Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: Thyroid cancer is increasing globally and is currently the most prevalent endocrine malignancy. Recent data show an increase in the incidence of thyroid cancer in the Kingdom of Saudi Arabia (KSA). Thyroid ultrasound and fine-needle aspiration cytology (FNAC) are the cornerstones in managing thyroid nodules. We conducted this study to evaluate the prevalence and the associated predictors for thyroid nodule Bethesda III-VI in eastern KSA.

Methods: A retrospective study was conducted between January 2015 and 31 August 2021. The participants were recruited patients who received a thyroid ultrasound and ultrasound-guided thyroid FNAC, using the thyroid imaging reporting and data system (TI-RADS) and the Bethesda Classification, respectively.

Result: Three hundred and ten patients who underwent thyroid FNAC were enrolled in the study. The median (interquartile, IQR) age was 47.0 (20.0) years, and 266 (85.8%) of them were females. The median (IQR) body mass index was 30.2 (7.6) kg/m². Out of these participants, 64.8% were euthyroid, 27.4% had hypothyroidism and 7.7% had hyperthyroidism. The ACR TI-RADS-3, 4 and 5 were 51.3%, 46.1% and 2.6%, respectively. The Bethesda outcome of thyroid FNAC I-VI was 5.2%, 63.9%, 15.5%, 5.8%, 3.5% and 6.1%, respectively. The risk for malignancy (Bethesda III-VI) was documented in 31.0% and atypia of undetermined significance was most prevalent (15.5%). A higher ACR TI-RADS score was associated with a higher risk of malignancy: ACR TI-RADS-3 (20.8%), ACR TI-RADS-4 (39.2%) and ACR TI-RADS-5 (87.5%). In a multivariate analysis, only the ACR TI-RADS score was significantly associated with the outcome of thyroid FNAC: ACR TI-RADS-4 [OR = 2.59 (95% CI = 1.54-4.36)] and ACR TI-RADS-5 [OR = 29.03 (95% CI = 3.44-245.07)].

Conclusion: There was a high prevalence of Bethesda III-VI and atypia of undetermined significance was most prevalent. A thyroid ultrasound report for TI-RADS was significantly associated with the outcome of thyroid FNAC and is a reliable tool in the absence of molecular testing for thyroid cancer.

Background: Lower extremity amputations from diabetic foot ulcers (DFUs) are rebounding, and new biomarkers that predict wound healing are urgently needed. Anaerobic bacteria have been associated with persistent ulcers and may be a promising biomarker beyond currently recommended vascular assessments. It is unknown whether anaerobic markers are simply a downstream outcome of peripheral arterial disease (PAD) and ischemia, however. Here, we evaluate associations between two measures of anaerobic bacteria-abundance and metabolic activity-and PAD.

Methods: We built a prospective cohort of 37 patients with baseline ankle brachial index (ABI) results. Anaerobic bacteria were measured in two ways: DNA-based total anaerobic abundance using 16S rRNA gene amplicon sequencing and resulting summed relative abundance, and RNA-based metabolic activity based on bacterial read annotation of metatranscriptomic sequencing. PAD was defined three ways: PAD diagnosis, ABI results, and a dichotomous definition of mild ischemia (versus normal) based on ABI values. Statistical associations between anaerobes and PAD were evaluated using univariate odds ratios (ORs) or Spearman's correlations.

Results: Total anaerobe abundance was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (OR_PAD = 0.47, 95% CI = 0.023-7.23, p = 0.60; Spearman's correlation coefficient_ABI = 0.24, p = 0.17; OR_{mild ischemia} = 0.25, 95% CI = 0.005-5.86, p = 0.42). Anaerobic metabolic activity was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (OR_PAD = 1.99, 95% CI = 0.17-21.44, p = 0.57; Spearman's correlation coefficient_ABI = 0.12, p = 0.52; OR_{mild ischemia} = 0.90, 95% CI = 0.03-15.16, p = 0.94).

Conclusion: Neither anaerobic abundance nor metabolic activity was strongly associated with our three definitions of PAD. Therefore, anaerobic bacteria may offer additional prognostic value when assessing wound healing potential and should be investigated as potential molecular biomarkers for DFU outcomes.

Background: There is paucity of literature on the impact of teriparatide on hip geometry and bone microarchitecture globally and none from the Indian subcontinent. This study examined the outcome of teriparatide therapy on vertebral fractures, bone mineral density (BMD), hip structural analysis (HSA), and trabecular bone score (TBS) in Indian postmenopausal women with severe osteoporosis.

