From liver to hormones: The endocrine consequences of cirrhosis.

Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.

Delayed-Onset Transient Hyperinsulinism in Infants with Very Low and Extremely Low Birth Weights: A Cohort Study.

We describe 16 infants born preterm with birth weights <1500 g and transient hyperinsulinism. The onset of hyperinsulinism was delayed and often coincident with clinical stabilization. We hypothesize that postnatal stress caused by prematurity and associated problems may contribute to development of delayed-onset transient hyperinsulinism.

Insulinas análogas de ação prolongada comparadas à insulina NPH para tratamento de diabetes mellitus tipo 2 em adultos: revisão rápida / Long-acting basal insulin analogues compared to nph insulin for type 2 diabetes mellitus in adults: rapid review

Tecnologia: Insulinas análogas de liberação prolongada versus insulina NPH (protamina neutra de Hagedorn). Indicação: Tratamento de adultos com diabetes mellitus tipo 2. Pergunta: Há diferenças de efeito nos principais desfechos de eficácia e segurança entre insulinas análogas de liberação prolongada versus insulina NPH no tratamento de pacientes com DM2? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada e incluída uma revisão sistemática. Conclusão: As insulinas análogas (glargina e detemir) não demonstraram superioridade nos desfechos de eficácia e segurança quando comparadas à insulina NPH, não demonstraram redução significativa em relação à mortalidade por todas as causas e complicações secundárias ao DM2. Quando comparadas à insulina NPH, foi observado redução na hipoglicemia confirmada e hipoglicemia noturna a favor das insulinas análogas e na hipoglicemia grave a favor da insulina detemir

Technology: Long-acting insulin analogues versus NPH insulin (human isophane insulin). Indication: Treatment of adults with type 2 diabetes mellitus. Question: Are there effect differences in key efficacy and safety outcomes between long-acting insulin analogues versus NPH insulin in the treatment of DM2 patients? Methods: Rapid review of evidence (overview) of systematic reviews, with a bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: A systematic review was selected and included. Conclusion: Analog insulins (glargine and detemir) did not demonstrate superiority in efficacy and safety outcomes when compared to NPH insulin, did not demonstrate a significant reduction in all-cause mortality and complications secondary to DM2. When compared to NPH insulin, a reduction in confirmed hypoglycemia and nocturnal hypoglycemia in favor of analogue insulins and in severe hypoglycemia in favor of insulin detemir was observed

Hypoglycemia in Infants with Hypoxic-Ischemic Encephalopathy Is Associated with Additional Brain Injury and Worse Neurodevelopmental Outcome.

OBJECTIVE: To determine the incidence of hypoglycemia among infants with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia, and to assess whether infants with hypoglycemia had more brain injury on magnetic resonance imaging (MRI) or differences in neurodevelopmental outcome. STUDY DESIGN: Single-center, retrospective cohort study including infants cooled for HIE. Hypoglycemia (blood glucose <36.0 mg/dL <2 hours and <46.8 mg/dL ≥2 hours after birth) was analyzed in the period before brain MRI. Brain injury was graded using a validated score. Motor and neurocognitive outcomes were assessed at 2 years for all survivors, and 5.5 years for a subset who had reached this age. RESULTS: Of 223 infants analyzed, 79 (35.4%) had hypoglycemia. MRI was performed in 187 infants. Infants with hypoglycemia (n = 65) had higher brain injury scores (P = .018). After adjustment for HIE severity, hypoglycemia remained associated with higher injury scores (3.6 points higher; 95% CI, 0.8-6.4). Hyperglycemia did not affect MRI scores. In survivors at 2 years (n = 154) and 5.5 years (n = 102), a univariable analysis showed lower 2-year motor scores and lower motor and cognitive scores at preschool age in infants with hypoglycemia. After adjustment for HIE severity, infants with hypoglycemia had 9 points lower IQs (P = .023) and higher odds of adverse outcomes at preschool age (3.6; 95% CI, 1.4-9.0). CONCLUSIONS: More than one-third of infants cooled for HIE had hypoglycemia. These infants had a higher degree of brain injury on MRI and lower cognitive function at preschool age. Strategies to avoid hypoglycemia should be optimized in this setting.

