|
1
|
Underland LJ, Kenigsberg Fechter L, Agarwal C, Sin S, Punjabi N, Heptulla R, Arens R. Insulin sensitivity and obstructive sleep apnea in adolescents with polycystic ovary syndrome. Minerva Endocrinol (Torino) 2024; 49:372-380. [PMID: 35388662 DOI: 10.23736/s2724-6507.22.03619-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) in adults is linked with insulin resistance (IR) and obstructive sleep apnea (OSA). However, less is known about these associations in adolescents. METHODS We studied three groups of adolescents: 27 obese PCOS (OPCOS) (ages 13-21), 11 normal-weight PCOS (NPCOS) (ages 13-21 years), and eight healthy controls (ages 18-21 years). A hyperinsulinemic euglycemic clamp study was performed in all groups to determine IR by insulin sensitivity (M/I). Polysomnography was performed to assess for OSA in OPCOS and NPCOS groups. We compared indices of IR among all groups and OSA among OPCOS, and NPCOS. RESULTS We noted that OPCOS and NPCOS and controls differed significantly in their IR. M/I was significantly lower in OPCOS vs. controls (P=0.0061), and also lower for NPCOS vs control but this approached but did not reach statistical significance (P=0.084). In addition, none of the NPCOS subjects had OSA compared to 42% of OPCOS (P=0.03). CONCLUSIONS Our study suggests OPCOS adolescents have increased IR compared to controls and NPCOS subjects. Higher IR for NPCOS vs controls approached but did not reach statistical significance. Larger studies are needed. In addition, adolescents with OPCOS are at a high risk for OSA.
Collapse
Affiliation(s)
- Lisa J Underland
- Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA -
| | | | - Chhavi Agarwal
- Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Sanghun Sin
- Division of Respiratory and Sleep Medicine, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Netra Punjabi
- Division of Pediatric Endocrinology, Lucile Packard Children's Hospital, Palo Alto, CA, USA
| | - Rubina Heptulla
- Division of Pediatric Endocrinology, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Raanan Arens
- Division of Respiratory and Sleep Medicine, Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| |
Collapse
|
|
2
|
Boldis BV, Grünberger I, Cederström A, Björk J, Nilsson A, Helgertz J. Early Life Factors and Polycystic Ovary Syndrome in a Swedish Birth Cohort. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:7083. [PMID: 37998314 PMCID: PMC10671095 DOI: 10.3390/ijerph20227083] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/02/2023] [Accepted: 11/14/2023] [Indexed: 11/25/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a medical condition with important consequences for women's well-being and reproductive outcomes. Although the etiology of PCOS is not fully understood, there is increasing evidence of both genetic and environmental determinants, including development in early life. We studied a population of 977,637 singleton women born in in Sweden between 1973 and 1995, followed sometime between the age 15 and 40. The incidence of PCOS was measured using hospital register data during 2001-2012, complemented with information about the women's, parents' and sisters' health and social characteristics from population and health care registers. Cox regression was used to study how PCOS is associated with intergenerational factors, and a range of early life characteristics. 11,594 women in the study sample were diagnosed with PCOS during the follow-up period. The hazard rate for PCOS was increased 3-fold (HR 2.98, 95% CI 2.43-3.64) if the index woman's mother had been diagnosed with PCOS, and with 1.5-fold (HR 1.51, 95% CI 1.39-1.63) if their mother had diabetes mellitus. We found associations of PCOS with lower (<7) one-minute Apgar score (HR 1.19, 95% CI 1.09-1.29) and with post-term birth (HR 1.19, 95% CI 1.13-1.26). Furthermore, heavy (10+ cigarettes/day) maternal smoking (HR 1.30, 95% CI 1.18-1.44) and maternal obesity (HR 1.90, 95% CI 1.62-2.36) were strongly associated with PCOS. This study finds support for the heritability and fetal origins of PCOS. Risk of PCOS could be reduced by further emphasizing the importance of maternal and early life health.
Collapse
Affiliation(s)
- Beata Vivien Boldis
- Department of Public Health Sciences, Stockholm University, 10691 Stockholm, Sweden; (I.G.); (A.C.)
- Epidemiology, Population Studies and Infrastructures (EPI@LUND), Department of Laboratory Medicine, Lund University, 22100 Lund, Sweden; (J.B.); (A.N.)
- Centre for Economic Demography, School of Economics and Management, Lund University, 22100 Lund, Sweden;
| | - Ilona Grünberger
- Department of Public Health Sciences, Stockholm University, 10691 Stockholm, Sweden; (I.G.); (A.C.)
| | - Agneta Cederström
- Department of Public Health Sciences, Stockholm University, 10691 Stockholm, Sweden; (I.G.); (A.C.)
| | - Jonas Björk
- Epidemiology, Population Studies and Infrastructures (EPI@LUND), Department of Laboratory Medicine, Lund University, 22100 Lund, Sweden; (J.B.); (A.N.)
| | - Anton Nilsson
- Epidemiology, Population Studies and Infrastructures (EPI@LUND), Department of Laboratory Medicine, Lund University, 22100 Lund, Sweden; (J.B.); (A.N.)
- Centre for Economic Demography, School of Economics and Management, Lund University, 22100 Lund, Sweden;
| | - Jonas Helgertz
- Centre for Economic Demography, School of Economics and Management, Lund University, 22100 Lund, Sweden;
- Department of Economic History, Lund University, 22100 Lund, Sweden
- Institute for Social Research and Data Innovation, Minnesota Population Center, University of Minnesota, Minneapolis, MN 55455, USA
| |
Collapse
|
|
3
|
Amin M, Horst N, Gragnoli C. Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome. J Ovarian Res 2023; 16:158. [PMID: 37563671 PMCID: PMC10416464 DOI: 10.1186/s13048-023-01205-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/16/2023] [Indexed: 08/12/2023] Open
Abstract
Polycystic ovarian syndrome (PCOS) is a disorder with a foundation of neuroendocrine dysfunction, characterized by increased gonadotropin-releasing hormone (GnRH) pulsatility, which is antagonized by dopamine. The dopamine receptor 2 (DRD2), encoded by the DRD2 gene, has been shown to mediate dopamine's inhibition of GnRH neuron excitability through pre- and post-synaptic interactions in murine models. Further, DRD2 is known to mediate prolactin (PRL) inhibition by dopamine, and high blood level of PRL have been found in more than one third of women with PCOS. We recently identified PRL as a gene contributing to PCOS risk and reported DRD2 conferring risk for type 2 diabetes and depression, which can both coexist with PCOS. Given DRD2 mediating dopamine's action on neuroendocrine profiles and association with metabolic-mental states related to PCOS, polymorphisms in DRD2 may predispose to development of PCOS. Therefore, we aimed to investigate whether DRD2 variants are in linkage to and/or linkage disequilibrium (i.e., linkage and association) with PCOS in Italian families. In 212 Italian families, we tested 22 variants within the DRD2 gene for linkage and linkage disequilibrium with PCOS. We identified five novel variants significantly linked to the risk of PCOS. This is the first study to identify DRD2 as a risk gene in PCOS, however, functional studies are needed to confirm these results.
Collapse
Affiliation(s)
- Mutaz Amin
- INSERM, US14-Orphanet, Paris, 75014, France
| | - Nicholas Horst
- Creighton University School of Medicine, Omaha, NE, 68124, USA
| | - Claudia Gragnoli
- Division of Endocrinology, Department of Medicine, Creighton University School of Medicine, Omaha, NE, 68124, USA.
- Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, 17033, USA.
- Molecular Biology Laboratory, Bios Biotech Multi-Diagnostic Health Center, Rome, 00197, Italy.
| |
Collapse
|
|
4
|
Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance. Int J Mol Sci 2023; 24:ijms24043140. [PMID: 36834549 PMCID: PMC9962893 DOI: 10.3390/ijms24043140] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/23/2023] [Accepted: 02/03/2023] [Indexed: 02/09/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Its heterogeneous clinical presentation is characterized by hyperandrogenemia, reproductive changes, polycystic ovary morphology, and insulin resistance (IR). The primary pathophysiological process in its multifactorial etiology has not yet been identified. However, the two most proposed core etiologies are the disruption of insulin metabolism and hyperandrogenemia, both of which begin to intertwine and propagate each other in the later stages of the disease. Insulin metabolism can be viewed as the interconnectedness of beta cell function, IR or insulin sensitivity, and insulin clearance. Previous studies of insulin metabolism in PCOS patients have yielded conflicting results, and literature reviews have focused mainly on the molecular mechanisms and clinical implications of IR. In this narrative review, we comprehensively explored the role of insulin secretion, clearance, and decreased sensitivity in target cells as a potential primary insult in PCOS pathogenesis, along with the molecular mechanism behind IR in PCOS.
Collapse
|
|
5
|
Amisi CA. Markers of insulin resistance in Polycystic ovary syndrome women: An update. World J Diabetes 2022; 13:129-149. [PMID: 35432749 PMCID: PMC8984569 DOI: 10.4239/wjd.v13.i3.129] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 09/14/2021] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.
