Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

Background  

There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet.     

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Objective

To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS.

Study design

A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates.

Results

Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed.

Conclusion

The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.     

Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study

Background

Individuals with Diabetes Mellitus (DM) are at increased risk for fracture due to the decrease in bone strength and quality. Serum procollagen type I intact N-terminal (P1NP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX) as markers of bone formation and resorption, respectively, have been reported to be decreased in T2DM. It remains unclear whether diabetes-associated alterations in the bone turnover of T2DM individuals are related to the longer duration of the disease or may occur earlier. Furthermore, previous studies on BTMs in T2DM individuals have mostly been done in postmenopausal women with T2DM, which might have masked the DM-induced alterations of bone turnover with concurrent estrogen deficiency. This study aims to assess the levels of serum P1NP and CTX as markers of bone turnover in premenopausal women with and without T2DM.

Methods

This cross-sectional study involves 41 premenopausal women with T2DM, and 40 premenopausal women without DM. Sampling was done consecutively. P1NP and CTX measurement was done using the electrochemi-luminescence immunoassay (ECLIA) method. Other data collected include levels of HbA1C, ALT, creatinine, eGFR and lipid profile.

Results

Median (interquartile range) P1NP in T2DM is 29.9 ng/ml (24.7–41.8 ng/ml), while in non-DM is 37.3 ng/ml, (30.8–47.3 ng/ml; p?=?0.007). Median (interquartile range) CTX in T2DM is 0.161 ng/ml (0.106–0.227 ng/ml), while in non-DM is 0.202 ng/ml (0.166–0.271 ng/ml; p?=?0.0035). Levels of P1NP and CTX in the T2DM group did not correlate with the duration of disease, age, BMI or the levels of HbA1C.

Conclusions

Premenopausal women with T2DM indeed have lower bone turnover when compared with non-DM controls. This significantly lower bone turnover process starts relatively early in the premenopausal age, independent of the duration of DM. Gaining understanding of the early pathophysiology of altered bone turnover may be key in developing preventive strategies for diabetoporosis.

     

Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome

Background  

We recently showed that women with four clinical phenotypes of polycystic ovary syndrome (PCOS) do not demonstrate anatomical evidence of elevated prenatal androgen exposure as judged by a lower ratio of the index (2D) to ring (4D) finger. However, those findings conflicted with a previous study where women with PCOS had lower right hand 2D:4D compared to healthy female controls. Both these studies used Vernier calipers to measure finger lengths - a method recently shown to be less reliable at obtaining finger length measurements than computer-assisted analysis.     

Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Background

The change of serum interleukin-6(IL-6) levels in women with polycystic ovary syndrome (PCOS), as well as the relations between IL-6 levels and body mass index (BMI), insulin resistance(IR) and androgen status of PCOS patients, are not fully understood.

Methods

A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Results

Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls) were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41–1.16, P<0.001), with significant heterogeneity across studies (I² = 91% and P<0.001). Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005). Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR) ratio and total testosterone ratio (T ratio), and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD) had tend to be stable since 2012(0.79 to 0.92).

Conclusions

A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS.     

Circulating vascular progenitor cells and central arterial stiffness in polycystic ovary syndrome

Objective

Subjects with Polycystic ovarian syndrome (PCOS) are at increased risk of Type 2 diabetes mellitus (T2DM). The mechanism of this enhanced risk is unclear. Circulating vascular progenitor cells (VPC) are immature bone marrow derived cells capable of differentiating into mature endothelial cells. VPC number/function and central arterial stiffness predict cardio-metabolic disease in at-risk populations.

Design

We studied VPC and arterial stiffness measures in non-obese PCOS subjects as compared to age and body mass index (BMI) matched healthy controls in a cross–sectional study.

Methods

Fourteen subjects with PCOS and 12 controls of similar age, BMI (all <30 kg/m²) and metabolic profile were studied. VPC number and in vitro function were studied by flow cytometry and tube formation assays respectively. Augmentation index (AIx), a measure of central arterial stiffness, and central (aortic) blood pressures (BP) were measured by applanation tonometry.

