Metabolic syndrome Samson, Susan L; Garber, Alan J
Endocrinology and metabolism clinics of North America,
03/2014, Letnik:
43, Številka:
1
Journal Article
Recenzirano
Metabolic syndrome is not a disease per se, but is a term that highlights traits that may have an increased risk of disease, approximately 2-fold for cardiovascular disease and 5-fold or more for ...type 2 diabetes mellitus. Obesity and insulin resistance are believed to be at the core of most cases of metabolic syndrome, although further research is required to truly understand the pathophysiology behind the syndrome and the gene-environment interactions that increase susceptibility. The mainstay of treatment remains lifestyle changes with exercise and diet to induce weight loss and pharmacologic intervention to treat atherogenic dyslipidemia, hypertension, and hyperglycemia.
Ghrelin: much more than a hunger hormone Pradhan, Geetali; Samson, Susan L; Sun, Yuxiang
Current opinion in clinical nutrition and metabolic care,
2013-November, 2013-Nov, 2013-11-00, 20131101, Letnik:
16, Številka:
6
Journal Article
Recenzirano
Odprti dostop
PURPOSE OF REVIEWGhrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelinʼs hallmark functions are its stimulatory effects on growth ...hormone release, food intake and fat deposition. Ghrelin is famously known as the ‘hunger hormone’. However, ample recent literature indicates that the functions of ghrelin go well beyond its role as an orexigenic signal. Here, we have reviewed some of the most recent findings on ghrelin and its signalling in animals and humans.
RECENT FINDINGSGhrelin regulates glucose homeostasis by inhibiting insulin secretion and regulating gluconeogenesis/glycogenolysis. Ghrelin signalling decreases thermogenesis to regulate energy expenditure. Ghrelin improves the survival prognosis of myocardial infarction by reducing sympathetic nerve activity. Ghrelin prevents muscle atrophy by inducing muscle differentiation and fusion. Ghrelin regulates bone formation and metabolism by modulating proliferation and differentiation of osteoblasts.
SUMMARYIn addition to ghrelinʼs effects on appetite and adiposity, ghrelin signalling also plays crucial roles in glucose and energy homeostasis, cardioprotection, muscle atrophy and bone metabolism. These multifaceted roles of ghrelin make ghrelin and GHS-R highly attractive targets for drug development. Ghrelin mimetics may be used to treat heart diseases, muscular dystrophy/sarcopenia and osteoporosis; GHS-R antagonists may be used to treat obesity and insulin resistance.
Pasireotide (Signifor
®
) long-acting release (LAR) is a next-generation somatostatin receptor ligand (SRL) approved for treatment of patients with acromegaly who have had an inadequate response to ...surgery or for whom surgery is not an option. Pasireotide LAR has been shown to be more effective than other SRLs in providing biochemical control in patients with acromegaly. However, hyperglycemia-related adverse events were more frequent in patients treated with pasireotide LAR than in those treated with other SRLs. Given the effectiveness of pasireotide LAR, it is important to understand whether these hyperglycemia-related events are manageable and, if so, the appropriate steps to take to manage them. In patients treated with pasireotide LAR, levels of fasting plasma glucose (FPG) and glycated hemoglobin (HbA
1c
) increased in the first 1–3 months and stabilized for as long as 26 months thereafter. In phase III trials of patients with acromegaly, only 3.4–3.8 % discontinued pasireotide LAR because of hyperglycemia-related adverse events. In cases in which pasireotide LAR was discontinued, FPG and HbA
1c
levels returned to baseline. Frequent monitoring of glucose levels is recommended, especially immediately after initiating and discontinuing pasireotide LAR. The treatment strategies suggested herein are made on the basis of available clinical data from healthy volunteers and post hoc analyses of phase III trials. Data from several clinical trials indicate a predictable and possibly reversible hyperglycemic effect that is manageable with proactive monitoring and available antidiabetic medications.
Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize outcomes. Given significant novel ...recent advances in understanding acromegaly natural history and individualized therapies, the Pituitary Society invited acromegaly experts to critically review the current literature in the context of Endocrine Society guidelines and Acromegaly Consensus Group statements. This update focuses on how recent key advances affect treatment decision-making and outcomes, and also highlights the likely role of recently FDA-approved therapies as well as novel combination therapies within the treatment armamentarium.
Abstract
BACKGROUND
Delayed hyponatremia is a common complication following transsphenoidal surgery (TSS) of pituitary lesions, which leads to significant patient morbidity, as well as increased ...hospital costs associated with readmission.
OBJECTIVE
To report the effects of fluid restriction, during a postoperative period of 4 d, to decrease rates and readmissions for hyponatremia in a cohort of patients undergoing TSS.
METHODS
Because of our observed postoperative rates of hyponatremia, we implemented 1000-mL fluid restriction limited to postoperative days (POD) 4 to 8 in consecutive patients undergoing surgery at our center between March 2018 and January 2019. Patients were monitored for the development of hyponatremia and readmissions. We compared outcomes with those of patients who had undergone TSS prior to fluid restriction.
RESULTS
Data from 57 patients who underwent TSS following implementation of fluid restriction were compared to prior patients who underwent TSS without restriction. The rate of hyponatremia in patients (n = 57) prior to fluid restriction was 12.3%. Following implementation of fluid restriction, we had zero cases of hyponatremia or readmissions. We found body mass index to be inversely related to the risk of hyponatremia and readmissions. Furthermore, male gender, follicle stimulating hormone and/or luteinizing hormone staining on pathology, and administration of preoperative and intraoperative glucocorticoids were associated with decreased risk of hyponatremia readmissions.
CONCLUSION
The implementation of 1000-mL fluid restriction between POD 4 and 8 is a highly successful and simple approach to decrease the risk of delayed hyponatremia after TSS.
This consensus statement provides (1) visual guidance in concise graphic algorithms to assist with clinical decision-making of health care professionals in the management of persons with type 2 ...diabetes mellitus to improve patient care and (2) a summary of details to support the visual guidance found in each algorithm.
The American Association of Clinical Endocrinology (AACE) selected a task force of medical experts who updated the 2020 AACE Comprehensive Type 2 Diabetes Management Algorithm based on the 2022 AACE Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan and consensus of task force authors.
This algorithm for management of persons with type 2 diabetes includes 11 distinct sections: (1) Principles for the Management of Type 2 Diabetes; (2) Complications-Centric Model for the Care of Persons with Overweight/Obesity; (3) Prediabetes Algorithm; (4) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Dyslipidemia; (5) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Hypertension; (6) Complications-Centric Algorithm for Glycemic Control; (7) Glucose-Centric Algorithm for Glycemic Control; (8) Algorithm for Adding/Intensifying Insulin; (9) Profiles of Antihyperglycemic Medications; (10) Profiles of Weight-Loss Medications (new); and (11) Vaccine Recommendations for Persons with Diabetes Mellitus (new), which summarizes recommendations from the Advisory Committee on Immunization Practices of the U.S. Centers for Disease Control and Prevention.
Aligning with the 2022 AACE diabetes guideline update, this 2023 diabetes algorithm update emphasizes lifestyle modification and treatment of overweight/obesity as key pillars in the management of prediabetes and diabetes mellitus and highlights the importance of appropriate management of atherosclerotic risk factors of dyslipidemia and hypertension. One notable new theme is an emphasis on a complication-centric approach, beyond glucose levels, to frame decisions regarding first-line pharmacologic choices for the treatment of persons with diabetes. The algorithm also includes access/cost of medications as factors related to health equity to consider in clinical decision-making.
Abstract
Purpose
The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical ...control while receiving injectable somatostatin receptor ligands (SRLs).
