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AIMS/HYPOTHESIS: Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question. METHODS: The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes. RESULTS: A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p<0.001). After multiple adjustments for age, BMI, uCCi, clinical (time between onset of COVID-19 symptoms and dyspnoea) and biological variables (eGFR, aspartate aminotransferase, white cell count, platelet count, C-reactive protein) on admission to hospital, diabetes remained associated with a higher risk of primary composite endpoint within 7 days (adjusted HR 1.42 [95% CI 1.17, 1.72], p<0.001) and 28 days (adjusted HR 1.30 [95% CI 1.09, 1.55], p=0.003), compared with individuals without diabetes. Using the same adjustment model, diabetes was associated with the risk of IMV, but not with risk of death, within 28 days of admission to hospital. CONCLUSIONS/INTERPRETATION: Our results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324736.
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COVID-19 , Diabetes Mellitus , COVID-19/epidemiologia , Estudos de Coortes , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Prognóstico , SARS-CoV-2RESUMO
Many variables impact islet isolation, including pancreas ischemia time. The ischemia time upper limit that should be respected to avoid a negative impact on the isolation outcome is not well defined. We have performed a retrospective analysis of all islet isolations in our center between 2008 and 2018. Total ischemia time, cold ischemia time, and organ removal time were analyzed. Isolation success was defined as an islet yield ≥200 000 IEQ. Of the 452 pancreases included, 288 (64%) were successfully isolated. Probability of isolation success showed a significant decrease after 8 hours of total ischemia time, 7 hours of cold ischemia time, and 80 minutes of organ removal time. Although we observed an impact of ischemia time on islet yield, a probability of isolation success of 50% was still present even when total ischemia time exceeds 12 hours. Posttransplantation clinical outcomes were assessed in 32 recipients and no significant difference was found regardless of ischemia time. These data indicate that although shorter ischemia times are associated with better islet isolation outcomes, total ischemia time >12 hours can provide excellent results in appropriately selected donors.
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Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Soluções para Preservação de Órgãos , Humanos , Isquemia , Pâncreas , Estudos RetrospectivosRESUMO
To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a 10-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% (6.2-8.0) (55 mmol/mol [44-64]) versus 8.0% (7.1-9.1) (64 mmol/mol [54-76]) before transplantation (p < .001). Seventeen of 23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patients (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml (0.2-1.2). Insulin requirements (UI/kg/day) were 0.3 (0.1-0.5) versus 0.5 (0.4-0.6) before transplantation (p < .001). Median (IQR) ß-score was 1 (0-4) (p < .05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow-up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.
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Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Glicemia , Diabetes Mellitus Tipo 1/cirurgia , Humanos , Estudos Retrospectivos , Suíça , Resultado do TratamentoRESUMO
A post hoc analysis of the Diabeloop WP7 multicentre, randomized controlled trial was performed to investigate the efficacy of the Diabeloop Generation-1 (DBLG1) closed-loop system in controlling the hypoglycaemia induced by physical activity (PA) in real-life conditions. Glycaemic outcomes were compared between days with and without PA in 56 patients with type 1 diabetes (T1D) using DBLG1 for 12 weeks. After the patient announces a PA, DBLG1 reduces insulin delivery and, if necessary, calculates the amount of preventive carbohydrates (CHO). Daily time spent in the interstitial glucose range less than 70 mg/dL was not significantly different between days with and without PA (2.0% ± 1.5% vs. 2.2% ± 1.1%), regardless of the intensity or duration of the PA. Preventive CHO intake recommended by the system was significantly higher in days with PA (41.1 ± 35.5 vs. 21.8 ± 28.5 g/day; P < .0001), and insulin delivery was significantly lower (31.5 ± 10.5 vs. 34.0 ± 10.5 U/day; P < .0001). The time spent in hyperglycaemia and the glycaemic variation coefficient increased significantly on days with PA. In real-life conditions, the use of DBLG1 avoids PA-induced hypoglycaemia. Insulin adjustments and preventive CHO recommendation may explain this therapeutic benefit.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Dieta , Exercício Físico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de InsulinaRESUMO
The authors regret a mistake in Table 1.
