Frailty, diabetes and cancer are associated with aging, but the relationship between these conditions is not well defined.

Aims: We studied older patients with cancer from the prospective single-center cohort ANCRAGE (ANalyses of CanceR in AGEd) aiming to determine the impact of type 2 diabetes (T2D) and its vascular complications (VC) on frailty and adverse outcomes (mortality, unplanned readmission) during follow-up.

Methods: Analysis of cohort patients ≥ 75 years, included between 2009 and 2017, who underwent a comprehensive geriatric assessment (CGA). Variables of interest were history of T2D and VC, tumor site and metastatic status, CGA including eight domains (social environment, functional status, mobility, nutrition, mood, cognition, polypharmacy and comorbidities) and frailty.

Results: Among 1092 patients (47% female, mean age 82 ± 5 years), 219 (20%) had a reported diagnosis of T2D at baseline including 152 (69%) with VC. The most common tumor sites were prostate (15%), breast (15%), skin (12%), and colorectum (11%); 29% of patients had a metastatic disease. Frailty was highly prevalent (84%). During follow-up (median of 15.3 months), 653 (60%) patients died (60% no T2D, 43% T2D without VC, 66% with VC). After adjustment for age, gender and metastatic status, diabetics with VC had a higher risk of all-cause death (aHR1.89, 1.24-2.86, p = 0.004). Death was more frequently due to a non-cancer cause (p < 0.001). No difference in unplanned readmissions was observed in the three groups. Frailty was an independent risk factor for mortality and unplanned readmissions (p < 0.001 both).

Conclusion: In older cancer patients from the prospective ANCRAGE cohort, all-cause mortality was significantly higher in frail patients and those with complicated T2D, a finding questioning the quality of care management in such vulnerable patients, and stimulating further research in this multidisciplinary field.
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http://dx.doi.org/10.1007/s40520-019-01362-9DOI Listing
September 2020

Association between sleep disturbances, fear of hypoglycemia and psychological well-being in adults with type 1 diabetes mellitus, data from cross-sectional VARDIA study.

Diabetes Res Clin Pract 2020 Feb 19;160:107988. Epub 2019 Dec 19.

Institut MITOVASC, UMR CNRS 6015, INSERM 1083, Université d'Angers, 3 rue Roger Amsler, 49100 Angers, France; Diabetes Department, CHU d'Angers, 4 rue Larrey, 49100 Angers, France. Electronic address:

Aim: To assess the relationship between sleep quality, fear of hypoglycemia, glycemic variability and psychological well-being in type 1 diabetes mellitus.

Methods: Our data were provided by the VARDIA Study, a multicentric cross-sectional study conducted between June and December 2015. Sleep characteristics were assessed by the Pittsburgh Sleep Quality Index (PSQI). Fear of hypoglycemia and psychological well-being were measured with the Hypoglycemia Fear Survey version II (HFS-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Glycemic variability (GV) was determined using the CV of three 7-point self-monitoring blood glucose profiles and the mean amplitude of glycemic excursion (MAGE).

Results: 315 patients were eligible for PSQI questionnaire analysis: 54% women, mean age 47 ± 15, mean diabetes duration of 24 ± 13 years, HbA1c of 7.6 ± 0.9% (60 ± 7,5mmol/mol). Average PSQI score was 6.0 ± 3.3 and 59.8% of the patients had a PSQI score > 5. HFS-II score and HADS were significantly higher among "poor" sleepers (p < 0.0001) and PSQI score was positively associated with HADS (β = 0.22; 95% CI = 0.08;0.35). GV evaluated by CV or MAGE did not differ between "poor" and "good" sleepers (p = 0.28 and 0.54, respectively).

Conclusions: Adult patients with type 1 diabetes have sleep disturbances which correlate with psychological well-being. This study suggests that psychological management can be a target to improve sleep quality in adults with type 1 diabetes mellitus.
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http://dx.doi.org/10.1016/j.diabres.2019.107988DOI Listing
February 2020

Association of Urine Haptoglobin With Risk of All-Cause and Cause-Specific Mortality in Individuals With Type 2 Diabetes: A Transethnic Collaborative Work.

Diabetes Care 2020 03 20;43(3):625-633. Epub 2019 Dec 20.

L'institut du thorax, INSERM, CNRS, University of Nantes, CHU Nantes, Nantes, France

Objective: Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes.

Research Design And Methods: We employed a transethnic approach with a cohort of Asian origin (Singapore) ( = 2,061) and a cohort of European origin (France) ( = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality.

Results: A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5-12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3-10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02-2.11], 2.28 [1.62-3.21], and 4.64 [3.39-6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15-2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09-3.42] and adjusted HR 1.49 [1.14-1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor.

