scholarly journals Therapeutic Potential of Retinoid X Receptor Modulators for the Treatment of the Metabolic Syndrome

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Jane A. Pinaire ◽  
Anne Reifel-Miller
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Additional Treatment ◽  
The Metabolic Syndrome ◽  
Prevalence Of Obesity ◽  
Receptor Modulators

The increasing prevalence of obesity is a fundamental contributor to the growing prevalence of the metabolic syndrome. Rexinoids, a class of compounds that selectively bind and activate RXR, are being studied as a potential option for the treatment of metabolic syndrome. These compounds have glucose-lowering, insulin-sensitizing, and antiobesity effects in animal models of insulin resistance and type 2 diabetes. However, undesirable side effects such as hypertriglyceridemia and suppression of the thyroid hormone axis also occur. This review examines and compares the effects of four RXR-selective ligands: LGD1069, LG100268, AGN194204, and LG101506, a selective RXR modulator. Similar to selective modulators of other nuclear receptors such as the estrogen receptor (SERMs), LG101506 binding to RXR selectively maintains the desirable characteristic effects of rexinoids while minimizing the undesirable effects. These recent findings suggest that, with continued research efforts, RXR-specific ligands with improved pharmacological profiles may eventually be available as additional treatment options for the current epidemic of obesity, insulin resistance, type 2 diabetes, and all of the associated metabolic sequelae.

scholarly journals Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

2020 ◽  
Vol 8 (1) ◽  
pp. e001425
Author(s):  
Cornelia Then ◽  
Christina Gar ◽  
Barbara Thorand ◽  
Cornelia Huth ◽  
Holger Then ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Vascular Complications ◽  
Model Assessment ◽  
Incident Type ◽  
The Metabolic Syndrome ◽  
Incident Type 2 Diabetes

IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

scholarly journals A szexuális funkciózavar és a metabolikus szindróma kapcsolata

2019 ◽  
Vol 160 (3) ◽  
pp. 98-103 ◽  
Author(s):  
Márta Zsoldos ◽  
Attila Pajor ◽  
Henriette Pusztafalvi
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Sexual Dysfunction ◽  
The Metabolic Syndrome ◽  
Atherogenic Lipid Profile ◽  
Arousal Response ◽  
Atherogenic Lipid

Abstract: The prevalence of the metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, obesity and depression have increased during the recent years. As the sexual dysfunction is also frequent, we aimed to search for the associations between sexual dysfunction and the metabolic syndrome and its components, respectively, by reviewing the literature. The clinical and biochemical components of the metabolic syndrome included cardiovascular disease, type 2 diabetes mellitus, visceral obesity and depression, furthermore, insulin resistance, atherogenic lipid profile, hypogonadism, chronic systemic inflammation and endothelial dysfunction were all demonstrated to affect adversely the sexual function. The dysfunction of the sexual arousal response shows a strong association in men and a milder one in women with the cardiovascular diseases and depression. Sexual function in diabetes mellitus is mostly impaired by microvascular injury, polyneuropathy and autonomic neuropathy. Erectile dysfunction and disorder of the female sexual arousal response and the orgasm, respectively, are associated with insulin resistance, atherogenic lipid profile and systemic inflammatory condition in overweight or obese patients. Sexual dysfunction particularly in men can be an early sign of the severe complications of metabolic syndrome. The pathogenetic link between the metabolic syndrome and the sexual dysfunction seems to be the insulin resistance. Both metabolic syndrome and sexual dysfunction can be restored by altering the lifestyle. Orv Hetil. 2019; 160(3): 98–103.

Insulin Resistance is the Best Predictor of the Metabolic Syndrome in Subjects With a First-Degree Relative With Type 2 Diabetes

Obesity ◽  
2010 ◽  
Vol 18 (9) ◽  
pp. 1781-1787 ◽  
Author(s):  
Kristina M. Utzschneider ◽  
Anne Van de Lagemaat ◽  
Mirjam V. Faulenbach ◽  
Julia H. Goedecke ◽  
Darcy B. Carr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Degree Relative ◽  
The Metabolic Syndrome

scholarly journals Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD

2007 ◽  
Vol 66 (1) ◽  
pp. 82-95 ◽  
Author(s):  
Robert H. Eckel
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Inflammatory Cytokines ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
The Metabolic Syndrome ◽  
Pro Inflammatory Cytokines