Does Universal Screening for Gestational Diabetes Mellitus Improve Neonatal Outcomes in a Socially Vulnerable Population: A Prospective Study in French Guiana.

Aims/Introduction: French Guiana has a high prevalence of metabolic diseases, which are risk factors for gestational diabetes mellitus. Despite routine screening for gestational diabetes, treatment is still challenging because of health inequalities and different cultural representations of disease and pregnancy. This study was conducted to assess the role of early and universal GDM screening on obstetrical and neonatal complications in a socially deprived population. Materials and Methods: A prospective study was conducted, in the level III maternity in French Guiana. Of 2136 deliveries, 223 had gestational diabetes mellitus, 110 of whom were followed-up for 6 month to detail their social and laboratory parameters. Results: The prevalence of gestational diabetes in French Guiana (Cayenne Hospital) was estimated at 10.3%. The study population was very precarious with 70% of patients on welfare (universal health coverage or state medical assistance). The following obstetrical complications were observed: cesarean delivery (32%), history of miscarriage (26%) and preeclampsia (7.4%). Nevertheless, neonatal complications were rarely present and included hypoglycemia (2.8%) and macrosomia (2.8%). Conclusion: In French Guiana, gestational diabetes mellitus is very common. However, in a context of widespread poverty and diverse cultural representations, universal screening and monitoring limited the risk of macrosomia.

Hipoglicemia grave e fatores de risco em pessoas com diabetes em unidade de internação: estudo caso controle / Severe hypoglycemia in people with diabetes in an inpatient unit: a case-control study

A hipoglicemia é uma das principais complicações frente ao manejo inadequado do diabetes, com destaque para a hipoglicemia grave que configura-se como um problema relevante para a manutenção da qualidade de vida dos indivíduos. Os objetivos do presente estudo foram caracterizar os episódios de hipoglicemia grave em pacientes com diabetes em unidades de internação clínica; analisar a associação entre os fatores de risco e os episódios de hipoglicemia grave de pacientes com diabetes em unidade de internação; estimar o tempo de sobrevida até o episódio hipoglicêmico grave. A metodologia empregada para esse estudo considerou casos episódios hipoglicêmicos graves, definidos por valores glicêmicos abaixo de 50 mg/dL. Foram considerados controles os episódios hipoglicêmicos não graves definidos por valores glicêmicos entre 51 a 70mg/dl. Considerou-se como fatores associados à hipoglicemia grave variáveis propostas pela revisão integrativa de literatura realizada para a construção dessa pesquisa. Ainda, também foi analisado o diagnóstico de enfermagem risco de glicemia instável da nomenclatura NANDA-I e sua pertinência quanto aos fatores de risco associados à ocorrência de episódios de hipoglicemia grave. A coleta de dados desenvolveu-se através de análise documental retrospectiva. Foram observados 47 episódios de hipoglicemia grave e 60 episódios de hipoglicemia não grave, respectivamente caso e controle. Os fatores de risco para hipoglicemia grave com evidências na literatura e que foram validados neste estudo caso- controle foram: escolaridade; terapia insulínica; uso de insulinas associadas; modificação recente da dose; insuficiência renal; outras comorbidades; episódio hipoglicêmico anterior e habilidade deficiente para o autocuidado. Identificou-se que o tempo de sobrevida até o episódio hipoglicêmico configura-se em uma curva descendente.A média de tempo que uma pessoa sobrevive até o desfecho de hipoglicemia grave mostrou que o paciente que tem diabetes e está internado tem chances progressivamente maiores de desenvolver episódio de hipoglicemia grave logo nos primeiros dias de internação. Frente aos resultados obtidos, sugere-se que novos estudos sejam realizados com o objetivo descrever aprofundadamente os mecanismos de associação destas variáveis com o episódio hipoglicêmico grave. A identificação da magnituddos fatores de risco para hipoglicemia grave, apresentada através do estudo caso-controle, fornece bases para a construção de instrumentos padronizados de avaliação adequada de pacientes com diabetes em unidades de internação.

