Fetuin-A – Alpha2-Heremans-Schmid Glycoprotein: From Structure to a Novel Marker of Chronic Diseases Part 2. Fetuin-A – A Marker of Insulin Resistance and Related Chronic Diseases

Summary Fetuin-A is a secretory liver glycoprotein with multiple physiological functions such as regulation of insulin resistance, tissue calcification, bone metabolism, cellular proteolytic activity, and self-proliferative signaling. Fetuin-A is a unique molecule which binds to the insulin receptor, modulating its sensitivity, and transducing “the physiological conditions” (serum levels of the metabolites like glucose, free fatty acids, inflammatory signals) from outside into inside the cells. Plasma fetuin-A levels correlate with reduced glucose tolerance and insulin resistance. Impaired insulin sensitivity leads to the development of metabolic syndrome, an increased risk for type 2 diabetes (T2DM), dyslipidaemias and cardiovascular diseases (CVDs). Furthermore, fetuin-A inversely correlates with inflammatory and activation biomarkers, e.g. in patients with T2DM. Thus, circulatory fetuin-A levels may have plausible predictive importance as a biomarker of risk of diabetes and negative acute phase protein. Dysregulated, it plays a crucial role in the pathogenesis of some metabolic disorders and clinical inflammatory conditions like metabolic syndrome, T2DM, CVDs, polycystic ovary syndrome (PCOS), etc.

Download Full-text

Metabolic Syndrome During Menopause

Current Vascular Pharmacology ◽

10.2174/1570161116666180904094149 ◽

2019 ◽

Vol 17 (6) ◽

pp. 595-603 ◽

Cited By ~ 4

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.

Download Full-text

Adiponectin and Polycystic Ovary Syndrome

Biological Research For Nursing ◽

10.1177/1099800410371824 ◽

2010 ◽

Vol 12 (1) ◽

pp. 62-72 ◽

Cited By ~ 15

Author(s):

Susan W. Groth

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Clinical Practice ◽

Polycystic Ovary Syndrome ◽

Disease Risk ◽

Polycystic Ovary ◽

Reproductive Age ◽

Ovary Syndrome ◽

Increased Risk

Introduction. Polycystic ovary syndrome (PCOS) has a prevalence of 5—8% in women of reproductive age. Women with PCOS have an increased risk of metabolic syndrome and associated comorbidities. Adiponectin is a circulating protein produced by adipocytes. Circulating levels of adiponectin are inversely related to adipocyte mass. Low levels occur with insulin resistance, type 2 diabetes, metabolic syndrome, and obesity-related cardiovascular disease. This article reviews the literature on the link between adiponectin and PCOS and the potential use of adiponectin as a biomarker for PCOS. Method. Data-based studies on adiponectin and PCOS and adiponectin measurement were identified through the Medline (1950—2009) and ISI Web of Knowledge (1973—2009) databases. Results. Fifteen studies related to adiponectin and PCOS met inclusion criteria and were included in this review. These studies present evidence that adiponectin is linked to insulin resistance, insulin sensitivity, body mass index (BMI), and adiposity. In women with PCOS, lower levels, as opposed to higher levels, of adiponectin occur in the absence of adiposity. Conclusion. The relationships between adiponectin and insulin resistance and sensitivity, metabolic syndrome, and BMI in women with PCOS suggest that adiponectin potentially could serve as a marker for disease risk and provide opportunity for earlier intervention if knowledge is successfully translated from laboratory to clinical practice. However, further study of the relationship between adiponectin and PCOS is required before there can be direct application to clinical practice.

Download Full-text

Case 11.1

Mayo Clinic Body MRI Case Review ◽

10.1093/med/9780199915705.003.0279 ◽

2014 ◽

pp. 531-532

Author(s):

Christine U. Lee ◽

James F. Glockner

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Reproductive Age ◽

Polycystic Ovaries ◽

Endocrine Disorder ◽

Secondary Amenorrhea ◽

Increased Risk

28-year-old woman with secondary amenorrhea and hirsutism Axial fat-suppressed 2D SSFP images (Figure 11.1.1) demonstrate multiple follicles arranged in the periphery of the ovaries bilaterally. Polycystic ovary syndrome PCOS is the most common endocrine disorder in women of reproductive age, affecting between 6% and 15%, depending on the criteria used for diagnosis. It typically presents with anovulatory or oligo-ovulatory menstrual cycles leading to oligomenorrhea, polycystic ovaries, and clinical and biochemical hyperandrogenism. PCOS is also associated with increased risk of obesity, insulin resistance, diabetes mellitus, metabolic syndrome, and infertility....

