Effect of intermittently scanned continuous glucose monitoring in people with diabetes with a psychosocial indication for initiation.

AIM: To understand the effect of intermittently scanned continuous glucose monitoring (isCGM) in people with diabetes with a 'psychosocial' indication for access. METHODS: The study utilized baseline and follow-up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes in the UK. Diabetes-related distress (DRD) was assessed using the two-item diabetes-related distress scale (DDS). Participants were categorized into two groups: high DRD (DDS score ≥ 3) and lower DRD (DDS score < 3). The t-test was used to assess the difference in the pre- and post-isCGM continuous variables. RESULTS: The study consisted of 17 036 people with diabetes, with 1314 (7%) using isCGM for 'psychosocial' reasons. Follow-up data were available for 327 participants, 322 (99%) of whom had type 1 diabetes with a median diabetes duration of 15 years; 75% (n = 241) had high levels of DRD. With the initiation of isCGM, after a mean follow-up period of 6.9 months, there was a significant reduction in DDS score; 4 at baseline versus 2.5 at follow-up (P < .001). The prevalence of high DRD reduced from 76% to 38% at follow-up (50% reduction in DRD, P < .001). There was also a significant reduction in HbA1c (78.5 mmol/mol [9.3%] at baseline vs. 66.5 mmol/mol [8.2%] at follow-up; P < .001). This group also experienced an 87% reduction in hospital admissions because of hyperglycaemia/diabetic ketoacidosis (P < .001). CONCLUSION: People with diabetes who had isCGM initiated for a psychosocial indication had high levels of DRD and HbA1c, which improved with the use of isCGM.

Assessing the androgenic and metabolic heterogeneity in polycystic ovary syndrome using cluster analysis.

INTRODUCTION: Some but not all women with polycystic ovary syndrome (PCOS) develop the metabolic syndrome (MS). The objective of this study was to determine if a subset of women with PCOS had higher androgen levels predisposing them to MS and whether routinely measured hormonal parameters impacted the metabolic syndrome score (siMS). METHODS: We included data from a discovery (PCOS clinic data) and a replication cohort (Hull PCOS Biobank) and utilized eight routinely measured hormonal parameters in our clinics (free androgen index [FAI], sex hormone-binding globulin, dehydroepiandrosterone sulphate (DHEAS), androstenedione, luteinizing hormone [LH], follicular stimulating hormone, anti-Müllerian hormone and 17 hydroxyprogesterone [17-OHP]) to perform a K-means clustering (an unsupervised machine learning algorithm). We used NbClust Package in R to determine the best number of clusters. We estimated the siMS in each cluster and used regression analysis to evaluate the effect of hormonal parameters on SiMS. RESULTS: The study consisted of 310 women with PCOS (discovery cohort: n = 199, replication cohort: n = 111). The cluster analysis identified two clusters in both the discovery and replication cohorts. The discovery cohort identified a larger cluster (n = 137) and a smaller cluster (n = 62), with 31% of the study participants. Similarly, the replication cohort identified a larger cluster (n = 74) and a smaller cluster (n = 37) with 33% of the study participants. The smaller cluster in the discovery cohort had significantly higher levels of LH (7.26 vs. 16.1 IU/L, p < .001), FAI (5.21 vs. 9.22, p < .001), androstenedione (3.93 vs. 7.56 nmol/L, p < .001) and 17-OHP (1.59 vs. 3.12 nmol/L, p < .001). These findings were replicated in the replication cohort. The mean (±SD) siMS score was higher in the smaller cluster, 3.1 (±1.1) versus 2.8 (±0.8); however, this was not statistically significant (p = .20). In the regression analysis, higher FAI (ß = .05, p = .003) and androstenedione (ß = .03, p = .02) were independently associated with a higher risk of SiMS score, while higher DHEAS levels were associated with a lower siMS score (ß = -.07, p = .03) CONCLUSION: We identified a subset of women in our PCOS cohort with significantly higher LH, FAI, and androstenedione levels. We show that higher levels of androstenedione and FAI are associated with a higher siMS, while higher DHEAS levels were associated with lower siMS.

