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1.
Artículo en Inglés | MEDLINE | ID: mdl-38614158

RESUMEN

We currently have a large sum of clinical and experimental data documenting the involvement of numerous adipokines in the maintenance of energy homeostasis in healthy individuals and their dysregulation in diseases such as obesity, metabolic syndrome or type 2 diabetes. Despite the impressive discoveries made in this field over many years, much remains to be done before understanding all the physiological and pathological implications, and hoping for the development of other effective and safe therapeutic strategies. Two original adipokines will be taken as examples to illustrate these remarks, chemerin and neuregulin 4.

2.
Orphanet J Rare Dis ; 19(1): 177, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678257

RESUMEN

BACKGROUND: Rare syndromes of lipodystrophy and insulin-resistance display heterogeneous clinical expressions. Their early recognition, diagnosis and management are required to avoid long-term complications. OBJECTIVE: We aimed to evaluate the patients' age at referral to our dedicated national reference center in France and their elapsed time from first symptoms to diagnosis and access to specialized care. PATIENTS AND METHODS: We analyzed data from patients with rare lipodystrophy and insulin-resistance syndromes referred to the coordinating PRISIS reference center (Adult Endocrine Department, Saint-Antoine Hospital, AP-HP, Paris), prospectively recorded between 2018 and 2023 in the French National Rare Disease Database (BNDMR, Banque Nationale de Données Maladies Rares). RESULTS: A cohort of 292 patients was analyzed, including 208 women, with the following diagnosis: Familial Partial LipoDystrophy (FPLD, n = 124, including n = 67 FPLD2/Dunnigan Syndrome); Acquired lipodystrophy syndromes (n = 98, with n = 13 Acquired Generalized Lipodystrophy, AGL); Symmetric cervical adenolipomatosis (n = 27, Launois-Bensaude syndrome, LB), Congenital generalized lipodystrophy (n = 18, CGL) and other rare severe insulin-resistance syndromes (n = 25). The median age at referral was 47.6 years [IQR: 31-60], ranging from 25.2 (CGL) to 62.2 years old (LB). The median age at first symptoms of 27.6 years old [IQR: 16.8-42.0]) and the median diagnostic delay of 6.4 years [IQR: 1.3-19.5] varied among diagnostic groups. The gender-specific expression of lipodystrophy is well-illustrated in the FPLD2 group (91% of women), presenting with first signs at 19.3 years [IQR: 14.4-27.8] with a diagnostic delay of 10.5 years [IQR: 1.8-27.0]. CONCLUSION: The national rare disease database provides an important tool for assessment of care pathways in patients with lipodystrophy and rare insulin-resistance syndromes in France. Improving knowledge to reduce diagnostic delay is an important objective of the PRISIS reference center.


Asunto(s)
Resistencia a la Insulina , Lipodistrofia , Humanos , Femenino , Masculino , Resistencia a la Insulina/fisiología , Lipodistrofia/diagnóstico , Lipodistrofia/metabolismo , Adulto , Persona de Mediana Edad , Adulto Joven , Francia , Adolescente , Derivación y Consulta
3.
Hum Reprod ; 39(6): 1167-1175, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38600622

RESUMEN

Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women. It is associated with increased risks of metabolic syndrome, Type 2 diabetes, cardiovascular diseases, mood disorders, endometrial cancer and non-alcoholic fatty liver disease. Although various susceptibility loci have been identified through genetic studies, they account for ∼10% of PCOS heritability. Therefore, the etiology of PCOS remains unclear. This review explores the role of epigenetic changes and modifications in circadian clock genes as potential contributors to PCOS pathogenesis. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNA changes, have been described in diseases related to PCOS, such as diabetes, cardiovascular diseases, and obesity. Furthermore, several animal models have illustrated a link between prenatal exposure to androgens or anti-Müllerian hormone and PCOS-like phenotypes in subsequent generations, illustrating an epigenetic programming in PCOS. In humans, epigenetic changes have been reported in peripheral blood mononuclear cells (PBMC), adipose tissue, granulosa cells (GC), and liver from women with PCOS. The genome of women with PCOS is globally hypomethylated compared to healthy controls. However, specific hypomethylated or hypermethylated genes have been reported in the different tissues of these women. They are mainly involved in hormonal regulation and inflammatory pathways, as well as lipid and glucose metabolism. Additionally, sleep disorders are present in women with PCOS and disruptions in clock genes' expression patterns have been observed in their PBMC or GCs. While epigenetic changes hold promise as diagnostic biomarkers, the current challenge lies in distinguishing whether these changes are causes or consequences of PCOS. Targeting epigenetic modifications potentially opens avenues for precision medicine in PCOS, including lifestyle interventions and drug therapies. However, data are still lacking in large cohorts of well-characterized PCOS phenotypes. In conclusion, understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS in the future.


