Among patients with atherosclerotic vascular disease, the addition of extended-release niacin–laropiprant to statin-based LDL cholesterol–lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events.
Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients — NEJM.
A Form of the Metabolic Syndrome Associated with Mutations in DYRK1B — NEJM.
A founder mutation was identified in DYRK1B, substituting cysteine for arginine at position 102 in the highly conserved kinase-like domain. The mutation precisely cosegregated with the clinical syndrome. Functional characterization of the disease gene revealed that nonmutant protein encoded by DYRK1B inhibits the SHH (sonic hedgehog) and Wnt signaling pathways and consequently enhances adipogenesis. Furthermore, DYRK1B promoted the expression of the key gluconeogenic enzyme glucose-6-phosphatase. The R102C allele showed gain-of-function activities by potentiating these effects. A second mutation, substituting proline for histidine 90, was found to cosegregate with a similar clinical syndrome in an ethnically distinct family.
These findings indicate a role for DYRK1B in adipogenesis and glucose homeostasis and associate its altered function with an inherited form of the metabolic syndrome.
TOPCAT trial shows no benefit of spironolactone in terms of death, hospitalization, aborted SCD in heart failure with preserved ejection fraction.
Spironolactone for Heart Failure with Preserved Ejection Fraction — NEJM.