Hypoglycemia is one of the main complications in the face of inadequate management of diabetes, where severe hypoglycemia is a relevant problem in terms of maintaining the quality of life of individuals. The objectives of the study were to characterize episodes of severe hypoglycemia in patients with diabetes in clinical inpatient units; to analyze the association between risk factors and episodes of severe hypoglycemia in patients with diabetes in the inpatient unit; estimate the survival time until the severe hypoglycemic episode. The methodology used for this study considered cases of severe hypoglycemic episodes, defined by glycemic values below 50 mg / dL. Non-severe hypoglycemic episodes were defined as controls defined by glycemic values between 51 to 70mg / dl. Factors associated with severe hypoglycemia were considered as variables proposed by the integrative literature review carried out for the construction of this research. Still, the Nursing Diagnosis Risk of Unstable Glycemia of the NANDA-I Nomenclature and its relevance regarding the risk factors associated with the occurrence of episodes of severe hypoglycemia were also analyzed. Data collection was developed through retrospective document analysis. 47 episodes of severe hypoglycemia and 60 episodes of non-severe hypoglycemia were analyzed, case and control, respectively. The risk factors for severe hypoglycemia with evidence in the literature that were validated in this case-control study were: education; insulin therapy; use of associated insulins; recent dose modification; renal insufficiency; other comorbidities; previous hypoglycemic episode and deficient ability for self-care. It was identified that the survival time until the hypoglycemic episode is configured in a descending curve. The average time that a person survives until the outcome of severe hypoglycemia showed that the patient who has diabetes and is hospitalized has a progressively greater chance of developing an episode of severe hypoglycemia in the first days of hospitalization. In view of the results obtained, it is suggested that further studies be carried out in order to describe in depth the mechanisms of association of these variables with the severe hypoglycemic episode. The identification of the magnitude of risk factors for severhypoglycemia, presented through the case-control study, provides the basis for the construction of standardized instruments for adequate assessment of patients with diabetes in inpatient units.

La hipoglucemia es una de las principales complicaciones ante el manejo inadecuado de la diabetes, donde la hipoglucemia severa es un problema relevante en cuanto al mantenimiento de la calidad de vida de los individuos. Los objetivos del estudio fueron caracterizar episodios de hipoglucemia severa en pacientes con diabetes en unidades de internación clínica; analizar la asociación entre factores de riesgo y episodios de hipoglucemia severa en pacientes con diabetes en la unidad de internación; Estime el tiempo de supervivencia hasta el episodio de hipoglucemia grave. La metodología utilizada para este estudio consideró casos de episodios hipoglucémicos graves, definidos por valores glucémicos inferiores a 50 mg / dL. Se consideraron controles los episodios hipoglucémicos no graves definidos como valores glucémicos entre 51 y 70 mg / dl. Los factores asociados a la hipoglucemia severa fueron considerados como variables propuestas por la revisión integradora de la literatura realizada para la construcción de esta investigación. Aún así, también se analizó el Diagnóstico de Enfermería Riesgo de Glucemia Inestable de la Nomenclatura NANDA-I y su relevancia con respecto a los factores de riesgo asociados a la ocurrencia de episodios de hipoglucemia severa. La recolección de datos se desarrolló a través del análisis retrospectivo de documentos. Se analizaron 47 episodios de hipoglucemia severa y 60 episodios de hipoglucemia no severa, caso y control, respectivamente. Los factores de riesgo de hipoglucemia severa con evidencia en la literatura que fueron validados en este estudio de casos y controles fueron: educación; terapia con insulina; uso de insulinas asociadas; modificación reciente de la dosis; insuficiencia renal; otras comorbilidades; episodio hipoglucémico previo y capacidad deficiente para el autocuidado. Se identificó que el tiempo de supervivencia hasta el episodio hipoglucémico se configura en una curva descendente. El tiempo promedio que una persona sobrevive hasta el resultado de una hipoglucemia severa mostró que el paciente que tiene diabetes y está hospitalizado tiene una probabilidad progresivamente mayor de desarrollar un episodio de hipoglucemia severa en los primeros días de hospitalización. A la vista de los resultados obtenidos, se sugiere realizar más estudios con el fin de describir en profundidad los mecanismos de asociación de estas variables con el episodio de hipoglucemia grave. La identificación de la magnitud de los factores de riesgo de hipoglucemia severa, presentada a través del estudio de casos y controles, proporciona la base para la construcción de instrumentos estandarizados para la evaluación adecuada de pacientes con diabetes en unidades de internación.

