Expert Review of Endocrinology & Metabolism最新文献

Introduction: In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development.

Areas covered: We performed a literature review searching for promising druggable biomarkers and potential treatments to be implemented in the next future. We focused on treatments which have already reached clinical experimentation, although in early phases. Six targets were identified, namely Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR. Even though biological rational is strong, so far reported efficacy outcomes are quite disappointing. The reason of that should be searched in the patients' heterogeneity, lack of biomarker selection, poor knowledge of interfering mechanisms as well as difficulties in patients accrual. Moreover, different ways to assess treatment efficacy should be considered, other than response rate, in light of the more indolent nature of NETs.

Expert opinion: Development of targeted treatments in PanNETs is still an uncovered area, far behind other more frequent cancers. Rarity of NETs led to accrual of unselected populations, possibly jeopardizing the drug efficacy. Better patients' selection, both in terms of topography, grading and biomarkers is crucial and will help understanding which role targeted therapies can really play in these tumors.

Introduction: Bariatric surgery has demonstrated long-term effectiveness in inducing weight loss and improving metabolic parameters for obesity. Single anastomosis duodeno-ileal (SADI) bypass and single anastomosis sleeve-ileal (SASI) bypass have both emerged as new promising bariatric procedures. In this paper, we review the existing literature and compare the outcomes of SADI and SASI bypass procedures in regard to weight loss, complication rate, and improvement of type II diabetes (T2DM). This has not yet been done in the preexisting literature.

Areas covered: We conducted a systematic literature search of electronic databases focusing on weight loss outcomes, rate of complications and remission, or improvement of T2DM and other obesity-related comorbidities. Seventeen studies on SADI and nine studies on SASI were included. Both are similar in terms of surgical technique and have demonstrated fewer complications when compared to other bariatric procedures. Mean preoperative BMI was similar in both study groups: 46.4 kg/m² in SADI and 48.8 kg/m² in SASI. Mean %EWL at 12 months in the SADI group was 74.1% compared to 77.4% in the SASI group. Preoperative severity of T2DM appeared to be higher in the SASI patient group, with a higher preoperative HbA1c and fasting blood glucose levels. T2DM resolution was achieved in a significant proportion of both SADI and SASI patient populations (78.5% in SADI and 89.0% in SASI). Complication rates were comparable for both procedures.

Expert opinion: Both SADI and SASI are effective in inducing weight loss at 12 months, with a low rate of major complications and mortality. From the studies included in this review, the SASI procedure had a higher impact on T2DM resolution compared to SADI.

Objective: To identify a preferred and cost-effective drug among Dipeptidyl peptidase-4 inhibitors (DPP4Is) for Indian patients with T2DM.

Methods: We performed a systematic literature search using standard databases for relevant literature. Original studies comparing the efficacy and/or safety of different DPP4Is were included. Two authors independently performed the literature search, screening, and collected relevant data from the selected studies. The costs of all brands of individual DPP4Is were noted and compared for lowest, highest, and average cost. Finally, we summarized the information with respect to Efficacy, safety, suitability, and cost to find the most cost-effective DPP4I.

Results: We found 13 eligible studies containing data on 15,720 subjects. These studies showed similar efficacy (or better) and safety with teneligliptin as compared to other DPP4Is. Teneligliptin also showed additional benefits other than the glycemic control. The average cost per tablet of teneligliptin 20 mg was markedly lower as compared to sitagliptin, vildagliptin, and other commonly used DPP4Is. Teneligliptin also outscored other commonly used DPP4Is in India in suitability and seems to have better patient compliance.

Conclusions: Teneligliptin 20 mg could be considered as the preferred and most cost-effective agent among commonly used DPP4Is for the effective management of patients with T2DM in India.

Introduction: Frailty is an emerging and newly recognized complication of diabetes in older people. However, frailty is not thoroughly investigated in diabetes outcome studies.

Areas covered: This manuscript reviews the effect of glycemic control and hypoglycemic therapy on the incidence of frailty in older people with diabetes.

Expert opinion: Current studies show that both low glycemia and high glycemia are associated with frailty. However, most of the studies, especially low glycemia studies, are cross-sectional or retrospective, suggesting association, rather than causation, of frailty. In addition, frail patients in the low glycemia studies are characterized by lower body weight or lower body mass index (BMI), contrary to those in the high glycemia studies, who are either overweight or obese. This may suggest that frailty has a heterogeneous metabolic spectrum, starting with an anorexic malnourished (AM) phenotype at one end, which is associated with low glycemia and a sarcopenic obese (SO) phenotype on the other end, which is associated with high glycemia. The current little evidence suggests that poor glycemic control increases the risk of frailty, but there is a paucity of evidence to suggest that tight glycemic control would reduce the risk of incident frailty. Metformin is the only well-studied hypoglycemic agent, so far, to have a protective effect against frailty independent of glycemic control in the non-frail older people with diabetes. However, once frailty is developed, the choice of the best hypoglycemic agent for these patients will be affected by the metabolic phenotype of frailty. For example, sodium glucose transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are appropriate in the SO phenotype due to their weight losing properties, while insulin therapy may be considered early in the AM phenotype due to its anabolic and weight gaining benefits. Future studies are still required to further investigate the metabolic effects of frailty on older people with diabetes, determine the most appropriate HbA1c target, and explore the most suitable hypoglycemic agent in each metabolic phenotype of frailty.

Background: This study aimed to investigate the association between serum liver enzymes and the presence of metabolic syndrome (MetS) among Bangladeshi adults.