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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/m2; 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, HbA1c, 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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Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/virologia , Pneumonia Viral/patologia , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/patologia , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/terapia , Prognóstico , Respiração Artificial/estatística & dados numéricos , Fatores de RiscoRESUMO
AIMS: To compare closed-loop (CL) and open-loop (OL) systems for glycaemic control in patients with type 1 diabetes (T1D) exposed to real-life challenging situations (gastronomic dinners or sustained physical exercise). METHODS: Thirty-eight adult patients with T1D were included in a three-armed randomized pilot trial (Diabeloop WP6.2 trial) comparing glucose control using a CL system with use of an OL device during two crossover 72-hour periods in one of the three following situations: large (gastronomic) dinners; sustained and repeated bouts of physical exercise (with uncontrolled food intake); or control (rest conditions). Outcomes included time in spent in the glucose ranges of 4.4-7.8 mmol/L and 3.9-10.0 mmol/L, and time in hypo- and hyperglycaemia. RESULTS: Time spent overnight in the tight range of 4.4 to 7.8 mmol/L was longer with CL (mean values: 63.2% vs 40.9% with OL; P ≤ .0001). Time spent during the day in the range of 3.9 to 10.0 mmol/L was also longer with CL (79.4% vs 64.1% with OL; P ≤ .0001). Participants using the CL system spent less time during the day with hyperglycaemic excursions (glucose >10.0 mmol/L) compared to those using an OL system (17.9% vs 31.9%; P ≤ .0001), and the proportions of time spent during the day with hyperglycaemic excursions of those using the CL system in the gastronomic dinner and physical exercise subgroups were of similar magnitude to those in the control subgroup (18.1 ± 6.3%, 17.2 ± 8.1% and 18.4 ± 12.5%, respectively). Finally, times spent in hypoglycaemia were short and not significantly different among the groups. CONCLUSIONS: The Diabeloop CL system is superior to OL devices in reducing hyperglycaemic excursions in patients with T1D exposed to gastronomic dinners, or exposed to physical exercise followed by uncontrolled food and carbohydrate intake.
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Diabetes Mellitus Tipo 1 , Adulto , Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício Físico , Controle Glicêmico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , RefeiçõesRESUMO
AIM: To evaluate the effect of adding the dipeptidyl-peptidase-4 inhibitor vildagliptin to insulin on the glycaemic control of patients with type 2 diabetes undergoing haemodialysis. METHODS: Overall, 65 insulin-treated patients with type 2 diabetes undergoing haemodialysis (HbA1c: 7.3% ± 1.1%; age: 70.5 ± 8.5 years) were randomized (1:1) either to receive vildagliptin 50 mg/day in addition to insulin (vildagliptin-insulin group) or to pursue their usual insulin regimen (insulin-only group). Continuous glucose monitoring (CGM) was performed for 48 ± 6 hours at baseline and at week 12. The primary study endpoint was change from baseline in mean interstitial glucose using CGM. The secondary endpoints included other CGM variables and glucose control markers. RESULTS: After 12 weeks, a greater reduction in mean CGM glucose from baseline was observed in the vildagliptin-insulin group compared with the insulin-only group, although the between-treatment difference was not statistically significant (mean difference [CI 95%]: -0.96 mmol/L [-2.09; 0.18] vs. -0.29 mmol/L [-1.29; 0.76], P = 0.32). However, a significant decrease from baseline in HbA1c, glycated albumin and insulin daily doses was observed in the vildagliptin-insulin group versus the insulin-only group (-0.6% [-1.19; -0.1], P < 0.01), in the vildagliptin-insulin group versus no change in the insulin-only group (-130.6 µmol/L [-271; 10.7] vs. +36.2 µmol/L [-164.4; 236.9], P = 0.04 and - 5.9 IU/day [-1.8; 7.1] vs. +1.1 IU/day [-14.5; 16.6], P = 0.01, respectively). There was no significant difference in the percentage of time spent in hypoglycaemia using CGM, occurrence of severe hypoglycaemia or number of adverse events. CONCLUSION: In this study, vildagliptin added to insulin improved glycaemic control with an associated insulin-sparing effect in patients with type 2 diabetes undergoing haemodialysis and was well tolerated.