Collapse
Affiliation(s)
- Chantal Anifa Amisi
- Endocrinology and Diabetes Unit, Department of Medicine, Universita Campus Bio-medico di Rome, Rome 00128, Italy
| |
Collapse
|
|
6
|
Zhou R, Bruns CM, Bird IM, Kemnitz JW, Dumesic DA, Abbott DH. Experimentally Induced Hyperinsulinemia Fails to Induce Polycystic Ovary Syndrome-like Traits in Female Rhesus Macaques. Int J Mol Sci 2022; 23:ijms23052635. [PMID: 35269778 PMCID: PMC8910161 DOI: 10.3390/ijms23052635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/12/2022] [Accepted: 02/23/2022] [Indexed: 11/16/2022] Open
Abstract
As in women with polycystic ovary syndrome (PCOS), hyperinsulinemia is associated with anovulation in PCOS-like female rhesus monkeys. Insulin sensitizers ameliorate hyperinsulinemia and stimulate ovulatory menstrual cycles in PCOS-like monkeys. To determine whether hyperinsulinemia (>694 pmol/L), alone, induces PCOS-like traits, five PCOS-like female rhesus monkeys with minimal PCOS-like traits, and four control females of similar mid-to-late reproductive years and body mass index, received daily subcutaneous injections of recombinant human insulin or diluent for 6−7 months. A cross-over experimental design enabled use of the same monkeys in each treatment phase. Insulin treatment unexpectedly normalized follicular phase duration in PCOS-like, but not control, females. In response to an intramuscular injection of 200 IU hCG, neither prenatally androgenized nor control females demonstrated ovarian hyperandrogenic responses while receiving insulin. An intravenous GnRH (100 ng/kg) injection also did not reveal evidence of hypergonadotropism. Taken together, these results suggest that experimentally induced adult hyperinsulinemia, alone, is insufficient to induce PCOS-like traits in female rhesus monkeys and to amplify intrinsic PCOS-like pathophysiology.
Collapse
Affiliation(s)
- Rao Zhou
- Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA; (R.Z.); (J.W.K.)
- Endocrinology Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA;
| | - Cristin M. Bruns
- Departments of Medicine, University of Wisconsin, Madison, WI 53715, USA;
| | - Ian M. Bird
- Endocrinology Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA;
- Departments of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA
| | - Joseph W. Kemnitz
- Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA; (R.Z.); (J.W.K.)
- Departments of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53715, USA
| | - Daniel A. Dumesic
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;
| | - David H. Abbott
- Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA; (R.Z.); (J.W.K.)
- Endocrinology Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA;
- Departments of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA
- Correspondence:
| |
Collapse
|
|
7
|
Livadas S, Anagnostis P, Bosdou JK, Bantouna D, Paparodis R. Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review. World J Diabetes 2022; 13:5-26. [PMID: 35070056 PMCID: PMC8771268 DOI: 10.4239/wjd.v13.i1.5] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/30/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) often coexists with a wide spectrum of dysglycemic conditions, ranging from impaired glucose tolerance to type 2 diabetes mellitus (T2D), which occur to a greater extent compared to healthy body mass index-matched women. This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities, such as insulin resistance. However, due to methodological flaws in the available studies and the multifaceted nature of the syndrome, there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated. The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS, the unique pathophysiological mechanisms underlying the progression of dysglycemia, the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population, as well as T2D risk after transition to menopause. Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided. Specifically, adoption of a healthy lifestyle with adherence to improved dietary patterns, such the Mediterranean diet, avoidance of consumption of endocrine-disrupting foods and beverages, regular exercise, and the effect of certain medications, such as metformin and glucagon-like peptide 1 receptor agonists, are discussed. Furthermore, the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.
Collapse
Affiliation(s)
| | - Panagiotis Anagnostis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54636, Greece
| | - Julia K Bosdou
- Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54636, Greece
| | - Dimitra Bantouna
- Department of Pathology and Cytology, University of Patras School of Medicine, Patras 10563, Greece
| | - Rodis Paparodis
- Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, OH 23456, United States
| |
Collapse
|
|
8
|
Zhao ZH, Wang XY, Schatten H, Sun QY. Single cell RNA sequencing techniques and applications in research of ovary development and related diseases. Reprod Toxicol 2021; 107:97-103. [PMID: 34896591 DOI: 10.1016/j.reprotox.2021.12.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/21/2021] [Accepted: 12/08/2021] [Indexed: 11/17/2022]
Abstract
The ovary is a highly organized composite of germ cells and various types of somatic cells, whose communications dictate ovary development to generate functional oocytes. The differences between individual cells might have profound effects on ovary functions. Single cell RNA sequencing techniques are promising approaches to explore the cell type composition of organisms, the dynamics of transcriptomes, the regulatory network between genes and the signaling pathways between cell types at the single cell resolution. In this review, we provide an overview of the currently available single cell RNA sequencing techniques including Smart-seq2 and Drop-seq, as well as their applications in biological and clinical research to provide a better understanding on the molecular mechanisms underlying ovary development and associated diseases.
Collapse
Affiliation(s)
- Zheng-Hui Zhao
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Xiao-Yu Wang
- School of Social Development and Public Policy, Beijing Normal University, Beijing, 100875, China
| | - Heide Schatten
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, United States
| | - Qing-Yuan Sun
- Fertility Preservation Lab, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
| |
Collapse
|
|
9
|
Abstract
PURPOSE OF REVIEW To provide an overview of mitochondrial functional alterations in women with polycystic ovary syndrome (PCOS). RECENT FINDINGS Although numerous studies have focused on PCOS, the pathophysiological mechanisms that cause this common disease remain unclear. Mitochondria play a central role in energy production, and mitochondrial dysfunction may underlie several abnormalities observed in women with PCOS. Recent studies associated mtDNA mutations and low mtDNA copy number with PCOS, and set out to characterize the potential protective role of mitochondrial and endoplasmic reticulum unfolded protein responses (UPR and UPR). SUMMARY Mitochondrial dysfunction likely plays a role in the pathogenesis of PCOS by increasing reactive oxygen (ROS) and oxidative stress. This occurs in a metabolic milieu often affected by insulin resistance, which is a common finding in women with PCOS, especially in those who are overweight or obese. Mutations in mtDNA and low mtDNA copy number are found in these patients and may have potential as diagnostic modalities for specific PCOS phenotypes. More recently, UPR and UPR are being investigated as potential cellular rescue mechanisms in PCOS, the failure of which may lead to apoptosis, and contribute to decreased reproductive potential.
Collapse
|
|
10
|
Kim K, Pollack AZ, Nobles CJ, Sjaarda LA, Zolton JR, Radoc JG, Schisterman EF, Mumford SL. Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: a prospective cohort study. Environ Health 2021; 20:64. [PMID: 34022900 PMCID: PMC8141255 DOI: 10.1186/s12940-021-00749-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 05/10/2021] [Indexed: 05/24/2023]
Abstract
BACKGROUND Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age. METHODS This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively. RESULTS Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19-0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure. CONCLUSIONS Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.
Collapse
Affiliation(s)
- Keewan Kim
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
| | | | - Carrie J. Nobles
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
| | - Lindsey A. Sjaarda
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
| | - Jessica R. Zolton
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
- Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 20892 Bethesda, Maryland USA
| | - Jeannie G. Radoc
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
| | - Enrique F. Schisterman
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
| | - Sunni L. Mumford
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive MSC 7004, Maryland 20892 Bethesda, USA
| |
Collapse
|
|
11
|
Hansen SL, Bojsen-Møller KN, Lundsgaard AM, Hendrich FL, Nilas L, Sjøberg KA, Hingst JR, Serup AK, Olguín CH, Carl CS, Wernblad LF, Henneberg M, Lustrup KM, Hansen C, Jensen TE, Madsbad S, Wojtaszewski JFP, Richter EA, Kiens B. Mechanisms Underlying Absent Training-Induced Improvement in Insulin Action in Lean, Hyperandrogenic Women With Polycystic Ovary Syndrome. Diabetes 2020; 69:2267-2280. [PMID: 32873590 DOI: 10.2337/db20-0062] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 08/24/2020] [Indexed: 11/13/2022]
Abstract
Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control (CON) women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle, improving glucose uptake and metabolism in both healthy individuals and patients with type 2 diabetes. In the current study, lean hyperandrogenic women with PCOS (n = 9) and healthy CON women (n = 9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole-body insulin action by 26% and insulin-stimulated leg glucose uptake by 53% together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in VO2max In skeletal muscle of CON but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole-body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose-handling proteins for insulin-stimulated glucose uptake in skeletal muscle and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.
Collapse
Affiliation(s)
- Solvejg L Hansen
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | | | - Anne-Marie Lundsgaard
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Frederikke L Hendrich
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Lisbeth Nilas
- Department of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Kim A Sjøberg
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Janne R Hingst
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Annette K Serup
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Carlos Henríquez Olguín
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Christian S Carl
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Louise F Wernblad
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Marie Henneberg
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Katja M Lustrup
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Christine Hansen
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Thomas E Jensen
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jørgen F P Wojtaszewski
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Erik A Richter
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Bente Kiens
- Molecular Physiology Section, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
|
12
|
Song Y, Wang H, Huang H, Zhu Z. Comparison of the efficacy between NAC and metformin in treating PCOS patients: a meta-analysis. Gynecol Endocrinol 2020; 36:204-210. [PMID: 31749393 DOI: 10.1080/09513590.2019.1689553] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
Our aim is to evaluate the clinical effectiveness and safety by comparing N-acetyl-cysteine (NAC) with metformin administrated by polycystic ovary syndrome (PCOS) patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. 10 studies were considered eligible for inclusion. NAC significantly reduced BMI and total testosterone, there was no significant difference in pregnancy rate, serum LH level, fasting insulin, and LH/FSH ratio. In conclusions, NAC may be considered as an alternative supplement to metformin, but large-scale randomized controlled trials are needed to assess the efficacy and safety of NAC in PCOS patients.
