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Background Cardiovascular disease (CVD) and nontraumatic lower-limb amputation (LLA) each results in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of CVD and LLA on the risk of mortality in people with type 1 diabetes. Methods We used pooled data from the SURGENE, GENEDIAB, and GENESIS prospective cohorts. Data were divided into: 1/absence of CVD (myocardial infarction and/or stroke) nor LLA, 2/history of CVD alone without LLA, 3/LLA alone without CVD or 4/both conditions at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was any death occurring during follow-up, regardless of the causes. Results Among 1169 participants (male 55%, age 40 ± 13 years, diabetes duration 23 ± 11 years), CVD, LLA or both were present at baseline in 49 (4.2%), 62 (5.3%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 304 (26%) participants during 17-year follow-up, corresponding to 18,426 person-years and an incidence rate of 16 (95%CI, 15–18) per 1000 person-years. The risk of death increased in individuals with baseline history of CVD (adjusted HR 2.00 [95% CI 1.34–3.01], p = 0.0008) or LLA (2.26 [1.56–3.28], p < 0.0001), versus no condition, with an additive effect in people with both conditions (5.32 [3.14–9.00], p < 0.0001). No incremental risk of death was observed in people with CVD versus LLA (0.87 [0.54–1.41]). Compared with no condition, CVD and LLA were similarly associated with reduced life expectancy during follow-up: 2.79 (95% CI 1.26–4.32) and 3.38 (1.87–4.88) years, respectively. Combined conditions expose to 7.04 (4.76–9.31) less years of life expectancy (all p < 0.0001). Conclusions CVD and LLA conferred a similar burden regarding mortality in type 1 diabetes population. Our findings encourage a careful consideration of people with type 1 diabetes and LLA as usually recommended for those with CVD, in terms of management of risk factors, treatments and prevention.

IntroductionThe offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. Orthèse diabète 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 this device in DFU healing.Research, design and methodsThe 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 Orthèse Diabète (experimental device), 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.ResultsAmong 112 randomized patients (men 78%, age 62±10 years), the primary outcome occurred in 19 (33%) participants using conventional device vs 19 (35%) Orthèse Diabète 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 Orthèse Diabète group than in the control group (15% vs 4%). Orthèse Diabète was less frequently worn than conventional devices (46% vs 66%, p=0.04).ConclusionsOrthèse Diabète, 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 numberNCT01956162.

Adrenogenital syndrome is commonly associated with a deficiency in 21-hydroxylase but can be present in other rare enzymatic blocks. We report here the case of a 31-year-old man who presented with bilateral painful testicle lesions leading to bilateral partial orchiectomy as they were suspected for malignancy. These lesions were finally identified as benign testicle adrenal rest tumors (TARTs), and the patient was actually belatedly diagnosed with primary adrenal insufficiency due to 2 mutations of the CYP11A1 gene encoding the cholesterol side-chain cleavage enzyme (P450scc); the mutations were 940G > A (p.Glu314Lys) and c.1393C > T (p.Arg465Trp). The same mutations were found in his 29-year-old sister, who was then also diagnosed for primary adrenal insufficiency. Deficiency in P450scc is an extremely rare genetic autosomal recessive disorder with around 40 described families in the literature and 30 different mutations. As the diagnosis of delayed onset of P450Scc mutation is difficult, this case illustrates the need for a systematic endocrinological assessment in any case of bilateral testicle lesions, thus avoiding unnecessary surgery.

Aims/hypothesisThis is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19).MethodsThe CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days.ResultsWe included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th–75th percentile) 28.4 (25.0–32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5–14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors.Conclusions/interpretationIn patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period.Trial registrationClinicaltrials.gov identifier: NCT04324736

Background Little is known about clinical events occurring in older patients with type 2 diabetes mellitus according to their therapeutic modalities based on the prescription of insulin and/or oral antidiabetic drugs. Objective The aim of this study was to compare the complications of diabetes and geriatric alterations that occurred according to three therapeutic modalities prescribed over 5 years. Methods A total of 616 patients from the GERODIAB cohort (mean age 77.1 years) were divided into three groups: an insulin-only group ( n = 200), a group receiving insulin and one or more oral antidiabetic drug ( n = 169), and an oral antidiabetic drug group without insulin ( n = 247). We compared the diabetic complications and geriatric alterations that occurred over 5 years in patients without these pre-existing complications. Results At inclusion, there was a significant difference between glycosylated hemoglobin values, and between the frequencies of most diabetic complications and geriatric alterations, with higher frequencies in the insulin group and lower frequencies in the oral antidiabetic drug group. At the end of the follow-up, there was still a significant difference between the mean glycosylated hemoglobin of the three groups (mean for all patients 7.4 ± 0.8%). The frequencies of new clinical events were high and they were generally higher in the insulin group. They were not significantly different between the three groups, with the exception of four events: heart failure, retinopathy, transfer to a nursing home (more frequent in the insulin group), and hypoglycemia (more frequent in the insulin + oral antidiabetic drug group). Some frequencies of the total diabetic complications (including complications at inclusion and at the follow-up) in the oral antidiabetic drug group were close to those in the insulin group, although only at inclusion. Mortality was higher in the insulin group and lower in the oral antidiabetic drug group. Conclusions The increased frequency of hypoglycemia in the insulin + oral antidiabetic drug group raises doubts about the value of continuing a secretagogue drug when insulin is introduced. As the vast majority of patients were not yet receiving antidiabetic drugs with cardiovascular action, our results on heart failure could help in conducting specific studies on these drugs in older patients with type 2 diabetes.

