scholarly journals 20 YEARS OF LEPTIN: Leptin in common obesity and associated disorders of metabolism

2014 ◽  
Vol 223 (1) ◽  
pp. T71-T81 ◽  
Author(s):  
Alex M DePaoli
Keyword(s):  
Clinical Trials ◽  
Body Weight ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Therapeutic Interventions ◽  
Ovary Syndrome ◽  
Comprehensive Overview ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

The molecular mechanisms of body weight and body composition regulation have long been a research focus in the hopes of identifying tractable pathways for therapeutic interventions for obesity and diabetes, as well as related disorders such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and polycystic ovary syndrome. The metabolic consequences of obesity and type 2 diabetes (T2D) were already a focus of the world's attention in 1994 when the discovery of leptin generated enormous enthusiasm for the potential to treat common (non-monogenic) obesity and its associated metabolic disorders with an adipokine hormone that regulated body weight as well as lipid and carbohydrate metabolism. Recombinant human leptin and many leptin analogs were developed and studied in animals and a few in human clinical trials. Overall, the opportunity for leptin as a therapeutic in unselected patients with obesity and T2D has not been substantiated in clinical trials. The potential for combination therapy suggested by clinical studies with leptin and pramlintide supports a path toward obesity treatment through the leptin pathway. The profound metabolic benefits seen with leptin in numerous forms of leptin deficiency, including lipodystrophy, provide hope for the opportunity to identify selected subsets of patients who could benefit from leptin treatment. This review provides a comprehensive overview of the clinical data on a subset of the potential utilities of leptin, specifically as a therapeutic for general or common obesity and its metabolic consequences including T2D and NAFLD/NASH.

scholarly journals Youth-Onset Type 2 Diabetes Manifestations in other Specialties: Its Many Disguises

2019 ◽  
Vol 74 (4) ◽  
pp. 339-347 ◽  
Author(s):  
Daniel Weghuber ◽  
Margarita Barrientos-Pérez ◽  
Margarita Kovarenko
Keyword(s):  
Type 2 Diabetes ◽  
Health Care Professionals ◽  
Acanthosis Nigricans ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Nonalcoholic Fatty Liver ◽  
Onset Type ◽  
Primary Health ◽  
Increased Risk

Background: Youth-onset type 2 diabetes (T2D) is increasing in many countries, creating large personal and societal burdens. While many primary health-care professionals (HCPs) are aware of the classic symptoms of T2D, there are several other manifestations that could indicate its presence. Summary: This narrative review summarizes information on these symptoms and indicators, focusing on those less well known. The classic symptoms and comorbidities include frequent urination, excessive thirst, metabolic syndrome, and obesity. In addition to these, the presence of dermatological (e.g., acanthosis nigricans, granuloma annulare, necrobiosis lipoidica diabeticorum, and scleredema), gynecological (e.g., polycystic ovary syndrome, oligomenorrhea, and vulvovaginitis), hepatological (e.g., nonalcoholic fatty liver disease), and psychiatric diseases (e.g., psychosis, depression, and autism) could indicate that a patient has T2D or is at increased risk of T2D. Other less well-known indicators include abnormal blood tests (e.g., oxidized lipids, inflammation markers, hepatokines, and adipokines), prescriptions for antipsychotic medications or statins, and disrupted sleep patterns. Key Message: Due to the diversity of T2D manifestations in young people, primary HCPs need to remain alert to its possible presence.

scholarly journals Pathophysiology of NASH in endocrine diseases

2021 ◽  
Author(s):  
Karim Gariani ◽  
François R Jornayvaz
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Polycystic Ovary ◽  
Hormone Deficiency ◽  
Male Hypogonadism ◽  
Ovary Syndrome ◽  
Nonalcoholic Fatty Liver ◽  
Endocrine Diseases ◽  
Global Health Issue

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. NAFLD encompasses a whole spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The latter can lead to hepatocellular carcinoma. Furthermore, NASH is the most rapidly increasing indication for liver transplantation in western countries and therefore represents a global health issue. The pathophysiology of NASH is complex and includes multiple parallel hits. NASH is notably characterized by steatosis as well as evidence of hepatocyte injury and inflammation, with or without fibrosis. NASH is frequently associated with type 2 diabetes and conditions associated with insulin resistance. Moreover, NASH may also be found in many other endocrine diseases such as polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or glucocorticoid excess, for example. In this review, we will discuss the pathophysiology of NASH associated with different endocrinopathies.

