Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine problem in women of reproductive age with a reported prevalence of up to 15%. Women with PCOS are potentially at increased risk of cardiovascular (CV) diseases from well-established risk factors, including insulin resistance, obesity, and type 2 diabetes. However data showing excess CV events in this population are still lacking.MethodsWe investigated the incidence and prevalence of type 2 diabetes and cardiovascular events (myocardial infarction, angina, heart failure, stroke and CV death) in a retrospective cohort of women with PCOS (total follow-up >12 000 person-years) The cohort consisted of 2301 women attending a specialty clinic from 1988 to 2009 in Leicestershire, UK (mean age 29·6 years [SD 9·1]).FindingsIncidence of type 2 diabetes, myocardial infarction, angina, heart failure, stroke, and CV death was respectively 3·6, 0·8, 1·0, 0·3, 0·0, and 0·4 per 1000 person-years. At the end of follow-up, prevalence of myocardial infarction in the age groups 45–54, 55–64, and older than 65 years were, respectively, 1·9%, 6·0%, and 27·3%, and of angina were 2·6%, 6·0%, and 27·3%. Age-group-specific odds ratios for prevalence of myocardial infarction and angina compared with the local female population (n=434 859) ranged between 2·6 (95% CI 1·0–6·3) and 12·9 (3·4–48·6) with the highest ratio being for myocardial infarction in the over-65 age group. Age, history of hypertension, and smoking had significant correlations with CV outcomes in women with PCOS (adjusted odds ratio 1·08 [95% CI 1·03–1·12], p<0·01 vs 9·94 (3·77–26·19), p<0·01 vs 3·33 [1·23–8·59], p<0·01).InterpretationWe have shown a high incidence and age-group-specific prevalence of type 2 diabetes, myocardial infarction, and angina in women with PCOS, with more than a quarter of those aged over 65 years having had a myocardial infarction or angina. These findings should be considered in treatment strategies, long-term planning, and CV risk reduction programmes for women with PCOS.FundingBritish Endocrine Society, National Institute for Health Research, and University of Leicester.     

Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with higher prevalence of cardiovascular risk factors but the relative prevalence of cardiovascular disease in women with PCOS has not previously been reported. We have compared cardiovascular mortality and morbidity in middle-aged women previously diagnosed with PCOS and age-matched control women. DESIGN: A retrospective cohort study of women diagnosed with PCOS in the United Kingdom before 1979. PATIENTS: Seventy cohort members died before 31 March 1999. Morbidity data were collected from 319 women with PCOS and 1060 age-matched control women. Sixty-one women with PCOS and 63 control women attended a clinical examination. MEASUREMENTS: Data were collected from death certificates, general practitioners' records and questionnaires with measurement of cardiovascular risk factors in a subsample of questionnaire respondents. RESULTS: All-cause and cardiovascular mortality in the cohort were similar to women in the general population (standardized mortality ratios (95% CI): 93 (72-117) and 78 (45-124), respectively). Women with PCOS had higher levels of several cardiovascular risk factors: diabetes (P = 0.002) hypertension (P = 0.04), hypercholesterolaemia (P < 0.001), hypertriglyceridaemia (P = 0.02) and increased waist:hip ratio (P = 0.004). After adjustment for BMI, odds ratios (OR) were 2.2 (0.9-5. 2) for diabetes, 1.4 (0.9-2.0) for hypertension and 3.2 (1.7-6.0) for hypercholesterolaemia. A history of coronary heart disease (CHD) was not significantly more common in women with PCOS (crude OR (95%CI) 1.5 (0.7-2.9)) but the crude OR for cerebrovascular disease was 2.8 (1.1-7.1). CONCLUSION: At long-term follow-up, a history of nonfatal cerebrovascular disease and cardiovascular risk factors including diabetes are more prevalent among women with polycystic ovary syndrome. Morbidity and mortality from of coronary heart disease among women with polycystic ovary syndrome is not as high as previously predicted. This finding challenges our understanding of the aetiology of coronary heart disease in women.     