Introduction Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system. Methods A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers. Baseline characteristics, reasons for IDegLira initiation, and modes of implementation were collected from the medical records. Changes in HbA 1c and body weight were determined in patients with available follow-up data (nearest 6-month visit). Results IDegLira was initiated in 629 patients previously treated with GLP-1RA alone (11.6%), insulin alone (31.5% including 16.5% with BI and 14.9% with multiple daily injections [MDI]) or a free combination of GLP-1RA and insulin (56.9% including 44.8% with BI and 12.1% with MDI), associated or not with oral agents. IDegLira starting dose (mean of 29 ± 11 dose steps) most often exceeded the recommended dose, and was significantly correlated with prior BI but not GLP-1RA dosage. At initiation, mean age, body mass index (BMI) and HbA 1c were 60.1 ± 10.2 years, 33.4 ± 6.2 kg/m 2 and 8.8 ± 1.7%, respectively. In 461 patients with available follow-up (median 178 days), HbA 1c decreased in all subgroups submitted to treatment intensification (− 1.7 ± 1.8% [ p <  0.0001], − 1.2 ± 1.8% [ p <  0.001] and − 0.8 ± 1.8% [ p =  0.0026] in patients with prior GLP-1RA, BI or MDI therapy, respectively) but also in those switching from BI and GLP-1RA free combination (− 0.2 ± 0.9%, p =  0.0419). Significant body weight gain occurred in patients previously treated with GLP-1RA alone (+ 1.5 ± 5.8 kg, p =  0.0572) or combined to BI (+ 1.0 ± 3.1 kg, p <  0.0001) while those on BI (− 1.4 ± 4.6 kg, p =  0.0139) or MDI (− 1.4 ± 5.0 kg, p =  0.0484) experienced weight loss. Conclusions While providing new information on the use of IDegLira in the French healthcare system, these data confirm the effectiveness of this fixed-ratio combination in the management of T2D.

A 57-year-old woman was found at home in quiet coma secondary to a deliberate insulin glargine injection. Due to the persistent hypoglycemia, she was referred to the ICU where she remained hypoglycemic for seven days. The patient presented recurrent episodes of hypoglycemia, even after day 7 and she received a total of 587 g of dextrose. Few data are available concerning the management of intoxication by long-lasting insulin. Our case illustrates the critical importance of admitting such patients in ICU for both close monitoring of blood sugar and dextrose administration. We discuss the discrepancy between the in vitro half-life of the insulin and the actual half-life with a “reservoir effect”. Eventually, we compare our case with the case-studies in the literature and summarize the review of those published cases.

La prise en charge des patients diabétiques âgés est devenue aujourd'hui un véritable problème de santé publique du fait de l'augmentation du nombre des malades. Dans cette population, les complications du diabète sont plus graves et s'intriquent avec les manifestations plus spécifiquement gérontologiques. L'évaluation gériatrique standardisée est indispensable pour définir la situation de chaque malade selon son degré d'autonomie et de dénutrition, ses fonctions cognitives et son environnement social. Les objectifs thérapeutiques doivent être individualisés en fonction de la présentation clinique du patient. L'insulinothérapie est fréquemment incontournable et nécessite l'éducation du patient ou de son entourage. La prise en charge des patients diabétiques âgés doit éviter un trop grand laxisme chez une personne restée en bonne santé mais aussi un activisme déraisonnable chez les sujets fragiles en raison du risque hypoglycémique.

La question de l'efficacité d'un équilibre glycémique optimal dans la prévention des complications macroangiopathiques du diabète a fait l'objet d'une récente polémique. Si les faits sont clairs pour la microangiopathie notamment au cours du diabète de type 1, ils paraissent moins certains pour les complications cardiovasculaires du diabète de type 2. Cette constatation vient de l'intrication des autres facteurs de risque cardiovasculaires qui sont très fréquents chez ces patients. Cependant, les études de suivi sur une longue durée s'inscrivent en faveur de l'intérêt d'un bon équilibre glycémique sur les complications macroangiopathiques. Les résultats négatifs sur la mortalité de l'étude ACCORD et les inquiétudes concernant la rosiglitazone ont conduit à la mise en place d'études sur la sécurité d'utilisation des nouvelles molécules. Tous ces travaux ont abouti à la démonstration de l'absence de risque des iDPP-4 et de l'effet très positif de certaines molécules de la classe des analogues du GLP-1 et des iSGLT2. Il reste à espérer que la récente mise au point de l'Académie de Médecine soulignant que les complications du diabète de type 2 exigent une prévention multifactorielle qui passe obligatoirement par un contrôle optimisé de l'équilibre glycémique mette fin à une polémique inutile et dangereuse pour nos malades.