Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4.

The epicardium plays a crucial role in embryonic heart development and adult heart repair; however, the molecular events underlying its maturation remain unknown. Wt1, one of the main markers of the embryonic epicardium, is essential for epicardial development and function. Here, we analyse the transcriptomic profile of epicardial-enriched cells at different stages of development and from control and epicardial-specific Wt1 knockout (Wt1KO) mice. Transcriptomic and cell morphology analyses of epicardial cells from epicardial-specific Wt1KO mice revealed a defect in the maturation process of the mutant epicardium, including sustained upregulation of Bmp4 expression and the inability of mutant epicardial cells to transition into a mature squamous phenotype. We identified Bmp4 as a transcriptional target of Wt1, thus providing a molecular basis for the retention of the cuboidal cell shape observed in the Wt1KO epicardium. Accordingly, inhibition of the Bmp4 signalling pathway both ex vivo and in vivo rescued the cuboidal phenotype of the mutant epicardium. Our findings indicate the importance of the cuboidal-to-squamous transition in epicardial maturation, a process regulated by Wt1.

[Detection of LADA-type diabetes in overweight diabetic patients. Is treatment with metformin suitable?]. / Detección de diabetes tipo LADA en pacientes diabéticos con exceso ponderal. 'Es adecuado el tratamiento con metformina?

OBJECTIVES: To detect type-1 LADA (latent auto-immune diabetes in adults) in adults with overweight. To describe the metabolic variations in these patients after metformin treatment. DESIGN: Observational, multi-centre study based on a series of cases. SETTING: Health centres in Barcelona province, Spain. PARTICIPANTS: Diabetic patients with overweight or obesity, diagnosed with diabetes for <2 years, aged between 35 and 65, and without clinical micro-macrovascular complications and without initial glycaemia-lowering drug treatment. INTERVENTION: Metformin administration (1700 mg/day). MEASUREMENTS: The metabolic control variable was HbA1c. Other variables measured were: body mass index (BMI), glucose in fast, insulinaemia, C-peptide, and insulin resistance (HOMA-IR). We determined ICA, GADAb and IA2Ab antibodies to diagnose LADA-type diabetes. RESULTS: In our sample of diabetics (N=103), we detected 3 type-1 LADA cases. These patients had higher levels of HbA1c, insulin and, especially, HOMA-IR. Metformin treatment for one year improved HbA1c in both groups (with and without type-1 LADA). However, the decrease in insulin one year afterwards was greater in type-1 LADA patients. CONCLUSIONS: The percentage of type-1 LADA in our sample made us wonder whether we should search for pancreatic antibodies more often in primary care. More studies on the prevalence of type-1 LADA in our country are needed, especially in diabetic patients with overweight. Type-1 LADA patients improved their metabolic control after metformin treatment and showed a drastic decrease in insulin levels. Further studies are needed to evaluate whether metformin improves metabolic control, even though it may not protect insulin reserves, and to contrast metformin with other drugs.

Detección de diabetes tipo LADA en pacientes diabéticos con exceso ponderal. ¿Es adecuado el tratamiento con metformina? / Detection of LADA-type diabetes in overweight diabetic patients. Is treatment with metformin suitable?

Objetivos. Detectar pacientes con diabetes tipo LADA (latent autoinmune diabetes of adult) tipo 1 en diabéticos adultos con sobrepeso y describir las variaciones metabólicas tras administrar metformina. Diseño. Estudio observacional, multicéntrico, basado en una serie de casos. Emplazamiento. Atención primaria, provincia de Barcelona. Participantes. Diabéticos con sobrepeso u obesidad, con diagnóstico de diabetes < 2 años, entre 35 y 65 años de edad, sin complicaciones microvasculares o macrovasculares ni tratamiento farmacológico inicial antidiabético. Intervención. Administración de metformina, 1.700 mg/día. Mediciones. La variable de control metabólico fue la hemoglobina glucosilada (HbA1c); otras variables fueron el índice de masa corporal (IMC), la glucemia en ayunas, la insulinemia, el péptido C y la valoración de la insulinorresistencia (HOMA-IR). Para el diagnóstico de diabetes tipo LADA se determinaron los anticuerpos ICA, anti-GAD y anti-IA2. Resultados. En la muestra de diabéticos estudiada (n = 103) se detectaron 3 casos de LADA tipo 1 (prevalencia del 2,9%; intervalo de confianza del 95%, 0,6-8,3%). Estos pacientes presentaron valores basales más elevados de HbA1c, insulina y sobre todo de HOMA-IR. El tratamiento con metformina mejoró la HbA1c en ambos grupos de pacientes (con o sin LADA de tipo 1). El descenso de la insulinemia al cabo de un año en los pacientes con LADA de tipo 1 fue más marcado que en el resto de diabéticos. Conclusiones. Dada su frecuencia, hay que reflexionar sobre si deberían buscarse con más frecuencia anticuerpos frente a células β pancreáticas en atención primaria. Los pacientes con LADA de tipo 1 presentaron buen control de la HbA1c en tratamiento con metformina y un drástico descenso de la insulina. Faltan estudios que evalúen si la metformina mejora el control glucémico, aunque tal vez no proteja la reserva insulínica, y confrontarla con otros fármacos

Objectives. To detect type-1 LADA (latent auto-immune diabetes in adults) in adults with overweight. To describe the metabolic variations in these patients after metformin treatment. Design. Observational, multi-centre study based on a series of cases. Setting. Health centres in Barcelona province, Spain. Participants. Diabetic patients with overweight or obesity, diagnosed with diabetes for <2 years, aged between 35 and 65, and without clinical micro-macrovascular complications and without initial glycaemia-lowering drug treatment. Intervention. Metformin administration (1700 mg/day). Measurements. The metabolic control variable was HbA1c. Other variables measured were: body mass index (BMI), glucose in fast, insulinaemia, C-peptide, and insulin resistance (HOMA-IR). We determined ICA, GADAb and IA2Ab antibodies to diagnose LADA-type diabetes. Results. In our sample of diabetics (N=103), we detected 3 type-1 LADA cases. These patients had higher levels of HbA1c, insulin and, especially, HOMA-IR. Metformin treatment for one year improved HbA1c in both groups (with and without type-1 LADA). However, the decrease in insulin one year afterwards was greater in type-1 LADA patients. Conclusions. The percentage of type-1 LADA in our sample made us wonder whether we should search for pancreatic antibodies more often in primary care. More studies on the prevalence of type-1 LADA in our country are needed, especially in diabetic patients with overweight. Type-1 LADA patients improved their metabolic control after metformin treatment and showed a drastic decrease in insulin levels. Further studies are needed to evaluate whether metformin improves metabolic control, even though it may not protect insulin reserves, and to contrast metformin with other drugs