Collapse
Affiliation(s)
- Yu Song
- Department of Obstetrics and Gynecology, The Third Hospital of Wuhan, Hubei, China
| | - Huimin Wang
- Department of Obstetrics and Gynecology, The Third Hospital of Wuhan, Hubei, China
| | - Hongli Huang
- Department of Obstetrics and Gynecology, The Third Hospital of Wuhan, Hubei, China
| | - Zhengyan Zhu
- Department of Obstetrics and Gynecology, The Third Hospital of Wuhan, Hubei, China
| |
Collapse
|
|
13
|
Dahan MH, Reaven G. Relationship among obesity, insulin resistance, and hyperinsulinemia in the polycystic ovary syndrome. Endocrine 2019; 64:685-689. [PMID: 30900204 PMCID: PMC6557720 DOI: 10.1007/s12020-019-01899-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 03/11/2019] [Indexed: 12/17/2022]
Abstract
PURPOSE To evaluate the relationship between obesity and insulin resistance among women with polycystic ovary syndrome (PCOS) using a gold standard test. METHODS A retrospective database analysis of 75 women with PCOS and 118 normal controls who underwent a modification of the insulin suppression test. The relationships between body mass index (BMI) and steady-state plasma glucose (SSPG) levels were investigated. RESULTS Mean SSPG score for PCOS subjects was statistically similar than that of the controls at all BMI groupings. Only when PCOS subjects reached a BMI of ≥30 kg/m2 that the PCOS subjects had higher mean SSPG score than the control subjects, although not significantly so (p = 0.07). The distribution of PCOS and control subjects in each SSPG quartile grouping was investigated. When comparing all PCOS and control subjects, PCOS subjects were more likely to be in the higher quartiles of SSPG score (p = 0.0001). However, when comparing the PCOS and control subjects, at each BMI grouping (<25, 25-29.9, and ≥30 kg/m2), there was no difference in the likelihood that a larger percent of subjects fell into a different quartile (p = 0.12, 0.69, 0.32, respectively). CONCLUSIONS PCOS subjects have increased magnitudes of insulin resistance when compared to ovulatory controls, when controlling for age, BMI, fasting glucose, and insulin levels. However, the magnitude of this insulin resistance in lean subjects is mild. Quantity of excess body fat, particularly subjects with a BMI of at least 30 kg/m2 is the primary predictor of insulin resistance of sufficient magnitude to put PCOS subjects at increased risk for metabolic abnormalities.
Collapse
Affiliation(s)
- Michael H Dahan
- Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, McGill University, Montreal, QC, Canada.
| | - Gerald Reaven
- Department of Internal Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA
| |
Collapse
|
|
14
|
Fisch SC, Nikou AF, Wright EA, Phan JD, Leung KL, Grogan TR, Abbott DH, Chazenbalk GD, Dumesic DA. Precocious subcutaneous abdominal stem cell development to adipocytes in normal-weight women with polycystic ovary syndrome. Fertil Steril 2019; 110:1367-1376. [PMID: 30503136 DOI: 10.1016/j.fertnstert.2018.08.042] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 07/31/2018] [Accepted: 08/15/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To examine whether abnormal subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes in polycystic ovary syndrome (PCOS) correlates with hyperandrogenism. DESIGN Prospective cohort study. SETTING Academic medical center. PATIENT(S) Eight normal-weight women with PCOS and eight normoandrogenic ovulatory (control) women matched for age and body mass index. INTERVENTION(S) Circulating hormone and metabolic measurements, intravenous glucose tolerance testing, total body dual-energy X-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S) In vitro ASC commitment to preadipocytes (ZFP423 protein expression, day 0.5), preadipocyte differentiation to adipocytes (PPARγ gene expression, day 3) and adipocyte lipid content (Oil-Red-O fluorescence, day 12) comparisons correlated with clinical outcomes. RESULT(S) In women with PCOS, SC abdominal ASCs compared with those of control women showed exaggerated commitment to preadipocytes and had greater lipid content in newly formed adipocytes after in vitro maturation. In all women combined, ZFP423 protein expression negatively correlated with fasting plasma glucose levels whereas the lipid content of newly formed adipocytes positively correlated with both PPARγ gene expression and serum free testosterone levels. CONCLUSION(S) In normal-weight women with PCOS compared with the control group, exaggerated SC abdominal ASC commitment to preadipocytes and enhanced adipocyte lipid content during maturation in vitro negatively and positively correlate with circulating fasting glucose and androgen levels, respectively, as a possible mechanism to maintain glucose-insulin homeostasis when fat accretion is accelerated.
Collapse
Affiliation(s)
- Samantha C Fisch
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California
| | - Ariella Farzan Nikou
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California
| | - Elizabeth A Wright
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California
| | - Julia D Phan
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California
| | - Karen L Leung
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California
| | - Tristan R Grogan
- Department of Medicine Statistics Core, University of California-Los Angeles, Los Angeles, California
| | - David H Abbott
- Department of Obstetrics and Gynecology, Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin
| | - Gregorio D Chazenbalk
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California
| | - Daniel A Dumesic
- Department of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, California.
| |
Collapse
|
|
15
|
Kampmann U, Knorr S, Fuglsang J, Ovesen P. Determinants of Maternal Insulin Resistance during Pregnancy: An Updated Overview. J Diabetes Res 2019; 2019:5320156. [PMID: 31828161 PMCID: PMC6885766 DOI: 10.1155/2019/5320156] [Citation(s) in RCA: 195] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 10/11/2019] [Accepted: 11/05/2019] [Indexed: 01/08/2023] Open
Abstract
Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially in women with gestational diabetes and type 2 diabetes. Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, and genetic and epigenetic contributions influence insulin resistance in pregnancy, but the causal mechanisms are complex and still not completely elucidated. In this review, we strive to give an overview of the many components that have been ascribed to contribute to the insulin resistance in pregnancy. Knowledge about the causes and consequences of insulin resistance is of extreme importance in order to establish the best possible treatment during pregnancy as severe insulin resistance can result in metabolic dysfunction in both mother and offspring on a short as well as long-term basis.
Collapse
Affiliation(s)
- Ulla Kampmann
- Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200 Aarhus N, Denmark
| | - Sine Knorr
- Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200 Aarhus N, Denmark
| | - Jens Fuglsang
- Department of Obstetrics and Gynecology, Aarhus University Hospital, 8200 Aarhus N, Denmark
| | - Per Ovesen
- Department of Obstetrics and Gynecology, Aarhus University Hospital, 8200 Aarhus N, Denmark
| |
Collapse
|
|
16
|
Tura A, Chemello G, Szendroedi J, Göbl C, Færch K, Vrbíková J, Pacini G, Ferrannini E, Roden M. Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index. Diabetologia 2018; 61:1135-1141. [PMID: 29484470 DOI: 10.1007/s00125-018-4568-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 01/18/2018] [Indexed: 10/17/2022]
Abstract
AIMS/HYPOTHESIS The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS). METHODS We analysed datasets of people that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n = 359 and n = 154, respectively). After a stepwise selection approach, the best model for M value prediction was applied to the validation cohort. This cohort was also divided into subgroups according to glucose tolerance, obesity category and age. RESULTS The new index, called PREDIcted M (PREDIM), was based on OGIS, BMI, 2 h glucose during OGTT and fasting insulin. Bland-Altman analysis revealed a good relationship between the M value and PREDIM in the validation dataset (only 9 of 154 observations outside limits of agreement). Also, no significant differences were found between the M value and PREDIM (equivalence test: p < 0.0063). Subgroup stratification showed that measured M value and PREDIM have a similar ability to detect intergroup differences (p < 0.02, both M value and PREDIM). CONCLUSIONS/INTERPRETATION The new index PREDIM provides excellent prediction of M values from OGTT or meal data, thereby allowing comparison of insulin sensitivity between studies using different tests.