Methodology: Ambulatory postmenopausal women above the age of 50 years with either severe osteoporosis or vertebral fractures, or both, were recruited. All patients received cholecalciferol (2000 IU/day), calcium carbonate (elemental calcium 1 g/day), and teriparatide (20 mcg subcutaneously/day) for 24 months. Baseline bone biochemistry, BMD, TBS, and HSA were assessed and repeated after 24 months of therapy. Incident vertebral and nonvertebral fractures were also studied.

Results: A total of 51 postmenopausal women with mean (SD) age of 65.7(8.6) years, and mean (SD) body mass index of 22.7 (3.5) kg/m² were recruited in this study. Vertebral fractures were present in 74.5% (38/51) at baseline. Following teriparatide therapy, significant improvement was observed in the BMD (g/cm²) at both the lumbar spine (0.706-0.758: p < 0.001) and femoral neck (0.551-0.579: p = 0.047) as well as the TBS (1.160-1.271: p < 0.001). Most indices of proximal hip geometry also showed significant improvement following teriparatide therapy at 24 months. Incident vertebral fractures were noted in only 7.8% (4/51) of participants, while 92% (47/51) of participants did not develop any new vertebral fractures on follow-up.

Conclusion: In South Indian postmenopausal women with either severe osteoporosis or vertebral fractures, or both, teriparatide was effective in improving the bone mineral parameters and bone quality.

In most patients, osteoporosis is diagnosed only after the occurrence of the first fragility fracture. It is of utmost importance to start osteoporosis medications immediately in these patients to prevent future fractures and also to reduce associated mortality and morbidity. There remains a hesitancy over initiating osteoporotic medications, specifically for antiresorptive agents like bisphosphonates following an acute fracture due to concern over their effect on fracture healing. The purpose of this review is to study the effect of the timing of initiation of different osteoporosis medications on healing after an acute fracture. Most of the human studies, including randomized control trials (RCTs), did not find any significant negative effect on fracture healing with early use of bisphosphonate after an acute fracture. Anabolic agents like teriparatide have shown either neutral or beneficial effects on fracture healing and thus can be started very early following any osteoporotic fracture. Although human studies on the early use of other osteoporosis medications like denosumab or strontium ranelate are very sparse in the literature, none of these medications have shown any evidence of delay in fracture healing. To summarize, among the commonly used anti-osteoporosis agents, both bisphosphonates and teriparatide are safe to be initiated in the early acute post-fracture period. Moreover, teriparatide has shown some evidence in favor of reducing fracture healing time.

Chronic kidney disease (CKD) affects around 10% of the global population and is most often caused by diabetes. Diabetes with CKD (diabetic kidney disease, DKD) is a progressive condition that may cause kidney failure and which contributes significantly to the excess morbidity and mortality in these patients. DKD is treated with direct disease-targeting therapies like blockers of the renin-angiotensin system, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and non-steroidal mineralocorticoid receptor antagonists as well as indirect therapies impacting hyperglycaemia, dyslipidaemia, obesity and hypertension, which all together reduce disease progression. While no glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are currently indicated to improve kidney outcomes, accumulating evidence from cardiovascular outcomes trials (CVOTs) corroborates a kidney-protective effect in people with T2D and CKD, and GLP-1 RAs are now mentioned in international treatment guidelines for type 2 diabetes (T2D) with CKD. GLP-1 RAs are indicated to improve glycaemia in people with T2D; certain GLP-1 RAs are also approved for weight management and to reduce cardiovascular risk in T2D. Ongoing pivotal trials are assessing additional indications, including T2D with CKD. In this article, we review and discuss kidney outcomes from a multitude of completed clinical trials as well as real-world evidence and ongoing clinical trials.

Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting women. It has traditionally been viewed as a primarily reproductive disorder; however, it is increasingly recognized as a lifelong metabolic disease. Women with PCOS are at increased risk of insulin resistance (IR), type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular disease. Although not currently a diagnostic criterion, IR is a cardinal pathophysiological feature and highly prevalent in women with PCOS. Androgens play a bidirectional role in the pathogenesis of IR, and there is a complex interplay between IR and androgen excess in women with PCOS. Skeletal muscle has a key role in maintaining metabolic homeostasis and is also a metabolic target organ of androgen action. Skeletal muscle is the organ responsible for the majority of insulin-mediated glucose disposal. There is growing interest in the relationship between skeletal muscle, androgen excess and mitochondrial dysfunction in the pathogenesis of metabolic disease in PCOS. Molecular mechanisms underpinning defects in skeletal muscle dysfunction in PCOS remain to be elucidated, but may represent promising targets for future therapeutic intervention. In this review, we aim to explore the role of skeletal muscle in metabolism, focusing particularly on perturbations in skeletal muscle specific to PCOS as observed in recent molecular and in vivo human studies. We review the possible role of androgens in the pathophysiology of skeletal muscle abnormalities in PCOS, and identify knowledge gaps, areas for future research and potential therapeutic implications. Despite increasing interest in the area of skeletal muscle dysfunction in women with PCOS, significant challenges and unanswered questions remain, and going forward, novel innovative approaches will be required to dissect the underlying mechanisms.