Asunto(s)
Relojes Circadianos , Metilación de ADN , Epigénesis Genética , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/genética , Femenino , Relojes Circadianos/genética , Animales
4.
Artículo en Inglés | MEDLINE | ID: mdl-38452868

RESUMEN

Lipodystrophy syndromes are rare diseases primarily affecting the development or maintenance of the adipose tissue but are also distressing indirectly multiple organs and tissues, often leading to reduced life expectancy and quality of life. Lipodystrophy syndromes are multifaceted disorders caused by genetic mutations or autoimmunity in the vast majority of cases. While many subtypes are now recognized and classified, the disease remains remarkably underdiagnosed. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of European centers of excellence working in the field of lipodystrophies aiming at promoting international collaborations to increase basic scientific understanding and clinical management of these syndromes. The network has developed a European Patient Registry as a collaborative research platform for consortium members. ECLip and ECLip registry activities involve patient advocacy groups to increase public awareness and to seek advice on research activities relevant from the patients perspective. The annual ECLip congress provides updates on the research results of various network groups members.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38287910

RESUMEN

CONTEXT: Outcome of craniopharyngioma is related to its locoregional extension, which impacts resectability and the risk of surgical complications. To maximize resection and minimize complications, optic tract localization, temporal lobe extension and hypothalamic involvement are essential for surgical management. OBJECTIVE: To assess the outcome of craniopharyngiomas depending on their relation to the hypothalamus location. METHODS: We conducted a retrospective analysis of 79 patients with a craniopharyngioma who underwent surgery from 2007 to 2022. Craniopharyngiomas were classified in three groups, depending on the type of hypothalamus involvement assessed by preoperative MRI: infra-hypothalamic (type A, n=33); perforating the hypothalamus (type B, n=40); supra-hypothalamic (type C, n=6). Surgical strategy was guided by the type of hypothalamic involvement, favoring endonasal approaches for type A and type B, and transcranial approaches for type C. RESULTS: Long-term disease control was achieved in 33/33 (100%), 37/40 (92%) and 5/6 (83%) patients in type A, B and C respectively. In type B, vision was improved in 32/36 (89%) patients, while hypothalamic function was improved, stable or worsened in 6/40 (15%), 32/40 (80%) and 2/40 (5%) patients respectively. Papillary craniopharyngiomas were found in 5/33 (15%), 9/40 (22%) and 3/6 (50%) patients in types A, B and C respectively. In four patients, BRAF/MEK inhibitors were used, with significant tumor shrinkage in all cases. CONCLUSION: Craniopharyngiomas located below the hypothalamus or perforating it can be safely treated by transsphenoidal surgery. For supra-hypothalamic craniopharyngiomas, postoperative results are less favorable, and documenting a BRAF-mutation may improve outcome, if targeted therapy was efficient enough to replace surgical debulking.

6.
Diabetes ; 73(2): 211-224, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37963392

RESUMEN

In humans, glucocorticoids (GCs) are commonly prescribed because of their anti-inflammatory and immunosuppressive properties. However, high doses of GCs often lead to side effects, including diabetes and lipodystrophy. We recently reported that adipocyte glucocorticoid receptor (GR)-deficient (AdipoGR-KO) mice under corticosterone (CORT) treatment exhibited a massive adipose tissue (AT) expansion associated with a paradoxical improvement of metabolic health compared with control mice. However, whether GR may control adipose development remains unclear. Here, we show a specific induction of hypoxia-inducible factor 1α (HIF-1α) and proangiogenic vascular endothelial growth factor A (VEGFA) expression in GR-deficient adipocytes of AdipoGR-KO mice compared with control mice, together with an increased adipose vascular network, as assessed by three-dimensional imaging. GR activation reduced HIF-1α recruitment to the Vegfa promoter resulting from Hif-1α downregulation at the transcriptional and posttranslational levels. Importantly, in CORT-treated AdipoGR-KO mice, the blockade of VEGFA by a soluble decoy receptor prevented AT expansion and the healthy metabolic phenotype. Finally, in subcutaneous AT from patients with Cushing syndrome, higher VEGFA expression was associated with a better metabolic profile. Collectively, these results highlight that adipocyte GR negatively controls AT expansion and metabolic health through the downregulation of the major angiogenic effector VEGFA and inhibition of vascular network development.