Collapse
Affiliation(s)
- Andrea Tura
- Metabolic Unit, CNR Institute of Neuroscience, Corso Stati Uniti 4, 35127, Padova, Italy.
| | - Gaetano Chemello
- Metabolic Unit, CNR Institute of Neuroscience, Corso Stati Uniti 4, 35127, Padova, Italy
| | - Julia Szendroedi
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Christian Göbl
- Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-maternal Medicine, Medical University of Vienna, Vienna, Austria
| | | | | | - Giovanni Pacini
- Metabolic Unit, CNR Institute of Neuroscience, Corso Stati Uniti 4, 35127, Padova, Italy
| | | | - Michael Roden
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| |
Collapse
|
|
17
|
Pande AR, Guleria AK, Singh SD, Shukla M, Dabadghao P. β cell function and insulin resistance in lean cases with polycystic ovary syndrome. Gynecol Endocrinol 2017; 33:877-881. [PMID: 28704124 DOI: 10.1080/09513590.2017.1342165] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Obesity is a major factor in development of insulin resistance (IR) and metabolic features in polycystic ovary syndrome (PCOS) patients. Nearly two-thirds patients with PCOS (30 of 37 confirmed cases of PCOS) in our previous community based study were lean, in contrast to Caucasians. Metabolic parameters including IR and β cell function have not been characterized well in this group of lean PCOS. To study the metabolic features including IR and β cell function in lean PCOS patients, 53 patients with BMI, <23 kg/m2 were compared with 71 obese PCOS and 45 age and body mass index matched controls. Lean patients had similar β cell function and IR as compared to controls and obese patients, though the latter group had more metabolic abnormality. Fasting c-peptide and its ratio to glucose were significantly higher in lean patients compared to controls. In subset of subjects with five point OGTT, disposition index and Matsuda index (MI) showed significant negative correlation with BMI and blood pressure. MI also negatively correlated with waist, WHR, and HOMAB. High fasting C-peptide is probably a class effect as is seen in both lean and obese PCOS.
Collapse
Affiliation(s)
- Arunkumar R Pande
- a Endocrinology , Sahara Hospital , Lucknow , India
- b Endocrinology , Endocrine Diabetes and Thyroid Clinic , Lucknow , India
| | - Ashwani Kumar Guleria
- c Department of Endocrinology , Sanjay Gandhi Post Graduate Institute of Medical Sciences , Lucknow , India
- d Amar Hospital , Patiala , India
| | | | - Manoj Shukla
- c Department of Endocrinology , Sanjay Gandhi Post Graduate Institute of Medical Sciences , Lucknow , India
| | - Preeti Dabadghao
- c Department of Endocrinology , Sanjay Gandhi Post Graduate Institute of Medical Sciences , Lucknow , India
| |
Collapse
|
|
18
|
Erkan G, Tayyar AT, Açmaz G, Müderris İİ, Başkol G, Bayram F. Role of osteocalcin, tumor necrosis factor-alpha and adiponectin in polycystic ovary syndrome patients with insulin resistance. Turk J Obstet Gynecol 2017; 14:89-93. [PMID: 28913143 PMCID: PMC5558419 DOI: 10.4274/tjod.61224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 03/16/2017] [Indexed: 12/01/2022] Open
Abstract
Objective: Insulin resistance (IR) seems to be the main pathogenic factor in polycystic ovary syndrome (PCOS). Adiponectin and tumor necrosis factor-alpha (TNF-α) are important in IR. The aim of this study was to evaluate the correlations of osteocalcin, adiponectin, and TNF-α with IR in PCOS. Materials and Methods: A total of 60 women were divided into two groups. The first group constituted 44 patients with PCOS and the control group comprised 16 healthy women. Osteocalcin, adiponectin, TNF-α levels, body mass index (BMI), and IR in the fasting state were assessed and correlations of these parameters were evaluated. Results: Homeostasis model assessment (HOMA)-IR, adiponectin, osteocalcin, and androstenedione levels were significantly increased in the PCOS group. A moderate positive correlation between BMI and HOMA-IR, a moderate negative correlation between TNF-α and osteocalcin, and a mild negative correlation between adiponectin and BMI were detected in PCOS. Conclusion: Osteocalcin may have impact on adiponectin, TNF-α, and IR levels in PCOS. Different osteocalcin levels in patients with PCOS may be responsible for explaining PCOS heterogeneity.
Collapse
Affiliation(s)
- Gönül Erkan
- Private Hüma Hospital, Clinic of Obstetrics and Gynecology, Kayseri, Turkey
| | - Ahter Tanay Tayyar
- Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital, Clinic of Obstetrics and Gynecology, İstanbul, Turkey
| | - Gökhan Açmaz
- Kayseri Training and Research Hospital, Clinic of Obstetrics and Gynecology, Kayseri, Turkey
| | - İptisam İpek Müderris
- Erciyes University Faculty of Medicine, Department of Obstetrics and Gynecology, Kayseri, Turkey
| | - Gülden Başkol
- Erciyes University Faculty of Medicine, Department of Biochemistry, Kayseri, Turkey
| | - Fahri Bayram
- Erciyes University Faculty of Medicine, Department of Clinical Endocrinology and Metabolism, Kayseri, Turkey
| |
Collapse
|
|
19
|
Skarra DV, Hernández-Carretero A, Rivera AJ, Anvar AR, Thackray VG. Hyperandrogenemia Induced by Letrozole Treatment of Pubertal Female Mice Results in Hyperinsulinemia Prior to Weight Gain and Insulin Resistance. Endocrinology 2017; 158:2988-3003. [PMID: 28911175 PMCID: PMC5659661 DOI: 10.1210/en.2016-1898] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 07/11/2017] [Indexed: 02/06/2023]
Abstract
Women with polycystic ovary syndrome (PCOS) diagnosed with hyperandrogenism and ovulatory dysfunction have an increased risk of developing metabolic disorders, including type 2 diabetes and cardiovascular disease. We previously developed a model that uses letrozole to elevate endogenous testosterone levels in female mice. This model has hallmarks of PCOS, including hyperandrogenism, anovulation, and polycystic ovaries, as well as increased abdominal adiposity and glucose intolerance. In the current study, we further characterized the metabolic dysfunction that occurs after letrozole treatment to determine whether this model represents a PCOS-like metabolic phenotype. We focused on whether letrozole treatment results in altered pancreatic or liver function as well as insulin resistance. We also investigated whether hyperinsulinemia occurs secondary to weight gain and insulin resistance in this model or if it can occur independently. Our study demonstrated that letrozole-treated mice developed hyperinsulinemia after 1 week of treatment and without evidence of insulin resistance. After 2 weeks of letrozole treatment, mice became significantly heavier than placebo mice, demonstrating that weight gain was not required to develop hyperinsulinemia. After 5 weeks of letrozole treatment, mice exhibited blunted glucose-stimulated insulin secretion, insulin resistance, and impaired insulin-induced phosphorylation of AKT in skeletal muscle. Moreover, letrozole-treated mice exhibited dyslipidemia after 5 weeks of treatment but no evidence of hepatic disease. Our study demonstrated that the letrozole-induced PCOS mouse model exhibits multiple features of the metabolic dysregulation observed in obese, hyperandrogenic women with PCOS. This model will be useful for mechanistic studies investigating how hyperandrogenemia affects metabolism in females.
Collapse
Affiliation(s)
- Danalea V. Skarra
- Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093
| | | | - Alissa J. Rivera
- Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093
| | - Arya R. Anvar
- Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093
| | - Varykina G. Thackray
- Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093
| |
Collapse
|
|
20
|
Al-Jefout M, Alnawaiseh N, Al-Qtaitat A. Insulin resistance and obesity among infertile women with different polycystic ovary syndrome phenotypes. Sci Rep 2017; 7:5339. [PMID: 28706269 PMCID: PMC5509707 DOI: 10.1038/s41598-017-05717-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/01/2017] [Indexed: 12/25/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common problem among Arab women and is the main cause of infertility due to anovulation. This study investigates insulin resistance (IR) and obesity in different PCOS phenotypes among infertile women (n = 213), of whom 159 had PCOS and 54 women without PCOS, recruited as a control group. Biometric, hormonal and clinical parameters were studied. IR was observed in 133 (83.6%) women with PCOS and in 25 (46.3%) women without PCOS (p < 0.001). IR was significantly associated with PCOS only among women with central obesity (χ2 = 35.0, p < 0.001) and not for the normal category (χ2 = 4.04, p < 0.058). The LH/FSH ratio was not significantly different among the PCOS group (n = 37, 23.3%) compared to the control group (n = 9, 16.7%) (p = 0.308). Among women with PCOS, the most common phenotype was type I (50.3%), with type III (29.6%), type II (14.5%) and type IV (5.7%). Type I had the highest values of fasting insulin (median = 12.98 mU/mL) and HOMA IR values (significant difference among the four phenotypes, p = 0.009 and 0.006, respectively) and is associated with severity of the disease. There was no difference in glucose levels.
Collapse
Affiliation(s)
- Moamar Al-Jefout
- Department of Obstetrics and Gynaecology, Mutah Medical Faculty, Mutah University, Mutah, Jordan. .,Department of Obstetrics and Gynaecology, CM&HS, UAEU, Al-Ain, UAE.
| | - Nedal Alnawaiseh
- Department of Public Health, Mutah Medical Faculty, Mutah University, Mutah, Jordan
| | - Aiman Al-Qtaitat
- Department of Anatomy and Histology, Mutah Medical Faculty, Mutah University, Mutah, Jordan
| |
Collapse
|
|
21
|
Song DK, Hong YS, Sung YA, Lee H. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance. PLoS One 2017; 12:e0178120. [PMID: 28542421 PMCID: PMC5444780 DOI: 10.1371/journal.pone.0178120] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 05/07/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT)-derived IR indices in lean women with PCOS. METHODS We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA)-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women. RESULTS Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05). Women with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (P<0.05). The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05). The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05). CONCLUSIONS Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.