The risk factors of gestational diabetes mellitus in patients with polycystic ovary syndrome: What should we care

The influencing factors of gestational diabetes mellitus (GDM) in the polycystic ovary syndrome (PCOS) patients remain unclear, we aimed to investigate the risk factors of GDM in patients with PCOS, to provide reliable evidence for the prevention and treatment of GDM in PCOS patients.PCOS patients treated in our hospital from January 1, 2019 to October 31, 2020 were included. The personal and clinical treatment details of GDM and no GDM patients were analyzed. Logistic regressions were performed to analyze the factors influencing the occurrence of GDM.A total of 196 PCOS patients were included, the incidence of GDM in patients with PCOS was 23.98%. There were significant differences in the age, body mass index, insulin resistance index, fasting insulin, testosterone, androstenedione, and sex hormone-binding protein between GDM and no GDM patients with PCOS (all P < .05), and no significant differences in the family history of GDM, the history of adverse pregnancy, and multiple pregnancies were found (all P > .05). Age ≥30 years (odds ratio (OR) 2.418, 95% confidence interval (CI) 1.181–3.784), body mass index ≥24 kg/m² (OR 1.973, 95%CI 1.266–3.121), insulin resistance index ≥22.69 (OR 2.491, 95%CI 1.193–4.043), fasting insulin ≥22.71 mIU/L (OR 2.508, 95%CI 1.166–5.057), testosterone ≥2.85 nmol/L (OR 1.821, 95%CI 1.104–2.762), androstenedione ≥6.63 nmol/L (OR 1.954, 95%CI 1.262–2.844), sex hormone-binding protein <64.22 nmol/L (OR 1.497, 95%CI 1.028–2.016) were the independent risk factors of GDM in patients with PCOS (all P < .05). The incidence of preeclampsia, premature delivery, premature rupture of membranes, polyhydramnios, and postpartum hemorrhage in the GDM group was significantly higher than that of the no-GDM group (all P < .05). There was no significant difference in the incidence of oligohydramnios between the 2 groups (P = .057).The incidence of GDM in PCOS patients is high, and the measures targeted at the risk factors are needed to reduce the occurrence of GDM in patients with PCOS.     

视黄醇结合蛋白4与多囊卵巢综合征及妊娠糖尿病

视黄醇结合蛋白4主要由肝脏合成,是血液中一种运送视黄醇的结合蚩白,亦是脂肪组织分泌的一种脂肪细胞因子.小鼠实验发现,其在组织中的过度表达可使磷脂酰肌醇3激酶活性下降,胰岛素受体底物1酪氨酸磷酸化降低.可能与胰岛素抵抗的发生有关.肥胖、糖耐量减低、胰岛素抵抗、多囊卵巢综合征、妊娠糖尿病患者血清中视黄醇结合蛋白4含量与正常者相比升高,其可能与此类疾病的发病机制有关.     

Insulin resistance syndrome in women with prior history of gestational diabetes mellitus

The purpose of this study was to determine the prevalence of insulin resistance syndrome (IRS) and the risk factors for developing IRS among women with a history of gestational diabetes mellitus (GDM), compared with controls over 11 postdelivery years. Assessments of 106 women with a prior history of GDM and 101 controls were done on six occasions from 4-11 yr after delivery. Tests included glucose, insulin, lipids, blood pressure, and body measurements. The risk of IRS was analyzed by Cox regression. The results were that 27.2% of GDM and 8.2% of controls developed IRS by 11 yr after delivery. The hazard of developing IRS was 5.6 times (95% confidence interval = 2.6-12.3) among women with prepregnant obesity (body mass index >27.3 kg/m(2)), compared with women without prepregnant obesity and 4.4 times (95% confidence interval = 1.7-11.1) in women with a history of GDM, compared with controls. At 11 yr after delivery, the cumulative hazard for developing IRS in the next 2 yr was 26 times higher among GDM with prepregnant obesity, compared with controls without prepregnant obesity. We concluded that obesity and GDM in a prior pregnancy are significant risk factors for developing IRS over time. Early detection of markers of IRS is vital for possible prevention of type 2 diabetes and cardiovascular adverse events in women.     

Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: A systematic review

BackgroundMetformin is an effective oral anti-hyperglycemic agent that is widely used to manage diabetes mellitus type 2 in the general population and more recently, in pregnancy. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus.Objectivei) To provide background for the use of metformin during pregnancy through a narrative review and ii) to critically appraise the published evidence on the efficacy and safety of using metformin during pregnancy through a systematic review.ResultsMetformin appears to be effective and safe for the treatment of gestational diabetes mellitus (GDM), particularly for overweight or obese women. However, patients with multiple risk factors for insulin resistance may not meet their treatment goals with metformin alone and may require supplementary insulin. Evidence suggests that there are potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. Furthermore, patients are more accepting of metformin than insulin. The use of metformin throughout pregnancy in women with polycystic ovary syndrome reduces the rates of early pregnancy loss and preterm labor and protects against fetal growth restriction. There have been no demonstrable teratogenic effects, intra-uterine deaths or developmental delays with the use of metformin.ConclusionsThe publications reviewed in this paper support the efficacy and safety of metformin during pregnancy with respect to immediate pregnancy outcomes. Because there are no guidelines for the continuous use of metformin in pregnancy, the duration of treatment is based on clinical judgment and experience on a case-by-case basis.     

Clinical review: Hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus

CONTEXT: At present, women with type 1 diabetes (DM1) are being treated with supraphysiological doses of exogenous insulin with the aim of providing a strict metabolic control, thereby avoiding the long-term complications of this disease. We hypothesized that PCOS would be especially prevalent in DM1, as might happen in any condition in which the ovary and the adrenals are exposed to excessive insulin concentrations. As will be seen in the present review, androgen excess and PCOS are very frequent complaints in women with DM1, yet nowadays hyperandrogenism is seldom diagnosed in these patients. EVIDENCE ACQUISITION: We conducted a systematic review of all the published studies addressing hyperandrogenic symptoms in women with DM1, identified through the Entrez-PubMed search engine, followed by a comprehensive review of the pathophysiology and clinical and laboratory features of PCOS in women with DM1. EVIDENCE SYNTHESIS: The prevalence of PCOS in adult women with DM1 is 12-18, 40, and 31% using National Institute for Child Health and Human Development, Rotterdam, and Androgen Excess Society criteria, respectively. Mild hirsutism and biochemical hyperandrogenism are present in 30 and 20% of the patients, respectively. In addition, menstrual abnormalities are observed in 20% of adult women with DM1, and a prevalence of 50% of polycystic ovarian morphology is reported. CONCLUSIONS: Physicians treating women with DM1 should be aware of the risk of hyperandrogenism in them and should include evaluation of hirsutism, menstrual abnormalities, and biochemical hyperandrogenism in their routine examinations. Future studies are needed to determine the best preventive and therapeutic options for the hyperandrogenism of these patients.     

多囊卵巢综合征与妊娠糖尿病

多囊卵巢综合征(PCOS)是女性最常见的内分泌紊乱疾病,而妊娠糖尿病(GDM)是妊娠期最常见的代谢紊乱性疾病,众多研究表明,PCOS患者妊娠后发生糖尿病的几率明显增高.胰岛素抵抗、肥胖以及血浆内脂素(visfatin)、视黄醇结合蛋白4浓度升高等是联系两者的可能机制.通过改变生活方式、减重及应用二甲双胍等,可以明显改善...     

Cardiovascular risk in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that has received an immense amount of attention in the recent years due to the possible associated risk of cardiovascular disease. Women with PCOS demonstrate an adverse cardiovascular profile characteristic of the cardiometabolic syndrome and an established risk of progression to type 2 diabetes. Despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease, it is unclear if they develop accelerated atherosclerosis. This article summarized the recent development and findings of cardiovascular risk in women with PCOS, and finally the therapeutic options will be discussed.     

Diabetes mellitus risk after hysterectomy: A population-based retrospective cohort study