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Adamantano , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Insulina , Diálise Renal , Vildagliptina , Adamantano/efeitos adversos , Idoso , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Estudos Prospectivos , Pirrolidinas , Vildagliptina/uso terapêuticoRESUMO
The recent advent of immune checkpoint inhibitors (ICI), including anti-programmed cell death 1 protein (anti-PD-1) agents has revolutionized the therapeutic approach of metastatic malignancies. Yet, ICI can disrupt immune tolerance resulting in enhanced immune activation in normal tissues with significant toxicity. A dysregulated activation of T-cells directed to normal tissues stands as the main mechanism of immune-related adverse events (irAE). To date, only two cases of immune-related inflammatory orbitopathy related to anti-PD-1 agents have been reported. This rare immune adverse event usually occurred early after ICI initiation. Here, we report the first case of late inflammatory orbitopathy occurring in a melanoma patient treated with pembrolizumab. Consequently, the occurrence of irAE under ICI should be monitored, even late after treatment instauration.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Inflamação/patologia , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Doenças Orbitárias/patologia , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Anti-Inflamatórios/administração & dosagem , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Melanoma/patologia , Metilprednisolona/administração & dosagem , Doenças Orbitárias/induzido quimicamente , Doenças Orbitárias/tratamento farmacológico , Prognóstico , Neoplasias Cutâneas/patologiaRESUMO
TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: -1.44% and G3: -1.48% vs. G1: -0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/administração & dosagem , Insulina/uso terapêutico , Pessoa de Meia-IdadeRESUMO
The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.
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Contaminação de Medicamentos/estatística & dados numéricos , Transplante das Ilhotas Pancreáticas/estatística & dados numéricos , Soluções para Preservação de Órgãos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Ilhotas Pancreáticas/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Infecções por Coronavirus , Hiperglicemia , Pandemias , Pneumonia Viral , Betacoronavirus , Glicemia , COVID-19 , Humanos , SARS-CoV-2RESUMO
Islet grafts isolated from young donors allow superior functional outcomes but are often associated with poor islet isolation yields. The objective of this study was to comparatively analyze the outcomes of islet isolation between young and older donors. We retrospectively analyzed 564 pancreas isolations performed at our institution. Isolation outcomes were compared between donors aged ≤20 years (n = 42, YD) and >20 years (n = 522, OD). Isolation procedure was identical in both groups. Prepurification percentage of embedded islets was higher in YD (44.3 ± 22.7% vs. 24.9 ± 20.9%, P < 0.001). This led to a lower recovery rate in YD (48% vs. 76%, P = 0.002) and hence lower postpurification IEQ/g pancreas in YD (2 412 ± 1 789 IEQ/g vs. 3 194 ± 1 892 IEQ/g, P = 0.01). Final yield was 180 982 ± 128 073 IEQ in YD and 244 167 ± 134 137 IEQ in OD, (P = 0.006). In vitro function was markedly, albeit nonsignificantly, higher in YD (SI: 4.5 ± 5.1 vs. 3.0 ± 5.7, P = 0.350). Proportion of transplanted preparations was similar in both groups, 38% (16/42) in YD vs. 43% (224/522) in OD, P = 0.628. In spite of isolation and purification difficulties, pancreases from young donors allowed similar islet transplantation rates as older donors. Efforts should be directed at improving islet extraction in these donors to realize their full potential for islet transplantation.
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Separação Celular/métodos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Pâncreas/citologia , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodos , Adolescente , Fatores Etários , Causas de Morte , Contagem de Células , Separação Celular/instrumentação , Criança , Isquemia Fria , Colagenases , Ficoll , Sobrevivência de Enxerto , Humanos , Transplante das Ilhotas Pancreáticas/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To evaluate the effects of the replacement of ceftriaxone by cefotaxime on the incidence of third-generation cephalosporin-resistant Enterobacterales (3GC-RE). PATIENTS AND METHODS: We conducted a 24-month monocentric prospective, stepped-wedge cluster randomized controlled trial. During the control phase of the study, clinicians prescribed either ceftriaxone or cefotaxime. During the intervention phase, they systematically prescribed cefotaxime. RESULTS: The cefotaxime/ceftriaxone ratio was inversely correlated with the incidence of 3GC-RE. All in all, 3GC-RE incidence was 1.05 (27/25,692) acquired cases/1000 hospitalization days during the control phase and 0.54 (11/20,419) acquired cases/1000 hospitalization days during the intervention phase (incidence rate ratio [IRR] = 0.51 [0.22-1.07], p = 0.06). In multivariable analysis, intervention phase (versus control phase) (p = 0.007), cefotaxime/ceftriaxone ratio (p = 0.003) and imported 3GC-RE (p = 0.005) were associated with the incidence of acquired cases of 3GC-RE. CONCLUSIONS: We found that replacing ceftriaxone with cefotaxime reduced the occurrence of 3GC-RE isolates. More studies are needed to confirm these results.