Collapse
Affiliation(s)
- Do Kyeong Song
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Young Sun Hong
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Yeon-Ah Sung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Hyejin Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
- * E-mail:
| |
Collapse
|
|
22
|
Stassek J, Erdmann J, Ohnolz F, Berg FD, Kiechle M, Seifert-Klauss V. C-Peptide, Baseline and Postprandial Insulin Resistance after a Carbohydrate-Rich Test Meal - Evidence for an Increased Insulin Clearance in PCOS Patients? Geburtshilfe Frauenheilkd 2017; 77:59-65. [PMID: 28190890 DOI: 10.1055/s-0042-119199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Introduction Known characteristics of patients with PCOS include infertility, menstrual disorders, hirsutism and also often insulin resistance. These symptoms increase with increasing body weight. In the LIPCOS study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS]) long-term changes of the PCOS in dependence on pregnancy and parenthood were systematically assessed. In the framework of the LIPCOS study, PCOS patients were given a standardised carbohydrate-rich test meal in order to examine glucose homeostasis and insulin secretion. The results were compared with those of a eumenorrhoeic control group who all had corresponding BMI values and corresponding ages. Methods and Patients 41 PCOS patients (without diabetes) and 68 controls received a standardised carbohydrate-rich test meal (260 kcal, 62 % carbohydrates, 32 % fat, 6 % proteins) in order to generate a submaximal insulin and glucose stimulation. The values were determined at baseline and postprandial after 60, 120 and 180 minutes. In addition, the corresponding C-peptide levels were recorded. Results In the PCOS patients (n = 41), the insulin secretion test after a standardised test meal showed almost identical baseline and postprandial insulin levels when compared with those of the age- and BMI-matched eumenorrhoeic controls (n = 68). In the PCOS patients, the baseline and postprandial glucose levels were significantly elevated (92.88 ± 10.28 [PCOS] vs. 85.07 ± 9.42 mg/dL [controls]; p < 0.001) so was C-peptide (p < 0.025). Conclusions In the present study we have shown for the first time that, after consumption of a standardised test meal, PCOS patients formally exhibit a higher fasting insulin resistance than controls. In spite of the higher stimulated C-peptide levels, the insulin levels did not increase more strongly with increasing glucose levels than in controls which may be indicative of a higher insulin clearance in PCOS patients.
Collapse
Affiliation(s)
- J Stassek
- Frauenklinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany
| | - J Erdmann
- Hochschule Weihenstephan-Triesdorf, Weidenbach, Germany
| | - F Ohnolz
- Frauenklinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany
| | - F D Berg
- Gemeinschaftspraxis Prof. Berg und Dr. Lesoine, München, Germany
| | - M Kiechle
- Frauenklinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany
| | - V Seifert-Klauss
- Frauenklinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany
| |
Collapse
|
|
23
|
Goyal M, Dawood AS. Debates Regarding Lean Patients with Polycystic Ovary Syndrome: A Narrative Review. J Hum Reprod Sci 2017; 10:154-161. [PMID: 29142442 PMCID: PMC5672719 DOI: 10.4103/jhrs.jhrs_77_17] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complex syndrome showing the clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Two phenotypes are present, either lean or obese, with different biochemical, hormonal, and metabolic profiles. Evidence suggests many treatment modalities that can be applied. However, many of these modalities were found to be not suitable for the lean phenotype of PCOS. Much contradictory research was found regarding lean patients with PCOS. The aim of this narrative review is to shed light on the debate prevailing regarding characteristics, as well as metabolic, hematological, and potential management modalities. Literature review was performed from January 1, 2000 to March 31, 2017 with specific word search such as lean PCOS, hormonal abnormalities in lean PCOS, and the management of lean PCOS. All retrieved articles were carefully assessed, and data were obtained. We could conclude that the debate is still prevailing regarding this specific lean population with PCOS, especially with regard to their characteristics and management modalities. Further studies are still required to resolve this debate on the presence of PCOS in lean women.
Collapse
Affiliation(s)
- Manu Goyal
- Department of Obstetrics and Gynecology, AIIMS, New Delhi, India
| | - Ayman S Dawood
- Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt
| |
Collapse
|
|
24
|
Dumesic DA, Akopians AL, Madrigal VK, Ramirez E, Margolis DJ, Sarma MK, Thomas AM, Grogan TR, Haykal R, Schooler TA, Okeya BL, Abbott DH, Chazenbalk GD. Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women. J Clin Endocrinol Metab 2016; 101:4178-4188. [PMID: 27571186 PMCID: PMC5095243 DOI: 10.1210/jc.2016-2586] [Citation(s) in RCA: 105] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
CONTEXT Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. OBJECTIVE This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. DESIGN This is a prospective cohort study. SETTING The setting was an academic medical center. PATIENTS Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. INTERVENTION(S) All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S) Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. RESULTS Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. CONCLUSION Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction.
Collapse
Affiliation(s)
- Daniel A Dumesic
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Alin L Akopians
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Vanessa K Madrigal
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Emmanuel Ramirez
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Daniel J Margolis
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Manoj K Sarma
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Albert M Thomas
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Tristan R Grogan
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Rasha Haykal
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Tery A Schooler
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Bette L Okeya
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - David H Abbott
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| | - Gregorio D Chazenbalk
- Department of Obstetrics and Gynecology (D.A.D., A.L.A., V.K.M., R.H., T.A.S., B.L.O, G.D.C.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Department of Medicine (E.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Radiological Science (D.J.M., M.K.S, A.M.T.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Medicine Statistics Core (T.R.G.), David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Obstetrics and Gynecology and Wisconsin National Primate Research Center (D.H.A), University of Wisconsin, Madison, Wisconsin
| |
Collapse
|
|
25
|
Cassar S, Misso ML, Hopkins WG, Shaw CS, Teede HJ, Stepto NK. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies. Hum Reprod 2016; 31:2619-2631. [DOI: 10.1093/humrep/dew243] [Citation(s) in RCA: 165] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2016] [Revised: 08/24/2016] [Accepted: 08/31/2016] [Indexed: 02/06/2023] Open
|
|
26
|
Reyes-Muñoz E, Ortega-González C, Martínez-Cruz N, Arce-Sánchez L, Estrada-Gutierrez G, Moran C, Sánchez-Serrano AP, Higareda-Sánchez R, de la Jara-Díaz JF. Association of obesity and overweight with the prevalence of insulin resistance, pre-diabetes and clinical-biochemical characteristics among infertile Mexican women with polycystic ovary syndrome: a cross-sectional study. BMJ Open 2016; 6:e012107. [PMID: 27449893 PMCID: PMC4964199 DOI: 10.1136/bmjopen-2016-012107] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVE To study the association of obesity and overweight with the prevalence of insulin resistance (IR), pre-diabetes and clinical-biochemical characteristics among infertile Mexican women with polycystic ovary syndrome (PCOS). DESIGN Retrospective cross-sectional study. SETTING Level-three medical institution, an infertility clinic in Mexico City. PARTICIPANTS We included infertile Mexican women with diagnosis of PCOS according to the Rotterdam criteria: group 1 (n=83), normal weight (body mass index (BMI) 18.5-24.9 kg/m(2)); group 2 (n=217), overweight (BMI 25-29.9 kg/m(2)); and group 3 (n=238), obese (BMI≥30 kg/m(2)). PRIMARY AND SECONDARY OUTCOME MEASURES IR was determined by homeostatic model assessment (HOMA) >2.5 and pre-diabetes by fasting glucose between 5.6 and 6.9 mmol/L and/or glucose value between 7.8 and 11 mmol/L at 2 hours during an oral glucose tolerance test. We compared clinical-biochemical characteristics among groups. RESULTS Prevalence of IR for groups 1, 2 and 3 was 19.3%, 56.2% and 78.2%; overweight and obesity increase the IR OR (CI 95%) to 5.3 (2.9 to 9.8) and 14.9 (8.0 to 28), respectively. Prevalence of pre-diabetes for groups 1, 2 and 3 was 7.2%, 17.5% and 31.5%; overweight and obesity increase the pre-diabetes OR (CI 95%) to 2.7 (1.1 to 6.7) and 5.9 (2.4 to 14), respectively. Acanthosis nigricans was more frequent in group 3 than group 1. Free Androgen Index (FAI) and thyroid-stimulating hormone (TSH) levels were lower in group 1 than in groups 2 and 3. Progesterone and sex hormone-binding globulin (SHBG) levels were higher in group 1 than in groups 2 and 3. Dehydroepiandrosterone sulfate (DHEA-S) was higher in group 1 than group 3. CONCLUSIONS Obese and overweight infertile Mexican women with PCOS, attending to an infertility clinic, have a higher prevalence of IR and pre-diabetes compared with normal-weight women with PCOS. Therapeutic interventions should include those that improved metabolic functioning prior to attempting pregnancy in these groups of women.