Asunto(s)
Glucocorticoides , Receptores de Glucocorticoides , Humanos , Ratones , Animales , Glucocorticoides/farmacología , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Angiogénesis , Adipocitos/metabolismo , Obesidad/metabolismo , Corticosterona/farmacología , Corticosterona/metabolismo , Tejido Adiposo/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
7.
Eur J Endocrinol ; 190(1): 23-33, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38128113

RESUMEN

OBJECTIVE: Underdiagnosis is an important issue in genetic lipodystrophies, which are rare diseases with metabolic, cardiovascular, gynecological, and psychological complications. We aimed to characterize the diagnostic pathway in these diseases from the patients' perspective. DESIGN: Cross-sectional study conducted through a self-reported patient questionnaire. METHODS: Patients with genetic lipodystrophy were recruited throughout the French national reference network for rare diseases of insulin secretion and insulin sensitivity. Patients completed a self-reported questionnaire on disease symptoms, steps leading to the diagnosis, and healthcare professionals involved. Descriptive analyses were conducted. RESULTS: Out of 175 eligible patients, 109 patients (84% women) were included; 93 had partial familial lipodystrophy and 16 congenital generalized lipodystrophy. Metabolic comorbidities (diabetes 68%, hypertriglyceridemia 66%, hepatic steatosis 57%), cardiovascular (hypertension 54%), and gynecologic complications (irregular menstruation 60%) were frequently reported. Median age at diagnosis was 30 years (interquartile range [IQR] 23-47). The overall diagnostic process was perceived as "very difficult" for many patients. It extended over 12 years (IQR 5-25) with more than five different physicians consulted by 36% of respondents, before diagnosis, for lipodystrophy-related symptoms. The endocrinologist made the diagnosis for 77% of the patients. Changes in morphotype were reported as the first symptoms by the majority of respondents. CONCLUSIONS: Diagnostic pathway in patients with genetic lipodystrophy is rendered difficult by the multisystemic features of the disease and the lack of knowledge of non-specialized physicians. Training physicians to systematically include adipose tissue examination in routine clinical evaluation should improve diagnosis and management of lipodystrophy and lipodystrophy-associated comorbidities.


Asunto(s)
Lipodistrofia Generalizada Congénita , Lipodistrofia , Humanos , Femenino , Adulto , Masculino , Estudios Transversales , Enfermedades Raras , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Lipodistrofia Generalizada Congénita/diagnóstico , Lipodistrofia Generalizada Congénita/genética
9.
Acta Neurochir (Wien) ; 165(11): 3409-3420, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37736839

RESUMEN

BACKGROUND: As the population ages, the number of elderly patients with an indication for pituitary surgery is rising. Information on the outcome of patients aged over 75 is limited. This study reports a large series assessing the feasibility of surgical resection in this specific age range, focusing on surgical complications and postoperative results. METHODS: A retrospective cohort study of patients with pituitary adenomas and Rathke's cleft cysts was conducted. All patients were aged 75 years or over and treated by a single expert neurosurgical team. A control population included 2379 younger adult patients operated by the same surgeons during the same period. RESULTS: Between 2008 and 2022, 155 patients underwent surgery. Indication was based on vision impairment in most patients (79%). Median follow-up was 13 months (range: 3-96). The first surgery was performed with an endoscopic transsellar approach, an extended endonasal transtuberculum approach and a microscopic transcranial approach in 96%, 3%, and 1% of patients, respectively. Single surgery was sufficient to obtain volume control in 97% of patients. From Kaplan-Meier estimates, 2-year and 5-year disease control with a single surgery were 97.3% and 86.2%, respectively. Resection higher than 80% was achieved in 77% of patients. No vision worsening occurred. In acromegaly and Cushing's disease, endocrine remission was obtained in 90% of non-invasive adenomas. Surgical complications were noted in 5% of patients, with 30-day mortality, hematoma, cerebrospinal fluid leak, meningitis, and epistaxis occurring in 0.6%, 0.6%, 1.9%, 0.6%, and 1.3% respectively. New endocrine anterior deficits occurred in only 5%, while no persistent diabetes insipidus was noted. Compared with younger patients, the complication rate was not statistically different. CONCLUSIONS: Surgery beyond the age of 75, mainly relying on an endoscopic endonasal transsellar approach, is effective and safe, provided that patients are managed in tertiary centers.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Adulto , Anciano , Humanos , Estudios Retrospectivos , Endoscopía/métodos , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Nariz , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/complicaciones , Adenoma/cirugía , Adenoma/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía
11.
Eur J Endocrinol ; 188(3)2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36806620

