Reproducibilidad de la curva de tolerancia a la glucosa en el diagnóstico de la diabetes mellitus gestacional

La diabetes mellitus gestacional (DMG) es la complicación endocrinológica más prevalente durante el embarazo (1). Se ha relacionado con resultados adversos perinatales tanto maternos como neonatales, así como aumento de riesgo a largo plazo para la madre de padecer diabetes mellitus y síndrome metabólico (1). Para el diagnóstico de la DMG se han propuesto varios protocolos que utilizan diferentes umbrales de la curva de tolerancia oral a la glucosa (CTG) y se sigue debatiendo cuál tiene más precisión diagnóstica (2–4). En consecuencia, existe una falta de consenso con respecto a las recomendaciones de cribado propuestas por las guías de práctica clínica (5–7). Sin embargo, la CTG tiene baja reproducibilidad lo cual es una limitante metodológica ya conocida (8–10). A pesar de lo anterior, las autoridades en este campo recomiendan establecer un diagnóstico de DMG basado Versión 1.0 Diciembre 2021 4 en el resultado de un único resultado alterado de CTG de 75 g durante la semana 24 a 28 de gestación (4,11,12). Esto contrasta con la recomendación de repetición de una CTG anormal en casi todos los escenarios clínicos para el diagnóstico de diabetes no gestacional (4). Recientemente, algunos investigadores han publicado estudios sobre la concordancia y la falta de reproducibilidad de la CTG de 75 g de un solo paso para el diagnóstico de DMG. Sin embargo, algunas deficiencias metodológicas restringen la validez de sus resultados (13,14). El objetivo de este estudio fue evaluar la reproducibilidad de la CTG de 75 g en mujeres embarazadas a las 24, 26 y 28 semanas de gestación. Se realizó un estudio observacional prospectivo mujeres mayores a 18 años cursando un embarazo sano las cuales fueron reclutadas en la clínica de atención prenatal de nuestro hospital. Se realizó una valoración clínica y se realizaron CTG de 75 g a las 24, 26 y 28 semanas de gestación. Todas las muestras de sangre se procesaron simultáneamente. En total se incluyeron 92 mujeres embarazadas con una edad promedio de 26.27 ± 6.51 años. Se encontró que 69 mujeres (75%) tuvieron una CTG normal en las tres pruebas de manera consecutiva. Veintitrés pacientes (25%) fueron diagnosticadas con DMG solo con una CTG alterada; de este grupo sólo 7 (30,4%) y 2 (8,6%) mantuvieron el diagnóstico en dos o tres CTG consecutivas, respectivamente. Al comparar contra solo hacer una prueba de CTG, los resultados de repetir la prueba 2 y 3 veces tuvieron baja sensibilidad (43.7% y 9.5%, respectivamente) y alta especificidad (100%) con un alto cociente de probabilidad positiva (43.7 y 9.5, respectivamente). Las desviaciones estándar (DE) y los límites de reproducibilidad fueron mayores en los casos que en los controles. En conclusión, la baja reproducibilidad de la CTG de 75 g es alarmante. Una CTG de 75 g parece ser insuficiente para realizar el diagnóstico de DMG y probablemente sea necesario realizar al menos una segunda prueba para corroborarlo o descartarlo. Este estudio plantea la base para comparar el impacto que tiene clasificar a las mujeres embarazadas con DMG con 1 sola CTG de 75 g contra corroborar el diagnóstico con una segunda o tercera prueba. Los estudios futuros deberán evaluar el impacto de realizar el diagnóstico de DMG solamente con 1 CTG de 75 g contra 2 o 3 pruebas alteradas y comparar los resultados neonatales y maternos obtenidos durante el mismo embarazo entre estos grupos