Collapse
Affiliation(s)
- Enrique Reyes-Muñoz
- Department of Endocrinology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | - Carlos Ortega-González
- Department of Endocrinology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | - Nayeli Martínez-Cruz
- Department of Endocrinology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | - Lidia Arce-Sánchez
- Department of Endocrinology, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | - Guadalupe Estrada-Gutierrez
- Biomedical Research Branch, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | - Carlos Moran
- Research Unit of Reproductive Medicine, Health Research Council, Mexican Institute of Social Security, IMSS, Mexico City, Mexico
| | - Ana Paola Sánchez-Serrano
- Division of Reproductive Medicine, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | - Rodolfo Higareda-Sánchez
- Division of Reproductive Medicine, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
| | | |
Collapse
|
|
27
|
Ouyang P, Wenger NK, Taylor D, Rich-Edwards JW, Steiner M, Shaw LJ, Berga SL, Miller VM, Merz NB. Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists. Biol Sex Differ 2016; 7:19. [PMID: 27034774 PMCID: PMC4815158 DOI: 10.1186/s13293-016-0073-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 03/21/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. METHODS The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. RESULTS To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific contributors to CV health and disease. Lack of sex-specific knowledge contributes to the CVD health disparities that women face. CONCLUSIONS The purpose of this review is to encourage investigators to consider ways to increase the usefulness of physiological and psychosocial data obtained from clinical populations, in an effort to improve the understanding of sex differences in clinical CVD research and health-care delivery for women and men.
Collapse
Affiliation(s)
- Pamela Ouyang
- />Johns Hopkins University, Baltimore, MD USA
- />Division of Cardiology, Johns Hopkins Bayview Medical Center, 301 Building, Suite 2400, 4940 Eastern Ave, Baltimore, MD 21224 USA
| | | | | | | | | | | | | | | | - Noel Bairey Merz
- />Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA USA
| |
Collapse
|
|
28
|
Mumm H, Altinok ML, Henriksen JE, Ravn P, Glintborg D, Andersen M. Prevalence and possible mechanisms of reactive hypoglycemia in polycystic ovary syndrome. Hum Reprod 2016; 31:1105-12. [DOI: 10.1093/humrep/dew046] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 02/23/2016] [Indexed: 12/18/2022] Open
|
|
29
|
Cardoso RC, Veiga-Lopez A, Moeller J, Beckett E, Pease A, Keller E, Madrigal V, Chazenbalk G, Dumesic D, Padmanabhan V. Developmental Programming: Impact of Gestational Steroid and Metabolic Milieus on Adiposity and Insulin Sensitivity in Prenatal Testosterone-Treated Female Sheep. Endocrinology 2016; 157:522-35. [PMID: 26650569 PMCID: PMC4733129 DOI: 10.1210/en.2015-1565] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Prenatally testosterone (T)-treated sheep present metabolic disruptions similar to those seen in women with polycystic ovary syndrome. These females exhibit an increased ratio of small to large adipocytes, which may be the earliest event in the development of adult insulin resistance. Additionally, our longitudinal studies suggest the existence of a period of compensatory adaptation during development. This study tested whether 1) in utero cotreatment of prenatally T-treated sheep with androgen antagonist (flutamide) or insulin sensitizer (rosiglitazone) prevents juvenile insulin resistance and adult changes in adipocyte size; and 2) visceral adiposity and insulin sensitivity are both unaltered during early adulthood, confirming the predicted developmental trajectory in this animal model. Insulin sensitivity was tested during juvenile development and adipose tissue distribution, adipocyte size, and concentrations of adipokines were determined during early adulthood. Prenatal T-treated females manifested juvenile insulin resistance, which was prevented by prenatal rosiglitazone cotreatment. Neither visceral adiposity nor insulin sensitivity differed between groups during early adulthood. Prenatal T-treated sheep presented an increase in the relative proportion of small adipocytes, which was not substantially prevented by either prenatal intervention. A large effect size was observed for increased leptin concentrations in prenatal T-treated sheep compared with controls, which was prevented by prenatal rosiglitazone. In conclusion, gestational alterations in insulin-glucose homeostasis likely play a role in programming insulin resistance, but not adipocyte size distribution, in prenatal T-treated sheep. Furthermore, these results support the notion that a period of compensatory adaptation of the metabolic system to prenatal T exposure occurs between puberty and adulthood.
Collapse
Affiliation(s)
- Rodolfo C Cardoso
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Almudena Veiga-Lopez
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Jacob Moeller
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Evan Beckett
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Anthony Pease
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Erica Keller
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Vanessa Madrigal
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Gregorio Chazenbalk
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Daniel Dumesic
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| | - Vasantha Padmanabhan
- Department of Pediatrics (R.C.C., A.V.-L., J.M., E.B., V.P.), University of Michigan, Ann Arbor, Michigan 48109; Department of Small Animal Clinical Sciences (A.P.), Michigan State University, East Lansing, Michigan 48824; and Department of Obstetrics and Gynecology (E.K., V.M., G.C., D.D.), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095
| |
Collapse
|
|
30
|
Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome. Endocr Rev 2015; 36:487-525. [PMID: 26426951 PMCID: PMC4591526 DOI: 10.1210/er.2015-1018] [Citation(s) in RCA: 608] [Impact Index Per Article: 60.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
Collapse
Affiliation(s)
- Daniel A Dumesic
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Sharon E Oberfield
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Elisabet Stener-Victorin
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - John C Marshall
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Joop S Laven
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| | - Richard S Legro
- Department of Obstetrics and Gynecology (D.A.D.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; Division of Pediatric Endocrinology (S.E.O.), Children's Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden; Center for Research in Reproduction and Division of Endocrinology (J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22903; Division of Reproductive Medicine (J.S.L.), Department of Obstetrics and Gynecology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
| |
Collapse
|
|
31
|
Pazderska A, Gibney J. Metabolic and lipoprotein aspects of polycystic ovarian syndrome. ACTA ACUST UNITED AC 2015. [DOI: 10.2217/clp.15.12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
32
|
Arduc A, Sarıcam O, Dogan BA, Tuna MM, Tutuncu YA, Isik S, Berker D, Sennaroglu E, Guler S. Should insulin resistance be screened in lean hirsute women? Gynecol Endocrinol 2015; 31:291-5. [PMID: 25561024 DOI: 10.3109/09513590.2014.994598] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The role of insulin resistance (IR) is well-documented in obese women with polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55 IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were recruited in the study (mean age 25.21 ± 6.1 versus 26.26 ± 4.6years; BMI 21.79 ± 1.7 versus 22.02 ± 2.2 kg/m(2), respectively). Significantly higher insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p < 0.05). These IR indices were similar between groups 1 and 2. The number of patients with IR (HOMA-IR > 2, FGIR < 7.2, or QUICKI < 0.357) was significantly higher in groups 1 and 2 than in group 3, but was similar between groups 1 and 2. A higher frequency of IR occurs in lean hirsute women regardless of they having PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some metabolic abnormalities in these patients.
Collapse
Affiliation(s)
- Ayse Arduc
- National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes, Endocrine and Obesity Branch, National Institutes of Health , Bethesda, MD , USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Shorakae S, Boyle J, Teede H. Polycystic ovary syndrome: a common hormonal condition with major metabolic sequelae that physicians should know about. Intern Med J 2014; 44:720-6. [DOI: 10.1111/imj.12495] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 06/01/2014] [Indexed: 01/13/2023]
Affiliation(s)
- S. Shorakae
- Diabetes and Vascular Medicine Unit, Monash Health; Monash University; Melbourne Victoria Australia
- Monash Centre for Health Research and Implementation (MCHRI); Monash University; Melbourne Victoria Australia
| | - J. Boyle
- Monash Centre for Health Research and Implementation (MCHRI); Monash University; Melbourne Victoria Australia
| | - H. Teede
- Diabetes and Vascular Medicine Unit, Monash Health; Monash University; Melbourne Victoria Australia
- Monash Centre for Health Research and Implementation (MCHRI); Monash University; Melbourne Victoria Australia
| |
Collapse
|
|
34
|
Ramezani Tehrani F, Minooee S, Azizi F. Comparison of various adiposity indexes in women with polycystic ovary syndrome and normo-ovulatory non-hirsute women: a population-based study. Eur J Endocrinol 2014; 171:199-207. [PMID: 24816947 DOI: 10.1530/eje-14-0094] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE Insulin resistance (IR) and metabolic disorders are common in polycystic ovary syndrome (PCOS). However, it is still not clear which adiposity marker could precisely predict metabolic syndrome (MetS) in women with PCOS and whether these indexes are different in normo-ovulatory non-hirsute women. DESIGN A case-control study was conducted on a total of 175 Iranian subjects with PCOS and 525 normal control subjects, aged 18-45 years. METHODS Waist circumference (WC), BMI, waist-to-hip ratio, lipid accumulation product (LAP) index, and visceral adiposity index (VAI) were examined and the homeostasis model assessment index was calculated. MetS was defined according to the joint interim statement. The receiver operating characteristic curves were used to evaluate the extent to which measures of adiposity can predict IR and MetS risk. RESULTS LAP index and VAI are two indicators (sensitivity and PPV of 70% (LAP index) and 60% (VAI), and 80% (LAP index) and 83% (VAI) respectively) that best predict IR in women with PCOS. Among healthy women, the LAP index and WC were better markers (sensitivity and PPV of 78% (LAP index) and 75% (VAI), and 82% (LAP index) and 81% (VAI) respectively). The two most reliable indicators for prediction of MetS among PCOS and normal women were the WC and VAI (sensitivity and PPV of 83% (WC) and 81% (VAI), and 97% (WC) and 95% (VAI) respectively) and the VAI and LAP index (sensitivity and PPV of 88% (VAI) and 83% (LAP index), and 98% (VAI) and 98% (LAP index) respectively) respectively. CONCLUSIONS While the appropriate adiposity indicators and their optimum cutoff values vary in women with PCOS, compared with the normal control subjects, the LAP index is an easily obtainable index that might be useful for screening of cardiometabolic complications among both groups.
