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Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.

Objective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor beta (TGFbeta)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Method(s): A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Result(s): We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFbeta signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. Conclusion(s): We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFbeta ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.Copyright © 2020 The authors Published by Bioscientifica Ltd.

Objective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor beta (TGFbeta)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Method(s): A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Result(s): We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFbeta signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. Conclusion(s): We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFbeta ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.Copyright © 2020 The authors Published by Bioscientifica Ltd.

A reduction in aerobic capacity and the shortening of telomeres are hallmarks of the ageing process. We examined whether a lower aerobic capacity is associated with shorter TL in skeletal muscle and/or leukocytes, across a wide age range of individuals. We also tested whether TL in human skeletal muscle (MTL) correlates with TL in leukocytes (LTL). Eighty-two recreationally active, healthy men from the Gene SMART cohort (31.4±8.2 years; body mass index (BMI)=25.3±3.3kg/m2), and 11 community dwelling older men (74.2±7.5years-old; BMI=28.7±2.8kg/m2) participated in the study. Leukocytes and skeletal muscle samples were collected at rest. Relative telomere length (T/S ratio) was measured by RT-PCR. Associations between TL, aerobic capacity (VO2 peak and peak power) and age were assessed with robust linear models. Older age was associated with shorter LTL (45% variance explained, P<0.001), but not MTL (P= 0.7). Aerobic capacity was not associated with MTL (P=0.5), nor LTL (P=0.3). MTL and LTL were correlated across the lifespan (rs=0.26, P=0.03). In healthy individuals, age explain most of the variability of LTL and this appears to be independent of individual aerobic capacity. Individuals with longer LTL also have a longer MTL, suggesting that there might be a shared molecular mechanism regulating telomere length.

Purpose: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Method(s): Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. Result(s): The normal ranges for young men (<=30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ~31%, while body mass index explained ~4%, of the variance in the ratios. Conclusion(s): We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.Copyright © 2019 Elsevier Inc.

Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms is well documented, providing evidence for a genetic contribution to the condition. This overview aims firstly to systematically summarise the current literature surrounding genetics and PCOS, and secondly, to assess the methodological quality of current systematic reviews and identify limitations. Four databases were searched to identify candidate gene systematic reviews, and quality was assessed with the AMSTAR tool. Genome-wide association studies (GWAS) were identified by a semi structured literature search. Of the candidate gene systematic reviews, 17 were of high to moderate quality and four were of low quality. A total of 19 gene loci have been associated with risk of PCOS in GWAS, and 11 of these have been replicated across two different ancestries. Gene loci were located in the neuroendocrine, metabolic, and reproductive pathways. Overall, the

Background: Polycystic ovary syndrome (PCOS) is a reproductive-metabolic condition. Insulin resistance is a hallmark of PCOS and is related to increased hyperandrogenism that drives inherent metabolic, reproductive and psychological features of the syndrome. Insulin resistance in women with PCOS is managed by weight loss, lifestyle interventions (i.e. exercise, diet) and insulin-sensitising medications. This manuscript describes the protocol of our study evaluating the effectiveness of high intensity intermittent training (HIIT) or moderate intensity exercise on cardiometabolic, reproductive and mental health in overweight women with PCOS. Methods/design: We will employ a three arm, parallel-group, randomised controlled trial recruiting 60 women diagnosed with PCOS, aged between 18 and 45 years and with a body mass index (BMI) greater than 25 kg/m 2 . Following screening and baseline testing, women will be randomised by simple randomisation procedure using computer generated sequence allocation to undergo one of two 12-week supervised interventions: either HIIT or moderate intensity exercise (standard supervised exercise), or to standard care [Con] (unsupervised lifestyle advice) at a 1:1:1 allocation ratio. The primary outcome for this trial is to measure the improvements in metabolic health; specifically changes in insulin sensitivity in response to different exercise intensities. Baseline and post-intervention testing include anthropometric measurements, cardiorespiratory fitness testing, reproductive hormone profiles (anti-müllerian hormone and steroid profiles), metabolic health, health-related quality of life and mental health questionnaires and objective and subjective lifestyle monitoring. Reporting of the study will follow the CONSORT statement. Discussion: This trial aims to demonstrate the comparative efficacy and maintenance of different exercise intensities to advance the understanding of PCOS management and provide insight into the optimal exercise int