Conclusions: Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.
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http://dx.doi.org/10.2337/dc19-1295DOI Listing
March 2020

Circulating TNF receptors and risk of renal disease progression, cardiovascular disease events and mortality in patients with diabetes: a systematic review and meta-analysis.

Endocrine 2020 04 7;68(1):32-43. Epub 2019 Dec 7.

Department of Nephrology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China.

Purpose: Inflammation plays an important role in the pathogenesis of diabetes complications. This study aims to assess the association between circulating inflammatory biomarkers TNF receptors (TNFRs) and the risk of renal disease progression, cardiovascular disease (CVD) events, and mortality in patients with diabetes.

Methods: PubMed and Embase databases were comprehensively searched up to March 2019. Data were extracted independently by two reviewers. A random effects model was performed for the pooled analyses.

Results: Five studies in 3316 subjects assessed TNFRs with renal disease in patients with type 1 diabetes and showed both TNFR-1 and TNFR-2 were consistently associated with the renal outcomes. Fourteen studies in 7696 subjects evaluated TNFRs in patients with type 2 diabetes. The pooled risk ratio per doubling increase in TNFR-1 and TNFR-2 for renal disease progression was more than two (2.64 [1.98, 3.52] and 2.23 [1.69, 2.94]). The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness. Moreover, higher TNFR-1 and TNFR-2 was also significantly associated with CVD events and mortality in patients with type 2 diabetes.

Conclusions: Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression, CVD events, and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future.
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http://dx.doi.org/10.1007/s12020-019-02153-yDOI Listing
April 2020

[Interest of the multidimensional prognostic index (MPI) as an assessment tool in hospitalized patients in geriatrics].

Geriatr Psychol Neuropsychiatr Vieil 2019 12;17(4):386-392

Service de gériatrie, CHU La Milétrie, Poitiers, France, Centre d'investigation clinique, CIC Inserm 1402, CHU La Milétrie, Poitiers, France.

The collection of prognostic information in the elderly is essential. The main objective was to perform a replication of the multidimensional prognostic index (MPI), to predict mortality at one-year in patients hospitalized in geriatric wards. Secondary objectives were to evaluate if the MPI was predictive of the length of hospital stay, and of rehospitalization in the following year.

Methods: Prospective study conducted from February 2015 to November 2016 at the University Hospital of Poitiers (Geriatrics department). A comprehensive geriatric assessment (number of treatment, lifestyle, autonomy, comorbidities, risk of pressure sore, nutritional and cognitive status) was used to calculate the MPI score and to categorize patients into three groups: low (MPI-1), moderate (MPI-2) and high (MPI-3) risk of mortality.

Results: 153 patients were included, with mean age 85.9 ± 5.4 years. Twenty-one patients (13.7%) belonged to MPI-1 group, 98 (64.1%) to MPI-2 group, and 34 (22.2%) to MPI-3 group. The number of deaths at one-year according to the MPI group was different (p < 0.01). The one-year prognostic performance of MPI was good (AUC at 0.76). MPI was also predictive of hospital length stay (p < 0.05).

Conclusion: MPI appears to be a relevant prognostic tool in the stratification of one-year mortality risk in elderly patients hospitalized in geriatrics.
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http://dx.doi.org/10.1684/pnv.2019.0823DOI Listing
December 2019

Bisphenol A, Chlorinated Derivatives of Bisphenol A and Occurrence of Myocardial Infarction in Patients with Type 2 Diabetes: Nested Case-Control Studies in Two European Cohorts.

Environ Sci Technol 2019 Aug 31;53(16):9876-9883. Epub 2019 Jul 31.

Université de Poitiers , School of Medicine and Pharmacy of Poitiers , F-86073 Poitiers , France.

A positive association between Bisphenol A (BPA) exposure and coronary heart disease has been shown, but not in patients with type 2 diabetes (T2D). During the treatment of drinking water, chlorination leads to the formation of chlorinated derivatives of Bisphenol A (ClxBPA), that have higher estrogenic activity than BPA. No evidence exists for a relationship between exposure to ClxBPA and myocardial infarction in patients with T2D. The objective of this study was to evaluate the relationship between exposure to BPA, ClxBPA and the occurrence of myocardial infarction (MI) in patients with T2D. Two nested case-control studies in two independent European cohorts were performed. Each case with incident MI during follow-up was matched to one control on age, sex, and personal cardiovascular history in the same cohort. Association between baseline urine concentrations of BPA and of ClxBPA and incident MI was determined. Exposure to BPA was 31% in the ESTHER cohort and 18% in the SURDIAGENE cohort. In a meta-analysis of the two studies, occurrence of MI was significantly associated with urine BPA detection: adjusted OR = 1.97 (1.05-3.70), = 0.04. Exposure to ClxBPA significantly differed in the SURDIAGENE and ESTHER studies: 24% and 8%, respectively ( = 0.0003). It was very strongly associated with MI in the SURDIAGENE cohort with an adjusted odds ratio (OR) of 14.15 (2.77-72.40) but this association was not replicated in the ESTHER study: adjusted OR: 0.17 (0.02-1.23). Whether these results may be explained by different water chlorination processes in France and Germany, resulting in different ClxBPA exposure levels, requires further investigation.
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http://dx.doi.org/10.1021/acs.est.9b02963DOI Listing
August 2019