Hypnic Headache Due to Hypoglycemia: A Case Report.

Hypnic headache (HH) is a rare primary headache disorder and pathophysiology is still poorly understood. It is considered a chronobiological disorder in almost all published cases. Few secondary cases have been described so far. We report a case of a 64-year-old woman presenting headaches exclusively during sleep and fulfilling the diagnostic criteria for HH, but a 72-hour glucose monitoring showed hypoglycemia episodes related to the onset of headaches. To our knowledge, this is the first report of symptomatic HHs associated with hypoglycemia and it suggests direct evidence of HH due to a metabolic disorder.

Hyperglycemia and Glucose Variability Are Associated with Worse Brain Function and Seizures in Neonatal Encephalopathy: A Prospective Cohort Study.

OBJECTIVES: To investigate how glucose abnormalities correlate with brain function on amplitude-integrated electroencephalography (aEEG) in infants with neonatal encephalopathy. STUDY DESIGN: Neonates born at full term with encephalopathy were enrolled within 6 hours of birth in a prospective cohort study at a pediatric academic referral hospital. Continuous interstitial glucose monitors and aEEG were placed soon after birth and continued for 3 days. Episodes of hypoglycemia (≤50 mg/dL; ≤2.8 mmol/L) and hyperglycemia (>144 mg/dL; >8.0 mmol/L) were identified. aEEG was classified in 6-hour epochs for 3 domains (background, sleep-wake cycling, electrographic seizures). Generalized estimating equations assessed the relationship of hypo- or hyperglycemia with aEEG findings, adjusting for clinical markers of hypoxia-ischemia (Apgar scores, umbilical artery pH, and base deficit). RESULTS: Forty-five infants (gestational age 39.5 ± 1.4 weeks) were included (24 males). During aEEG monitoring, 16 episodes of hypoglycemia were detected (9 infants, median duration 77.5, maximum 220 minutes) and 18 episodes of hyperglycemia (13 infants, median duration 237.5, maximum 3125 minutes). Epochs of hypoglycemia were not associated with aEEG changes. Compared with epochs of normoglycemia, epochs of hyperglycemia were associated with worse aEEG background scores (B 1.120, 95% CI 0.501-1.738, P < .001), less sleep-wake cycling (B 0.587, 95% CI 0.417-0.757, P < .001) and more electrographic seizures (B 0.433, 95% CI 0.185-0.681, P = .001), after adjusting for hypoxia-ischemia severity. CONCLUSIONS: In neonates with encephalopathy, epochs of hyperglycemia were temporally associated with worse global brain function and seizures, even after we adjusted for hypoxia-ischemia severity. Whether hyperglycemia causes neuronal injury or is simply a marker of severe brain injury requires further study.

Pitfalls in the diagnosis of insulin autoimmune syndrome (Hirata's disease) in a hypoglycemic child: a case report and review of the literature.