Download Full-text

Developmental origin of polycystic ovary syndrome - a hypothesis

Journal of Endocrinology ◽

10.1677/joe.0.1740001 ◽

2002 ◽

Vol 174 (1) ◽

pp. 1-5 ◽

Cited By ~ 276

Author(s):

DH Abbott ◽

DA Dumesic ◽

S Franks

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Regulatory Region ◽

Later Life ◽

Ovary Syndrome ◽

Increased Risk ◽

Genetically Determined ◽

Lh Secretion

Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.

Download Full-text

Mechanisms Involved in Intrauterine Growth Restriction in Patients With Polycystic Ovary Syndrome: Primary and Secondary Prevention of Metabolic Syndrome and Cancer Risk in the Adult Life of Offspring

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1508 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A741-A742

Author(s):

Domingo Mugnolo ◽

Erica Giraldo ◽

Maria Perez Lana ◽

Susana Beatriz Campeni

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Fetal Programming ◽

Intrauterine Growth Restriction ◽

Polycystic Ovary ◽

Adult Life ◽

Ovary Syndrome ◽

Intrauterine Growth ◽

Increased Risk

Abstract Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that affects between 5- 10% of women of reproductive age. It is currently considered a complex and multifactorial disease with metabolic, cardiovascular implications and represents per se an increased cancer risk. PATIENTS with PCOS routinely have menstrual disorders, hyperandrogenism, infertility and reproductive complications such as recurrent abortions, gestational diabetes, intrauterine growth restriction, pregnancy induced hypertension that give rise to underweight newborns and condition metabolic diseases to adult life and increased risk of cancer, especially breast and endometrial cancer. Insulin resistance and hyperandrogenism are the most important etiopathogenic factors in PCOS. On the other hand, subjects exposed to an adverse microenvironment in the intrauterine stage develop compensating responses to survive, a process called fetal programming. Prenatal exposure to androgens and/or insulin resistance may act as fetal programming factors and cause restriction of intrauterine growth, obesity and insulin resistance in offspring. Newborn may have an increased risk of metabolic syndrome, increased incidence of hypertensive, type 2 diabetes, heart disease and cerebrovascular disease. Prevention of these complications will be achieved if women with Polycystic Ovary Syndrome are treated appropriately throughout their lives, but especially before and during their pregnancy. Only in this way can the risk of them be reduced, representing a better quality and greater life expectancy.

Download Full-text

A study of metabolic syndrome in women with polycystic ovary syndrome at tertiary care center

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20212187 ◽

2021 ◽

Vol 10 (6) ◽

pp. 2427

Author(s):

Chelsae Kuntal ◽

Jyotsna Vyas ◽

Asha Chaudhary ◽

Sunita Hemani ◽

Lata Rajoria

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Urban Areas ◽

Polycystic Ovary ◽

Tertiary Care ◽

Reproductive Age ◽

Ovary Syndrome ◽

Hormonal Profile ◽

Increased Risk

Background: Polycystic ovary syndrome is a common endocrinopathy in women of reproductive age with prevalence of 6-10% which is characterized by hyper androgenic features and chronic oligo – anovulation and polycystic ovary morphology. Most women with polycystic ovary syndrome are also characterized by metabolic abnormalities like insulin resistance, hyperinsulinemia, dyslipidemia and abdominal obesity, these forming risk factors for metabolic syndrome. The objective of the study was to compare the clinical, biochemical and hormonal profile of polycystic ovary syndrome patients with and without metabolic syndrome.Methods: A comparative cross- sectional study was undertaken on 79 PCOS women diagnosed with PCOS according to Rotterdam criteria, in which the clinical data and hormonal profile of two groups of polycystic ovary syndrome women with and without metabolic syndrome was compared.Results: The mean age of 79 patients in this study group with and without metabolic syndrome was 26.17±3.18 and 25.57±3.41 years respectively. There were more patients from urban areas as compared to rural areas and maximum patients. Significantly higher number of PCOS women with metabolic syndrome had hirsutism and acanthosis nigricans than those without metabolic syndrome. Mean value of Waist circumference, systolic BP pressure, diastolic BP, S. Triglyceride and fasting glucose were higher and HDL levels were lower in women with metabolic syndrome than those without metabolic syndrome. Fasting insulin and HOMA-IR values were significantly higher in PCOS women with metabolic syndrome in comparison to those without metabolic syndrome.Conclusion: PCOS is not only is the most frequent cause of anovulation, but it is also associated with characteristic metabolic disturbances that may have important implications for the long term health. Metabolic syndrome is a cluster of endocrine disturbances, including insulin resistance, dyslipidemia, obesity, and hypertension. It is associated with a two-fold increased risk of cardiovascular disease and a five-fold increased risk of type 2 diabetes. This illustrates the importance of early detection of insulin resistance and metabolic syndrome with subsequent application of preventive measures in women with polycystic ovary syndrome.

Download Full-text

Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

Mediators of Inflammation ◽

10.1155/2011/389317 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 20

Author(s):

Anna M. Fulghesu ◽

Francesca Sanna ◽

Sabrina Uda ◽

Roberta Magnini ◽

Elaine Portoghese ◽

...

