Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Heterozygous familial hypercholesterolemia (HeFH) is one of the most common monogenic disorders and is safely treatable with lipid-lowering medication. However, most individuals with HeFH remain untreated and undetected, especially in paediatric populations where the potential for long-term therapeutic benefit is higher. Here, we review the recent literature on health economic outcomes for the detection and management of FH in children.

Recent findings: A targeted literature review identified eight studies evaluating detection and management strategies for paediatric FH populations in the last 25 years. Most studies conducted modelled cost-effectiveness analyses to understand the long-term impact of these strategies on health outcomes and the financial impact on the healthcare system. All studies reported that detection and management of HeFH in paediatric populations was cost-effective, regardless of the age of the children. However, cost-effectiveness varied depending on the method of case ascertainment - targeted screening was generally cheaper overall, but less effective, than whole-of-population screening, although both methods were generally cost-effective.

Summary: Detection and management of HeFH in paediatric populations is a cost-effective way to significantly lower the burden of disease later in life for these individuals. These strategies should be implemented across healthcare systems.

Purpose of review: The aim of this review is to present the clinical indications of apolipoprotein C-III (apoC3) inhibition in the therapeutic arsenal for the treatment of lipid disorders and associated risks and to compare the most advanced modalities of apoC3 inhibition currently available or in development, specifically APOC3 antisense oligonucleotides (ASO) and small interfering RNA (siRNA).

Recent findings: ApoC3 inhibition significantly decreases triglyceride levels by mechanisms coupling both lipoprotein lipase (LPL) upregulation and LPL-independent mechanisms. The main apoC3 inhibitors in advanced clinical development are the GalNAc-ASO olezarsen and the GalNAc-siRNA plozasiran. Clinical studies conducted with volanesorsen, the olezarsen precursor, showed a favorable effect on hepatic steatosis (nonalcoholic fatty liver disease, NAFLD). Olezarsen does not appear to be associated with the main side effects attributed to volanesorsen including thrombocytopenia. Plozasiran is in advanced clinical development and requires subcutaneous injection every 3 months and present to-date an efficacy and safety profile comparable to that of the monthly ASO.

Summary: Inhibition of apoC3 is effective across all the spectrum of hypertriglyceridemia, might have a favorable effect on hepatic steatosis (NAFLD) and the effect of apoC3 inhibition on cardiovascular risk is not limited to its effect on plasma triglycerides. APOC3 GalNAc-conjugated ASO and siRNA are both effective in decreasing plasma apoC3 and triglyceride levels.

Purpose of review: The aim of this review was to understand the role of multifactorial chylomicronemia syndrome (MFCS) as a cause of severe hypertriglyceridemia; to distinguish it from other causes of severe hypertriglyceridemia; and to provide a rational approach to treatment.

Recent findings: There have been advances in understanding the genetic underpinning of MFCS, and a better appreciation as to how to differentiate it from the much rarer familial chylomicronemia syndrome, in which there are substantial differences in the approach to their treatment. New approaches to triglyceride lowering will help reduce the risk of pancreatitis, the major complication of MFCS.

Summary: MCSF is a condition in which plasma triglyceride levels are severely elevated, usually to due exacerbation of common genetic forms of hypertriglyceridemia by secondary causes of hypertriglyceridemia and/or triglyceride-raising drugs. Triglyceride-induced pancreatitis can be prevented by markedly reducing triglyceride levels by treating secondary causes and/or eliminating of triglyceride-raising drugs, and by using triglyceride-lowering drugs, especially fibrates. MFCS also increases cardiovascular disease risk, for which lifestyle measures and drugs are required.

Purpose of review: To present recent evidence that strengthens the concept that exogenous pollutants contribute to adipose dysfunction and increased rates of disease and to highlight the ineffective regulation of this risk as industry switches to related but similarly toxic variants.

Recent findings: Substitutes for common phthalates and the highly regulated bisphenol A (BPA) show similar deleterious effects on adipocytes. The well tolerated limit for BPA exposure has been reduced in Europe to below the level detected in recent population studies. Additionally, the role for BPA-induced inflammation mediated by interleukin 17a has been described in animal and human studies.

Summary: Despite experimental and associative evidence that supports plastics and plastic associated chemicals deleteriously influencing adipose homeostatasis and contributing to metabolic diseases, structurally related alternate chemicals are being substituted by manufacturers to circumvent trailing regulatory actions.

Purpose of review: To identify recent literature evaluating the efficacy of psychosocial and behavioral interventions for people with type 1 diabetes (T1D).

Recent findings: Interventions generally produce benefits for psychosocial and behavioral outcomes, and some also positively impact glycemia. Addressing psychosocial concerns during routine provider visits had mixed results; some studies found that structured tools improved well being, while others found they could derail conversations, or contribute to worsening glycemia due to a lack of time to review medical concerns. Integrating behavioral health providers in routine care, however, had a positive impact on glycemic outcomes. Stepped care interventions show promise for both children and adults, as they maximize available resources while contributing to improved well being. Group interventions, delivered either virtually or in-person, demonstrated benefits for diabetes distress, depressive symptoms, family conflict, and health behaviors, but had limited impact on positive parenting skills. Gaps in the current literature include limited research among adults and no research among older adults, as well as a lack of pragmatic research emphasizing implementation of effective interventions.

Summary: A wide range of interventions have demonstrated positive impacts on well being among people with T1D; more research is needed to identify strategies to routinely integrate psychosocial and behavioral support in clinical care.