Update of variants identified in the pancreatic β-cell K ATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes

The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.P30 DK020595/NH/NIH HHS/United States K23 DK094866/NH/NIH HHS/United States R03 DK103096/NH/NIH HHS/United States 1-11-CT-41/American Diabetes Association/International R01 DK104942/DK/NIDDK NIH HHS/United States WT_/Wellcome Trust/United Kingdom WT098395/Z/12/Z/WT_/Wellcome Trust/United Kingdom UL1 TR000430/NH/NIH HHS/United States P30 DK020595/DK/NIDDK NIH HHS/United States UL1 TR000430/TR/NCATS NIH HHS/United States 1-17-JDF-008/American Diabetes Association/International 105636/Z/14/Z/WT_/Wellcome Trust/United Kingdom 110675/European Association for the Study of Diabetes-Novo Nordisk/International 16/0005407/DUK_/Diabetes UK/United Kingdom R01 DK104942/NH/NIH HHS/United States R03 DK103096/DK/NIDDK NIH HHS/United States K23 DK094866/DK/NIDDK NIH HHS/United Statespublished version, accepted version (12 month embargo), submitted versio

Ni-based bimetallic heterogeneous catalysts for energy and environmental applications

Bimetallic catalysts have attracted extensive attention for a wide range of applications in energy production and environmental remediation due to their tunable chemical/physical properties. These properties are mainly governed by a number of parameters such as compositions of the bimetallic systems, their preparation method, and their morphostructure. In this regard, numerous efforts have been made to develop “designer” bimetallic catalysts with specific nanostructures and surface properties as a result of recent advances in the area of materials chemistry. The present review highlights a detailed overview of the development of nickel-based bimetallic catalysts for energy and environmental applications. Starting from a materials science perspective in order to obtain controlled morphologies and surface properties, with a focus on the fundamental understanding of these bimetallic systems to make a correlation with their catalytic behaviors, a detailed account is provided on the utilization of these systems in the catalytic reactions related to energy production and environmental remediation. We include the entire library of nickel-based bimetallic catalysts for both chemical and electrochemical processes such as catalytic reforming, dehydrogenation, hydrogenation, electrocatalysis and many other reactions

Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated ABCC8 permanent neonatal diabetes

Objective ABCC8 mutations cause neonatal diabetes that can be transient (TNDM) or less commonly permanent (PNDM); ~90% individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of permanent and transient forms of ABCC8-NDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. Research Design and Methods We studied all 24 individuals with ABCC8-PNDM diagnosed in the UK, Italy, France or USA known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analysed using non-parametric statistical methods. Results Long-term data were obtained for 21/24 individuals (median follow-up 10.0 (4.1-13.2) years). 18/21 remained on sulfonylureas without insulin at most recent follow-up. Glycemic control improved on sulfonylureas (pre-sulfonylurea vs 1-year post-transfer HbA1c 7.2% vs 5.7%, p=0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, p=0.04), n=16. Relatively high doses were used (1-year vs 10-year dose 0.37 vs 0.25mg/kg/day glyburide, p=0.50), without any severe hypoglycemia. Neurological features were reported in 13/21 individuals: these improved following sulfonylurea transfer in 7/13. The commonest features were learning difficulties (52%), developmental delay (48%), and ADHD (38%). Conclusions Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment

Implementing personalized medicine with asymmetric information on prevalence rates

Although personalized medicine is becoming the new paradigm to manage some diseases, the economics of personalized medicine have only focused on assessing the efficiency of specific treatments, lacking a theoretical framework analyzing the interactions between pharmaceutical firms and healthcare systems leading to the implementation of personalized treatments. We model the interaction between the hospitals and the manufacturer of a new treatment as an adverse selection problem where the firm does not have perfect information on the prevalence across hospitals of the genetic characteristics of the patients making them eligible to receive a new treatment. As a result of the model, hospitals with high prevalence rates benefit from the information asymmetry only when the standard treatment is inefficient when applied to the patients eligible to receive the new treatment. Otherwise, information asymmetry has no value. Personalized medicine may be fully or partially implemented depending on the proportion of high prevalence hospitals