The metabolic syndrome represents a summation of obesity-driven risk factors for atherosclerotic CVD and type 2 diabetes. Definitions of the syndrome vary but in general agree closely in identifying subjects. The relationships between the metabolic syndrome and atherosclerotic CVD and diabetes also vary, with relative risks of approximately 1·5–3·0 and approximately 3·0–5·0 respectively. Insulin resistance appears to explain much of the pathophysiology of the syndrome. Both increased fatty acid flux and an excess of circulating pro-inflammatory cytokines are likely mediators. With increased waist circumference, increases in fatty acid delivery to the liver result in higher rates of hepatic glucose production and increases in the secretion of apoB-containing lipoproteins. Concomitant changes in HDL ensue, including a replacement of the cholesterol content with TAG, an accelerated clearance from the plasma and thus a reduced number of HDL particles. Typically also present are increases in small dense LDL. Hypertension in part relates to the insulin resistance, but may involve other mechanisms. Impaired fasting glucose often relates to defects in insulin secretion in addition to insulin resistance, and probably more than any other component of the syndrome predicts the increased incidence of type 2 diabetes. Although not included in the diagnostic criteria, increases in pro-inflammatory cytokines and pro-thrombotic factors, in addition to decreases in plasma adiponectin, may also contribute to the increased incidence of atherosclerotic CVD and diabetes. In general, the greater the number of metabolic syndrome components, the greater the risk for these outcomes. The cytokines and pro-thrombotic factors also appear to contribute.

scholarly journals Evaluate the effects of metabolic syndrome in adolescents and children

2020 ◽  
Vol 7 (3) ◽  
pp. 287-292
Author(s):  
Rui-Min Jia ◽  
Xiao-Ning Yan ◽  
Jing Sun
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Obese Children ◽  
The Metabolic Syndrome ◽  
Disease Outcomes ◽  
High Prevalence ◽  
Underlying Pathophysiology

AbstractThe metabolic syndrome (MS) in adolescents and children can cause serious consequences that lead researchers to pay efforts to study in such area. Presently, MS definition is still not standardized. Different versions of MS definition have been used by numerous studies, which may be a problem to identify MS and then to predict and prevent clinical diseases. The pediatric literature shows that insulin resistance and obesity might be the key underlying pathophysiology of MS to cause many related diseases. High prevalence of MS is in overweight and obese children and adolescents. This article focuses on such above issues and also effects of MS on two main disease outcomes: cardiovascular disease and type 2 diabetes.

PM20D1 Is a Circulating Biomarker Closely Associated with Obesity, Insulin resistance and Metabolic Syndrome

2021 ◽  
Author(s):  
Ranyao Yang ◽  
Yue Hu ◽  
Chi Ho Lee ◽  
Yan Liu ◽  
Candela Diaz-Canestro ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Amino Acids ◽  
Metabolic Complications ◽  
The Metabolic Syndrome ◽  
Clinical Biomarkers ◽  
The Impact ◽  
Circulating Levels

Objective: Peptidase M20 domain containing 1 (PM20D1), a secreted enzyme catalysing condensation of fatty acids and amino acids into the bioactive lipids N-acyl amino acids (NAAA), induces uncoupling protein 1 (UCP1)-independent adaptive thermogenesis in brown/beige adipocytes in mice. This study aimed to explore the associations of the circulating levels of PM20D1 and major NAAA with obesity-related metabolic complications in humans. Design and Methods: Serum concentrations of PM20D1 and NAAA (C18:1-Leu and C18:1-Phe) in 256 Chinese subjects, including 78 lean and 178 overweight/obese individuals with or without diabetes, were measured with immunoassays and liquid chromatography-mass spectrometry respectively. The impact of sulfonylurea and rosiglitazone on their circulating levels was examined in 62 patients with type 2 diabetes. Results: Serum PM20D1 level was significantly elevated in overweight/obese individuals, and was closely associated with circulating levels of C18:1-Leu and C18:1-Phe. Furthermore, serum PM20D1, C18:1-Leu and C18:1-Phe concentrations correlated positively with several parameters of adiposity as well as fasting and 2-h postprandial glucose, HbA1c, fasting insulin, and HOMA-IR independent of BMI and age. Moreover, a significant elevation in PM20D1, C18:1-Leu and C18:1-Phe concentrations corresponding with increases in the number of components of the metabolic syndrome (MetS) was observed. Treatment with sulfonylurea significantly decreased circulating PM20D1, C18:1-Leu and C18:1-Phe in patients with type 2 diabetes. Conclusions: Increased serum levels of PM20D1 and its catalytic products NAAA are closely associated with obesity-related glucose dysregulation, insulin resistance and MetS, and can be potentially used as clinical biomarkers for diagnosing and monitoring these disorders.

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