Methods
In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 IGF-1 ≤ 1.0 × upper limit of normal ULN; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures.
Results
Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience.
Conclusions
OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.
We examined the effects of combined pioglitazone (peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonist) and exenatide (GLP‐1 receptor agonist) therapy on hepatic fat content and plasma ...adiponectin levels in patients with type 2 diabetes (T2DM). Twenty‐one T2DM patients (age = 52 ± 3 years, BMI = 32.0 ± 1.5, hemoglobin A1c (HbA1c) = 8.2 ± 0.4%) on diet and/or metformin received additional treatment with either pioglitazone 45 mg/day for 12 months (n = 10) or combined therapy with pioglitazone (45 mg/day) and exenatide (10 µg subcutaneously twice daily) for 12 months (n = 11). At baseline, hepatic fat content and plasma adiponectin levels were similar between the two treatment groups. Pioglitazone reduced fasting plasma glucose (FPG) (P < 0.05), fasting free fatty acid (FFA) (P < 0.05), and HbA1c (Δ = 1.0%, P < 0.01), while increasing plasma adiponectin concentration by 86% (P < 0.05). Hepatic fat (magnetic resonance spectroscopy (MRS)) was significantly reduced following pioglitazone treatment (11.0 ± 3.1 to 6.5 ± 1.9%, P < 0.05). Plasma triglyceride concentration decreased by 14% (P < 0.05) and body weight increased significantly (Δ = 3.7 kg). Combined pioglitazone and exenatide therapy was associated with a significantly greater increase in plasma adiponectin (Δ = 193%) and a significantly greater decrease in hepatic fat (12.1 ± 1.7 to 4.7 ± 1.3%) and plasma triglyceride (38%) vs. pioglitazone therapy despite the lack of a significant change in body weight (Δ = 0.2 kg). Hepatic injury biomarkers aspartate aminotransferase and alanine aminotransferase (ALT) were significantly decreased by both treatments; however, the reduction in ALT was significantly greater following combined pioglitazone and exenatide therapy. We conclude that combined in patients with T2DM, pioglitazone and exenatide therapy is associated with a greater reduction in hepatic fat content as compared to the addition of pioglitazone therapy (Δ = 61% vs. 41%, P < 0.05).
Acromegaly is an insidious neuroendocrine disorder caused by hypersecretion of growth hormone (GH) by a somatotroph adenoma. Somatostatin receptor ligands (SRLs) are recommended as first-line medical ...therapy in patients for whom surgery has failed or is contraindicated. There are 5 known somatostatin receptor subtypes (SSTRs), 2 of which, i.e. SSTR2 and SSTR5, are expressed by a majority of somatotroph adenomas. The currently available SRLs, i.e. octreotide and lanreotide, primarily bind to SSTR2. Pasireotide (SOM230) is a new multireceptor-targeted SRL which has a broader binding profile and an increased affinity for SSTR1, 2, 3, and 5.
PubMed searches were performed to identify all of the available published English language data on pasireotide with regard to the mechanism of action, in vitro effects, and clinical data.
Preclinical studies have demonstrated that pasireotide has a broader range of functional activity than octreotide. Recently, the efficacy of pasireotide in attenuating GH and insulin-like growth factor 1 (IGF-1) levels in patients with acromegaly has been evaluated in phase III clinical trials. Pasireotide demonstrated superiority over octreotide in achieving biochemical control (i.e. GH ≤2.5 µg/l and age- and sex-matched IGF-1 normalization) in patients with acromegaly, as well as significant efficacy in treating patients who were previously inadequately controlled on the maximum allowed doses of octreotide and lanreotide. Pasireotide-induced hyperglycemia was the most concerning adverse event but was reversible upon discontinuation of pasireotide.
The clinical data support pasireotide as a promising new therapy for the treatment of acromegaly, and the long-acting formulation was recently approved in the US and Europe for the treatment of acromegaly.
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