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Cefotaxima , Ceftriaxona , Humanos , Cefotaxima/farmacologia , Cefotaxima/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Estudos ProspectivosRESUMO
INTRODUCTION: The transition from paediatric to adult diabetes care (TPA) of children/adolescents with type 1 diabetes (T1D) represents a unique challenge and remains a critical phase in the T1D care pathway. This study aims to describe and understand the experience of the transition process from a participant's perspective in young adults who are living in France with T1D and to measure their satisfaction. METHODS: An online questionnaire was presented to people with T1D in France on a global online participant community platform. The questionnaire was developed by a scientific committee including paediatric and adult diabetologists and refined by a group of participants. Thematic qualitative analysis was performed on the responses. RESULTS: A total of 104 respondents were included in the survey (mean age 24.4 years [95% CI 23.8-25.0]; 61.5% female). The mean age at the time of transition was 18.4 years (95% CI 17.8-18.9), and 56% of respondents had their first adult diabetology follow-up in the same institution. During TPA, of the 76 participants who experienced personal issues, 74% experienced at least one issue with their diabetes management in the months following the transition. In the following months, 61% experienced new or unexpected problems in monitoring their diabetes after transition and 44% reported unusual glycaemic imbalances, including hypoglycaemia (8%) and hyperglycaemia (9%) requiring hospitalisation. Presence of personal issues during TPA was significantly associated with occurrence of problems with diabetes management or glycaemic imbalance. Three factors identified for a successful transition were (i) early meeting with the 'adult' diabetes care team, (ii) letting the participants choose the right age to leave paediatric clinic and (iii) having good diabetes control at the beginning of the TPA process. CONCLUSION: Most young adults with T1D report experiencing issues around TPA with significant consequences on their disease management. Hence, it is necessary to identify these issues to better support them and improve diabetes management during this phase.
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Aim: To evaluate the evolution of glycemic outcomes in patients living with type 1 diabetes (T1D) after 1 year of use of the MiniMed 780G advanced hybrid closed-loop (AHCL) system. Methods: We conducted an observational, retrospective, multicentric study in 20 centers in France. The primary objective was to evaluate the improvement in glycemic control after 1-year use of AHCL. The primary endpoint was the variation of time in range (TIR) between pre-AHCL and after 1-year use of AHCL. Secondary objectives were to analyze the glycemic outcomes after 3, 6, and 12 months of AHCL use, the safety, and the long-term observance of AHCL. Results: Two hundred twenty patients were included, and 200 were analyzed for the primary endpoint. 92.7% of patients continued to use AHCL. After 1 year of use of AHCL, TIR was 72.5% ± 10.6% (+9.1%; 95% confidence interval [CI] [7.6-10.5] compared to pre-AHCL initiation, P < 0.001), HbA1c 7.1% ± 0.7% (-0.5%; 95% CI [-0.6 to -0.4]; P < 0.001), time below range 2.0% [1.0; 3.0] (0.0% [-2.0; 0.0], P < 0.001), and time above range 24.8% ± 10.9% (-7.3%; 95% CI [-8.8 to -5.7]; P < 0.001). More patients achieved the glycemic treatment goals of HbA1c <7.0% (45.1% vs. 18.1%, P < 0.001) and TIR >70% (59.0% vs. 29.5% P < 0.001) when compared with pre-AHCL. Five patients experienced severe hypoglycemia events and two patients experienced ketoacidosis. Conclusion: After 1 year of use of AHCL, people living with T1D safely improved their glucose control and a higher proportion of them achieved optimal glycemic control.
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Automonitorização da Glicemia , Glicemia , Diabetes Mellitus Tipo 1 , Controle Glicêmico , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Estudos Retrospectivos , Masculino , Feminino , França , Adulto , Glicemia/análise , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Controle Glicêmico/métodos , Insulina/administração & dosagem , Insulina/uso terapêutico , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Resultado do Tratamento , Hipoglicemia/prevenção & controle , Hipoglicemia/induzido quimicamenteRESUMO
Liver receptor homolog (LRH-1) is an orphan nuclear receptor (NR5A2) that regulates cholesterol homeostasis and cell plasticity in endodermal-derived tissues. Estrogen increases LRH-1 expression conveying cell protection and proliferation. Independently, estrogen also protects isolated human islets against cytokine-induced apoptosis. Herein, we demonstrate that LRH-1 is expressed in islets, including ß-cells, and that transcript levels are modulated by 17ß-estradiol through the estrogen receptor (ER)α but not ERß signaling pathway. Repression of LRH-1 by siRNA abrogated the protective effect conveyed by estrogen on rat islets against cytokines. Adenoviral-mediated overexpression of LRH-1 in human islets did not alter proliferation but conferred protection against cytokines and streptozotocin-induced apoptosis. Expression levels of the cell cycle genes cyclin D1 and cyclin E1 as well as the antiapoptotic gene bcl-xl were unaltered in LRH-1 expressing islets. In contrast, the steroidogenic enzymes CYP11A1 and CYP11B1 involved in glucocorticoid biosynthesis were both stimulated in transduced islets. In parallel, graded overexpression of LRH-1 dose-dependently impaired glucose-induced insulin secretion. Our results demonstrate the crucial role of the estrogen target gene nr5a2 in protecting human islets against-stressed-induced apoptosis. We postulate that this effect is mediated through increased glucocorticoid production that blunts the pro-inflammatory response of islets.