Keyword(s):

Insulin Resistance ◽

Immune Response ◽

Inflammatory Cytokines ◽

Polycystic Ovary ◽

Serum Levels ◽

Low Grade ◽

Increased Risk ◽

Altered Immune Response ◽

Hs Crp ◽

Activated Monocytes

Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β) and lipokines (leptin, adiponectin), the reactant hs-CRP, andin vitroinflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.

Download Full-text

Metabolic syndrome and the menopause

Menopause International: The Integrated Journal of Postreproductive Health ◽

10.1258/mi.2007.007032 ◽

2008 ◽

Vol 14 (1) ◽

pp. 21-25 ◽

Cited By ~ 43

Author(s):

Risto J Kaaja

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Pharmacological Therapy ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Atherogenic Dyslipidaemia ◽

Ovarian Syndrome

The metabolic syndrome consists of a combination of risk factors that include abdominal obesity, atherogenic dyslipidaemia, hypertension and insulin resistance. It increases the risk of cardiovascular disease and type 2 diabetes. The increased risk of cardiovascular disease is higher in women than in men. The first manifestation of metabolic syndrome may occur in pregnancy presenting as gestational diabetes or preeclampsia. Both conditions are associated with increased insulin resistance. Also metabolic syndrome is more common in polycystic ovarian syndrome. It has been suggested that there is a metabolic syndrome resulting from the menopause due to estrogen deficiency, as many of the risk factors are more prevalent in postmenopausal women. Also estrogen replacement improves insulin sensitivity and reduces the risk of diabetes. The key elements in managing the metabolic syndrome are weight reduction, increasing physical activity and diet modification. If blood pressure, lipid and glycaemic control are not achieved through these interventions then pharmacological therapy will be required.

Download Full-text

Inflammation as a Link between Obesity and Metabolic Syndrome

Journal of Nutrition and Metabolism ◽

10.1155/2012/476380 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 140

Author(s):

Faloia Emanuela ◽

Michetti Grazia ◽

De Robertis Marco ◽

Luconi Maria Paola ◽

Furlani Giorgio ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Visceral Obesity ◽

Low Grade ◽

Subsequent Increase ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Inflammatory State

The metabolic syndrome is a complex of clinical features leading to an increased risk for cardiovascular disease and type 2 diabetes mellitus in both sexes. Visceral obesity and insulin resistance are considered the main features determining the negative cardiovascular profile in metabolic syndrome. The aim of this paper is to highlight the central role of obesity in the development of a chronic low-grade inflammatory state that leads to insulin resistance, endothelial and microvascular dysfunctions. It is thought that the starting signal of this inflammation is overfeeding and the pathway origins in all the metabolic cells; the subsequent increase in cytokine production recruits immune cells in the extracellular environment inducing an overall systemic inflammation. This paper focuses on the molecular and cellular inflammatory mechanisms studied until now.

Download Full-text

Association of Insulin Resistance, β-Cell Function Impairment and Calcium, Magnesium, and Fetuin-A Concentrations in Women with Type 2 Diabetes Mellitus

Acta Facultatis Medicae Naissensis ◽

10.1515/afmnai-2016-0020 ◽

2016 ◽

Vol 33 (3) ◽

pp. 187-197

Author(s):

Shatha Rouf Moustafa

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cell Function ◽

Serum Levels ◽

Control Group ◽

Β Cell ◽

Fetuin A ◽

Function Impairment ◽

Β Cell Function

SummaryInsulin resistance and β-cell function impairment play a role in the pathogenesis of type 2 diabetes (T2DM). Insulin signaling is inhibited by fetuin-A, an abundant plasma protein. Fetuin-A is also a candidate marker of the T2DM risk. This case-control study aimed to determine whether fetuin-A serum level is related to insulin resistance, β-cell function impairment, and total and ionized Ca and Mg serum levels in Erbil patients with T2DM.A total of 60 patients with T2DM were recruited, and 30 healthy persons were included in the control group. Fetuin-A and insulin concentrations were measured through ELISA. Other biochemical parameters were determined spectrophotometrically. Insulin resistance (HOMA2IR), insulin sensitivity (HOMA2%S), and β-cell function were examined by using a homeostatic model assessment 2 (HOMA2).Fasting serum insulin, fetuin-A serum levels, and HOMA2IR were significantly increased. HOMA2%S of the patients with diabetes was significantly lower than that of the control group. The total serum and ionized Ca and Mg contents and the Ca/Mg ratio were reduced in the patients.Therefore, fetuin-A is related to T2DM pathogenesis and is strongly associated with insulin resistance and glycemic control in T2DM patients. Future large-scale studies are necessary to validate fetuin-A as an indicator of IR in T2DM patients.

Download Full-text