Collapse
Affiliation(s)
- Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research CenterEndocrine Research CenterResearch Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, PO Box 19395-4763, Tehran, Iran
| | - Sonia Minooee
- Reproductive Endocrinology Research CenterEndocrine Research CenterResearch Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, PO Box 19395-4763, Tehran, Iran
| | - Fereidoun Azizi
- Reproductive Endocrinology Research CenterEndocrine Research CenterResearch Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, PO Box 19395-4763, Tehran, Iran
| |
Collapse
|
|
35
|
Assessment of insulin resistance in lean women with polycystic ovary syndrome. Fertil Steril 2014; 102:250-256.e3. [DOI: 10.1016/j.fertnstert.2014.04.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 03/07/2014] [Accepted: 04/03/2014] [Indexed: 12/13/2022]
|
|
36
|
Sravan Kumar P, Ananthanarayanan PH, Rajendiran S. Cardiovascular risk markers and thyroid status in young Indian women with polycystic ovarian syndrome: A case-control study. J Obstet Gynaecol Res 2014; 40:1361-7. [DOI: 10.1111/jog.12346] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 11/01/2013] [Indexed: 11/28/2022]
|
|
37
|
Abstract
Polycystic ovary syndrome (PCOS), a heterogeneous and chronic condition, today affects about 5% of women of reproductive age. PCOS is strongly associated with states of insulin resistance and hyperinsulinemia. Risk factors include genetics, metabolic profiles, and the in utero environment. Long-term consequences of PCOS include metabolic complications such as diabetes, obesity, and cardiovascular disease. Dysregulation of insulin action is closely linked to the pathogenesis of PCOS. However, whether insulin resistance is the causative factor in the development of PCOS remains to be ascertained. Moreover, the mechanism by which insulin resistance may lead to reproductive dysfunction requires further elucidation.
Collapse
Affiliation(s)
- Anindita Nandi
- Division of Endocrinology and Metabolism, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY 10003, USA
| | - Zijian Chen
- Division of Endocrinology and Metabolism, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY 10003, USA
| | - Ronak Patel
- Division of Endocrinology and Metabolism, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY 10003, USA
| | - Leonid Poretsky
- Division of Endocrinology and Metabolism, Department of Medicine, Gerald J. Friedman Diabetes Institute, Beth Israel Medical Center, Albert Einstein College of Medicine, 317 East 17th Street, 7th Floor, New York, NY 10003, USA.
| |
Collapse
|
|
38
|
Bozdag G, Yildiz BO. Insulin resistance in polycystic ovary syndrome: maker or marker? ACTA ACUST UNITED AC 2014. [DOI: 10.1586/eog.09.73] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
|
|
39
|
Veiga-Lopez A, Moeller J, Patel D, Ye W, Pease A, Kinns J, Padmanabhan V. Developmental programming: impact of prenatal testosterone excess on insulin sensitivity, adiposity, and free fatty acid profile in postpubertal female sheep. Endocrinology 2013; 154:1731-42. [PMID: 23525243 PMCID: PMC4016698 DOI: 10.1210/en.2012-2145] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2012] [Accepted: 03/05/2013] [Indexed: 11/19/2022]
Abstract
Prenatal T excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested whether increases in visceral adiposity, adipocyte size, and total free fatty acids underlie the insulin resistance seen in prenatal T-treated female sheep. At approximately 16 months of age, insulin resistance and adipose tissue partitioning were determined via hyperinsulinemic euglycemic clamp and computed tomography, respectively, in control and prenatal T-treated females. Three months later, adipocyte size and free fatty acid composition were determined. Results revealed that at the postpubertal time points tested, insulin sensitivity was increased, visceral adiposity and adipocyte size in both the sc and the visceral compartments were reduced, and circulating palmitic acid was increased in prenatal T-treated females relative to controls. In parallel studies, 20-month-old prenatal T-treated females tended to have increased basal insulin to glucose ratio. Relative to earlier findings of reduced insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in free fatty acid metabolism a few months later correspond to a time point when the insulin sensitivity indices of prenatal T-treated animals appear to shift toward insulin resistance. In summary, current findings of improved insulin sensitivity and reduced visceral adiposity in postpubertal prenatal T-treated sheep relative to our earlier findings of reduced insulin sensitivity during early postnatal life and adulthood are indicative of a period of developmental adaptation.
Collapse
Affiliation(s)
- A Veiga-Lopez
- Department of Pediatrics and Reproductive Sciences Program, University of Michigan, 300 North Ingalls Building, Room 1137, Ann Arbor, Michigan 48109-0404, USA
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Huang G, Coviello A. Clinical update on screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes 2012; 19:512-9. [PMID: 23108199 DOI: 10.1097/med.0b013e32835a000e] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in premenopausal women. This review discusses the screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with PCOS, highlighting significant recent developments. RECENT FINDINGS PCOS is a complex genetic disorder with multiple susceptibility genes as well as environmental factors influencing the expression of various PCOS phenotypes. The first genome-wide association study of PCOS identified susceptibility loci on chromosome 2 near the luteinizing hormone receptor gene LHCGR and chromosome 9 near the obesity gene DEEND1A. Women with PCOS are affected by a variety of metabolic disorders, including insulin resistance, metabolic syndrome, type-2 diabetes, dyslipidemia and obesity. Recently, it has been established that women with PCOS have a high risk of nonalcoholic fatty liver disease. These metabolic disturbances are associated with an increased risk of cardiovascular disease (CVD). Although women with PCOS have higher rates of cardiovascular risk factors and intermediate markers of CVD, studies definitively documenting increased CVD are lacking. SUMMARY The high prevalence of metabolic disorders and CVD risk factors in women with PCOS highlights the need for early screening, diagnosis and treatment of these disorders to promote long-term health and possibly prevent CVD.
Collapse
Affiliation(s)
- Grace Huang
- Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA
| | | |
Collapse
|
|
41
|
Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33:981-1030. [PMID: 23065822 PMCID: PMC5393155 DOI: 10.1210/er.2011-1034] [Citation(s) in RCA: 1146] [Impact Index Per Article: 88.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Genetic disruption of insulin signaling in the brain has indicated that this pathway is important for ovulation and body weight regulation. These insights have been directly translated into a novel therapy for PCOS with insulin-sensitizing drugs. Furthermore, androgens contribute to insulin resistance in PCOS. PCOS may also have developmental origins due to androgen exposure at critical periods or to intrauterine growth restriction. PCOS is a complex genetic disease, and first-degree relatives have reproductive and metabolic phenotypes. Several PCOS genetic susceptibility loci have been mapped and replicated. Some of the same susceptibility genes contribute to disease risk in Chinese and European PCOS populations, suggesting that PCOS is an ancient trait.
Collapse
|
|
42
|
Abstract
When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mechanisms behind this conundrum: individuals who exhibit metabolic dysfunction, diabetes and elevated cardiovascular disease risk despite a lean body type, and individuals who are relatively protected from these dangers despite significant obesity. Study of this second group of 'metabolically healthy obese' people in particular has been revealing because such individuals exhibit specific, identifiable, anatomic, cellular and molecular features that set them apart from the rest of us who suffer declining health with increasing weight. Here, we examine some of these features, including some mouse models that are informative of mechanism, and suggest hypotheses for further study, including the possibility that genes and pathways of the immune system might offer new diagnostic or therapeutic targets.
Collapse
Affiliation(s)
- Gerald V Denis
- Immunology Training Program , Cancer Research Center and Boston Nutrition Obesity Research Center, Boston University School of Medicine, 72 East Concord St. Room K520, Boston, MA, USA.
| | | |
Collapse
|
|
43
|
Cebeci F, Onsun N, Mert M. Insulin resistance in women with hirsutism. Arch Med Sci 2012; 8:342-6. [PMID: 22662009 PMCID: PMC3361048 DOI: 10.5114/aoms.2012.28563] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2010] [Revised: 10/10/2010] [Accepted: 10/20/2010] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION There are still not enough data showing whether patients with idiopathic hirsutism (IH) also have insulin resistance. The association between polycystic ovary syndrome (PCOS) and insulin resistance is well documented in the literature, but the Rotterdam Consensus has concluded that principally obese women with PCOS should be screened for the metabolic syndrome. We intended to investigate the presence/absence of insulin resistance in non-obese women with hirsutism. MATERIAL AND METHODS Twenty-eight women with PCOS (14 non-obese and 14 obese), 12 non-obese with IH, and 16 non-obese healthy women were included in the study. The presence of insulin resistance was investigated by using basal insulin levels and the homeostasis model assessment (HOMA) score in the study group. RESULTS Patients with obese and nonobese PCOS had significantly (p < 0.05) higher basal insulin levels and HOMA scores than IH and control subjects. Insulin levels and HOMA scores did not differ between obese and non-obese PCOS patients. Patients with IH did not show any difference from the control group. CONCLUSIONS Insulin resistance exists in non-obese women with PCOS as well as obese women with PCOS. The PCOS is associated with insulin resistance independent of obesity. Insulin resistance should be assessed in all hirsute women with PCOS regardless of their body mass index. More studies in larger numbers of patients should be performed to investigate the role of insulin resistance in women with IH.
