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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.A robust signature of circulating inflammatory proteins is causally associated with 10-year risk of progression to end-stage renal disease in diabetic patients

Aims/hypothesisRecently, safety data signalled an increased risk of amputations in people taking canagliflozin, a sodium−glucose cotransporter 2 (SGLT2) inhibitor. If this side effect is due to drug-induced hypovolaemia, diuretics should also increase that risk. The aim of this study was to analyse the association between diuretic use and the risk of lower limb events (LLEs) in people with type 2 diabetes.MethodsSURDIAGENE (SUivi Rénal, DIAbète de type 2 et GENEtique) is a prospective observational cohort that includes people with type 2 diabetes enrolled from 2002 to 2012 and followed-up until onset of LLE, death or 31 December 2015, whichever came first. Primary outcome was the first occurrence of LLE, a composite of lower limb amputation (LLA) and lower limb revascularisation (LLR). The rates of primary outcome were compared between participants taking and not taking diuretics at baseline in a Cox-adjusted model.ResultsAt baseline, of the 1459 participants included, 670 were taking diuretics. In participants with and without diuretics, the mean ages were 67.1 and 62.9 years and 55.8% and 59.8% were men, respectively. During a median follow-up of 7.1 years, the incidence of LLE was 1.80 per 100 patient-years in diuretic users vs 1.00 in non-users (p < 0.001). The HR for LLE in users vs non-users was 2.08 (95% CI 1.49, 2.93), p < 0.001. This association remained significant in a multivariable-adjusted model (1.49 [1.01, 2.19]; p = 0.04) and similar after considering death as a competing risk (subhazard ratio 1.89 [1.35, 2.64]; p < 0.001). When separated, LLA but not LLR, was associated with the use of diuretics: 2.01 (1.14, 3.54), p = 0.02 and 1.05 (0.67, 1.64), p = 0.84, respectively, in the multivariable-adjusted model.Conclusions/interpretationAmong people with type 2 diabetes treated with diuretics, there was a significant increase in the risk of LLE, predominantly in the risk of LLA.

Aims/hypothesisTenascin-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.MethodsWe 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.ResultsWe 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/interpretationIn 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.

PurposeTo determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak.Materials and methodsA 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 (CTcovid) and whole chest CT scan activities (CTchest) 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.ResultsFive hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CTchest 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 CTcovid on CTchest 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 CTcovid (r = 0.73, p = 3.10−16) but no link with the number of positive RT-PCR results.ConclusionIn 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 (CTtotal) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CTcovid).• Across the country, the ratio CTcovid/CTtotalvaried 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.

Aims/hypothesisN-terminal pro-B-type natriuretic peptide (NT-proBNP) is the gold standard prognostic biomarker for diagnosis and occurrence of heart failure. Here, we compared its prognostic value for the occurrence of congestive heart failure with that of plasma mid-region pro-adrenomedullin (MR-proADM), a surrogate for adrenomedullin, a vasoactive peptide with vasodilator and natriuretic properties, in people with type 2 diabetes.MethodsPlasma MR-proADM concentration was measured in baseline samples of a hospital-based cohort of consecutively recruited participants with type 2 diabetes. Our primary endpoint was heart failure requiring hospitalisation.ResultsWe included 1438 participants (age 65 ± 11 years; 604 women and 834 men). Hospitalisation for heart failure occurred during follow-up (median 64 months) in 206 participants; the incidence rate of heart failure was 2.5 (95% CI 2.2, 2.9) per 100 person-years. Plasma concentrations of MR-proADM and NT-proBNP were significantly associated with heart failure in a Cox multivariable analysis model when adjusted for age, diabetes duration, history of coronary heart disease, proteinuria and baseline eGFR (adjHR [95%CI] 1.83 [1.51, 2.21] and 2.20 [1.86, 2.61], respectively, per 1 SD log10 increment, both p < 0.001). MR-proADM contributed significant supplementary information to the prognosis of heart failure when we considered the clinical risk factors (integrated discrimination improvement [IDI, mean ± SEM] 0.021 ± 0.007, p = 0.001) (Table 3). Inclusion of NT-proBNP in the multivariable model including MR-proADM contributed significant complementary information on prediction of heart failure (IDI [mean ± SEM] 0.028 ± 0.008, p < 0.001). By contrast, MR-proADM did not contribute supplementary information on prediction of heart failure in a model including NT-proBNP (IDI [mean ± SEM] 0.003 ± 0.003, p = 0.27), with similar results for heart failure with reduced ejection fraction and preserved ejection fraction.Conclusions/interpretationMR-proADM is a prognostic biomarker for heart failure in people with type 2 diabetes but gives no significant complementary information on prediction of heart failure compared with NT-proBNP.

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.

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 95% [0.8–1.1], ORa 1.3 CI 95% [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 95% [2.2–3.0] and ORa: 1.8 CI 95% [1.6–2.1] respectively than those using an IUD. Conclusion Women seeing medical professionals for contraception are more likely to have Pap tests.

Background Cardiovascular disease and kidney damage are tightly associated in people with type 2 diabetes. Experimental evidence supports a causal role for vasopressin (or antidiuretic hormone) in the development of diabetic kidney disease (DKD). Plasma copeptin, the COOH-terminal portion of pre-provasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the development and progression of DKD. Here we assessed the association of plasma copeptin with the risk of cardiovascular events during follow-up in two prospective cohorts of type 2 diabetic patients, and we examined if this association could be mediated by deleterious effects of vasopressin on the kidney. Methods We studied 3098 and 1407 type 2 diabetic patients from the French cohorts DIABHYCAR and SURDIAGENE, respectively. We considered the incidence during follow-up (median: 5 years) of a combined end point composed of myocardial infarction, coronary revascularization, hospitalization for congestive heart failure, or cardiovascular death. Copeptin concentration was measured in baseline plasma samples by an immunoluminometric assay. Results The cumulative incidence of cardiovascular events during follow-up by sex-specific tertiles of baseline plasma copeptin was 15.6% (T1), 18.7% (T2) and 21.7% (T3) in DIABHYCAR (p = 0.002), and 27.7% (T1), 34.1% (T2) and 47.6% (T3) in SURDIAGENE (p < 0.0001). Cox proportional hazards survival regression analyses confirmed the association of copeptin with cardiovascular events in both cohorts: hazard ratio with 95% confidence interval for T3 vs. T1 was 1.29 (1.04–1.59), p = 0.02 (DIABHYCAR), and 1.58 (1.23–2.04), p = 0.0004 (SURDIAGENE), adjusted for sex, age, BMI, duration of diabetes, systolic blood pressure, arterial hypertension, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, estimated glomerular filtration rate (eGFR), urinary albumin concentration (UAC), active tobacco smoking, and previous history of myocardial infarction at baseline. No interaction was observed between plasma copeptin and eGFR (p = 0.40) or UAC (p = 0.61) categories on the risk of cardiovascular events in analyses of pooled cohorts. Conclusions Plasma copeptin was positively associated with major cardiovascular events in people with type 2 diabetes. This association cannot be solely accounted for by the association of copeptin with kidney-related traits.

Background: iron deficiency (ID) is frequent in older patients. Purpose: to evaluate the association between ID and survival in patients ≥ 75 years old with confirmed solid tumors. Methods: a retrospective monocentric study including patients between 2009 and 2018. ID, absolute ID (AID) and functional ID (FID) were defined according to the European Society for Medical Oncology (ESMO) criteria. Severe ID was defined by a ferritin level < 30 µg/L. Results: in total, 556 patients were included, the mean age was 82 (±4.6) years, 56% were male, the most frequent cancer was colon cancer (19%, n = 104), and metastatic cancers were found in 38% (n = 211). Median follow-up time: 484 [190–1377] days. In anemic patients, ID and FID were independently associated with an increased risk of mortality (respectively, HR 1.51; p = 0.0065 and HR 1.73; p = 0.0007). In non-anemic patients, FID was independently associated with better survival (HR 0.65; p = 0.0495). Conclusion: in our study, ID was significantly associated with survival, and with better survival for patients without anemia. These results suggest that attention should be paid to the iron status in older patients with tumors and raise questions about the prognostic value of iron supplementation for iron-deficient patients without anemia.

Background Data on the relationship between potassium intake and major cardiovascular events (MACE) in patients with diabetes are scarce. We aim to study the association between estimated potassium intake and risk of MACE in individuals with type 2 diabetes. Methods The discovery cohort consisted of 1572 participants with type 2 diabetes from a secondary hospital. The validation cohort consisted of 1430 participants with diabetes from a multicenter study (Chronic Renal Insufficiency Cohort, CRIC). Potassium intake was estimated from potassium in spot urine using Kawasaki formula and in 24-h urine collection in two cohorts, respectively. The primary outcome was MACE defined as a composite of myocardial infarction, stroke and cardiovascular death. Results During a median of 8.2 years of follow-up, 341 MACE events were identified in discovery cohort. Compared to the lowest tertile, participants with potassium intake in the top tertile had 34% lower risk for MACE after adjustment for cardio-renal risk factors (adjusted hazard ratio, aHR [95% CI], 0.66 [0.49–0.89]). This inverse association was more pronounced in participants with normal or moderately elevated albuminuria as compared to those with severely elevated albuminuria (urine albumin-to-creatinine ratio > 300 mg/g, p for interaction < 0.05). In consistence, a higher potassium intake was independently associated with a lower risk of MACE in CRIC participants with diabetes and moderately elevated albuminuria (aHR 0.61 [0.42–0.90], top vs. lowest tertile). Conclusions A high level potassium intake estimated from urine potassium excretion was independently associated with a low risk of MACE in patients with type 2 diabetes. Increasing potassium intake may be a potential effective strategy for cardiovascular risk reduction beyond controlling traditional risk factors.