Purpose: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Method(s): Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. Result(s): The normal ranges for young men (<=30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ~31%, while body mass index explained ~4%, of the variance in the ratios. Conclusion(s): We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.Copyright © 2019 Elsevier Inc.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a reproductive-metabolic condition. Insulin resistance is a hallmark of PCOS and is related to increased hyperandrogenism that drives inherent metabolic, reproductive and psychological features of the syndrome. Insulin resistance in women with PCOS is managed by weight loss, lifestyle interventions (i.e. exercise, diet) and insulin-sensitising medications. This manuscript describes the protocol of our study evaluating the effectiveness of high intensity intermittent training (HIIT) or moderate intensity exercise on cardiometabolic, reproductive and mental health in overweight women with PCOS. METHODS/DESIGN: We will employ a three arm, parallel-group, randomised controlled trial recruiting 60 women diagnosed with PCOS, aged between 18 and 45 years and with a body mass index (BMI) greater than 25 kg/m2. Following screening and baseline testing, women will be randomised by simple randomisation procedure using computer generated sequence allocation to undergo one of two 12-week supervised interventions: either HIIT or moderate intensity exercise (standard supervised exercise), or to standard care [Con] (unsupervised lifestyle advice) at a 1:1:1 allocation ratio. The primary outcome for this trial is to measure the improvements in metabolic health; specifically changes in insulin sensitivity in response to different exercise intensities. Baseline and post-intervention testing include anthropometric measurements, cardiorespiratory fitness testing, reproductive hormone profiles (anti-müllerian hormone and steroid profiles), metabolic health, health-related quality of life and mental health questionnaires and objective and subjective lifestyle monitoring. Reporting of the study will follow the CONSORT statement. DISCUSSION: This trial aims to demonstrate the comparative efficacy and maintenance of different exercise intensities to advance the understanding of PCOS management and provide insight into the optimal exercise inten

Polycystic ovary syndrome (PCOS) is associated with worsened metabolic risk factors attributed to the interrelated effects of insulin resistance (IR), hyperandrogenism, sympathetic nervous system (SNS) dysfunction and chronic low grade inflammation. HMW-adiponectin is inversely associated with IR and metabolic disorders. Lower HMW-adiponectin levels are reported in PCOS however the regulatory mechanisms remain unclear. We explored the regulatory mechanisms for HMW-adiponectin in a cross sectional study of 46 PCOS (Rotterdam criteria) and 23 control women recruited from the community. Fasting lipids, total testosterone, sex hormone binding globulin (SHBG), highly sensitive C-reactive protein, HMW-adiponectin, muscle sympathetic nerve activity (as burst frequency (bursts/min) on microneurography) were measured and an oral glucose tolerance test was performed with IR determined on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). HMW-adiponectin was lower in PCOS after adjustment for age and BMI (2.2(2.3) mug/mL vs 3(2.5) mug/mL, adjusted P = .047). HMW-adiponectin correlated with SHBG, HOMA-IR, fasting insulin, triglycerides, high density lipoprotein cholesterol (HDL-C) and free androgen index (FAI) in all participants (r = .468 P < .001, r = -.429 P < .001, r = -.425 P < .001, r = -.324 P = .008, r = .347 P = .005 and r = -.456 P < .001 respectively) and in PCOS (r = .522 P < .001, r = -.476 P = .001, r = -.509 P < .0001, r = -.384 P = .01, r = .461 P = .002 and r = -.503 P < .001 respectively). Metabolic syndrome was significantly associated with lower HMW-adiponectin levels in all participants (odds ratio 0.033, 95% CI 0.002, 0.498 P = .014) and in PCOS (odds ratio 0.024, 95% CI 0.001, 0.652 P = .027). Burst frequency was significantly lower in PCOS (25.7(10.5) vs 21.6(13.7) bursts per minute, P = .037) and correlated significantly with HMW-adiponectin (r = -.326 P = .049). On multiple regression analysis burst frequency (B = -0.684 P = .011) and SHBG

