Current Opinion in Endocrinology & Diabetes and Obesity最新文献

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.

Purpose of review: The purpose of this review is to provide a comprehensive overview into the diagnosis and management of fibrous dysplasia (FD) in children.

Recent findings: FD is a mosaic disorder arising from somatic Gα s variants, leading to impaired osteogenic cell differentiation. Fibro-osseous lesions expand during childhood and reach final disease burden in early adulthood. The mainstay of treatment focuses on surgical correction of skeletal deformities, physiatric care, and medical management of associated hyperfunctioning endocrinopathies. Bisphosphonates may be helpful to treat bone pain, but do not alter lesion quality or progression. Emerging evidence suggests that the RANKL inhibitor denosumab may be effective in improving lesion activity and mineralization, however further studies are needed to determine the potential utility of this and other novel therapies, particularly in children with FD.

Summary: Management of children with FD has unique challenges related to skeletal growth and age-related lesion progression. Inclusion of children in clinical research is critical to develop effective treatment strategies to treat FD lesions and prevent their development.

Purpose of review: Bone accrual during childhood and adolescence is critical for the attainment of peak bone mass and is a major contributing factor towards osteoporosis in later life. Bone mass accrual is influenced by nonmodifiable factors, such as genetics, sex, race, ethnicity, and puberty, as well as modifiable factors, such as physical activity and diet. Recent progress in bone imaging has allowed clinicians and researchers to better measure the morphology, density, and strength of the growing skeleton, thereby encompassing key characteristics of peak bone strength. In this review, the patterning of bone accrual and contributors to these changes will be described, as well as new techniques assessing bone mass and strength in pediatric research and clinical settings.

Recent findings: This review discusses factors influencing peak bone mass attainment and techniques used to assess the human skeleton.

Summary: The rate of bone accrual and the magnitude of peak bone mass attainment occurs in specific patterns varying by sex, race, ethnicity, longitudinal growth, and body composition. Physical activity, diet, and nutritional status impact these processes. There is a need for longitudinal studies utilizing novel imaging modalities to unveil factors involved in the attainment and maintenance of peak bone strength.

Purpose of review: A recent increase in legislation in the United States prohibiting gender-affirming care (GAC) for transgender youth follows a wave of its politicization despite support from all pertinent mainstream medical associations. This review describes the standards of GAC for transgender youth, the origins of legislation prohibiting this care, a review of current legislation in the United States and a discussion on the impact on patients, providers, and the medical field.

Recent findings: A critical evaluation of historical parallels and current organizations supporting this legislation reveals it stems not from concerns within the medical field but from political and religious interests. This intrusion sets a dangerous precedent, undermining evidence-based medicine, providers' ability to practice according to standards of care, and patients' and guardians' autonomy and medical decision-making. This wave of antitrans rhetoric and legislation has resulted in threats to health providers and hospitals, 'moral distress" in providers, and migration of providers and patients from hostile states.

Summary: Similar to antiabortion legislation, these legislative efforts will likely result in negative health outcomes and worsening disparities. The medical community must confront these forces directly through an understanding of the political and structural forces at play and adopting strategies to leverage collective power.

Purpose of review: Familial hypercholesterolemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to atherosclerotic cardiovascular disease (ASCVD). The risk of ASCVD can be substantially reduced with lipid-lowering treatment (LLT). However, adherence to LLT remains a major challenge in FH patients and an under-recognized issue. We review several barriers to treatment adherence and implementation strategies for improving adherence in patients with FH.

Recent findings: Barriers that negatively affect patient adherence to treatment include the misunderstanding of perceived and actual risk of FH and the benefits of LLT, inadequate knowledge, lack of standardization of treatment, insufficient monitoring of LDL-cholesterol level, and inequalities in healthcare resources. Education of patients, carers and healthcare providers, guideline-directed treatment goals, regular monitoring, medication regimen simplification and greater access to established and new drugs are crucial enablers for improving adherence to treatment. However, given FH is present from birth, strategies for life-long adherence from childhood or young adulthood is critically important and requires further study. To be effective, strategies should be multifaceted, targeted and patient-centred involving a multidisciplinary-team with support from family, communities and peer groups.

Summary: FH confers a significant risk for ASCVD from a young age. Achieving better medication adherence is foundational for improving clinical outcomes and reducing the burden of atherosclerosis over a lifetime. Identification of key barriers and enablers are critical for implementing better adherence to treatment across the life-course of patients with FH.