Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS ...would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up.
One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, 95% CI 1.85-1.92). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 95% CI 3.92-17.72 versus 4.86 per 1,000 person-years 95% CI 2.13-9.62, p > 0.05; overweight/obese: 28.64 95% CI 19.55-40.60 versus 14.1 per 1,000 person-years 95% CI 8.20-22.76, p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio OR = 1.71 95% CI 1.08-2.69, p < 0.05) and elevated triglyceride (OR = 6.63 95% CI 1.23-35.69, p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias.
High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.
IntroductionType 2 diabetes is preventable in subjects with impaired glucose tolerance based on 2-hour plasma glucose (2hPG) during 75 g oral glucose tolerance test (OGTT). We incorporated routine ...biochemistry to improve the performance of a non-invasive diabetes risk score to identify individuals with abnormal glucose tolerance (AGT) defined by 2hPG≥7.8 mmol/L during OGTT.Research design and methodsWe used baseline data of 1938 individuals from the community-based “Better Health for Better Hong Kong - Hong Kong Family Diabetes Study (BHBHK-HKFDS) Cohort” recruited in 1998–2003. We incorporated routine biochemistry in a validated non-invasive diabetes risk score, and evaluated its performance using area under receiver operating characteristics (AUROC) with internal and external validation.ResultsThe AUROC of the original non-invasive risk score to predict AGT was 0.698 (95% CI, 0.662 to 0.733). Following additional inclusion of fasting plasma glucose, serum potassium, creatinine, and urea, the AUROC increased to 0.778 (95% CI, 0.744 to 0.809, p<0.001). Net reclassification improved by 31.9% (p<0.001) overall, by 30.8% among people with AGT and 1.1% among people without AGT. The extended model showed good calibration (χ2=11.315, p=0.1845) and performance on external validation using an independent data set (AUROC=0.722, 95% CI, 0.680 to 0.764).ConclusionsThe extended risk score incorporating clinical and routine biochemistry can be integrated into an electronic health records system to select high-risk subjects for evaluation of AGT using OGTT for prevention of diabetes.
Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to ...compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case–control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3–43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1–5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.
For the treatment of β-thalassemia and sickle cell disease (SCD), pharmacological induction of fetal hemoglobin (HbF) production may be a promising approach. To date, numerous studies have been done ...on identifying the novel HbF-inducing agents and understanding the underlying mechanism for stimulating the HbF production. In this review, we have summarized the identified HbF-inducing agents by far. By examining the action mechanisms of the HbF-inducing agents, various studies have suggested that despite the ability of stimulating HbF production, the chemotherapeutic agents could not be practically applied for treating β-hemoglobinopathies, especially β-thalassemia, due to the their cytotoxicity and growth-inhibitory effect. Owing to this therapeutic obstacle, much effort has been put on identifying new HbF-inducing agents from the natural world with the combination of efficacy, safety, and ease of use. Therefore, this review aims to (i) reveal the novel screening platforms for identifying potential inducers with high efficiency and accuracy and to (ii) summarize the new identified natural remedies for stimulating HbF production. Hopefully, this review can provide a new insight into the current status and future perspectives in fetal hemoglobin reactivation for treating β-thalassaemia and SCD.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects reproductive aged women. PCOS is characterised by excess androgen levels. It is well established that PCOS is often ...associated with various metabolic perturbations and multiple cardiometabolic risk factors, such as visceral adiposity, insulin resistance, adverse lipid profile, and type 2 diabetes mellitus (T2DM). However, there is a scarcity of long-term data, especially from non-European populations, regarding the progression of cardiometabolic traits among women with PCOS.In order to address some of the current knowledge gaps, in this dissertation, I have examined the progression of glucose intolerance, cardiometabolic risk factors and subclinical atherosclerosis in Chinese women with PCOS. I postulated that women with PCOS would have higher risk of diabetes, subclinical atherosclerosis and cardiovascular diseases. I have compared the overall incidence rate and age-specific incidence rates of diabetes in PCOS women against that of non-PCOS healthy women and the population incidence rate in Hong Kong. Independent predictors of progression of T2DM and carotid intima media thickness (IMT), which was utilised as a surrogate marker for the prediction of subclinical atherosclerosis, were examined respectively in PCOS. Lastly, I hypothesised visceral adiposity strongly contributed to cardiometabolic traits, especially insulin resistance, in PCOS.One hundred and ninety-nine Chinese pre-menopausal PCOS women from the Prince of Wales Hospital (PWH) PCOS Registry were previously evaluated as part of a cross-sectional study between 2003 and 2007. They were recalled for detailed clinical and metabolic evaluation at the Diabetes Mellitus & Endocrine Research Centre at the PWH as part of this follow-up study (during 2016-2017). Sonographic assessment with the measurement of mesenteric, preperitoneal and subcutaneous fat thickness; as well as carotid IMT were also conducted in PCOS women. In the long-term prospective studies, results of all PCOS women were compared to non-PCOS healthy control cohort who underwent the same metabolic and imaging evaluation at baseline, with recent follow-up evaluation completed approximately 10 years after the baseline assessment; whereas, in the cross-sectional study, results of all PCOS women were compared to healthy women controls with normal glucose tolerance completed the same metabolic and imaging evaluation around year 2013.With the use of standard OGTT assessment for comprehensive glycaemia status screening, Chinese women with PCOS were found to be at approximately 6-fold risk of developing diabetes compared with healthy control subjects. For women aged 30- 39, incidence rate of T2DM for PCOS women was approximately 10-fold higher than the incidence rate of age-matched general female population. Diabetes onset was on average 10 years earlier among PCOS women than in controls. Data also highlighted the presence of hyperandrogenism appears to impact on diabetes risk. Increased carotid IMT was observed in PCOS women after approximately 10 years of followup, suggesting progression of subclinical atherosclerosis. Follow-up carotid IMT was significantly associated with baseline insulin resistance and mesenteric fat thickness of women with PCOS; and this relationship persisted even after adjustment for baseline carotid IMT, age, follow-up duration, and FAI. Data showed visceral adiposity is significantly higher in PCOS subjects compared with healthy controls. Visceral adiposity and hyperandrogenism are major determinant of insulin resistance in PCOS women. Moreover, PCOS women are more insulin resistant compared to healthy controls after adjusting for the degree of visceral adiposity.Taken together, these findings highlight the high risk of diabetes and cardiometabolic diseases among Chinese PCOS women. Results herein may help inform the planning of metabolic screening and monitoring of cardiovascular risk factors among Chinese women with PCOS, and to facilitate earlier detection and optimal management of this high-risk population to reduce the risk of progression to diabetes and its associated complications.
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