Background Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycemia (HH) not addressed as a potential differential diagnosis in current pediatric guidelines. We present a case of IAS in a child with no previous history of autoimmune disease, no previous intake of triggering medications and absence of genetic predisposition. Case presentation A 6-year-old boy presented with recurrent HH (blood glucose of 26 mg/dL [1.4 mmol/L] and insulin of 686 µU/mL). Abdominal imaging was normal. After multiple therapeutic failures, we hypothesized misuse of exogenous insulin and factitious hypoglycemia. Council of Guardianship had the child separated from his mother, but insulin levels remained high. A chromatography test was then performed which showed high titers of endogenous insulin autoantibody (IAA) with early dissociation from the insulin molecule. The human leukocyte antigen (HLA) test showed a DRB1 *13:01/*08:02 genotype. The patient was advised to control food intake and physical activity routines. During a 5-year follow-up, hypoglycemic episodes were sparse, despite high insulin levels. Conclusions Misdiagnosis of IAS with factitious hypoglycemia may happen if IAS is not considered as a differential diagnosis, leading to potential traumatic consequences. Further efforts should be made to increase awareness of IAS as a differential diagnosis of hypoglycemia and to include it in pediatric guidelines.

Autism spectrum disorders: let's talk about glucose?

Autism spectrum disorders (ASD) are characterized by disconnectivity due to disordered neuronal migration, and by neuronal mitochondrial dysfunction. Different pathways involved in neuronal migration are affected by intrauterine hyperglycemia and hyperinsulinemia, while prolonged neonatal hypoglycemia may cause mitochondrial dysfunction. Our hypothesis was that conditions leading to intrauterine hyperglycemia or neonatal hypoglycemia would influence ASD pathogenesis. In this study, we identified risk factors for ASD by searching PubMed with the MeSH terms "autism spectrum disorder" and "risk factors". We then analyzed the relationship between the risk factors and glucose abnormalities in the mother and the offspring. The relationship between glucose abnormalities and risk factors such as obesity, excessive maternal weight gain, or diabetes mellitus is evident. For risk factors such as malformations or exposure to selective serotonin reuptake inhibitors, the relationship is speculative. In rodents, for example, intrauterine hyperglycemia is associated with malformations, independent of maternal diabetes. In their turn, selective serotonin reuptake inhibitors reduce the signs of neonatal hypoglycemia. Going undetected, prolonged hypoglycemia may harm the neonatal brain. Importantly, our group demonstrated that either high-carbohydrate diets or physical inactivity the day before delivery may influence neonatal glycemia. In that study, of 158 neonates selected to be screened according to maternal lifestyle risk factors, 48 had hypoglycemia. Of note, five of them had not been identified with current screening programs. Controlled studies are needed to clarify whether maternal interventions aiming at maintaining glycemic control, together with screening programs for neonatal hypoglycemia based on maternal lifestyle risk factors and on exposure to specific prenatal medications can reduce the prevalence of ASD.

Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic Resonance Imaging in Hypoxic Ischemic Encephalopathy.

OBJECTIVE: To investigate whether the early glycemic profile in infants with hypoxic ischemic encephalopathy is associated with distinct patterns of brain injury on magnetic resonance imaging (MRI). STUDY DESIGN: We performed a secondary analysis of 178 prospectively enrolled infants who received therapeutic hypothermia for hypoxic ischemic encephalopathy. Glycemic profiles were identified by glucose concentrations within 24 hours after birth: normoglycemia (all glucose concentrations of >47 to ≤150 mg/dL; n = 62); hypoglycemia (≥1 concentration ≤47 mg/dL; n = 17); hyperglycemia (≥1 concentration >150 mg/dL; n = 76); and labile glucose (both hypoglycemia and hyperglycemia; n = 23). Patterns of brain injury were identified for 151 infants based on Barkovich scores from the postrewarming brain MRIs at a median age of 9 days. RESULTS: A normal brain MRI was reported in 37 of 62 infants (60%) with normal blood glucose values compared with 37 of 116 infants (32%) with an abnormal glucose profile (adjusted for Sarnat stage of encephalopathy and Apgar score at 5 minutes; P = .02). The distribution of MRI patterns of brain injury differed among the glycemic groups (P = .03). The odds of predominant watershed or focal-multifocal injury was higher in infants with hypoglycemia (aOR, 6; 95% CI, 1.5-24.2) and labile glucose (6.6; 95% CI, 1.6-27) compared with infants with normoglycemia. Infants with labile glucose had higher odds (5.6; 95% CI, 1.1-29.3) of predominant basal ganglia or global injury compared with infants with normal blood glucose values. CONCLUSIONS: The early glycemic profile in infants with hypoxic ischemic encephalopathy is associated with specific patterns of brain injury on MRI. Further investigation is needed to explore its prognostic significance and role as a phenotype biomarker.