Early Clinical Expressions of Insulin Resistance: The Real Enemy to Look For

ABSTRACT The type 2 diabetes mellitus epidemic threatens public healthcare systems worldwide. Efforts to prevent chronic complications of diabetes and reduce their associated mortality have been ineffective. Hence, early prevention of type 2 diabetes mellitus and cardiovascular disease needs to be prioritized. This strategy, however, must be centered not on an approach based on hyperglycemia but on early pathophysiologic mechanisms, such as insulin resistance. Nonalcoholic fatty liver disease, androgenic alopecia, acanthosis nigricans, and polycystic ovarian syndrome are all well-accepted early clinical manifestations of insulin resistance that represent, in themselves, a risk for further development of type 2 diabetes and that appear years before hyperglycemia. Therefore, focusing efforts on detecting and rigorously treating patients with early clinical expression of insulin resistance (insulin resistance clinical syndrome) is probably the course of action that needs to be taken to counterbalance the type 2 diabetes mellitus epidemic

Participants’ awareness of ethical compliance, safety and protection during participation in pharmaceutical industry clinical trials: a controlled survey

Background: The rapid increase of industry-sponsored clinical research towards developing countries has led to potentially complex ethical issues to assess. There is scarce evidence about the perception of these participants about the ethical compliance, security, and protection. We sought to evaluate and contrast the awareness and perception of participants and non-participants of industry-sponsored research trials (ISRT) on ethical, safety, and protection topics. Methods: A Cases-control survey conducted at twelve research sites in México. Previous and current participants of ISRT (cases) as well as non-participants (controls) with one of four chronic diseases, were asked to complete the survey which focused on ethical compliance and protection issues of ISRT, and the perception of participating in a trial. Results: A total of 604 cases and 604 controls were surveyed. Cases significantly answered that ethics committees are aware of what is happening in studies (50.5% vs. 33.8%, P=≤ 0.001), and that medical care of industry-sponsored research trials is better than their usual medical care (77.2% vs. 38.2%, P=<0.001).Thesameproportionofcasesand controls thought patients must receive economical reimbursement for participating in a research study (49.5% vs. 53.1%, P=0.205). The informed consent of the pharmaceutical clinical trial was fully read by 90.4% of the cases. Most cases were satisfied or very satisfied with their overall study participation (35.6 and 62.3%, respectively). Conclusion: Previous and current participants of industry-sponsored research trials have a more positive attitude towards ethics committees, the quality of medical care of the research trials, and the main purpose of economical reimbursements, when compared to non-participants. Keywords: Good clinical practices, Perception, Clinical trials, Pharmaceutical industry, Ethics committee

Participants' perception of pharmaceutical clinical research: a cross-sectional controlled study

Background: There is scarce scientific information assessing participants’ perception of pharmaceutical research in developed and developing countries concerning the risks, safety, and purpose of clinical trials. Methods: To assess the perception that 604 trial participants (cases) and 604 nonparticipants (controls) of pharmaceutical clinical trials have about pharmaceutical clinical research, we surveyed participants with one of four chronic diseases from 12 research sites throughout Mexico. Results: Participation in clinical trials positively influences the perception of pharmaceutical clinical research. More cases (65.4%) than controls (50.7%) perceived that the main purpose of pharmaceutical research is to cure more diseases and to do so more effectively. In addition, more cases considered that there are significant benefits when participating in a research study, such as excellent medical care and extra free services, with this being the most important motivation to participate for both groups (cases 52%, controls 54.5%). We also found a sense of trust in their physicians to deal with adverse events, and the perception that clinical research is a benefit to their health, rather than a risk. More controls believed that clinical trial participants’ health is put at risk (57% vs 33.3%). More cases (99.2%) than controls (77.5%) would recommend participating in a clinical trial, and 90% of cases would enroll in a clinical trial again. Conclusion: Participation in clinical trials positively influences the perception that participants have about pharmaceutical clinical research when compared to nonparticipants. This information needs to be conveyed to clinicians, public health authorities, and general population to overcome misconceptions

Supplementary Material: Diagnostic Tests for Differentiation between Cushing´s Syndrome and Non-Neoplastic Hypercortisolism: A Systematic Review and Meta-analysis