The long-term impact of glucose monitoring with the FreeStyle Libre on glycaemic control and hypoglycaemia awareness in people with type 1 diabetes: Insights from the Association of British Clinical Diabetologists national audit.

AIMS: To investigate the change in glycated haemoglobin (HbA1c), hypoglycaemia awareness and diabetes-related distress in people with type 1 diabetes (T1D) using FreeStyle Libre (FSL) over a 2-year follow-up period. METHODS: FSL user data from U.K wide hospitals collected during routine clinical care were analysed. People living with T1D were categorised into four groups based on the duration of follow-up. Group I (< 1 year, n = 6940), group II (1 to 1.5 years, n = 662), group III (1.5 to 2 years, n = 385), and group IV (> 2 years, n = 642). The t-test was used to compare the baseline and follow-up HbA1c, GOLD score (a measure of hypoglycaemia awareness) and diabetes-related distress scale (DDS score) (quality of life measure). RESULTS: The study consisted of 16,834 people, with follow-up data available for 8,629 participants. The change in HbA1c, GOLD and DDS score from baseline within the follow-up sub-groups (group I vs group II vs group III vs group IV) was HbA1c (-6 vs -6 vs -4 vs -4 mmol/mol; p < 0.001) (-0.55 vs -0.55 vs -0.37 vs -0.37 %), GOLD score (-0.31 vs -0.45 vs -0.26 vs -0.42; p < 0.0001 group I, II, IV and p 0.07 group III), and DDS score(-0.59 vs -0.58 vs -0.63 vs -0.50; p < 0.001), respectively. CONCLUSIONS: In people with T1D, FSL use resulted in a sustained improvement in HbA1c, hypoglycaemia awareness and diabetes-related distress for over two years.

Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. AIM: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. DATA SOURCE: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. DATA SYNTHESIS: Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI  - 0.49 to  - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI  - 1.34 to  - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD:  - 0.47; 95% CI  - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD:  - 0.37 µg/dL; 95% CI  - 0.05 to  - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD:  - 1.67; 95% CI  - 2.27 to  - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. CONCLUSION: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. PROSPERO REGISTRATION NO: CRD42020178783.

Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. DESIGN: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I² = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I² = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I² = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I² = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. CONCLUSIONS: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

Effect of pharmacological interventions on lipid profiles and C-reactive protein in polycystic ovary syndrome: A systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.

Impact of pharmacological interventions on anthropometric indices in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight. OBJECTIVE: To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021. STUDY SELECTION: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020. DATA EXTRACTION: Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: 80 RCTs were included in the meta-analysis. Metformin vs placebo showed significant reduction in the mean body weight (MD: -3.13 kg; 95% confidence interval [CI]: -5.33 to -0.93, I² = 5%) and the mean body mass index (BMI) (MD: -0.75 kg/m2 ; 95% CI: -1.15 to -0.36, I² = 0%). There was a significant reduction in the mean BMI with orlistat versus placebo (MD: -1.33 kg/m²; 95% CI: -2.16 to -0.66, I² = 0.0%), acarbose versus metformin (MD: -1.26 kg/m²; 95% CI: -2.13 to -0.38, I² = 0%), and metformin versus pioglitazone (MD: -0.91 kg/m²; 95% CI: -1.62 to -0.19, I² = 0%). A significant increase in the mean BMI was also observed in pioglitazone versus placebo (MD: + 2.59 kg/m²; 95% CI: 1.78-3.38, I² = 0%) and in rosiglitazone versus metformin (MD: + 0.80 kg/m²; 95% CI: 0.32-1.27, I² = 3%). There was a significant reduction in the mean waist circumference (WC) with metformin versus placebo (MD: -1.21 cm; 95% CI: -3.71 to 1.29, I² = 0%) while a significant increase in the mean WC with pioglitazone versus placebo (MD: + 5.45 cm; 95% CI: 2.18-8.71, I² = 0%). CONCLUSION: Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.

Time in range following flash glucose monitoring: Relationship with glycaemic control, diabetes-related distress and resource utilisation in the Association of British Clinical Diabetologists national audit.