Both glucocentric and cardiocentric approaches are necessary for a resilient disease such as diabetes.

Diabetes mellitus (DM) is a complex disease that compromises almost all systems in the human organism. Independently of the intrinsic mechanisms, the source of all consequences of DM is hyperglycemia, a condition associated to intense metabolic changes that will lead to increased morbidity and mortality in the long term. Several different therapeutic hypoglycemic oral agents were developed and significantly facilitated the treatment of hyperglycemia acting at different sites, since patients could take more than one agent. This glucocentric approach was somehow criticized as those hypoglycemic drugs have shown weaker than expected benefits in terms of cardiovascular outcomes and there was a sub use of statins and antihypertensive agents in this population. On the other hand, the catastrophic cardiovascular consequences of hypoglycemia in older adults submitted to tight glycemic control and the results of recent clinical trials that showed impressive reduction in cardiovascular outcomes with less potent antidiabetic agents seem to pave the way to a cardiocentric approach including a lax treatment of DM. Interestingly, the results obtained in recent studies with SGLT2 inhibitors are being mostly attributed to mechanisms other than its hypoglycemic effect in spite of including patients at high cardiovascular risk already taking hypoglycemic agents. Considering the worldwide growing number of patients with diabetes, caregivers must follow a dialectical thinking and choose a synthesis approach where glycemic control is the first and foremost target to be achieved, followed by control of cardiovascular risk factors.

Hipoglucemia post cirugía bariátrica. Presentación de un caso con buena respuesta a octreótide / HYPOGLYCEMIA COMPLICATING BARIATRIC SURGERY. CASE REPORT WITH SUCCESSFUL RESPONSE TO OCTROTIDE

El Bypass Gástrico (BPG) representa la herramienta terapéutica más efectiva para el manejo de la obesidad. Sin embargo, la hipoglucemia con neuroglucopenia post BPG es una complicación que se describe cada vez con mayor frecuencia. Se presenta el caso de una paciente con hipoglucemia hiperinsulinémica (HH) post BPG y los distintos esquemas terapéuticos utilizados, pudiendo controlar finalmente los valores de glucemia con octreótide y evitando así, la realización de una pancreatectomía para el tratamiento de las hipoglucemias

Gastric Bypass (GBP) is the most effective treatment for patients with severe obesity. Hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly late complication of GBP. A case of a post GBP hyperinsulinemic hypoglycemia is reported, and the different drugs used for its treatment, being able to control the glycemia with octreotide and avoiding a pancreatectomy surgery as hypoglycemia treatment

Eficacia y seguridad de la insulina glargina 300 unidades ml versus insulina glargina 100 unidades ml en pacientes adultos con diabetes mellitus tipo 2 mal controlada en tratamiento basal-bolo con análogos de la insulina, que persisten con episodios de hipoglicemia severa a predominio nocturno / Efficacy and safety of insulin glargine 300 ml units versus insulin glargine 100 ml units in adult patients with type 2 diabetes mellitus poorly controlled in basal-bolus treatment with insulin analogues, which persist with episodes of severe hypoglycemia at nighttime prevalence