Context: Differential diagnosis between Cushing’s syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing’s syndrome) is crucial. Due to worldwide corticotropin-releasing hormone test CRH shortage, accuracy of alternative tests to Dexamethasone (Dex)-CRH is clearly needed. Objective: Asses the diagnostic accuracy of Dex-CRH, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. Methods: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. Data Synthesis: A total of 26 articles (2059 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 87% (81-91%; I2 34%) and 91% (85-94%; I2 15%), MSC 91% (85-94%; I2 65%) and 80% (70-88%; I2 70%), and LNSC 78% (66-86%; I2 54%) and 88% (83-92%; I2 36%), respectively. SROC areas under the curve were Dex-CRH 0.949, desmopressin test 0.941, MSC 0.939, and LNSC 0.940 without visual or statistical significance. The overall risk of studies bias was moderate. Conclusion: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. Our results should increase clinicians’ confidence when deciding which test to perform when facing this challenging differential diagnosis. Key Words: Cushing’s syndrome, neoplastic endogenous hypercortisolism, non-neoplastic hypercortisolism, pseudoCushing’s, dexamethasone CRH test, desmopressin test, salivary cortisol, midnight serum cortiso

Variation in hypoglycemia ascertainment and report in type 2 diabetes observational studies: a meta-epidemiological study

Introduction Observational studies constitute an important evidence base for hypoglycemia in diabetes management. This requires consistent and reliable ascertainment and reporting methodology, particularly in studies of type 2 diabetes where hypoglycemia risk is heterogeneous. Therefore, we aimed to examine the definitions of hypoglycemia used by observational studies of patients with type 2 diabetes. Research design and methods We conducted a meta-epidemiological review of observational studies reporting on hypoglycemia or evaluating glucose-lowering medications in adults with type 2 diabetes. MEDLINE and Google Scholar were searched from January 1970 to May 2018. The definitions of non-severe, severe and nocturnal hypoglycemia were examined.Results We reviewed 243 studies: 47.7% reported on non-severe hypoglycemia, 77.8% on severe hypoglycemia and 16.9% on nocturnal hypoglycemia; 5.8% did not specify. Among 116 studies reporting non-severe hypoglycemia, 18.1% provided no definition, 23.3% used glucose values, 38.8% relied on patient-reported symptoms, 17.2% accepted either glucose values or patient-reported symptoms and 2.6% relied on International Classification of Disease (ICD) codes. Among 189 studies reporting severe hypoglycemia, 11.1% provided no definition, 53.4% required symptoms needing assistance, 3.7% relied on glucose values, 14.8% relied on ICD codes, 2.6% relied on ICD codes or glucose values and 15.9% required both symptoms needing assistance and glucose values. Overall, 38.2% of non-severe and 67.7% of severe hypoglycemia definitions were consistent with the International Hypoglycemia Study Group.Conclusions The marked heterogeneity in how hypoglycemia is defined in observational studies may contribute to the inadequate understanding and correction of hypoglycemia risk factors among patients with type 2 diabetes

Sheehan’s Syndrome Revisited: Underlying Autoimmunity or Hypoperfusion?

Sheehan’s syndrome remains a frequent obstetric complication with an uncertain pathophysiology. We aimed to assess the incidence of hypopituitarism (≥2 hormonal axis impairment) within the first six postchildbirth months and to determine the existence of anti-pituitary antibodies. From 2015 to 2017, adult pregnant women, who developed moderate to severe postpartum hemorrhage (PPH), were consecutively included in the study. Pituitary function was assessed 4 and 24 weeks after PPH. At the end of the study, anti-pituitary antibodies were assessed. Twenty women completed the study. Mean age was 26.35 (±5.83) years. The main etiology for severe PPH was uterine atony (65%) which resulted mostly in hypovolemic shock grades III-IV. Within the first four weeks after delivery, 95% of patients had at least one hormonal pituitary affected and 60% of the patients fulfilled diagnostic criteria for hypopituitarism. At the end of the study period, five patients (25%) were diagnosed with hypopituitarism (GH and cortisol axes affected). Anti-pituitary antibodies were negative in all patients. At 6 months follow-up, one in every four women with a history of moderate-to-severe PPH was found with asymptomatic nonautoimmune-mediated hypopituitarism. The role of autoimmunity in Sheehan’s syndrome remains uncertain. Further studies are needed to improve the remaining knowledge gaps