scholarly journals Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

2020 ◽  
Vol 21 (21) ◽  
pp. 8147
Author(s):  
Kok-Min Seow ◽  
Yi-Wen Chang ◽  
Kuo-Hu Chen ◽  
Chi-Chang Juan ◽  
Chen-Yu Huang ◽  
...  
Keyword(s):  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Surgical Approaches ◽  
Ovary Syndrome ◽  
Antral Follicles ◽  
Body Weight Reduction ◽  
Laparoscopic Ovarian Drilling ◽  
Ovarian Drilling

Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5–10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5–15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30–90% and final pregnancy rates of 13–88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of “toxic” follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the “hypothalamus–pituitary–ovary” axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.

scholarly journals The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management

2021 ◽  
Vol 14 (11) ◽  
pp. 1185
Author(s):  
Amandine Bernard ◽  
Aurore Danigo ◽  
Sylvie Bourthoumieu ◽  
Mohamad Mroué ◽  
Alexis Desmoulière ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pain Management ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Pain Perception ◽  
Pain Modulation ◽  
Comprehensive Overview ◽  
Sensory Nervous System

Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management.

The Impact of Obesity on Incidence of Type 2 Diabetes Mellitus (T2DM) among Women with Polycystic Ovary Syndrome (PCOS)

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1612-P
Author(s):  
NADIRA SULTANA KAKOLY ◽  
ARUL EARNEST ◽  
HELENA TEEDE ◽  
LISA MORAN ◽  
DEBORAH LOXTON ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
The Impact

Effects of diacerein intake on cardiometabolic profiles in type 2 diabetics: a systematic review and meta-analysis of clinical trials.

2020 ◽  
Vol 27 ◽  
Author(s):  
Peyman Nowrouzi-Sohrabi ◽  
Reza Tabrizi ◽  
Mohammad Jalali ◽  
Navid Jamali ◽  
Shahla Rezaei ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Body Weight ◽  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Hdl Cholesterol ◽  
Cochrane Central Register ◽  
Statistical Heterogeneity

Introduction: A systematic review and meta-analysis of clinical trials was undertaken to evaluate the effect of diacerein intake on cardiometabolic profiles in patients with type 2 diabetes mellitus (T2DM). Methods: Electronic databases such as PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched from inception to 31 July 2019. Statistical heterogeneity was evaluated using Cochran’s Q test and I-square (I2 ) statistic. Data were pooled using random-effect models and weighted mean difference (WMD). Results: From 1,733 citations, seven clinical trials were eligible for inclusion and meta-analysis. A significant reduction in hemoglobin A1c (HbA1c) (WMD -0.73; 95%CI -1.25 to -0.21; P= 0.006; I2 = 72.2%) and body mass index (BMI) (WMD -0.55; 95%CI -1.03 to -0.07; P= 0.026; I2 = 9.5%) were identified. However, no significant effect of diacerein intake was identified on fasting blood sugar (FBS) (WMD - 9.00; 95%CI -22.57 to 4.57; P= 0.194; I2 = 60.5%), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD 0.39; 95%CI 0.95 to 1.73; P= 0.569; I2 = 2.2%), body weight (WMD -0.54; 95%CI -1.10 to 0.02; P= 0.059), triglycerides (WMD -0.56; 95%CI -24.16 to 23.03; P= 0.963; I2 = 0.0%), total-cholesterol (WMD -0.21; 95%CI -12.19 to 11.78; P= 0.973; I2 = 0.0%), HDL-cholesterol (WMD -0.96; 95%CI -2.85 to 0.93; P= 0.321; I2 = 0.0%), and LDL-cholesterol levels (WMD -0.09; 95%CI -8.43 to 8.25; P= 0.983; I2 = 37.8%). Conclusion: Diacerein intake may reduce HbA1c and BMI; however, no evidence of effect was observed for FBS, HOMA-IR, body weight, triglycerides, total-cholesterol, HDL-cholesterol or LDL-cholesterol.

Metabolic Syndrome During Menopause

2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Natural Menopause ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

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