Results

Subjects with PCOS had a reduced number, mean±SEM, of circulating CD34⁺133⁺ VPCs (317.5±51.0 vs. 558.3±101.2, p = 0.03) and impaired in vitro tube formation (completed tube area 1.0±0.06 vs. 1.2±0.05×10⁶ µm² p = 0.02). PCOS subjects had significantly higher AIx (18.4±1.9% vs. 4.9±2.0%) and this difference remained significant even after adjustments for age, BMI and smoking (p = 0.003) in multivariate analyses. Central systolic and pulse pressure were higher in PCOS subjects but these differences were not statistically significant after adjustment for age. Brachial systolic and pulse pressures were similar. VPC number/function and arterial stiffness or BP measures were not correlated.

Conclusions

Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness. These changes in novel vascular risk markers may explain the enhanced risk of T2DM and CVD in PCOS.     

Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries

Background  

Maintenance of ovarian blood flow (OBF) is suggested to be important for regular ovulation in women with polycystic ovaries (PCO). The purpose of the present study was to investigate whether electro-acupuncture (EA) of different frequencies and intensities can improve the OBF of anaesthetized rat in the animal model of PCO.     

Association between the prevalence of hyperuricemia and reproductive hormones in polycystic ovary syndrome

Background

The prevalecne of hyperuricemia in polycystic ovary syndrome (PCOS) is still uncertain. We aimed to investigate the prevalence of hyperuricemia in PCOS and to determine the influence of reproductive hormones on uric acid concentration.

Methods

This retrospective cross-sectional study was performed at a large reproductive medicine center. Between March 2007 and October 2016, a total of 1,183 women with PCOS and 10,772 women without PCOS were included. PCOS was diagnosed according to the Rotterdam criteria. Anthropometric parameters, blood pressure, uric acid, reproductive hormones, glucose and lipids were measured in all subjects.

Results

The serum uric acid (SUA) level was higher in women with PCOS than in women without PCOS. The prevalence of hyperuricemia in women with PCOS (25.48%) was significantly higher than that in women without PCOS (8.74%). Analysis stratified for age and body mass index (BMI) showed that both the SUA level and the prevalence of hyperuricemia were higher in women with PCOS of different age and BMI groups than in women without PCOS. After adjusting for age, BMI and estimated glomerular filtration rate (eGFR), logistic regression analysis revealed that the luteinizing/follicle-stimulating hormone (LH/FSH) ratio (odds ratio (OR)?=?1.20, 95% CI?=?1.01–1.43) and testosterone level (OR?=?1.56, 95% CI?=?1.27–1.90) were positively associated with the prevalence of hyperuricemia in females with PCOS.

Conclusions

The serum uric acid (SUA) level and the prevalence of hyperuricemia markedly increased in women with PCOS. The testosterone level was positively associated with the SUA level and the prevalence of hyperuricemia in females with PCOS.

     

Time Trends in Ischemic Stroke among Type 2 Diabetic and Non-Diabetic Patients: Analysis of the Spanish National Hospital Discharge Data (2003-2012)

Background

Type 2 Diabetes (T2DM) is the most rapidly increasing risk factor for ischemic stroke. We aimed to compare trends in outcomes for ischemic stroke in people with or without diabetes in Spain between 2003 and 2012.

Methods

We selected all patients hospitalized for ischemic stroke using national hospital discharge data. We evaluated annual incident rates stratified by T2DM status. We analyzed trends in the use of diagnostic and therapeutic procedures, patient comorbidities, and in-hospital outcomes. We calculated in-hospital mortality (IHM), length of hospital stay (LOHS) and readmission rate in one month after discharge. Time trend on the incidence of hospitalization was estimated fitting Poisson regression models by sex and diabetes variables. In-hospital mortality was analyzed using logistic regression models separate for men and women. LOHS were compared with ANOVA or Kruskal-Wallis when necessary.

Results

We identified a total of 423,475 discharges of patients (221,418 men and 202,057 women) admitted with ischemic stroke as primary diagnosis. Patients with T2DM accounted for 30.9% of total. The estimated incidence rates of discharges increased significantly in all groups. The incidence of hospitalization due to stroke (with ICD9 codes for stroke as main diagnosis at discharge) was higher among those with than those without diabetes in all the years studied. T2DM was positively associated with ischemic stroke with an adjusted incidence rate ratio (IRR) of 2.27 (95% CI 2.24–2.29) for men and 2.15 (95%CI 2.13–2.17) for women. Over the 10 year period LOHS decreased significantly in men and women with and without diabetes. Readmission rate remained stable in diabetic and non diabetic men (around 5%) while slightly increased in women with and without diabetes. We observed a significant increase in the use of fibrinolysis from 2002–2013. IHM was positively associated with older age in all groups, with Charlson Comorbidity Index > 3 and atrial fibrillation as risk factors. The IHM did not change significantly over time among T2DM men and women ranging from 9.25% to 10.56% and from 13.21% to 14.86%, respectively; neither did among non-diabetic women. However, in men without T2DM IHM decreased significantly over time. Diabetes was associated to higher IHM only in women (OR 1.07; 95% CI, 1.05–1.11).