Polycystic ovary syndrome (PCOS) is associated with worsened metabolic risk factors attributed to the interrelated effects of insulin resistance (IR), hyperandrogenism, sympathetic nervous system (SNS) dysfunction and chronic low grade inflammation. HMW-adiponectin is inversely associated with IR and metabolic disorders. Lower HMW-adiponectin levels are reported in PCOS however the regulatory mechanisms remain unclear. We explored the regulatory mechanisms for HMW-adiponectin in a cross sectional study of 46 PCOS (Rotterdam criteria) and 23 control women recruited from the community. Fasting lipids, total testosterone, sex hormone binding globulin (SHBG), highly sensitive C-reactive protein, HMW-adiponectin, muscle sympathetic nerve activity (as burst frequency (bursts/min) on microneurography) were measured and an oral glucose tolerance test was performed with IR determined on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). HMW-adiponectin was lower in PCOS after adjustment for age and BMI (2.2(2.3) mug/mL vs 3(2.5) mug/mL, adjusted P = .047). HMW-adiponectin correlated with SHBG, HOMA-IR, fasting insulin, triglycerides, high density lipoprotein cholesterol (HDL-C) and free androgen index (FAI) in all participants (r = .468 P < .001, r = -.429 P < .001, r = -.425 P < .001, r = -.324 P = .008, r = .347 P = .005 and r = -.456 P < .001 respectively) and in PCOS (r = .522 P < .001, r = -.476 P = .001, r = -.509 P < .0001, r = -.384 P = .01, r = .461 P = .002 and r = -.503 P < .001 respectively). Metabolic syndrome was significantly associated with lower HMW-adiponectin levels in all participants (odds ratio 0.033, 95% CI 0.002, 0.498 P = .014) and in PCOS (odds ratio 0.024, 95% CI 0.001, 0.652 P = .027). Burst frequency was significantly lower in PCOS (25.7(10.5) vs 21.6(13.7) bursts per minute, P = .037) and correlated significantly with HMW-adiponectin (r = -.326 P = .049). On multiple regression analysis burst frequency (B = -0.684 P = .011) and SHBG

Background: To investigate the association of adipocytokines and other inflammatory markers with development of GDM. Method(s): Serum adipocytokines and inflammatory markers were studied at 12 to 15 weeks gestation using biobanked control samples from a randomised trial. Study participants were identified as high risk for GDM using a validated clinical risk prediction tool. Markers were tested using commercial ELISA kits for high molecular weight (HMW) adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, visfatin, omentin-1, sex-hormone binding globulin, monocyte chemoattractant protein, and asymmetrical dimethylarginine. The association between each biomarker and development of GDM at 24 to 28 weeks was evaluated using multivariable logistic regression analysis adjusted for maternal factors. Result(s): There were no differences in age, parity, country of birth, smoking, body mass index, or family history of diabetes in women with normal glucose tolerance (n = 78) and women who developed GDM (n = 25). Women with GDM were more likely to have a past history of GDM (P = 0.004). HMW adiponectin (odds ratio OR 0.37 [95% confidence interval 0.19-0.74]), omentin-1 (0.97 [0.94-0.99]), and IL-6 (1.87[1.03-3.37]) were associated with development of GDM, after adjustment for maternal age, body mass index, and past history of GDM. The other markers were not associated with GDM development. Conclusion(s): Decreased high molecular weight adiponectin and omentin-1 and increased IL-6 may enhance sensitivity of early risk prediction tools for women at high risk of GDM. This may allow early identification and opportunities for prevention of GDM and adverse outcomes. Further research is required in large validation studies to confirm these results.Copyright © 2017 John Wiley & Sons, Ltd.