Research design and methods: A total of 602 participants (424 males and 178 females) were enrolled in this cross-sectional study. Serum levels of liver enzymes (ALT, AST, GGT and ALP) and other biochemical parameters were measured by standard colorimetric methods. The relationship between liver enzymes and MetS was assessed by multivariable logistic regression models.

Results: Overall, the prevalence of MetS was 34.9% among the participants. Of the four liver enzymes, the mean levels of serum ALT and GGT were significantly higher among subjects with MetS than those without MetS (p < 0.01). When liver enzyme levels were categorized into normal and elevated ranges, MetS and its component's prevalence was higher in the elevated group except for ALP. Serum ALT and GGT showed a significant relationship with the maximum components of MetS. According to the logistic regression analysis, elevated levels of ALT and GGT were significantly associated with the prevalence of MetS (p < 0.01 and p < 0.001, respectively).

Conclusions: This study showed that elevated ALT and GGT levels were independently associated with MetS and its components.

Introduction: Endocrine-disrupting chemicals (EDCs) have gained more importance in the past decade, mostly due to their role in the pathogenesis of disease, especially in carcinogenesis. However, there is limited literature on the environmental burden on some of the less common endocrine neoplasia.

Areas covered: This review focuses on both observational and experimental studies linking exposure to EDCs and endocrine neoplasia specifically pituitary, thyroid, adrenal and neuroendocrine tumors. Following PRISMA guidelines, a search of English peer-reviewed literature was performed using Medline and Google Scholar, giving preference to recent publications.

Expert opinion: Exposure to EDC occurs not only in the household but also at work, whether it is in the office, factory, or farm and during transport from one location to another. Many studies have evaluated the effect of single environmental agents; however, humans are rarely exposed to only one EDC. Different EDCs and different levels of exposure may interact together to provide either a synergistic and/or an antagonistic disruption on human health, and hence a complex mechanism to elucidate. The ultimate adverse effect is difficult to predict, as it is not only influenced by the degree of exposure, but also by genetics, lifestyle, comorbidities, and other stressors.

Introduction: Testosterone replacement therapy is a promising and growing field in modern healthcare. Several novel testosterone preparations aiming at providing an efficient drug without side effects have been developed in recent years. Several oral, nasal, gel, and self-injection preparations are now available, providing a wide variety of options customized to each individual's needs.

Areas covered: We searched Google Scholar for keywords related to the different types of testosterone replacement therapy. This review provides information about the benefits and side effects of the newest testosterone preparations, aiming at giving a summary of the options with regard to testosterone replacement therapy to healthcare professionals.

Expert opinion: As testosterone replacement therapy is increasing in popularity, the development of novel ways of administration minimizing side effects associated with testosterone replacement therapy is growing. Nowadays, hypogonadal patients have several options to treat their conditions and can choose the most beneficial method for their individual condition.

Introduction: To date, the 21^st Century has witnessed key developments in the management of diabesity (a conflation of obesity and Type 2 Diabetes Mellitus [T2D]), including Glucagon Like Peptide 1 (GLP1) receptor agonist therapies, and recently the 'designer' GLP1 Poly-agonist Peptides (GLP1PPs).

Areas covered: A PubMed search of published data on the GLP1PP class of therapies was conducted. The gut-brain axis forms complex multi-directional interlinks that include autonomic nervous signaling, components of the gut microbiota (including metabolic by-products and gram-negative cell wall components [e.g. endotoxinaemia]), and incretin hormones that are secreted from the gut in response to the ingestion of nutrients. The development of dual-incretin agonist therapies includes combinations of the GLP1 peptide with Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (Gcg), Cholecystokinin (CCK), Peptide YY (PYY), and Glucagon-Like Peptide 2 (GLP2). Triple incretin agonist therapies are also under development.

Expert opinion: At the dawn of a new era in the therapeutic management of diabesity, the designer GLP1PP class holds great promise, with each novel combination building on a preexisting palimpsest of clinical data and insights. Future innovations of the GLP1PP class will likely enable medically induced weight loss and glycemic control in diabesity to rival or even out-perform those resulting from bariatric surgery.

Introduction: Hypocholesterolemia results from genetic - both monogenic and polygenic - and non-genetic causes and can sometimes be a source of clinical concern. We review etiologies and sequelae of hypocholesterolemia and therapeutics inspired from genetic hypocholesterolemia.

Areas covered: Monogenic hypocholesterolemia disorders caused by the complete absence of apolipoprotein (apo) B-containing lipoproteins (abetalipoproteinemia and homozygous hypobetalipoproteinemia) or an isolated absence of apo B-48 lipoproteinemia (chylomicron retention disease) lead to clinical sequelae. These include gastrointestinal disturbances and severe vitamin deficiencies that affect multiple body systems, i.e. neurological, musculoskeletal, ophthalmological, and hematological. Monogenic hypocholesterolemia disorders with reduced but not absent levels of apo B lipoproteins have a milder clinical presentation and patients are protected against atherosclerotic cardiovascular disease. Patients with heterozygous hypobetalipoproteinemia have somewhat increased risk of hepatic disease, while patients with PCSK9 deficiency, ANGPTL3 deficiency, and polygenic hypocholesterolemia typically have anunremarkable clinical presentation.

Expert opinion: In patients with severe monogenic hypocholesterolemia, early initiation of high-dose vitamin therapy and a low-fat diet are essential for optimal prognosis. The molecular basis of monogenic hypocholesterolemia has inspired novel therapeutics to help patients with the opposite phenotype - i.e. elevated apo B-containing lipoproteins. In particular, inhibitors of PCSK9 and ANGPTL3 show important clinical impact.