INTRODUCCIÓN: La Diabetes Mellitus tipo 2 (DM2) es una condición metabólica crónica caracterizada por la resistencia a la insulina y producción de insulina pancreática insuficiente, lo que resulta en altos niveles de glucosa en sangre (hiperglicemia). Está asociada con la obesidad, la poca actividad física y la mala alimentación; su morbimortalidad está determinada por las complicaciones microvasculares y macrovasculares. La DM2 representa entre el 90 y 95 % de todos los casos de Diabetes Mellitus (DM). En el Perú, la DM es la quinta causa de muerte entre todas las enfermedades. Además, en base a información actualizada al 2016, se estima que aproximadamente 932,531 peruanos se encuentran viviendo con DM, resultando en una prevalencia de 2,891.79 casos por cada 100,000 personas. En el contexto de EsSalud, se estima que aproximadamente 700,000 asegurados padecen de esta enfermedad, esto es, el 7 % de la población afiliada. TECNOLOGÍAS SANITARIA DE INTERÉS: Insulina Glargina: La actividad principal de la insulina, incluida la insulina glargina, es la regulación del metabolismo de la glucosa. La insulina y sus análogos reducen los niveles de glucosa en sangre, estimulan la captación de glucosa periférica, principalmente a través del músculo esquelético y la grasa, e inhiben la producción de la glucosa hepática. También inhiben la lipólisis y proteólisis, y aumentan la síntesis de proteínas (European Medicines Agency, 2018). METODOLOGÍA: Se realizó una búsqueda sistemática de literatura con el objetivo de identificar evidencia sobre la eficacia y seguridad de Gla-300 versus Gla-100 en pacientes adultos con DM2 mal controlada en tratamiento basal-bolo con análogos de la insulina (Gla-100 y Lispro), que persisten con episodios de hipoglicemia severa a predominio nocturno. Se utilizó las bases de datos The Cochrane Library, Medline y TRIPDATABASE, priorizándose evidencia proveniente de revisiones sistemáticas o meta-análisis de ensayos clínicos. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluación de tecnologías sanitarias y guías de práctica clínica, incluyendo Scottish Medicines Consortium (SMC), The National Institute for Health and Care Excellence (NICE), The Canadian Agency for Drugs and Technologies in Health (CADTH) y páginas web de organizaciones especializadas en diabetes. Se hizo una búsqueda adicional en la página web de clinicaltrials.gov , para poder identificar ensayos clínicos en curso o que no hayan sido publicados. La búsqueda sistemática se basó en una metodología escalonada, la cual consistió en la búsqueda inicial de estudios secundarios (tipo revisiones sistemáticas de ensayos clínicos) que respondan a la pregunta PICO, seguido de la búsqueda de estudios primarios (tipo ensayos clínicos aleatorizados). RESULTADOS: Una de las complicaciones más frecuentemente asociada al tratamiento farmacológico de la DM2 es la hipoglicemia, que se define como una concentración de glucosa en sangre <70 mg/dL. Esta complicación puede producir síntomas autonómicos como sudoración, temblor y taquicardia, y síntomas neurológicos como pérdida del conocimiento, convulsiones y coma. La hipoglicemia ocurre con mayor frecuencia en pacientes con tratamiento intensivo con insulina, estimándose tasas de episodios/año en torno al 30 %, con un 2 % de episodios severos (estos últimos que requieren de asistencia de otra persona para ser tratada). En EsSalud, los pacientes con DM2 insulino-requiriente son tratados con las siguientes opciones: insulina regular, insulina NPH humana, insulina lispro e insulina glargina; todas en concentración de 100 unidades/ml. A pesar de esta variedad, los médicos especialistas solicitan la aprobación de uso de insulina glargina de 300 unidades/ml (Gla-300), no incluido en el Petitorio Farmacológico de EsSalud, considerando que este podría ofrecer un beneficio adicional respecto a insulina glargina de 100 unidades/ml (Gla-100) en pacientes adultos con DM2 insulino-requiriente, que persisten con episodios de hipoglicemia severa a predominio nocturno a pesar del uso de Gla-100. Tras nuestra búsqueda sistemática de literatura, se identificaron dos guías de práctica