Background: Polycystic ovary syndrome (PCOS) is associated with features linked to metabolic syndrome including visceral obesity, dyslipidemia and impaired glucose homeostasis. Recent studies suggest that these metabolic effects are linked to a low-grade chronic inflammation with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle. Adipose tissue produces immunomodulatory adipocytokines which contribute to regulation of insulin sensitivity, reproduction and cardiovascular function. Limited evidence is available on the role of adipocytokines in PCOS. Aim(s): This study investigated the relationships between PCOS status, adipocytokines and aetiological features of PCOS. Method(s): In an observational study of community recruited PCOS and controls, we measured serum HMW-adiponectin, omentin, resistin, interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), plasminogen activator inhibotir-1(PAI-1), high sensitivity CRP (hs-CRP), androgens, SHBG, fasting glucose and insulin levels. Result(s): Forty-nine women with PCOS (age 29.8 +/- 5.9 years, BMI: 29.0 +/- 5.4 kg/m2) and 25 healthy controls (age 37.6 +/- 7.8 years, BMI: 28.9 +/- 4.0 kg/m2) were recruited. Homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.006), free androgen index (FAI) (P = 0.01) and Ferriman-Galway score (P < 0.001) were higher in PCOS. For adipocytokines, women with PCOS had lower omentin [median (IQR): 68.76(67.17) vs 112.45(67.42)] (P = 0.01) and higher hs-CRP [median (IQR): 2.15 (3.4) vs 1.00 (2.1)] (P = 0.03) after adjustment for age and BMI. On assessment of non-obese and obese subgroups, HMWadiponectin and omentin were lower in obese women with PCOS compared to obese controls (P = 0.022 and P = 0.034 respectively) and nonobese PCOS (P = 0.028 and P = 0.016 respectively). Among women with PCOS, HMW-adiponectin was negatively correlated with HOMA-IR and FAI, however only the correlation between HMW-adiponectin and FAI

Background: To investigate the association of adipocytokines and other inflammatory markers with development of GDM. Method(s): Serum adipocytokines and inflammatory markers were studied at 12 to 15 weeks gestation using biobanked control samples from a randomised trial. Study participants were identified as high risk for GDM using a validated clinical risk prediction tool. Markers were tested using commercial ELISA kits for high molecular weight (HMW) adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, visfatin, omentin-1, sex-hormone binding globulin, monocyte chemoattractant protein, and asymmetrical dimethylarginine. The association between each biomarker and development of GDM at 24 to 28 weeks was evaluated using multivariable logistic regression analysis adjusted for maternal factors. Result(s): There were no differences in age, parity, country of birth, smoking, body mass index, or family history of diabetes in women with normal glucose tolerance (n = 78) and women who developed GDM (n = 25). Women with GDM were more likely to have a past history of GDM (P = 0.004). HMW adiponectin (odds ratio OR 0.37 [95% confidence interval 0.19-0.74]), omentin-1 (0.97 [0.94-0.99]), and IL-6 (1.87[1.03-3.37]) were associated with development of GDM, after adjustment for maternal age, body mass index, and past history of GDM. The other markers were not associated with GDM development. Conclusion(s): Decreased high molecular weight adiponectin and omentin-1 and increased IL-6 may enhance sensitivity of early risk prediction tools for women at high risk of GDM. This may allow early identification and opportunities for prevention of GDM and adverse outcomes. Further research is required in large validation studies to confirm these results.Copyright © 2017 John Wiley & Sons, Ltd.