Conclusions

Our national data show that incidence rate of ischemic stroke hospitalization increased significantly during the period of study (2003–2012). People with T2DM have more than double the risk of ischemic stroke after adjusting for other risk factors. Women with T2DM had poorer outcomes- IHM and readmission rates- than diabetic men. Diabetes was an independent factor for IHM only in women.     

Menstrual Disorders and Androgen-Related Traits in Young Women with Type 1 Diabetes Mellitus: a Clinical Study

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM).Methods: Fifty-three women with T1DM (duration 8.0 ± 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 ± 4.3 years vs. 21.2 ± 2.7 years vs. 20.8 ± 3.1 years; P>.05) and body mass index (BMI) (22.2 ± 2.7 kg/m² vs. 21.9 ± 2.0 kg/m² vs. 21.4 ± 1.9 kg/m²; P>.05) were prospectively recruited.Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 ± 1.3 vs. 12.0 ± 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 ± 1.2 years). There were no differences in total testosterone (0.43 ± 0.14 ng/mL vs. 0.39 ± 0.14 ng/mL; P>.05), dehydroepiandrosterone sulfate (DHEA-S) (269 ± 112 μg/dL vs. 238 ± 106 μg/dL; P>.05) or Δ4-androstenedione (2.4 ± 1.3 ng/mL vs. 1.9 ± 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 ± 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 ± 0.54 vs. 7.88 ± 1.21 vs. 1.6 ± 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 ± 112 μg/dL vs. 297 ± 100 μg/dL; P>.05).Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations.     

Discordance between Prevalent Vertebral Fracture and Vertebral Strength Estimated by the Finite Element Method Based on Quantitative Computed Tomography in Patients with Type 2 Diabetes Mellitus

Background

Bone fragility is increased in patients with type 2 diabetes mellitus (T2DM), but a useful method to estimate bone fragility in T2DM patients is lacking because bone mineral density alone is not sufficient to assess the risk of fracture. This study investigated the association between prevalent vertebral fractures (VFs) and the vertebral strength index estimated by the quantitative computed tomography-based nonlinear finite element method (QCT-based nonlinear FEM) using multi-detector computed tomography (MDCT) for clinical practice use.

Research Design and Methods

A cross-sectional observational study was conducted on 54 postmenopausal women and 92 men over 50 years of age, all of whom had T2DM. The vertebral strength index was compared in patients with and without VFs confirmed by spinal radiographs. A standard FEM procedure was performed with the application of known parameters for the bone material properties obtained from nondiabetic subjects.

Results

A total of 20 women (37.0%) and 39 men (42.4%) with VFs were identified. The vertebral strength index was significantly higher in the men than in the women (P<0.01). Multiple regression analysis demonstrated that the vertebral strength index was significantly and positively correlated with the spinal bone mineral density (BMD) and inversely associated with age in both genders. There were no significant differences in the parameters, including the vertebral strength index, between patients with and without VFs. Logistic regression analysis adjusted for age, spine BMD, BMI, HbA1c, and duration of T2DM did not indicate a significant relationship between the vertebral strength index and the presence of VFs.

Conclusion

The vertebral strength index calculated by QCT-based nonlinear FEM using material property parameters obtained from nondiabetic subjects, whose risk of fracture is lower than that of T2DM patients, was not significantly associated with bone fragility in patients with T2DM. This discordance may indirectly suggest that patients with T2DM have deteriorated bone material compared with nondiabetic subjects, a potential cause of bone fragility in T2DM patients.     

Inhibin secretion in women with the polycystic ovary syndrome before and after treatment with progesterone

Objectives  

It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS). However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH.     

Polycystic ovary syndrome in Indian women: a mass spectrometry based serum metabolomics approach

Introduction

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous endocrinological disorder with uncertain pathogenesis and is very common in women of reproductive age. There are few reports of utilizing metabolomics approach to understand the complex pathophysiology of PCOS. However, excluding one previous NMR-based metabolomics study, none of the study was conducted in Indian population.

Objective

The study aims to compare the serum metabolomic profile of PCOS women with controls from the Eastern region of India.

