Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

OBJECTIVE—Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating insulin resistance in overweight women with PCOS

Inflammatory and other biomarkers: role in pathophysiology and prediction of gestational diabetes mellitus

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM.Sally K. Abell, Barbora De Courten, Jacqueline A. Boyle and Helena J. Teed

Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome

Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS). A non-classical body mass index (BMI) threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m²). Measurements included plasma 25-hydroxyvitamin D (25OHD), insulin resistance (glucose infusion rate (GIR; mg/m²/min), fasting glucose and insulin, and glycated haemoglobin), visceral fat, mid-thigh IMAT (computed tomography) and total body fat (dual-energy X-ray absorptiometry). Women with both PCOS and low 25OHD levels had the lowest GIR (all p < 0.05). Higher IMAT was associated with lower 25OHD (B = -3.95; 95% CI -6.86, -1.05) and GIR (B = -21.3; 95% CI -37.16, -5.44) in women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p < 0.044), but no associations were observed when stratified by PCOS status. Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women

Engaging rural women in healthy lifestyle programs: insights from a randomized controlled trial

Published online: 16 September 2015Background: The obesity epidemic is well established, particularly in rural settings. Programs promoting healthy lifestyles for rural women are urgently needed; however, participant engagement is challenging. In the context of a large randomized controlled trial targeting the prevention of weight gain in rural women, we explored successful recruitment strategies and aimed to understand participants’ barriers, enablers and reasons for program participation. Methods: We recruited women (aged 18–55 years) from the general rural Australian population. A mixed-methods approach was applied to explore factors that influenced program participation, including quantitative questionnaires for all participants (n = 649) and qualitative semi-structured interviews conducted for a subgroup of participants (n = 45). Data were collected at three time points: baseline, 6 and 12 months post program commencement. Results: We recruited 649 rural women through a community communication and partnering strategy, a program marketing campaign and mobilization of social networks. Program participants were diverse across education and income levels and were representative of the wider Australian regional population. Factors that influenced program engagement were divided into personal (perceived program benefits and program accessibility) and social (peer persuasion and support). Identified enablers included convenience of the program location, perceived program utility, such as weight management and optimization of lifestyle choices, as well as attending the program with peer support. Barriers to engagement, which are likely exacerbated in rural communities included lack of anonymity, self-consciousness and segregated social networks in rural settings. Participants reported that eliciting local support and maximizing publicity is fundamental to improving future program engagement. Conclusion: Multiple program promotion strategies including communication, marketing and partnering, as well as mobilization of social networks and peer persuasion, enabled engagement of rural women into a healthy lifestyle program. These recruitment strategies are consistent with successful strategies utilized previously to recruit urban-dwelling women into lifestyle programs. Future engagement efforts in rural settings could be enhanced by hosting multiple sessions within existing socio-cultural networks and assuring participants that they will not need to share their personal health information with others in their community. Trial registration: Australia & New Zealand Clinical Trial Registry. Trial number ACTRN12612000115831. Date of registration 24 January 2012.Samantha L. Kozica, Cheryce L. Harrison, Helena J. Teede, Sze Ng, Lisa J. Moran and Catherine B. Lombar

Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome

Abstract not availableL.J. Moran, H.J. Teede, M. Noakes, P.M. Clifton, R.J. Norman and G.A. Witterthttp://www.jendocrinolinvest.it/jei/en/abstract.cfm?articolo_id=902

Metabolic inflexibility in women with polycystic ovary syndrome : a systematic review

Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic inflexibility, is a marker of blunted metabolism. We conducted a systematic review on metabolic inflexibility in women with PCOS. We searched MEDLINE, EMBASE and Cochrane central (inception-October 2018) for studies evaluating metabolic inflexibility and reporting on changes in Respiratory Quotient (ΔRQ). We extracted data and assessed quality using The Newcastle–Ottawa Scale. We included five prospective cohort studies (461 women). Three compared PCOS women to unaffected subjects, one to women with obesity or T2DM, and one to adolescent girls; all had medium quality. Three studies showed higher metabolic inflexibility in women with PCOS (ΔRQ range 0.05–0.098) compared to unaffected subjects. Women with PCOS had similar metabolic inflexibility compared to those with T2DM (ΔRQ 0.05 ± 0.03 vs 0.06 ± 0.04, p = .98) and obesity (p = .06). Inflexibility was higher in hyperandrogenemic women with PCOS (ΔRQ 0.091 ± 0.060 vs 0.120 ± 0.010, p = .014). ΔRQ was lower in PCOS women with insulin resistance vs those with normal insulin sensitivity (0.04 ± 0.02 vs. 0.07 ± 0.04, p = .007). In conclusion, women with polycystic ovary syndrome appear to have higher metabolic inflexibility associated with hyperandrogenemia and insulin resistance