Background: Polycystic ovary syndrome (PCOS) is associated with features linked to metabolic syndrome including visceral obesity, dyslipidemia and impaired glucose homeostasis. Recent studies suggest that these metabolic effects are linked to a low-grade chronic inflammation with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle. Adipose tissue produces immunomodulatory adipocytokines which contribute to regulation of insulin sensitivity, reproduction and cardiovascular function. Limited evidence is available on the role of adipocytokines in PCOS. Aim(s): This study investigated the relationships between PCOS status, adipocytokines and aetiological features of PCOS. Method(s): In an observational study of community recruited PCOS and controls, we measured serum HMW-adiponectin, omentin, resistin, interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), plasminogen activator inhibotir-1(PAI-1), high sensitivity CRP (hs-CRP), androgens, SHBG, fasting glucose and insulin levels. Result(s): Forty-nine women with PCOS (age 29.8 +/- 5.9 years, BMI: 29.0 +/- 5.4 kg/m2) and 25 healthy controls (age 37.6 +/- 7.8 years, BMI: 28.9 +/- 4.0 kg/m2) were recruited. Homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.006), free androgen index (FAI) (P = 0.01) and Ferriman-Galway score (P < 0.001) were higher in PCOS. For adipocytokines, women with PCOS had lower omentin [median (IQR): 68.76(67.17) vs 112.45(67.42)] (P = 0.01) and higher hs-CRP [median (IQR): 2.15 (3.4) vs 1.00 (2.1)] (P = 0.03) after adjustment for age and BMI. On assessment of non-obese and obese subgroups, HMWadiponectin and omentin were lower in obese women with PCOS compared to obese controls (P = 0.022 and P = 0.034 respectively) and nonobese PCOS (P = 0.028 and P = 0.016 respectively). Among women with PCOS, HMW-adiponectin was negatively correlated with HOMA-IR and FAI, however only the correlation between HMW-adiponectin and FAI

BACKGROUND: To investigate the association of adipocytokines and other inflammatory markers with development of GDM. METHODS: Serum adipocytokines and inflammatory markers were studied at 12 to 15 weeks gestation using biobanked control samples from a randomised trial. Study participants were identified as high risk for GDM using a validated clinical risk prediction tool. Markers were tested using commercial ELISA kits for high molecular weight (HMW) adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, visfatin, omentin-1, sex-hormone binding globulin, monocyte chemoattractant protein, and asymmetrical dimethylarginine. The association between each biomarker and development of GDM at 24 to 28 weeks was evaluated using multivariable logistic regression analysis adjusted for maternal factors. RESULTS: There were no differences in age, parity, country of birth, smoking, body mass index, or family history of diabetes in women with normal glucose tolerance (n = 78) and women who developed GDM (n = 25). Women with GDM were more likely to have a past history of GDM (P = 0.004). HMW adiponectin (odds ratio OR 0.37 [95% confidence interval 0.19-0.74]), omentin-1 (0.97 [0.94-0.99]), and IL-6 (1.87[1.03-3.37]) were associated with development of GDM, after adjustment for maternal age, body mass index, and past history of GDM. The other markers were not associated with GDM development. CONCLUSIONS: Decreased high molecular weight adiponectin and omentin-1 and increased IL-6 may enhance sensitivity of early risk prediction tools for women at high risk of GDM. This may allow early identification and opportunities for prevention of GDM and adverse outcomes. Further research is required in large validation studies to confirm these results.

SCOPE: Maternal vitamin D deficiency has been implicated in adverse pregnancy outcomes. However, the association between vitamin D and inflammation, particularly adipokines, remains unexplored in pregnancy. METHODS AND RESULTS: In 102 overweight or obese pregnant women at high-risk of gestational diabetes mellitus (GDM), we investigated relationships between maternal 25-hydroxyvitamin D (25(OH)D) concentrations at 12-15 wk gestation (baseline) and serum lipids, inflammatory markers, novel adipokines (omentin-1, visfatin, high molecular weight (HMW) adiponectin), and subsequent pregnancy outcomes (GDM, preeclampsia, preterm birth [PTB]). After adjustment for maternal factors (age, BMI, parity, ethnicity, and smoking status), baseline 25(OH)D concentrations were inversely associated with total cholesterol and triglycerides, and positively associated with HMW-adiponectin. Higher baseline 25(OH)D concentrations were associated with decreased fasting and 1-h post-OGTT glucose and reduced risk of GDM at 26-28 wk, as well as with longer gestation and reduced risk of PTB upon additional adjustment for caesarean section. Adding HMW-adiponectin to the multivariable models attenuated most associations, and HMW-adiponectin was a significant predictor in the models. CONCLUSION: Our findings suggest that lower maternal 25(OH)D concentrations in overweight/obese pregnant women at high-risk of GDM are associated with increased cardiometabolic risks during pregnancy and adverse pregnancy outcomes, and that these associations may be mediated by HMW-adiponectin.