Methods

PCOS women (n?=?35) and healthy control women (n?=?30) undergoing tubal ligation were recruited for this study. Serum metabolic profiles were generated using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–mass spectrometry (GC-MS). Multivariate statistical analysis was applied to spectral data obtained from both the LC-MS/MS and GC/MS.

Results

Nine metabolites were identified to be most significantly dysregulated in sera of PCOS women; however, few other identified metabolites were also altered but with lesser significance. Amongst these metabolites, riboflavin, sucrose, adenine and N-acetyl glycine, phosphoric acid and cortisol were down-regulated, whereas, thymine, cystathionine, and phenylalanine were up-regulated in PCOS when compared with controls. The observed changes in metabolite expression suggested alterations in aminoacyl-tRNA biosynthesis, metabolism of nitrogen, alanine-aspartate-glutamate, galactose, glycine-serine-threonine, and pyrimidine-purine among several metabolic pathways possibly implicated in these PCOS women.

Conclusion

The altered metabolites identified in PCOS women of Eastern Indian population, provide insight into current perceptive of the disease pathology, metabolic involvements, and may be considered as putative markers of PCOS.

     

Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross sectional study

Background  

Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical polyneuropathy (DSP) impact multiple modalities of sensation including light touch, temperature, position sense and vibration perception. No study to date has examined the mechanosensitivity of peripheral nerves during limb movement in this population. The objective was to determine the unique effects T2DM and DSP have on nerve mechanosensitivity in the lower extremity.     

Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors,and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

Background  

Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO.     

Association of TRB3 Q84R polymorphism with polycystic ovary syndrome in Chinese women

Background  

Tribbles 3 (TRB3) affects insulin signalling by inhibiting insulin-stimulated Akt phosphorylation and subsequent activation. A single nucleotide polymorphism located in the second extron of the human TRB3 gene is thought to be associated with insulin resistance. The latter is a core abnormality in PCOS independent of obesity. The present study was designed to clarify the relationships of TRB3 Q84R polymorphism with PCOS in a Chinese women group.     

Risk of coronary artery stenosis in Iranian type 2 diabetics: is there a role for matrix metalloproteinase-3 gene (-1612 5A/6A) polymorphism?

Aim  

To investigate the association of matrix metalloproteinase-3 (MMP-3) polymorphism with susceptibility to coronary artery stenosis (CAS) and the number of diseased vessels in patients with type 2 diabetes mellitus (T2DM).     

The Incidence and Prevalence of Diabetes Mellitus and Related Atherosclerotic Complications in Korea: A National Health Insurance Database Study

Aims/Introduction

The incidence and prevalence of type 2 diabetes mellitus (T2DM) and related macrovascular complications in Korea were estimated using the Health Insurance Review and Assessment (HIRA) database from 2007–2011, which covers the claim data of 97.0% of the Korean population.

Materials and Methods

T2DM, coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral artery disease (PAD) were defined according to ICD-10 codes. We used the Healthcare Common Procedure Coding System codes provided by HIRA to identify associated procedures or surgeries. When calculating incidence, we excluded cases with preexisting T2DM within two years before the index year. A Poisson distribution was assumed when calculating 95% confidence intervals for prevalence and incidence rates.

Results

The prevalence of T2DM in Korean adults aged 20–89 years was 6.1–6.9% and the annual incidence rates of T2DM ranged from 9.5–9.8/1,000 person-year (PY) during the study period. The incidence rates of T2DM in men and women aged 20–49 years showed decreasing patterns from 2009 to 2011 (P<0.001); by contrast, the incidence in subjects aged 70–79 years showed increased patterns from 2009 to 2011 (P<0.001). The incidence rates of CAD and CVD in patients newly diagnosed with T2DM were 18.84/1,000 PY and 11.32/1,000 PY, respectively, in the year of diagnosis. Among newly diagnosed individuals with T2DM who were undergoing treatment for PAD, 14.6% underwent angioplasty for CAD during the same period.

Conclusions

Our study measured the national incidences of T2DM, CAD, CVD, and PAD, which are of great concern for public health. We also confirmed the relatively higher risk of CAD and CVD newly detected T2DM patients compared to the general population in Korea.     

The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes

Background  

The aim of the study was to optimize protocols for finding and identifying serum proteins that are differentially expressed in persons with normal glucose tolerance (NGT) compared to individuals with type 2 diabetes mellitus (T2DM).