AIMS: The aim of this study was to understand the relationship between time in range (TIR) achieved using the isCGM with changes in glycaemic control, diabetes-related distress (DRD) and resource utilisation in people living with diabetes. METHODS: Clinicians from 106 National Health System (NHS) UK hospitals submitted isCGM user baseline and follow-up data in a web-based tool held within the UK NHS network. Linear regression analysis was used to identify the relationship between follow-up glucose TIR (3.9-10 mmol/L) categories (TIR% 50-70 and TIR% >70) with change in haemoglobin A1c (HbA1c), DRD and Gold score (measure of hypoglycaemia unawareness, where a score ≥4 suggests impaired awareness of hypoglycaemia). RESULTS: Of 16,427 participants, 1241 had TIR follow-up data available. In this cohort, the mean TIR was 44.8% (±22.5). With the use of isCGM, at 7.9 months mean follow-up, improvements were observed in HbA1c (-6.9 [13.5] mmol/mol, p < 0.001), Gold score (-0.35 [1.5], p < 0.001) and Diabetes Distress Screening (-0.73 [1.23], p < 0.001). In the regression analysis restricted to people living with type 1 diabetes, TIR% 50-70 was associated with a -8.9 mmol/mol (±0.6, p < 0.001) reduction in HbA1c; TIR% >70 with a -14 mmol/mol (±0.8, p < 0.001) reduction in HbA1c. Incremental improvement in TIR% was also associated with significant improvements in Gold score and DRD. TIR% >70 was associated with no hospital admissions due to hypoglycaemia, hyperglycaemia/diabetic ketoacidosis, and a 60% reduction in the paramedic callouts and 77% reduction in the incidence of severe hypoglycaemia. CONCLUSION: In a large cohort of UK isCGM users, we demonstrate a significant association of higher TIR% with improvement in HbA1c, hypoglycaemia awareness, DRD and resource utilisation.

The Effect of Thiazolidinediones in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. METHODS: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. RESULTS: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03-3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13-1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77-3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07-1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD - 0.20 mmol/L; 95% CI - 0.38 to - 0.03, p = 0.02) and fasting insulin levels (MD - 11.47 mmol/L; 95% CI - 20.20, - 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD - 0.62; 95% CI - 1.25-0.00, p = 0.05). CONCLUSION: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO REGISTRATION NO: CRD42020178783.

Diagnostic Value of Non-invasive Liver Function Tests in Liver Fibrosis and Changes in These Parameters Post-metabolic Surgery.

PURPOSE: This study aimed to ascertain the diagnostic accuracy of non-invasive liver function tests in liver fibrosis and assess their changes after metabolic surgery. MATERIALS AND METHODS: 1005 individuals with severe obesity who were referred for metabolic surgery were analysed. All participants had blood samples taken for liver enzymes and lipid profile. In addition, hepatic indexes, including AAR, APRI, NFS and Fibrosis-4 (FIB4), were checked. Furthermore, all participants underwent two-dimensional shear wave elastography (2D-SWE). All investigations were repeated 6-8 months after metabolic surgery. The receiver operating characteristic (ROC) curve and the area under the ROC curve was utilised to determine the optimal cut-off values for baseline study parameters. Logistic regression was applied to predict the relationship between study parameters-as predictors-and change in 2D-SWE. RESULTS: AST/ALT (AAR) was the most sensitive (79%) pre-operative non-invasive serological marker for detecting liver fibrosis, whereas NAFLD Fibrosis Score (NFS) was the most specific (84%). AST/upper limit of the normal AST range × 100/platelets (× 109/L) (APRI) showed a positive correlation with 2D-SWE post-metabolic surgery (p-value = 0.021). Regression analysis from both adjusted and unadjusted models showed that baseline AAR was a predictor of postoperative liver status in terms of hepatic fibrosis. CONCLUSION: AAR has a high sensitivity, whereas NFS exhibits a high specificity in diagnosing liver fibrosis. The authors recommend using both investigations in conjunction with 2D-SWE to increase the likelihood of detecting liver fibrosis.

Unilateral adrenal infarction in pregnancy with associated acute hypoadrenalism and subsequent spontaneous biochemical and radiological resolution.

Adrenal infarction is a rare cause of abdominal pain during pregnancy, and if missed, it can result in devastating clinical consequences for the mother and the child. The authors report a case of a young female who presented with severe abdominal pain and nausea. The biochemistry showed raised inflammatory markers and significant lactic acidosis. As the cause of the symptoms was not clear and the patient continued to deteriorate, a contrast-enhanced CT abdomen and pelvis was done which was suggestive of an acute left adrenal infarction. Subsequently, the patient was confirmed to have biochemical hypoadrenalism and required replacement doses of hydrocortisone until recovery of the adrenal glucocorticoid reserve and anticoagulation for the duration of pregnancy. We discuss the workup including diagnostic imaging, follow-up, and considerations for future pregnancies in this case.

Genetic risk for the polycystic ovary syndrome, bone mineral density and fractures in women and men: A UK Biobank Mendelian randomisation study.

INTRODUCTION: There is conflicting data on the effect of polycystic ovary syndrome (PCOS) on bone mineral density (BMD) and fracture risk. Recent genetic data suggest that men may also carry genetic risk factors for PCOS; the associations of these factors with parameters of bone health remains unknown. We aimed to investigate if the genetic risk of PCOS is associated with BMD and fracture risk in women and men in the UK Biobank dataset. METHODS: We used Mendelian randomisation (MR) analysis to test the association of genetic risk of excess testosterone in PCOS with BMD and fractures in the UK biobank study. The MR analysis was performed using linear regression analysis with the weighted genetic risk score (wGRS) as an independent variable adjusting for age, BMI and population eigenvectors. The horizontal pleiotropy in the MR analysis was tested using MR-Egger regression analysis. RESULTS: The study consisted of 221,086 Caucasian women (mean age ± SD: 56.7 ± 7.9 years, mean body mass index [BMI] ± SD: 27.0 ± 5.1 kg/m2, mean BMD ± SD: 0.50 ± 0.11 g/cm2) and 187,816 Caucasian men (mean age ± SD: 57.1 ± 8.1 years, mean BMI ± SD: 27.7 ± 4.1 kg/m2 and mean BMD ± SD: 0.56 ± 0.12 g/cm2). Women and men self-reported 24,797 (11%) and 17,076 (10%) fractures over the last 5 years, respectively. The MR analysis showed that one SD increase in the wGRS for clinical or biochemical hyperandrogenism in PCOS was associated with significantly higher heel BMD (Beta = 0.0007 [±0.0002], P-value = 0.001) and a significantly reduced risk of fractures (OR = 0.97, P-value = 0.003) in women. A similar wGRS in men was not associated with BMD or risk of fractures. CONCLUSION: In this study, we showed that the excess genetic risk for hyperandrogenism in women with PCOS is associated with a higher BMD and reduced risk of fractures.

Impact of metformin on the clinical and metabolic parameters of women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

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.

Effect of Curcumin on Glycaemic and Lipid Parameters in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects women of reproductive age. It is associated with menstrual disturbances, hyperandrogenism, and polycystic ovaries. In addition to this, it results in altered anthropometric parameters, insulin resistance, and subsequently untoward cardio-metabolic sequelae. Therapeutic approaches that target weight loss and improve insulin sensitivity are used to address the metabolic complications in PCOS. Curcumin is a phytochemical which exhibits anti-inflammatory and anti-oxidant properties, and therefore, its use in PCOS has been a subject of substantial interest and research. The aim of this study was to synthesize the existing evidence on the effects of curcumin on glycaemic and lipid parameters in PCOS. We searched PubMed, Embase, Web of Science, Scopus, and ClinicalTrials databases from inception to June 07, 2021. Only randomized controlled trials (RCT) presenting sufficient data on glycemic and lipid parameters in patients with PCOS at baseline and the end of the follow-up period in each group were included. Meta-analysis of five RCTs showed a significant reduction on fasting glucose (WMD: - 3.68 mg/dL, 95% CI: - 5.11, - 2.25, p < 0.00001, I2 = 18%), insulin levels (WMD: - 1.72 µUI/mL, 95% CI: - 2.53, -0.92, p < 0001, I2 = 41%), and HOMA-IR index (WMD: - 0.94, 95% CI: - 1.73, - 0.16, p = 0.02, I2 = 90%) after curcumin therapy. None of the lipid indices were significantly altered by curcumin. Curcumin administration in PCOS resulted in significant improvement in glycaemic parameters; however, no significant changes were seen in lipid parameters with its use.

Association between Thyroid Hormones and Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis in Obese Individuals Undergoing Bariatric Surgery.

Background: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatic fibrosis have emerged as one of the leading causes of chronic liver disease. The prevalence of the NAFLD spectrum has increased, which can be attributed to the rise in obesity. As NAFLD can ultimately lead to liver cirrhosis, it is imperative to identify modifiable risk factors associated with its onset and progression to provide timely intervention to prevent potentially disastrous consequences. Considering the pivotal role of the endocrine axis in several metabolic pathways such as obesity and insulin resistance, thyroid hormones are crucial in the pathophysiology of NAFLD. The study is focused on the identification of an association between thyroid function and radiographic and histological parameters of NAFLD in patients with severe obesity. Methods: Ninety patients were recruited for this study and underwent initial assessments, including demographic profiles, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least 2 weeks before liver biopsy. Results: Among the 90 participants, 80% were women. The mean age was 38.5±11.1 years, and the mean body mass index (BMI) was 45.46±6.26 kg/m2. The mean levels of serum T3 and free T4 in patients with positive histology were not statistically significant compared with patients with negative histology. Furthermore, there was no statistical significance in the mean T3 and free T4 levels between patients diagnosed with hepatic steatosis or fibrosis (on ultrasonography and elastography) and those with negative hepatic imaging. Serum levels of thyroid-stimulating hormone (TSH) were negatively correlated with ultrasonography (P=0.007). Binary logistic regression analysis revealed that none of the thyroid hormones was a predictive factor for liver histology in both adjusted and crude models. Conclusion: The results from our analysis did not suggest an association between thyroid hormones and NAFLD, which is in line with several previously published studies. However, the authors note that there are published data that do propose a link between the two entities. Therefore, well-designed large-scale clinical studies are required to clarify this discrepancy.

Therapeutics for type-2 diabetes mellitus: a glance at the recent inclusions and novel agents under development for use in clinical practice.

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.

Refractory hypokalaemia and hypertension with metabolic alkalosis: an acute presentation of Cushing's disease secondary to a pituitary macroadenoma.

A 68-year-old woman presented with right arm cellulitis, not responsive to oral antibiotics. Intravenous antibiotics were commenced, and an ultrasound scan confirmed a collection that was surgically drained. She developed refractory hypokalaemia with normal magnesium, no gastrointestinal losses and no iatrogenic cause. She was hypertensive, hyperglycaemic, alkalotic, clinically obese with proximal myopathy and skin bruising. These clinical findings and refractory hypokalaemic hypertension with metabolic alkalosis raised a suspicion of Cushing's syndrome (CS). 24-hour urinary free cortisol (24 hours) was grossly raised on two occasions. The adrenocorticotropic hormone (ACTH) was significantly raised at 154 ng/L, confirming ACTH-dependant CS. A CT scan of the thorax, abdomen and pelvis excluded an ectopic source of hypercortisolaemia. MRI pituitary revealed an invasive macroadenoma. Treatment with endoscopic debulking resulted in the resolution of hypokalaemia and metabolic alkalosis with significant improvement in hyperglycaemia and hypertension.

Severe proximal myopathy secondary to Hashimoto's thyroiditis.

Muscular symptoms in hypothyroidism are common, including myalgia, fatigue and cramps; however, a significantly raised creatine kinase and muscle weakness are rare. Differential diagnosis of patients presenting with muscle weakness and a raised creatine kinase is wide, and hypothyroidism is rarely considered. We report this case of a 30-year-old female presenting with proximal muscle weakness as her primary symptom, hypothyroid symptoms of 3-month duration and a significantly raised creatine kinase. After ruling out other causes of a raised creatine kinase, thyroxine replacement was commenced, which led to complete resolution of her proximal weakness, myalgia and normalisation of creatine kinase level. This case illustrates severe proximal myopathy can be secondary to hypothyroidism, symptoms can resolve with thyroxine replacement and emphasises the importance of measuring thyroid function in patients with proximal weakness/myalgia and a significantly raised creatine kinase.