clínica (GPC) una elaborada por la Red Escocesa Intercolegiada sobre Directrices (SIGN, por sus siglas en inglés) y otra elaborada por la Diabetes Canada; una sinopsis de la evidencia publicado por el Instituto Nacional de Salud y Cuidados de Excelencia del Reino Unido (NICE, por sus siglas en inglés); y un ensayo clínico controlado aleatorizado (ECA) de fase III con un periodo de seguimiento de 6 meses (EDITION 1) y su extensión hasta los 12 meses. CONCLUSIONES: La única evidencia disponible a la actualidad que evalúa nuestra pregunta clínica en formato PICO proviene del estudio EDITION 1. Este estudio fue un ensayo clínico de no inferioridad y de etiqueta abierta que comparó la eficacia y seguridad de Gla-300 versus Gla-100 en pacientes con DM2 en tratamiento intensivo con insulina basal-bolo, con un periodo de seguimiento de 6 meses. El estudio EDITION 1 tuvo una serie de limitaciones metodológicas que afectaron la validez interna de sus resultados, incluyendo el diseño de etiqueta abierta del estudio (no ciego), la posible confusión por el ajuste de la dosis de insulina prandial, y el posible conflicto de interés. Este estudio no demostró que Gla-300 ofrezca un beneficio clínico en comparación con Gla-100 sobre la reducción del riesgo de hipoglicemia nocturna severa. Específicamente, no se reportaron diferencias estadísticamente significativas entre ambos grupos, esto pudo deberse a un tamaño de muestra insuficiente para detectar diferencias en este desenlace. Por otra parte, la reducción estadísticamente significativa de los eventos de hipoglicemia nocturna confirmada o severa con Gla-300, no se tradujo en un beneficio clínicamente importante. Otros desenlaces considerados de importancia para la presente evaluación, como el porcentaje de pacientes con HbA1c <7.0 %, la hipoglicemia severa en general y los EA, totales y serios, no mostraron diferencias significativas entre Gla-300 y Gla-100. En consecuencia, la evidencia científica disponible a la actualidad no permite sustentar un beneficio neto de Gla-300 respecto a Gla-100 en nuestra población de interés. Adicionalmente, se debe tener en cuenta que Gla-300 es un medicamento de alto costo, no solo en base a su costo unitario, sino también debido al gran número de pacientes con dicha condición (carga de la enfermedad) y la cronicidad de su uso. En ese sentido, la aprobación de uso de Gla-300 en EsSalud no es justificable al no haber demostrado un beneficio adicional respecto a las opciones terapéuticas disponibles en la institución, que a su vez son menos costosas. El IETSI no aprueba el uso de insulina glargina 300 unidades/ml en pacientes adultos con DM2 mal controlada en tratamiento basal-bolo con análogos de la insulina (Gla-100 y Lispro), que persisten con episodios de hipoglicemia severa a predominio nocturno.

Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes.

: Older adults with diabetes are at higher risk for atherosclerotic cardiovascular disease (ASCVD) than younger adults with diabetes and older adults without diabetes. The rationale to implement ASCVD risk-lowering therapies in older adults with diabetes is compelling. Recommendations for lifestyle modification, lipid-lowering therapy, blood pressure management, blood glucose control, and aspirin therapy are often based on studies that show their efficacy in younger populations. However, the risks associated with each of these interventions increase with age, and favorable risk-to-benefit ratios demonstrated in younger adults with diabetes are less certain in older populations. The variability in health status among older adults is pertinent. Those with robust health are more likely to tolerate and derive benefit from many therapies when compared with those who have more complex health including frailty. Age- and/or frailty-stratified data to help clarify these relationships are sparse. In this Perspective, current recommendations for modifying ASCVD risk are described with a review of the pertinent literature that guides their application in older adults. A pragmatic approach to the treatment of ASCVD risk factors in older adults with diabetes is presented.