With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D. Areas covered: This review focuses on agents that have been utilized, including inhaled insulin preparations, pramlintide, metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dual SGLT1/2 inhibitors. Furthermore, with approval of the first hybrid closed loop (CL) system, the development of dual hormone CL systems is being explored. While the most common agent applied to these dual systems has been glucagon, research has been conducted to assess how some of the adjunctive therapies described above could aide with achieving postprandial glucose control while on CL insulin delivery. Expert opinion: By becoming less insulin-centric and incorporating some of these other agents, it is possible we may be able to better combat T1D.

ContextMost heritable causes of low bone mass in children occur due to mutations affecting type 1 collagen. We describe two related patients with low bone mass and fracture without mutations in the type 1 collagen genes.Case descriptionWe describe the index case of a 10-year-old girl with low-impact fractures in childhood and her 59-year-old father with traumatic fractures in adulthood, both with low bone mineral density. They were found to have the same heterozygous missense mutation in the WNT1 gene (p.Gly222Arg), occurring in a highly conserved WNT motif in close proximity to the Frizzled binding site.ConclusionsThe WNT-ligand WNT1, signaling through the canonical WNT-β­catenin pathway, plays a critical role in skeletal development, adult skeletal homeostasis, and bone remodeling. Biallelic mutations have been described and are associated with moderate to severe osteogenesis imperfecta, in some cases with extra-skeletal manifestations. Patients with monoallelic mutations, as in our case, seem to present with low bone mineral density and less severe disease. The phenotypic difference between biallelic and monoallelic mutations highlights that the aberrant protein in monoallelic mutations may exert a dominant negative effect on the wild type protein as heterozygous carriers in families with biallelic disease are usually asymptomatic. With better understanding of disorders associated with WNT1 mutations, therapies targeting this signaling pathway may offer therapeutic benefit.

Despite the widespread availability of insulin pumps, continuous glucose sensors, and insulin analogs with rapid-acting pharmacokinetic profiles, most people with type 1 diabetes fail to meet recommended glycemic targets, rates of severe hypoglycemia remain unacceptably high, and the burden of care on patients and loved ones exacts an enormous psychosocial toll. The combination of continuous glucose monitoring with insulin delivery into an integrated automated system promises to improve diabetes control while at the same time reduce the burden of care. A wide variety of automated insulin delivery systems, ranging in scope from simple pump suspension to reduce hypoglycemia, to complex multiple hormone systems under separate regulation and delivery, have been studied in both controlled inpatient settings and more free-ranging outpatient environments. Preliminary findings have been positive, with most studies demonstrating reduction in overall glucose levels, increased time-in-target range, and reductions in exposure to hypoglycemia. As these systems move closer to commercialization, the focus of ongoing efforts will need to address the continuing challenges of sensor accuracy and reliability, connectivity issues, and human factors considerations.

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Introducción: Los tumores de células germinales intracraneales constituyen un grupo infrecuente de neoplasias que afectan principalmente a la población pediátrica. Su presentación clínica varía en función de la localización y el tamaño del tumor. Las lesiones localizadas en la región pineal a menudo causan hidrocefalia obstructiva, mientras que las lesiones de localización supraselar, usualmente se asocian a disfunción del eje hipotálamo-hipofisario. Un tumor germinal de localización pineal que curse con endocrinopatías es una entidad extremadamente rara. Por tanto, reportamos el caso de un paciente masculino de 16 años de edad, con panhipopituitarismo secundario a un germinoma pineal.  Material y métodos: Este paciente fue referido al Departamento de Emergencias tras presentar hipernatremia en un análisis sanguíneo de rutina. Se presentó con polidipsia, poliuria y fatiga de un año de evolución. Las evaluaciones clínicas y pruebas de laboratorio reportaron diabetes insípida, panhipopituitarismo y hemianopsia bitemporal. El paciente recibió terapia de sustitución hormonal y tres meses después, la resonancia magnética de seguimiento reveló una masa en el área pineal que, a través de una posterior evaluación, fue diagnosticada como germinoma. Conclusión: Luego de tratamiento con quimioterapia y radiación, hubo una resolución completa de la lesión. Sin embargo, no hubo mejoría clínica significativa y el paciente continúo necesitando terapia de reemplazo hormonal.