[This retracts the article DOI: 10.1177/2042018820923474.].

The coronavirus disease 2019 (COVID-19) pandemic affected at least 200 million individuals worldwide and resulted in nearly 5 million deaths as of October 2021. According to the latest data from the International Diabetes Federation (IDF) in 2021, the diabetes pandemic has affected 537 million people and is associated with 6.7 million deaths. Given the high prevalence of both diabetes and COVID-19 and common pathological outcomes, a bidirectional relationship could have a catastrophic outcome. The increased risk of COVID-19 in those with obesity and diabetes and higher morbidity and mortality has received considerable attention. However, little attention has been given to the relationship between COVID-19 and microvascular complications. Indeed, microvascular complications are associated with an increased risk of cardiovascular disease (CVD) and mortality in diabetes. This review assesses the evidence for an association between diabetic microvascular complications (neuropathy, nephropathy, and retinopathy) and COVID-19. It draws parallels between the pathological changes occurring in the microvasculature in both diseases and assesses whether microvascular disease is a prognostic factor for COVID-19 outcomes in diabetes.

Background: Evidence investigating sleep pattern in relation to bone health in elderly participants with osteoporosis remains sparse. We aimed to assess the relationship between sleep pattern incorporating five sleep characteristics (snoring, midnight waking up, insomnia, sleep duration, and daytime napping) and bone mineral density (BMD) in elderly participants with osteoporotic fracture.

Methods: A cross-sectional study was conducted to include eligible elderly patients from the Department of Orthopedics who were admitted to hospital due to an osteoporotic fracture. Sleep pattern was constructed based on total sleep scores and categorized into healthy, intermediate, and poor pattern groups. Multivariable logistic regression model was used to assess sleep pattern in relation to risk of low BMD.

Results: A total of 169 elderly patients with osteoporotic fracture were included in this study (mean age: 71.91 years; 87.57% females). There were 36 (21.30%), 107 (63.31%), and 26 (15.38%) patients with healthy, intermediate, and poor sleep pattern, respectively. Compared with healthy sleep pattern, no significant relationship between intermediate sleep pattern and BMD was detected [odds ratio (OR) = 1.72, 95% confidence interval (CI): 0.74, 3.97, p = 0.21), while poor pattern was significantly associated with decreased BMD (OR = 3.50, 95% CI: 1.10, 11.14, p = 0.034).

Conclusion: The majority of elderly patients with osteoporotic fracture had unhealthy sleep pattern; poor sleep pattern was significantly related to reduced BMD when compared with healthy pattern. Further high-quality evidence is needed to assess and validate the relationship between sleep pattern and risk of low BMD in the elderly.

Background: In recent years, many studies have reported the relationship between non-alcoholic fatty liver disease (NAFLD) and sex hormones, especially total testosterone (TT) and sex hormone-binding globulin (SHBG). However, the relationship between sex hormones and the severity of NAFLD is still unclear.

Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to 31 August 2021. Values of weighted mean differences (WMDs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the relationship between TT, SHBG and the severity of NAFLD in males.

Results: A total of 2995 patients with NAFLD from 10 published cross-sectional studies were included for further analysis. The meta-analysis indicated that the moderate-severe group had a lower TT than the mild group in males with NAFLD (WMD: -0.35 ng/ml, 95% CI = -0.50 to -0.20). TT and SHBG were important risk factors of moderate-severe NAFLD in males (OR_TT = 0.79, 95% CI = 0.73 to 0.86; OR_SHBG = 0.22, 95% CI = 0.12 to 0.39; p < 0.001). Moreover, when the analysis was limited to men older than age 50, SHBG levels were lower in those with moderate-severe disease (WMD: -11.32 nmol/l, 95% CI = -14.23 to -8.40); while for men with body mass index (BMI) >27 kg/m², moderate-severe NAFLD had higher SHBG levels than those with mild disease (WMD: 1.20 nmol/l, 95% CI = -2.01 to 4.42).

Conclusion: The present meta-analysis shows that lower TT is associated with the severity of NAFLD in males, while the relationship between SHBG and severity of NAFLD is still to be further verified.