No association between fear of hypoglycemia and blood glucose variability in type 1 diabetes: The cross-sectional VARDIA study.

J Diabetes Complications 2019 08 10;33(8):554-560. Epub 2019 May 10.

L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.

Aims: In type 1 diabetes (T1D), treatment efficacy is limited by the unpredictability of blood glucose results and glycemic variability (GV). Fear of Hypoglycemia (FOH) remains a major brake for insulin treatment optimization. We aimed to assess the association of GV with FOH in participants with T1D in an observational cross-sectional study performed in 9 French Diabetes Centres (NCT02790060).

Methods: Participants were T1D for ≥5 years, aged 18-75 years, on stable insulin therapy for ≥3 months. The coefficient of variation (CV) of blood glucose and mean amplitude of glycemic excursions (MAGE) were used to assess GV from 7-point self-monitoring of blood glucose (SMBG). FOH was assessed using the validated French version of the Hypoglycemia Fear Survey-II (HFS-II) questionnaire.

Results: Among a total of 570 recruited participants, 298 were suitable for analysis: 46% women, 58% on continuous subcutaneous insulin infusion [CSII], mean age 49 ± 16 years, HbA1c 7.5 ± 0.9%, HFS-II score 67 ± 18 and 12% with recent history of severe hypoglycemia during the previous 6 months, mean CV 39.8 ± 9.7% and MAGE 119 ± 42 mg/dL. CV and MAGE did not significantly correlate with HFS-II score (R = -0.05;P = 0.457 and R = 0.08;P = 0.170). Participants with severe hypoglycemia in the previous 6 months had higher HFS scores. Participants with higher HFS scores presented more hypoglycemias during follow-up.

Conclusions: FOH as determined using the HFS-II questionnaire was not associated with 7-point SMBG variability in participants with T1D, but was associated with a positive history of severe hypoglycemia. Higher FOH was associated with higher frequency of hypoglycemia during follow-up.
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http://dx.doi.org/10.1016/j.jdiacomp.2019.05.003DOI Listing
August 2019

Changes in Albuminuria But Not GFR are Associated with Early Changes in Kidney Structure in Type 2 Diabetes.

J Am Soc Nephrol 2019 06;30(6):1049-1059

Department of Pathology, University of Washington, Seattle, Washington.

Background: In type 1 diabetes, changes in the GFR and urine albumin-to-creatinine ratio (ACR) are related to changes in kidney structure that reflect disease progression. However, such changes have not been studied in type 2 diabetes.

Methods: Participants were American Indians with type 2 diabetes enrolled in a clinical trial of losartan versus placebo. We followed a subset who underwent kidney biopsy at the end of the 6-year trial, with annual measurements of GFR (by urinary clearance of iothalamate) and ACR. Participants had a second kidney biopsy after a mean follow-up of 9.3 years. We used quantitative morphometric analyses to evaluate both biopsy specimens.

Results: Baseline measures for 48 participants (12 men and 36 women, mean age 45.6 years) who completed the study included diabetes duration (14.6 years), GFR (156 ml/min), and ACR (15 mg/g). During follow-up, glomerular basement membrane (GBM) width, mesangial fractional volume, and ACR increased, and surface density of peripheral GBM and GFR decreased. After adjustment for sex, age, ACR, and each morphometric variable at baseline, an increase in ACR during follow-up was significantly associated with increases in GBM width, mesangial fractional volume, and mean glomerular volume, and a decrease in surface density of peripheral GBM. Decline in GFR was not associated with changes in these morphometric variables after additionally adjusting for baseline GFR.

Conclusions: In American Indians with type 2 diabetes and preserved GFR at baseline, increasing ACR reflects the progression of earlier structural glomerular lesions, whereas early GFR decline may not accurately reflect such lesions.
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http://dx.doi.org/10.1681/ASN.2018111166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551789PMC
June 2019

A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes.