We explored whether hysterectomy with or without bilateral oophorectomy was associated with the increasing incidence of diabetes mellitus (DM) in an East Asian population. This was a retrospective population-based cohort study that analyzed DM risk in Taiwanese women, using a health insurance research database of 1998 to 2013 containing nearly 1 million people. We identified 7088 women aged 30 to 49 years who had undergone hysterectomy with or without oophorectomy. The comparison group included 27,845 women without a hysterectomy who were randomly selected from the population and matched to women in the hysterectomy group by age (exact year) and year of the surgery. DM comorbidities were identified. The incidence and hazard ratios for DM were calculated with Cox proportional hazard regression models. The median ages of patients in the hysterectomy and comparison groups were both approximately 44 years. After a median 7.1 years of follow-up, the incidence of DM was 40% higher in the hysterectomized women as compared with the comparisons (9.12 vs 6.78/1000 person-years, P < .001), with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI] = 1.23 –1.52). However, the DM risk was not increased in the women with hysterectomy plus oophorectomy (aHR=1.28, 95% CI = 0.93–1.76). Furthermore, among women aged 30 to 39 years, 40 to 49 years, the risk in hysterectomized women was higher than the comparisons (aHR = 1.75, 95% CI = 1.27–2.41; aHR = 1.33, 95% CI = 1.19–1.49, respectively). Our study provides essential and novel evidence for the association between hysterectomy and DM risk in women aged 30 to 49 years, which is relevant to these women and their physicians. Physicians should be aware of the increased DM risk associated with hysterectomy and take this into consideration when evaluating a patient for a hysterectomy. The current results might help gynecologists prevent DM and encourage diagnostic and preventive interventions in appropriate patients.     

1型糖尿病与多囊卵巢综合征

多囊卵巢综合征(PCOS)是育龄期女性最常见的内分泌疾病之一.研究显示,1型糖尿病患者中PCOS或高雄激素血症的发病率非常高,且这些患者的临床表现较轻.传统观点认为肥胖和胰岛索抵抗是PCOS的常见原因,但是不能用于解释此类PCOS的发病机制.现对1型糖尿病合并PCOS的发病机制、危害和防治手段进行阐述.     

The prevalence of polycystic ovaries in women with a history of gestational diabetes

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities reflect a common pathophysiological basis, we examined the prevalence of ultrasound-based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy. PATIENTS AND DESIGN: We studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro-Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11-36) and 29 (17-49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of beta-cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm. RESULTS: Women with previous GDM had higher fasting glucose (5.4 (4. 8-6.0) vs. 4.7 (4.4-5.0) mmol/l, P<0.0001) and features reminiscent of syndrome X: higher BMI (26.4 (22.8-31.4) vs. 23.8 (21. 0-27.5) kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79-0.88) vs. 0. 77 (0.73-0.81), P<0.0001), fasting insulin (165 (68-299) vs. 54 (24-156) pmol/l, P<0.0001), triglycerides (1.1 (0.8-1.6) vs. 0.8 (0.6-1.1) mmol/l, P<0.0001) and lower insulin sensitivity (%S) (27 (16-62) vs. 86 (34-139)%, P<0.0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), chi2 = 9.86, P = 0. 002 overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post-GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), chi2 = 7.03, P = 0.008). CONCLUSIONS: We found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These findings confirm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.     

Inflammatory markers in women with a recent history of gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a risk factor for both Type 2 diabetes (DM2) and insulin-resistance syndrome (IRS). C-reactive protein (CRP), fibrinogen and leukocyte count are increased in the IRS and predict DM2 and cardiovascular disease (CVD). The chemochine monocyte chemoattractant protein-1 (MCP-1/CCL2) is also elevated in DM2 and CVD. Recent evidence suggests a relation between chronic inflammation and GDM, but post-delivery information on inflammatory markers in these high-risk women is lacking. Serum levels of CRP, fibrinogen, MCP-1/ CCL2, and leukocyte blood count have been assessed in 26 women with and 26 women without a recent history of GDM, matched for age, body mass index (BMI), post-partum duration and parity. DM2 was excluded in all the participants by an oral glucose tolerance test (OGTT). Women with previous GDM showed significantly higher CRP (p=0.007) and fibrinogen (p=0.02) serum concentrations, whereas MCP-1/CCL2 serum levels and leukocyte blood count were comparable in the two groups. Overall, CRP levels significantly correlated with BMI (r=0.40, p=0.03), waist-to-hip ratio (WHR) (r=0.44, p=0.001), fasting insulin (r=0.27, p=0.04), insulin-resistance assessed by means of the homeostatic model (HOMA) (r=0.28, p=0.04), and fibrinogen concentration (r=0.49, p=0.0001). At linear regression analysis, only WHR and fibrinogen were independently associated with CRP levels. In conclusion, the increase of inflammatory markers may be one of the first detectable disorders in healthy women at high risk of DM2 and IRS, like those with a GDM history.