Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) ...and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.
The FreeStyle Libre (FSL) flash glucose-monitoring device was made available on the U.K. National Health Service (NHS) drug tariff in 2017. This study aims to explore the U.K. real-world experience ...of FSL and the impact on glycemic control, hypoglycemia, diabetes-related distress, and hospital admissions.
Clinicians from 102 NHS hospitals in the U.K. submitted FSL user data, collected during routine clinical care, to a secure web-based tool held within the NHS N3 network. The
and Mann-Whitney
tests were used to compare the baseline and follow-up HbA
and other baseline demographic characteristics. Linear regression analysis was used to identify predictors of change in HbA
following the use of FSL. Within-person variations of HbA
were calculated using Formula: see text.
Data were available for 10,370 FSL users (97% with type 1 diabetes), age 38.0 (±18.8) years, 51% female, diabetes duration 16.0 (±49.9) years, and BMI of 25.2 (±16.5) kg/m
(mean ±SD). FSL users demonstrated a -5.2 mmol/mol change in HbA
, reducing from 67.5 (±20.9) mmol/mol (8.3%) at baseline to 62.3 (±18.5) mmol/mol (7.8%) after 7.5 (interquartile range 3.4-7.8) months of follow-up (
= 3,182) (
< 0.0001). HbA
reduction was greater in those with initial HbA
≥69.5 mmol/mol (>8.5%), reducing from 85.5 (±16.1) mmol/mol (10%) to 73.1 (±15.8) mmol/mol (8.8%) (
< 0.0001). The baseline Gold score (score for hypoglycemic unawareness) was 2.7 (±1.8) and reduced to 2.4 (±1.7) (
< 0.0001) at follow-up. A total of 53% of those with a Gold score of ≥4 at baseline had a score <4 at follow-up. FSL use was also associated with a reduction in diabetes distress (
< 0.0001). FSL use was associated with a significant reduction in paramedic callouts and hospital admissions due to hypoglycemia and hyperglycemia/diabetic ketoacidosis.
We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.
Introduction:
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Metabolic consequences associated with PCOS include, but are not limited to, ...insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). This narrative review aims to provide a comprehensive overview of the potential therapeutic roles of the incretin-based therapies in the management of PCOS.
Methods:
We performed a systematic search of databases including PubMed, MEDLINE and EMBASE up to 1 October 2020. We developed a search string of medical subject headings (MeSH) including the terms PCOS, incretin mimetics, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 receptor antagonists (GLP-1 RAs), liraglutide, exenatide, semaglutide, dipeptidyl peptidase-4 (DPP-4) inhibitors, combined with IR, testosterone and sex hormone-binding globulin (SHBG).
Results:
We identified 854 relevant articles and, after the initial screening, eight interventional animal studies, one observational animal study, 14 interventional human studies, two case–control studies and one systematic review were included. These studies showed the potential significant roles of GLP-1 RAs and DPP-4 inhibitors in the management of PCOS, with significant improvements in the metabolic parameters, including substantial weight reduction and improved insulin sensitivity. These agents also improved the hormonal parameters through decreased free androgen and increased SHBG. Moreover, they improved menstrual regularity, increased fertility with enhanced ovulation and pregnancy in obese women with PCOS.
Conclusion:
GLP-1 RAs and DPP-4 inhibitors have a promising therapeutic role in PCOS; however, larger clinical trials are needed to establish the role of incretin-based therapies in the management of PCOS.
Diabetes mellitus (DM) is a chronic, progressive, and multifaceted illness resulting in significant physical and psychological detriment to patients. As of 2019, 463 million people are estimated to ...be living with DM worldwide, out of which 90% have type-2 diabetes mellitus (T2DM). Over the years, significant progress has been made in identifying the risk factors for developing T2DM, understanding its pathophysiology and uncovering various metabolic pathways implicated in the disease process. This has culminated in the implementation of robust prevention programmes and the development of effective pharmacological agents, which have had a favourable impact on the management of T2DM in recent times. Despite these advances, the incidence and prevalence of T2DM continue to rise. Continuing research in improving efficacy, potency, delivery and reducing the adverse effect profile of currently available formulations is required to keep pace with this growing health challenge. Moreover, new metabolic pathways need to be targeted to produce novel pharmacotherapy to restore glucose homeostasis and address metabolic sequelae in patients with T2DM. We searched PubMed, MEDLINE, and Google Scholar databases for recently included agents and novel medication under development for treatment of T2DM. We discuss the pathophysiology of T2DM and review how the emerging anti-diabetic agents target the metabolic pathways involved. We also look at some of the limiting factors to developing new medication and the introduction of unique methods, including facilitating drug delivery to bypass some of these obstacles. However, despite the advances in the therapeutic options for the treatment of T2DM in recent years, the industry still lacks a curative agent.
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We ...extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10
). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10
) and the risk of type 2 diabetes (P=6.1×10
) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10
). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10
), and pentose and glucuronate interconversions (P=3.0×10
) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.