Nat Med 2019 05 22;25(5):805-813. Epub 2019 Apr 22.

Research Division, Joslin Diabetes Center, Boston, MA, USA.

Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
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http://dx.doi.org/10.1038/s41591-019-0415-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508971PMC
May 2019

Socioeconomic position and exposure to multiple environmental chemical contaminants in six European mother-child cohorts.

Int J Hyg Environ Health 2019 06 19;222(5):864-872. Epub 2019 Apr 19.

ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain. Electronic address:

Background: Human exposure to environmental chemical contaminants at critical periods of development can lead to lifelong health consequences. Traditionally, socioeconomically disadvantaged groups are thought to experience higher contaminant exposures; however, this relationship may not hold for all contaminants.

Methods: Using data from six European birth cohorts (1301 mother-child pairs), we determined biomarkers of exposure to 41 contaminants in biological samples from children (6-12 years) and their mothers during pregnancy, including organochlorine compounds (OCs), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFASs), metals, phthalate metabolites, phenols, and organophosphate (OP) pesticide metabolites. We analyzed these biomarkers with several socioeconomic position (SEP) indicators (maternal education, employment status and family affluence scale).

Results: Higher SEP was associated with higher concentrations of several chemicals during pregnancy, including certain PFASs, mercury, arsenic, several phenols, and OP pesticides. Similarly, childhood concentrations of OCs, PFASs, mercury, arsenic, and bisphenol A were higher in higher SEP groups. Conversely, cadmium exposure during pregnancy and exposure to lead and phthalate metabolites in childhood were higher in lower SEP. Principal components representing multiple pollutant exposures showed similar association with SEP.

Conclusions: This study demonstrates that environmental chemical contaminant exposure during fetal and childhood life is not exclusively associated to lower SEP and that for several contaminants higher SEP groups incur higher exposure levels.
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http://dx.doi.org/10.1016/j.ijheh.2019.04.002DOI Listing
June 2019

Pap tests for cervical cancer screening test and contraception: analysis of data from the CONSTANCES cohort study.

BMC Cancer 2019 Apr 5;19(1):317. Epub 2019 Apr 5.

Clinical Research Centree CIC1402, INSERM, Department of Obstetrics, Gynecology, and Reproductive Medicine Poitiers University Hospital Centre, University of Poitiers, Poitiers, France.

Background: In France, a Pap test for cervical cancer screening is recommended every three years for all sexually active women aged 25 to 65 years. Modes of contraception (any or no contraception, with or without a visit to a physician, and with or without a gynecological examination) may influence adhesion to screening: women who use intrauterine device (IUD) should be more up to date with their cervical cancer screening more often than those using other means of contraception. Our objectives were to analyze the association between modes of contraception and Pap tests for screening.

Methods: This cross sectional study is based on the CONSTANCES cohort enabled us to include 16,764 women aged 25-50 years. The factors associated with adhesion to cervical cancer screening (defined by a report of a Pap test within the previous 3 years) was modeled by logistic regression. Missing data were imputed by using multiple imputations. The multivariate analyses were adjusted for sex life, social and demographic characteristics, and health status.

Results: Overall, 11.2% (1875) of the women reported that they were overdue for Pap test screening. In the multivariate analysis there was no significant difference between women using an IUD and those pills or implant of pap test overdue ORa:0.9 CI [0.8-1.1], ORa 1.3 CI [0.7-2.7] respectively. Women not using contraceptives and those using non-medical contraceptives (condoms, spermicides, etc.) were overdue more often ORa: 2.6 CI [2.2-3.0] and ORa: 1.8 CI [1.6-2.1] respectively than those using an IUD.

Conclusion: Women seeing medical professionals for contraception are more likely to have Pap tests.
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http://dx.doi.org/10.1186/s12885-019-5477-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451274PMC
April 2019

Urine metabolites are associated with glomerular lesions in type 2 diabetes.

Metabolomics 2018 06 8;14(6):84. Epub 2018 Jun 8.

University of California San Diego, San Diego, CA, USA.

Introduction: Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives: We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods: Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson's correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results: Participants (n = 62, mean age 45 ± 10 years) had mean ± standard deviation glomerular filtration rate of 137 ± 50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14-85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r = 0.29, P = 0.030 and r = 0.50, P < 0.001) and total filtration surface per glomerulus (partial r = 0.32, P = 0.019 and r = 0.43, P = 0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r = 0.32, P = 0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P = 0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P = 0.022).

Conclusions: Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.
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http://dx.doi.org/10.1007/s11306-018-1380-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461445PMC
June 2018
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