RESUMEN

OBJECTIVE: The adipogenic PPARG-encoded PPARγ nuclear receptor also displays essential placental functions. We evaluated the metabolic, reproductive, and perinatal features of patients with PPARG-related lipodystrophy. METHODS: Current and retrospective data were collected in patients referred to a National Rare Diseases Reference Centre. RESULTS: 26 patients from 15 unrelated families were studied (18 women, median age 43 years). They carried monoallelic PPARG variants except a homozygous patient with congenital generalized lipodystrophy. Among heterozygous patients aged 16 or more (n = 24), 92% had diabetes, 96% partial lipodystrophy (median age at diagnosis 24 and 37 years), 78% hypertriglyceridaemia, 71% liver steatosis, and 58% hypertension. The mean BMI was 26 ± 5.0 kg/m2. Women (n = 16) were frequently affected by acute pancreatitis (n = 6) and/or polycystic ovary syndrome (n = 12). Eleven women obtained one or several pregnancies, all complicated by diabetes (n = 8), hypertension (n = 4), and/or hypertriglyceridaemia (n = 10). We analysed perinatal data of patients according to the presence (n = 8) or absence (n = 9) of a maternal dysmetabolic environment. The median gestational age at birth was low in both groups (37 and 36 weeks of amenorrhea, respectively). As expected, the birth weight was higher in patients exposed to a foetal dysmetabolic environment of maternal origin. In contrast, 85.7% of non-exposed patients, in whom the variant is, or is very likely to be, paternally-inherited, were small for gestational age. CONCLUSIONS: Lipodystrophy-related PPARG variants induce early metabolic complications. Our results suggest that placental expression of PPARG pathogenic variants carried by affected foetuses could impair prenatal growth and parturition. This justifies careful pregnancy monitoring in affected families.


Asunto(s)
Hipertensión , Hipertrigliceridemia , Lipodistrofia , Pancreatitis , Recién Nacido , Humanos , Femenino , Embarazo , Adulto , PPAR gamma/genética , Estudios Retrospectivos , Enfermedad Aguda , Placenta , Parto
12.
Ann Endocrinol (Paris) ; 83(6): 461-468, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36206842

RESUMEN

Lipodystrophy syndromes are rare diseases with defects in the development or maintenance of adipose tissue, frequently leading to severe metabolic complications. They may be genetic or acquired, with variable clinical forms, and are largely underdiagnosed. The European Consortium of Lipodystrophies, ECLip, is a fully functional non-profit network of European centers of excellence working in the field of lipodystrophies. It provides a favorable environment to promote large Europe-wide and international collaborations to increase the basic scientific understanding and clinical management of these diseases. It works with patient advocacy groups to increase public awareness. The network also promotes a European Patient Registry of lipodystrophies, as a collaborative research platform for consortium members. The annual congress organized gives an update of the findings of network research groups, highlighting clinical and fundamental aspects. The talks presented during the meeting in Cambridge, UK, in 2022 are summarized in these minutes.


Asunto(s)
Lipodistrofia , Humanos , Tejido Adiposo , Lipodistrofia/terapia , Lipodistrofia/genética , Síndrome , Reino Unido
13.
Diabetologia ; 65(9): 1436-1449, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35701673

RESUMEN

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.


Asunto(s)
COVID-19 , Diabetes Mellitus , COVID-19/epidemiología , Estudios de Cohortes , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , Pronóstico , SARS-CoV-2
14.
Eur J Endocrinol ; 187(1): 123-134, 2022 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-35521700