Assuntos
Apoptose , Regulação da Expressão Gênica , Células Secretoras de Insulina/metabolismo , Receptores Citoplasmáticos e Nucleares/biossíntese , Estresse Fisiológico , Adenoviridae , Animais , Linhagem Celular Tumoral , Colesterol/biossíntese , Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclina E/genética , Ciclina E/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios/genética , Estrogênios/metabolismo , Humanos , Insulina/genética , Insulina/metabolismo , Secreção de Insulina , Camundongos , Camundongos Knockout , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 11-beta-Hidroxilase/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
BACKGROUND AND AIM: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC. METHODS: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality. RESULTS: Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin. CONCLUSIONS: One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.
Assuntos
Testes de Função do Córtex Suprarrenal , Doenças das Glândulas Suprarrenais/diagnóstico , Hemodinâmica , Hidrocortisona/sangue , Cirrose Hepática/diagnóstico , Doenças das Glândulas Suprarrenais/sangue , Doenças das Glândulas Suprarrenais/mortalidade , Doenças das Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Cosintropina , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/sangue , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Regulação para CimaRESUMO
The year 2021 saw the 100-year celebration of the discovery of insulin as a treatment for type 1 diabetes, saving lives of people previously condemned by the disease. However, insulin replacement, so different from physiological secretion, remains a challenge. Until the 1990s, people living with type 1 diabetes were treated with two injections of intermediate insulin and prandial regular insulin injections. Their kinetics led to frequent hypoglycemia, justifying meals taken at fixed times, with fixed amount of carbohydrates avoiding fast sugars. The development of rapid and then long acting insulin analogues in the 1990s and 2000s and the principle of patient empowerment have reduced these constraints by introducing the notion of functional insulin therapy, dissociating meals managed by rapid insulins from basal insulin (= insulin for living). Meals can be taken at variable times, with variable carbohydrate content and without food restrictions. But the revolution started 5 years ago, with the development of continuous glucose monitoring systems, freeing the patient from blood glucose controls, coupled thereafter to an insulin pump driven by artificial intelligence in the very recent hybrid closed-loop systems. These systems showed significant glucose control improvement, together with reduction of both the time spent in hypoglycemia and the mental burden on the individual, pending a cure for the disease for the next century.
Title: Cent ans après la découverte de l'insuline : une nouvelle révolution pour les patients vivant avec un diabète de type 1 ? Abstract: L'année 2021 a vu célébrer le centenaire de la découverte de l'insuline comme traitement du diabète de type 1, sauvant la vie de personnes condamnées auparavant par la maladie. La substitution insulinique, tellement différente de la sécrétion physiologique, reste cependant un défi. Jusque dans les années 1990, les personnes vivant avec un diabète de type 1 étaient traitées par deux injections d'insuline intermédiaire, d'une durée d'action de 12 à 16 h, et des injections d'insuline rapide humaine, d'une durée d'action de 7 h environ, dont la cinétique entraînait des hypoglycémies fréquentes justifiant des repas pris à heures fixes, une quantité de glucides fixe et des collations obligatoires en évitant les sucres rapides. Le développement des analogues rapides (durée d'action de 4 h) puis lents (sans pic d'action) de l'insuline dans les années 1990 et 2000 et de l'éducation thérapeutique ont permis un allègement de ces contraintes. Ils ont permis aussi l'essor de l'insulinothérapie fonctionnelle, dissociant les repas, gérés par les insulines rapides, de l'insuline lente (c'est-à-dire l'insuline vitale), permettant des repas à horaires variables, à contenus variables et sans restriction d'aliments. Mais la grande révolution vient de ces cinq dernières années, avec l'apparition des capteurs de mesure du glucose en continu, libérant le patient des contrôles glycémiques capillaires, couplés par la suite à une pompe à insuline pilotée par une intelligence artificielle dans les systèmes très récents de boucle fermée hybride. Ces systèmes permettent une amélioration majeure du contrôle de la glycémie, en réduisant à la fois le temps passé en hypoglycémie et la charge mentale de la personne.