Feasibility and acceptability of a proposed trial of acupuncture as an adjunct to lifestyle interventions for weight loss in Polycystic Ovary Syndrome: a qualitative study

Background: Polycystic Ovary Syndrome (PCOS) is a common female reproductive disorder with multiple manifestations. Weight management is a key therapeutic goal. Acupuncture is a potential adjunctive weight loss treatment in non-PCOS populations. We aimed to engage patients in co-design and assess the feasibility and acceptability of methods for a randomised controlled trial (RCT) on acupuncture and telephone-based health coaching for weight management in overweight or obese women with PCOS using qualitative methods. Methods: We recruited women who had PCOS and were aged 18-45 years and with a body mass index of 25 kg/m² and over, using social media. Two face-to-face focus group meetings and three semi-structured telephone interviews were conducted (n = 10). We analysed data using thematic analysis and aimed to compare and contrast motivations for joining the trial between women who were actively trying to conceive (n = 7) and not trying to conceive (n = 3). Attitudes to, knowledge and experiences of acupuncture; perceptions and attitudes towards the interventions in the RCT (real acupuncture, sham acupuncture and telephone-based health coaching); the outcomes of importance; and barriers and facilitators to successful trial recruitment and retention were collected. Results: Women were both acupuncture-naive and acupuncture-experienced. Overall, attitudes towards acupuncture were positive, and the trial design was acceptable with appointment flexibility requested. Ideal enrolment time, if women were trying to conceive, was six months prior to conception. Women supported three-month intervention and the use of sham acupuncture as a control. Financial incentives were not believed to be necessary, and women spoke of altruistic intentions in enrolling for such a trial. Women who were trying to conceive voiced a need for support from their family, health coaches, and peers. The telephone-based health coaching offered welcome support and accountability, noted as possible facilitators of weight loss. Conclusions: Our findings show that acupuncture is a likely acceptable adjunct to lifestyle interventions for weight loss in PCOS, and that a sham-controlled trial is feasible and acceptable to PCOS women. Further research is required in order to evaluate the efficacy of acupuncture together with lifestyle for weight management in PCOS.Carolyn Ee, Caroline Smith, Michael Costello, Freya MacMillan, Lisa Moran, Brandi Baylock and Helena Teed

Comprehensive assessment of the hemostatic system in polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) affects 12 to 19% of women and has reproductive and metabolicfeatures (endothelial dysfunction, increased diabetes, and cardiovascular risk factors). It also appears to have altered coagulation and fibrinolysis with a prothrombotic state with epidemiological evidence of increased venous thromboembolism. We aimed to comprehensively assess hemostasis in women with PCOS versus control women. In an established case-control cohort of lean, overweight, and obese women with (n = 1 07) and without PCOS (n = 67), with existing measures of plasminogen activator inhibitor 1 (PAI-1 ), asymmetric dimethylarginine (ADMA), hormonal, and metabolic markers, we also assessed prothrombin fragments 1 and 2 (PF1 &amp; 2), plasminogen, tissue plasminogen activator (tPA), and thrombin generation (TG). Higher levels of ADMA (0.70 vs. 0.39 mumol/L, p &lt; 0.01 ), PAI-1 (4.80 vs. 3.66 U/ml, p &lt; 0.01 ), and plasminogen (118.39 vs. 108.46%, p &lt; 0.01) were seen in PCOS versus controls, and persisted after adjustment for age and body mass index (BMI). PF1 &amp; 2 was marginally lower (180.0 vs. 236.0 pmolfl, p 0.05), whereas tPA and TG were not different between groups, after adjustment for age and BMI. Significant relationships were observed between hormonal and metabolic factors with ADMA and PAI-1. We demonstrate impaired fibrinolysis in PCOS. In the context of abnormal endothelial function and known hormonal and metabolic abnormalities, this finding may underpin an increased risk of cardiovascular disease and venous thrombosis in PCOS

Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans

Background Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. Methods and Results Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity. Conclusion Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease