Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis.

AIMS: To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes. METHODS: People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA1c included as a time-dependent variable was fitted to these data. RESULTS: Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002-1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03-1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c . CONCLUSIONS: In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures.

Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis.

BACKGROUND: Low and high birthweight is known to increase the risk of acute and longer-term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. OBJECTIVE: The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. METHODS: We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. RESULTS: Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density-lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. CONCLUSIONS: This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials.

Temporal and external validation of a prediction model for adverse outcomes among inpatients with diabetes.

AIM: To temporally and externally validate our previously developed prediction model, which used data from University Hospitals Birmingham to identify inpatients with diabetes at high risk of adverse outcome (mortality or excessive length of stay), in order to demonstrate its applicability to other hospital populations within the UK. METHODS: Temporal validation was performed using data from University Hospitals Birmingham and external validation was performed using data from both the Heart of England NHS Foundation Trust and Ipswich Hospital. All adult inpatients with diabetes were included. Variables included in the model were age, gender, ethnicity, admission type, intensive therapy unit admission, insulin therapy, albumin, sodium, potassium, haemoglobin, C-reactive protein, estimated GFR and neutrophil count. Adverse outcome was defined as excessive length of stay or death. RESULTS: Model discrimination in the temporal and external validation datasets was good. In temporal validation using data from University Hospitals Birmingham, the area under the curve was 0.797 (95% CI 0.785-0.810), sensitivity was 70% (95% CI 67-72) and specificity was 75% (95% CI 74-76). In external validation using data from Heart of England NHS Foundation Trust, the area under the curve was 0.758 (95% CI 0.747-0.768), sensitivity was 73% (95% CI 71-74) and specificity was 66% (95% CI 65-67). In external validation using data from Ipswich, the area under the curve was 0.736 (95% CI 0.711-0.761), sensitivity was 63% (95% CI 59-68) and specificity was 69% (95% CI 67-72). These results were similar to those for the internally validated model derived from University Hospitals Birmingham. CONCLUSIONS: The prediction model to identify patients with diabetes at high risk of developing an adverse event while in hospital performed well in temporal and external validation. The externally validated prediction model is a novel tool that can be used to improve care pathways for inpatients with diabetes. Further research to assess clinical utility is needed.

Predicting inpatient hypoglycaemia in hospitalized patients with diabetes: a retrospective analysis of 9584 admissions with diabetes.

AIMS: To explore whether a quantitative approach to identifying hospitalized patients with diabetes at risk of hypoglycaemia would be feasible through incorporation of routine biochemical, haematological and prescription data. METHODS: A retrospective cross-sectional analysis of all diabetic admissions (n=9584) from 1 January 2014 to 31 December 2014 was performed. Hypoglycaemia was defined as a blood glucose level of <4 mmol/l. The prediction model was constructed using multivariable logistic regression, populated by clinically important variables and routine laboratory data. RESULTS: Using a prespecified variable selection strategy, it was shown that the occurrence of inpatient hypoglycaemia could be predicted by a combined model taking into account background medication (type of insulin, use of sulfonylureas), ethnicity (black and Asian), age (≥75 years), type of admission (emergency) and laboratory measurements (estimated GFR, C-reactive protein, sodium and albumin). Receiver-operating curve analysis showed that the area under the curve was 0.733 (95% CI 0.719 to 0.747). The threshold chosen to maximize both sensitivity and specificity was 0.15. The area under the curve obtained from internal validation did not differ from the primary model [0.731 (95% CI 0.717 to 0.746)]. CONCLUSIONS: The inclusion of routine biochemical data, available at the time of admission, can add prognostic value to demographic and medication history. The predictive performance of the constructed model indicates potential clinical utility for the identification of patients at risk of hypoglycaemia during their inpatient stay.

All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study.

AIM: The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. METHODS: We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n=8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n=16,541). RESULTS: Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56-0.74, P-value<0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53-0.76, P -value=0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83-1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. CONCLUSIONS: GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.

ß-Adrenergic receptor antagonists and fracture risk: a meta-analysis of selectivity, gender, and site-specific effects.

UNLABELLED: By meta-analysis, the risk of fracture was 15% lower in patients treated with ß-adrenergic blockers compared to controls independent of gender, fracture site, and dose. This might be attributable to ß1-selective blockers. INTRODUCTION: The aim of this study is to determine by meta-analysis whether ß-adrenergic blockers (BBs) reduce fracture risk and whether the effect, if demonstrable, is dependent upon selectivity, dose, gender, or fracture site. METHODS: A literature search was performed in electronic databases MEDLINE, EMBASE, and reference sections of relevant articles to identify eligible studies. Adjusted estimates of fracture risk effect size (ES) were pooled across studies using fixed or random-effects (RE) meta-analysis as appropriate. Dose-related effects were evaluated using meta-regression. To explore the relative efficacy of ß1-selective blockers in comparison to nonselective BBs, adjusted indirect comparison was performed. RESULTS: A total of 16 studies (7 cohort and 9 case-control studies), involving 1,644,570 subjects, were identified. The risk of any fracture was found to be significantly reduced in subjects receiving BBs as compared to control subjects (16 studies, RE pooled ES = 0.86, 95% CI 0.78-0.93; I(2) = 87 %). In a sensitivity analysis limited to those studies deemed to be most robust, the BB effect to reduce fracture risk was sustained (four studies, pooled ES = 0.79, 95% CI 0.67-0.94; I(2) = 96%). The risk of a hip fracture was lower in both women and men receiving BBs (women: pooled ES = 0.86, 95% CI 0.80-0.91; I(2) = 1% and men: pooled ES = 0.80, 95% CI 0.71-0.90; I(2) = 0%). Similar risk reductions were found for clinical vertebral and forearm fractures, although statistical significance was not reached. The reduction in risk did not appear to be dose-related (test for a linear trend p value 0.150). Using adjusted indirect comparisons, it was estimated that ß1-selective agents were significantly more effective than nonselective BBs in reducing the risk of any fracture (six studies, ß1-selective blockers vs. nonselective BBs: RE pooled ES = 0.82, 95% CI = 0.69-0.97). CONCLUSIONS: The findings suggest that the risk of fracture is approximately 15% lower in patients treated with BBs compared to controls independent of gender, fracture site, and dose. This risk reduction might be associated with the effects of ß1-selective blockers.

Impact of diabetes on inpatient mortality and length of stay for elderly patients presenting with fracture of the proximal femur.

INTRODUCTION: Osteoporosis-related fractures of the proximal femur cause significant morbidity and result in an economic burden on societies. It remains debatable whether diabetic patients with proximal fracture of the femur demonstrate poorer outcomes in terms of hospital stay and mortality compared to non-diabetic controls. METHODS: All patients over 65years old admitted to the University Hospital Birmingham during 2007-2010 with a diagnosis of a fracture of the proximal femur (total 1468 including 197 patients with diabetes) were analysed. Eligibility and case definitions were ascertained using electronic records. Multivariate analyses were conducted to control for the confounding effect of covariates, which may be associated with the outcomes of interest on the basis of biological plausibility and known risks. RESULTS: In-patient mortality was estimated at 14.2% and 12% for the diabetic and non-diabetic patients respectively. Diabetes was not found to be a significant predictor of in-patient mortality, before and after adjustment for the covariates [Adjusted odds ratio 1.01 (95% CI 0.62-1.65)], in contrast to advancing age, male gender, co-morbidity score, low albumin and high creatinine concentrations. Similarly, median length of stay was greater in the diabetes patients, yet only by a day (20 versus 19 days). This was not statistically significant in either the unadjusted (p=0.17) or in the multivariate analysis (p=0.06). CONCLUSIONS: Diabetic patients admitted with fracture of the proximal femur did not demonstrate significantly poorer outcomes in terms of in-patient mortality and length of stay compared to non-diabetic patients.

Performance of the mini nutritional assessment score in the detection of vitamin D status in an elderly Greek population.

The primary aim of the study was to explore the potential relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and Mini Nutritional Assessment (MNA) score, a surrogate for protein energy undernutrition, in elderly (≥65 years old) subjects with and without a hip fracture. A secondary aim of the study was to provide estimates of the MNA discriminatory performance in the detection of subjects with low levels of 25(OH)D (<20 ng/ml). The study population consisted of 101 patients with a hip fracture, recruited from a single urban Hospital in Athens, Greece, and 85 community dwelling subjects with no history of hip fracture. Serum 25(OH)D was measured, nutritional status was determined by the MNA questionnaire in all subjects, and linear correlation between variables was investigated. Receiver operator characteristic (ROC) curve analysis was performed and discriminatory performance was further assessed by calculating positive and negative likelihood ratios (LR). MNA scores were significantly correlated with 25(OH)D levels (rho=0.685, p<0.001) and this finding was robust in both groups and unaffected by gender. ROC curve analysis demonstrated an area under the curve (AUC) of 0.860 [standard error (SE): 0.026, 95% confidence interval (CI): 0.810-0.910], which provided a significantly better estimation of 25(OH)D status than simple guess (p<0.001). The lowest cutoff value in MNA score, providing a sensitivity over 90% was 25.25, which was associated with a sensitivity of 90.9% and a specificity of 53.6%. The same analysis revealed acceptable results only within hip fracture patients. MNA score might be a satisfactory surrogate marker for 25(OH)D levels with which it is linearly correlated. However, it appears that its discriminatory performance, as a diagnostic tool for 25(OH)D insufficiency, is rather suboptimal.

Long-term effects of thyroid fine-needle biopsy on the thyroid-related biochemical parameters.

AIMS: Thyroid fine-needle biopsy (FNB) is a simple, reliable, inexpensive and generally safe diagnostic procedure in the management of thyroid nodules. FNB may trigger biochemical alterations through destruction of thyroid follicles. We aimed to investigate long-term post-FNB alterations in serum thyroid-related parameters. METHODS: One hundred and ten consecutive patients with thyroid nodular disease were subjected to FNB. Thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3), thyroglobulin (Tg), thyroglobulin autoantibodies (anti-Tg), thyroid-peroxidase autoantibodies (anti-TPO) were measured in all subjects at baseline, 10 days, 2 and 6 months. Subsequently, patients were divided into subgroups according to the technique of FNB, the presence of disease characteristics as thyroid autoimmunity (Hashimoto's thyroiditis), goitre, singularity-maximum diameter-blood pattern of the nodule(-s), the number of passes and the administration of L-thyroxine (LT4). RESULTS: A significant increase in Tg, anti-Tg and FT3 levels was observed. These alterations were more prominent within patients with dominant nodule's maximum diameter ≥ 2 cm or without Hashimoto's thyroiditis. Tg and anti-Tg levels were significantly increased only in patients not being on LT4. On the other hand, FNB technique did not affect any of the measured parameters. CONCLUSION: Our data suggest that FNB results in statistically significant but clinically insignificant increases in Tg, anti-Tg and FT3 levels, implying a thyroid trauma of some level, more likely to happen in patients with larger nodules. The FNB technique used has no effect on the thyroid-related biochemical parameters.

Selenomethionine treatment in patients with autoimmune thyroiditis: a prospective, quasi-randomised trial.

AIMS: To test whether selenium administration affects autoantibodies to thyroid peroxidase (anti-TPO) and thyroglobulin (anti-TG) titres in chronic autoimmune (Hashimoto's - HT) thyroiditis. METHODS: A prospective, open-label, quasi-randomised study in 86 HT patients (n = 86) assigned to either selenomethionine (Seme) 200µg daily for 3 months (Se3, n = 15) or 6 months (Se6, n = 46) or placebo (Control, n = 25). Serum Se, anti-TPO, anti-TG and thyroid hormones were measured in all patients at baseline, 3 and 6 months. A subgroup of 18 patients (twelve on Se6 and six controls) were subjected in thyroid fine-needle biopsy at baseline and 6 months to detect changes in lymphocyte infiltration. RESULTS: No significant difference in anti-TPO levels was recorded after 3 (p = 0.88) or 6 months (p = 0.62) on Seme. Anti-TG levels decreased both at 3 months (p = 0.001) and 6 months (p = 0.001). No significant changes in thyroid stimulating hormone, free thyroxine and free triiodothyronine levels or in the lymphocytes' number in thyroid cytology specimens were detected. Age, gender, duration of disease, baseline anti-TPO levels and per cent change in Se levels could not predict the response of anti-TPO levels to Seme administration. CONCLUSION: Our data suggest that Seme administration in pharmacological doses for a period of 6 months seems to have no significant effect on serum thyroid auto-antibodies' levels or lymphocyte infiltration of the thyroid gland.

The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis was to evaluate the role of androgens or androgen-modulating agents on the probability of pregnancy achievement in poor responders undergoing IVF. METHODS: Medline, EMBASE, CENTRAL, Scopus and Web of Science databases were searched for the identification of randomized controlled trials evaluating the administration of testosterone, dehydroepiandrosterone (DHEA), aromatase inhibitors, recombinant luteinizing hormone (rLH) and recombinant human chorionic gonadotrophin (rhCG) before or during ovarian stimulation of poor responders. RESULTS: In two trials involving 163 patients, pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy [risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%] and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. No significant differences in clinical pregnancy and live birth rates were observed between patients who received DHEA and those who did not. Similarly, (i) the use of aromatase inhibitors, (ii) addition of rLH and (iii) addition of rhCG in poor responders stimulated with rFSH for IVF were not associated with increased clinical pregnancy rates. In the only eligible study that provided data, live birth rate was increased in patients who received rLH when compared with those who did not (RD: +19%, 95% CI:+1 to +36%). CONCLUSIONS: Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF.

Thyroid diseases and female reproduction.

Thyroid diseases are very common in women of reproductive age. The aim of this study was to review the current evidence on physiology, pathophysiology, diagnosis and management of women with thyroid disorders that are currently seeking fertility, undergoing assisted reproduction technologies (ART) or being pregnant. Normal thyroid function is essential for normal function of the gonadal axis, thus important in maintaining normal reproductive capacity. On the contrary, any type of thyroid dysfunction may reduce the likelihood of pregnancy; the latter can be restored to normal after appropriate treatment. Over eight million children have been born as a result of assisted reproduction techniques (ART) since 1978. As these procedures are becoming more common in clinical practice, the exact impact of thyroid status on reproductive outcomes as well as that of drugs used in ART on thyroid function has to be fully elucidated. Maternal thyroid function is crucial, especially during the first weeks of gestation, for offspring's wellness and brain development. On the other hand, normal physiological mechanisms during gestation can have a major impact on maternal thyroid function. As human chorionic gonadotropin (hCG) has a thyroid stimulating hormone (TSH)-like effect, high hCG concentrations are associated with thyroid stimulation, both functionally (lower serum TSH concentrations) and anatomically (increased thyroid volume). Although the association between maternal hypothyroidism and increased perinatal morbidity has been described for over a century, more recently, even the presence of anti-thyroid antibodies has been associated with adverse pregnancy outcomes, such as recurrent abortions and placental abruption. This is of major clinical significance, as anti-thyroid antibodies are surprisingly prevalent in pregnancy, especially during the first two trimesters.

Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis.

WHAT IS KNOWN AND OBJECTIVES: Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom-based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta-analysis of relevant randomized double-blind placebo-controlled (RCT) were performed. DATA SOURCES, EXTRACTION AND ANALYSIS: A literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL and the reference lists of relevant studies. Responders to treatment (>30% reduction in mean pain score) and dropouts due to lack of efficacy were used as primary outcome measures. Dropout rates and incidence of common adverse outcomes were also investigated. Four RCTs, reporting data on 2040 patients, were reviewed and three of them using PG were included in the meta-analysis. RESULTS: Pregabalin at a dose of 600, 450 and 300 mg per day is effective in FBM compared to placebo (NNT: 7, upper 95% CI: 12, 450 mg). A number of adverse events (AE), such as dizziness, somnolence, dry mouth, weight gain, peripheral oedema, is consistently associated with treatment at any dose and could lead one out of four patients to quit treatment (NNH: 6, lower 95% CI: 4, 600 mg). Indirect comparison meta-analysis suggests that PB at a dose of 450 mg per day could result in more responders than at 300 mg, but this result needs to be interpreted with caution as there were no significant differences between 600 and 300 mg or between 600 and 450 mg. Data on GP is limited. WHAT IS NEW AND CONCLUSIONS: The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible. Further evidence is necessary for more conclusive inferences.

A2delta ligands gabapentin and pregabalin: future implications in daily clinical practice.

Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2delta ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe. Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.

Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis.

Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine essential for osteoclast differentiation, activation, and survival. Denosumab, a human monoclonal antibody against RANKL, constitutes a promising antiresorptive agent for osteoporosis. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2009. We selected randomized controlled trials (RCTs) of denosumab in women with low bone mass that described the changes on bone markers and bone mineral density (BMD) as well as the adverse events including fracture risk. We analyzed data from nine RCTs involving 10 329 participants. Although denosumab universally decreased bone markers and increased lumbar and hip BMD, the efficacy evaluation based on percentage (%) mean change from the baseline was not possible due to missing data. Denosumab was not associated with a significant reduction in fracture risk [OR (95% CI) 0.74 (0.33 to 1.64), p=0.45]. Increased risk of serious adverse events [OR (95% CI) 1.83 (1.10 to 3.04), p=0.02] and serious infections [OR (95% CI) 4.45 (1.15 to 17.14), p=0.03] were evident. In conclusion, although effective as an antiresorptive agent, denosumab has not yet proved its efficacy on fracture risk reduction while increased infection risk questions its safety.

Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis.

BACKGROUND: Conflicting results regarding adiponectin levels in women with polycystic ovary syndrome (PCOS) have been reported. To evaluate adiponectin levels in PCOS, a systematic review of all studies comparing adiponectin levels in women with PCOS with healthy controls and a meta-analysis of those involving women with similar body mass index (BMI) were performed. The influence of possible effect modifiers, such as insulin resistance (IR) and testosterone, was investigated. The influence of obesity was investigated through a 'nested' meta-analysis after within-study BMI stratification and appropriate pooling. METHODS: Literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL (through June 2008), references from relevant studies and personal contact with the authors. Thirty-one studies, reporting data on 3469 subjects, were reviewed and 16 included in the main meta-analysis. RESULTS: Women with PCOS demonstrated significantly lower adiponectin values [weighted mean difference (95% confidence interval) -1.71 (-2.82 to -0.6), P < 10(-4)], yet with significant between-study heterogeneity. Lower adiponectin levels are associated with the IR observed in women with PCOS, compared with controls. IR, but not total testosterone, was found significant among biological parameters explored in the meta-regression model. Hypoadiponectinaemia was present in both lean and obese women with PCOS when compared with non-PCOS counterparts. Data on high molecular weight (HMW) adiponectin are limited (three studies). CONCLUSIONS: After controlling for BMI-related effects, adiponectin levels seem to be lower in women with PCOS compared with non-PCOS controls. Low levels of adiponectin in PCOS are probably related to IR but not to testosterone. Total adiponectin should not be used as a biomarker of PCOS severity. Further investigation is needed for HMW adiponectin levels in PCOS.