Collapse
Affiliation(s)
- Filiz Cebeci
- Department of Dermatology, Vakif Gureba Teaching Hospital, Istanbul, Turkey
| | - Nahide Onsun
- Department of Dermatology, Vakif Gureba Teaching Hospital, Istanbul, Turkey
| | - Meral Mert
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul Medical Faculty, Istanbul University, Turkey
| |
Collapse
|
|
44
|
Bellanger S, Battista MC, Fink GD, Baillargeon JP. Saturated fatty acid exposure induces androgen overproduction in bovine adrenal cells. Steroids 2012; 77:347-53. [PMID: 22245830 PMCID: PMC3848974 DOI: 10.1016/j.steroids.2011.12.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2011] [Accepted: 11/22/2011] [Indexed: 12/01/2022]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenemia, from ovarian and adrenal origin, and is characterized by insulin resistance (IR). Studies found that raising in vivo non-esterified fatty acid (NEFA) levels, which induces lipotoxicity, increases androgen levels and IR. The aim of this study was therefore to determine the effects of in vitro over-exposure to NEFA on androgen synthesis in a bovine adrenocortical cell model. METHODS Bovine fasciculata/reticularis cells were cultured for 2days in the absence or presence of ACTH (10nmol/L) or Forskolin (fsk, 10μmol/L), alone or in combination with the saturated fatty acid (FA) palmitate (100μmol/L). Steroid production was measured in medium and corrected for initial cell seeding count. CYP17 protein expression and ERK1/2 phosphorylation were assessed by Western blotting. RESULTS Under unstimulated conditions, dehydroepiandrosterone (DHEA) levels were barely detected and no difference was observed after palmitate exposure, which was also the case for CYP17 expression and ERK1/2 phosphorylation. Under stimulation, palmitate exposure increased DHEA production by 38% and 69%, for ACTH and fsk, respectively, as compared to untreated conditions (Ps⩽0.05). In palmitate-treated vs untreated cells, fsk-stimulated ERK1/2 phosphorylation was reduced by 46% (P=0.0047), but stimulated CYP17 expression was not significantly affected. CONCLUSION In a model of androgen-producing cells, under stimulated conditions, overexposure to saturated FAs significantly increases androgen production and reduces MEK/ERK activation. Therefore, this study is the first to demonstrate that lipotoxicity can directly trigger androgen overproduction in vitro, in addition to its well-described impact on IR, which strongly supports a central role of lipotoxicity in PCOS pathophysiology.
Collapse
Affiliation(s)
- Sylvain Bellanger
- Division of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4
| | - Marie-Claude Battista
- Division of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4
| | - Guy D. Fink
- Department of Clinical Biochemistry, Centre Hospitalier Universitaire de Sherbrooke, Québec, Canada J1H 5N4
| | - Jean-Patrice Baillargeon
- Division of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4
- Corresponding author. Address: Division of Endocrinology, Department of Medicine, Université de Sherbrooke, 3001, 12th Ave. North, Sherbrooke, Quebec, Canada J1H 5N4. Tel.: +1 819 564 5243; fax: +1 819 564 5292. (J.-P. Baillargeon)
| |
Collapse
|
|
45
|
Barber TM, Franks S. The link between polycystic ovary syndrome and both Type 1 and Type 2 diabetes mellitus: what do we know today? WOMEN'S HEALTH (LONDON, ENGLAND) 2012; 8:147-54. [PMID: 22375718 DOI: 10.2217/whe.11.94] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Polycystic ovary syndrome (PCOS) and Type 2 diabetes mellitus (T2D) are both obesity-related conditions that share epidemiological and pathophysiological factors. Insulin resistance is a key factor whereby obesity influences the expression of each condition. However, the mechanisms by which insulin resistance contributes towards the manifestation of PCOS and T2D differ in important ways: in PCOS, compensatory hyperinsulinemia results in pleiotropic effects including co-gonadotrophic stimulation of ovarian and adrenal steroidogenesis; in T2D, insulin resistance contributes towards β-cell exhaustion and ultimately to hyposecretion of insulin with resultant dysglycemia. The link between PCOS and Type 1 diabetes mellitus is believed to implicate supraphysiological concentrations of insulin within the systemic circulation. Further progression of the obesity epidemic will ensure even greater prominence of important obesity-related conditions such as PCOS and T2D. Research to gain a clearer understanding of the mechanisms linking each condition should be a priority.
Collapse
Affiliation(s)
- Thomas M Barber
- Institute of Reproductive & Developmental Biology, Imperial College (Hammersmith Campus), London, W12 0NN, UK.
| | | |
Collapse
|
|
46
|
Laflamme DP. Companion Animals Symposium: Obesity in dogs and cats: What is wrong with being fat? J Anim Sci 2011; 90:1653-62. [PMID: 21984724 DOI: 10.2527/jas.2011-4571] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Few diseases in modern pets are diet induced. One possible exception to this is obesity, which is ultimately caused by consuming more calories than needed by the dog or cat. Although fat is the most concentrated and efficiently stored source of calories, and protein least so, an excess of calories from any source will contribute to adiposity. Obesity is an excess of body fat sufficient to result in impairment of health or body function. In people, this is generally recognized as 20 to 25% above ideal BW. This degree of excess is important in dogs as well. A lifelong study in dogs showed that even moderately overweight dogs were at greater risk for earlier morbidity; these dogs required medication for chronic health problems sooner than their lean-fed siblings. The average difference in BW between groups was approximately 25%. Obese cats also face increased health risks, including an increased risk of arthritis, diabetes mellitus, hepatic lipidosis, and early mortality. The risk for development of diabetes increases about 2-fold in overweight cats and about 4-fold [corrected] in obese cats. Altered adipokine secretion appears to be an important mechanism for the link between excess BW and many diseases. Once considered to be physiologically inert, adipose tissue is an active producer of hormones, such as leptin and resistin, and cytokines, including many inflammatory cytokines such as tumor necrosis factor-α, IL-1β and IL-6, and C-reactive protein. The persistent, low-grade inflammation secondary to obesity is thought to play a causal role in chronic diseases such as osteoarthritis, cardiovascular disease, diabetes mellitus, and others. For example, tumor necrosis factor-α alters insulin sensitivity by blocking activation of insulin receptors. In addition, obesity is associated with increased oxidative stress, which also may contribute to obesity-related diseases. Management of obesity involves nutritional modification as well as behavioral modification. Increased protein intake combined with reduced calorie intake facilitates loss of body fat while minimizing loss of lean body mass. Limiting treats to 10% of calorie intake and increasing exercise both aid in successful BW management.
Collapse
Affiliation(s)
- D P Laflamme
- Nestle Purina PetCare Research, Checkerboard Square-2S, St. Louis, MO 63164, USA.
| |
Collapse
|
|
47
|
Ketel IJG, Serne EH, Ijzerman RG, Korsen TJM, Twisk JW, Hompes PGA, Smulders YM, Homburg R, Vorstermans L, Stehouwer CDA, Lambalk CB. Insulin-induced capillary recruitment is impaired in both lean and obese women with PCOS. Hum Reprod 2011; 26:3130-7. [DOI: 10.1093/humrep/der296] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
|
|
48
|
Geller DH, Pacaud D, Gordon CM, Misra M. State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS). INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY 2011; 2011:9. [PMID: 21899727 PMCID: PMC3180691 DOI: 10.1186/1687-9856-2011-9] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Accepted: 08/26/2011] [Indexed: 12/14/2022]
Abstract
PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.
Collapse
Affiliation(s)
- David H Geller
- Division of Pediatric Endocrinology, Cedars-Sinai Medical Center, David Geffen-UCLA School of Medicine 8700 Beverly Blvd,, Rm 4220, Los Angeles, CA 90048, USA.
| | | | | | | | | |
Collapse
|
|
49
|
Hudecova M, Holte J, Olovsson M, Larsson A, Berne C, Poromaa IS. Diabetes and impaired glucose tolerance in patients with polycystic ovary syndrome--a long term follow-up. Hum Reprod 2011; 26:1462-8. [DOI: 10.1093/humrep/der065] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
|
|
50
|
Traub ML. Assessing and treating insulin resistance in women with polycystic ovarian syndrome. World J Diabetes 2011; 2:33-40. [PMID: 21537458 PMCID: PMC3083905 DOI: 10.4239/wjd.v2.i3.33] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2010] [Revised: 12/10/2010] [Accepted: 12/17/2010] [Indexed: 02/05/2023] Open
Abstract
Polycystic ovarian syndrome (PCOS) is a highly prevalent hormonal and metabolic disorder among reproductive aged women worldwide. Women with PCOS have widely varying phenotypes and seek medical care for differing reasons. In addition to concern for menstrual cycle function, ovulation, hirsutism and acne, many PCOS women have abnormal glucose metabolism. While diabetes mellitus and impaired glucose tolerance are easily diagnosed, the diagnosis of and concern for insulin resistance as a precursor disorder is underappreciated. Insulin resistance may be the first important marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery disease.
Collapse
Affiliation(s)
- Michael L Traub
- Michael L Traub, Island Reproductive Services, Staten Island, NY 10314, United States
| |
Collapse
|