Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis

Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis

A Practical Approach to the Treatment of Low-Risk Childhood Fever

Fever is a common symptom of childhood infections that in itself does not require treatment. The UK’s National Institute for Health and Care Excellence (NICE) advises home-based antipyretic treatment for low-risk feverish children only if the child appears distressed. The recommended antipyretics are ibuprofen or paracetamol (acetaminophen). They are equally recommended for the distressed, feverish child; therefore, healthcare professionals, parents and caregivers need to decide which of these agents to administer if the child is distressed. This narrative literature review examines recent data on ibuprofen and paracetamol in feverish children to determine any clinically relevant differences between these agents. The data suggest that these agents have similar safety profiles in this setting and in the absence of underlying health issues, ibuprofen seems to be more effective than paracetamol at reducing NICE’s treatment criterion, ‘distress’ (as assessed by discomfort levels, symptom relief, and general behavior)