RESUMEN

Objective: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a heterogeneous disease characterized by adrenal macronodules and variable levels of cortisol excess, with not clearly established clinical diagnostic criteria. It can be caused by ARMC5 germline pathogenic variants. In this study, we aimed to identify predictive criteria for ARMC5 variants. Methods: We included 352 consecutive index patients from 12 European centers, sequenced for germline ARMC5 alteration. Clinical, biological and imaging data were collected retrospectively. Results: 52 patients (14.8%) carried ARMC5 germline pathogenic variants and showed a more distinct phenotype than non-mutated patients for cortisol excess (24-h urinary free cortisol 2.32 vs 1.11-fold ULN, respectively, P < 0.001) and adrenal morphology (maximal adrenal diameter 104 vs 83 mm, respectively, P < 0.001) and were more often surgically or medically treated (67.9 vs 36.8%, respectively, P < 0.001). ARMC5-mutated patients showed a constant, bilateral adrenal involvement and at least a possible autonomous cortisol secretion (defined by a plasma cortisol after 1 mg dexamethasone suppression above 50 nmol/L), while these criteria were not systematic in WT patients (78.3%). The association of these two criteria holds a 100% sensitivity and a 100% negative predictive value for ARMC5 pathogenic variant. Conclusion: We report the largest series of index patients investigated for ARMC5 and confirm that ARMC5 pathogenic variants are associated with a more severe phenotype in most cases. To minimize negative ARMC5 screening, genotyping should be limited to clear bilateral adrenal involvement and autonomous cortisol secretion, with an optimum sensitivity for routine clinical practice. These findings will also help to better define PBMAH diagnostic criteria.


Asunto(s)
Glándulas Suprarrenales , Hidrocortisona , Glándulas Suprarrenales/patología , Proteínas del Dominio Armadillo/genética , Humanos , Hiperplasia/genética , Hiperplasia/patología , Estudios Retrospectivos
15.
Diabetes Obes Metab ; 24(8): 1565-1577, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35445532

RESUMEN

AIM: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromes treated with metreleptin in a national reference network, in a real-life setting. PATIENTS AND METHODS: Clinical and metabolic data from patients receiving metreleptin in France were retrospectively collected, at baseline, at 1 year and at the latest follow-up during treatment. RESULTS: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD; n = 28) and partial lipodystrophy (PLD; n = 19) received metreleptin over the last decade. At baseline, the median (interquartile range [IQR]) patient age was 29.3 (16.6-47.6) years, body mass index was 23.8 (21.2-25.7) kg/m2 and serum leptin was 3.2 (1.0-4.9) ng/mL, 94% of patients had diabetes (66% insulin-treated), 53% had hypertension and 87% had dyslipidaemia. Metreleptin therapy, administered for a median (IQR) of 31.7 (14.2-76.0) months, was ongoing in 77% of patients at the latest follow-up. In patients with GLD, glycated haemoglobin (HbA1c) and fasting triglyceride levels significantly decreased from baseline to 1 year of metreleptin treatment, from 8.4 (6.5-9.9)% [68 (48-85) mmol/mol] to 6.8 (5.6-7.4)% [51(38-57) mmol/mol], and 3.6 (1.7-8.5) mmol/L to 2.2 (1.1-3.7) mmol/L, respectively (P < 0.001), with sustained efficacy thereafter. In patients with PLD, HbA1c was not significantly modified (7.7 [7.1-9.1]% [61 (54-76) mmol/mol] at baseline vs. 7.7 [7.4-9.5]% [61(57-80) mmol/mol] at 1 year), and the decrease in fasting triglycerides (from 3.3 [1.9-9.9] mmol/L to 2.5 [1.6-5.3] mmol/L; P < 0.01) was not confirmed at the latest assessment (5.2 [2.2-11.3] mmol/L). However, among PLD patients, at 1 year, 61% were responders regarding glucose homeostasis, with lower baseline leptin levels compared to nonresponders, and 61% were responders regarding triglyceridaemia. Liver enzymes significantly decreased only in the GLD group. CONCLUSIONS: In this real-life setting study, metabolic outcomes are improved by metreleptin therapy in patients with GLD. The therapeutic indication for metreleptin needs to be clarified in patients with PLD.


Asunto(s)
Lipodistrofia Generalizada Congénita , Lipodistrofia , Adolescente , Adulto , Humanos , Leptina/análogos & derivados , Leptina/uso terapéutico , Lipodistrofia/tratamiento farmacológico , Lipodistrofia Generalizada Congénita/tratamiento farmacológico , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome , Adulto Joven
16.
Ann Endocrinol (Paris) ; 83(3): 199-202, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35436501

RESUMEN

Several lines of evidence show that gonadal functions and insulin sensitivity display multifaceted relationships, which extend far beyond the well-known association between polycystic ovary syndrome (PCOS), obesity, and metabolic syndrome. In this brief review, we will summarize the main findings showing the pathophysiological role of insulin resistance in impairing reproductive functions. Extreme phenotypes of severe insulin resistance, due to primary defects in insulin receptor or to lipodystrophy syndromes, provide unique opportunities for the modeling of interactions between insulin signaling and ovarian endocrine functions. In addition, recent studies further suggest that common forms of dysfunctional adiposity, as well as altered production of adipokines, could underlie important pathophysiological links between metabolic syndrome and infertility.


Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico , Síndrome del Ovario Poliquístico , Femenino , Fertilidad , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Obesidad/complicaciones , Síndrome del Ovario Poliquístico/complicaciones
19.
Eur J Endocrinol ; 185(4): 453-462, 2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34292171

RESUMEN

AIMS: LMNA-linked familial partial lipodystrophy type 2 (FPLD2) leads to insulin resistance-associated metabolic complications and cardiovascular diseases. We aimed to characterise the disease phenotype in a cohort of patients carrying an LMNA founder variant. METHODS: We collected clinical and biological data from patients carrying the monoallelic or biallelic LMNA p.(Thr655Asnfs*49) variant (n = 65 and 13, respectively) and 19 non-affected relative controls followed-up in Reunion Island Lipodystrophy Competence Centre, France. RESULTS: Two-thirds of patients with FPLD2 (n = 51) and one-third of controls (n = 6) displayed lipodystrophy and/or lean or android morphotype (P = 0.02). Although age and BMI were not statistically different between the two groups, the insulin resistance index (median HOMA-IR: 3.7 vs 1.5, P = 0.001), and the prevalence of diabetes, dyslipidaemia, and non-alcoholic fatty liver disease were much higher in patients with FPLD2 (51.3 vs 15.8%, 83.3 vs 42.1%, and 83.1 vs 33.3% (all P ≤ 0.01), respectively). Atherosclerosis tended to be more frequent in patients with FPLD2 (P = 0.07). Compared to heterozygous, homozygous patients displayed more severe lipoatrophy and metabolic alterations (lower BMI, fat mass, leptin and adiponectin, and higher triglycerides P ≤ 0.03) and tended to develop diabetes more frequently, and earlier (P = 0.09). Dilated cardiomyopathy and/or rhythm/conduction disturbances were the hallmark of the disease in homozygous patients, leading to death in four cases. CONCLUSIONS: The level of expression of the LMNA 'Reunionese' variant determines the severity of both lipoatrophy and metabolic complications. It also modulates the cardiac phenotype, from atherosclerosis to severe cardiomyopathy, highlighting the need for careful cardiac follow-up in affected patients.


Asunto(s)
Cardiomiopatías/genética , Lamina Tipo A/genética , Lipodistrofia Parcial Familiar/genética , Enfermedades Metabólicas/genética , Adulto , Cardiomiopatías/epidemiología , Estudios de Casos y Controles , Femenino , Efecto Fundador , Frecuencia de los Genes , Heterocigoto , Homocigoto , Humanos , Laminopatías/complicaciones , Laminopatías/epidemiología , Laminopatías/genética , Lipodistrofia Parcial Familiar/complicaciones , Lipodistrofia Parcial Familiar/epidemiología , Masculino , Enfermedades Metabólicas/epidemiología , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Reunión/epidemiología , Adulto Joven
20.
Adv Physiol Educ ; 45(2): 390-398, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33961515

RESUMEN

The COVID-19 crisis necessitated abrupt transition to remote learning in medical schools. We aimed to assess the impact of COVID-19 on French undergraduate students and teachers, to identify practice changes, and to evaluate successes and areas for improvement of this remote learning experience. Data from 2 online questionnaires were analyzed with 509 participants among students and 189 among teachers from Sorbonne University. Responses to multiple choice, Likert response scale, and open-ended questions were evaluated. COVID-19 had negative impact on teaching continuity. Sixty-seven percent of students were in a dropout situation, and many suffered from psychological stress, leading to set up of a psychological support unit. Although most teachers (81%) and students (72%) had limited knowledge of digital resources, distance learning was quickly implemented, with a predominant use of Zoom. The analysis of several parameters revealed that students were significantly more satisfied than teachers by remote learning. Nevertheless, both students and teachers agreed to replace classical lectures by digital media and to promote in-person teaching in small interactive groups. This paper shares tips for faculty rapidly establishing remote learning. This comparative study of the students' and teachers' points of view underlines that new medical curricula should include more digital contents. We make recommendations regarding general university organization, equipment, and curricular development for long-term implementation of digital resources with reinforced relationships between faculty and students.


Asunto(s)
COVID-19 , Educación a Distancia , Educación de Pregrado en Medicina , Estudiantes de Medicina , Francia , Humanos , Internet
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