Polycystic ovary syndrome (PCOS) increases the risk of metabolic syndrome and non-alcoholic-fatty-liver disease (NAFLD). Vitamin D supplementation may exert positive effects on liver biochemistry in ...patients with NAFLD; however, its effects on PCOS are unknown. This randomized, double-blind, placebo-controlled study explored the effect of vitamin D supplementation on cardiovascular risk factors (high-sensitivity C-reactive protein (
-CRP), weight, body mass index (BMI), lipid profile, glucose levels, insulin levels, the homeostatic model assessment-insulin resistance (HOMA-IR), hormones (free androgen index (FAI), testosterone, sex hormone binding globulin (SHBG), and liver markers (alanine aminotransferase (ALT), hyaluronic acid (HA), N-terminal pro-peptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases-1 (TIMP-1), and the enhanced liver fibrosis (ELF) score). Forty women with PCOS were recruited and randomized to vitamin D (3200 IU) or placebo daily for 3 months. All outcomes were measured at baseline and 3 months follow-up (FU). Greater increases in vitamin D levels were shown in the supplementation group (vitamin D, baseline: 25.6 ± 11.4 nmol/L, FU: 90.4 ± 19.5 nmol/L vs. placebo, baseline: 30.9 ± 11.1 nmol/L, FU: 47.6 ± 20.5 nmol/L,
< 0.001). Between groups comparisons (% baseline change) revealed significant differences in ALT (
= 0.042) and a weak effect indicating a greater reduction in the HOMA-IR in the vitamin D group (
= 0.051). No further between group differences were seen in other cardiovascular risk factor, liver markers, or hormones. This study supports beneficial effects of vitamin D supplementation on liver markers and modest improvements in insulin sensitivity in vitamin D deficient women with PCOS.
We carried out a genome-wide association study (GWAS) of LDL-c response to statin using data from participants in the Collaborative Atorvastatin Diabetes Study (CARDS; n = 1,156), the ...Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; n = 895), and the observational phase of ASCOT (n = 651), all of whom were prescribed atorvastatin 10 mg. Following genome-wide imputation, we combined data from the three studies in a meta-analysis. We found associations of LDL-c response to atorvastatin that reached genome-wide significance at rs10455872 (P= 6.13 × 10−9) within the LPA gene and at two single nucleotide polymorphisms (SNP) within the APOE region (rs445925; P= 2.22 × 10−16 and rs4420638; P= 1.01 × 10−11) that are proxies for the ∊2 and ∊4 variants, respectively, in APOE. The novel association with the LPA SNP was replicated in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial (P= 0.009). Using CARDS data, we further showed that atorvastatin therapy did not alter lipoprotein(a) Lp(a) and that Lp(a) levels accounted for all of the associations of SNPs in the LPA gene and the apparent LDL-c response levels. However, statin therapy had a similar effect in reducing cardiovascular disease (CVD) in patients in the top quartile for serum Lp(a) levels (HR = 0.60) compared with those in the lower three quartiles (HR = 0.66; P= 0.8 for interaction). The data emphasize that high Lp(a) levels affect the measurement of LDL-c and the clinical estimation of LDL-c response. Therefore, an apparently lower LDL-c response to statin therapy may indicate a need for measurement of Lp(a). However, statin therapy seems beneficial even in those with high Lp(a).
Context:
Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition.
Aim:
...To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS.
Data source:
We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022.
Data synthesis:
Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
Results:
In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: −5.33, −0.93), body mass index (BMI) by 0.82 kg/m² (95% CI: −1.22, −0.41), fasting blood glucose standardised mean difference (SMD): −0.23; 95% CI: −0.40, −0.06, low-density lipoprotein cholesterol (LDL-C) (SMD: −0.41; 95% CI: −0.85, 0.03), total testosterone (SMD: −0.33; 95% CI: −0.49, −0.17), androstenedione (SMD: −0.45; 95% CI: −0.70, −0.20), 17-hydroxyprogesterone (17-OHP) (SMD: −0.58; 95% CI: −1.16, 0.00) and increase the likelihood of clinical pregnancy rate odds ratio (OR): 3.00; 95% CI: 1.95, 4.59 compared with placebo.
Conclusion:
In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.
Purpose:
Free androgen index (FAI) and anti-Mullerian hormone (AMH) are independently associated with polycystic ovary syndrome (PCOS). This study aimed to describe the relationship between these two ...markers and health-related quality of life (HR-QoL) in women with PCOS.
Methods:
This cross-sectional study consisted of 81 women in the Hull PCOS biobank, who fulfilled the Rotterdam consensus criteria for the diagnosis of PCOS. The primary outcome was to measure the various domains of the QoL in the modified polycystic ovary syndrome questionnaire (MPCOSQ).
Results:
Mean age of the study participants was 28 ± 6.0 years, mean body mass index (BMI) 33.5 ± 7.8 kg/m
2
, mean FAI (6 ± 5.5), free testosterone (2.99 ± 0.75) and mean AMH (3.5 ± 0.8 units). In linear regression analysis, the FAI was associated with overall mean MPCOSQ score (Beta = 0.53,
P
-value = 0.0002), and with depression (Beta = 0.45,
P
-value = 0.01), hirsutism (Beta = 0.99,
P
-value = 0.0002) and menstrual irregularity (Beta = 0.31,
P
-value = 0.04). However, with adjustment for age and BMI, FAI was only associated with the hirsutism domain (Beta = 0.94,
P
-value = 0.001) of the MPCOSQ. FAI was also associated with the weight domain (Beta = 0.63
P
-value = 0.005) of MPCOSQ. However, AMH was not associated with the overall mean MPCOSQ score or with any of its domains.
Conclusion:
FAI but not AMH was associated with QoL in women with PCOS, and this effect was mediated by BMI.
PDF
