Association between BMI and osteoporotic fractures at different sites in Chinese women: a case-control retrospective study in Changsha.

BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.

Association between thyroid autoimmunity and bone mineral density in patients with type 2 diabetes mellitus: a cross-sectional study.

PURPOSE: The purpose of this study was to analyze the relationship between thyroid autoimmunity and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM), and to further explore the influence of thyroid autoimmunity on diabetic osteoporosis. METHODS: A total of 601 T2DM patients were included and divided into two groups according to thyroid autoantibodies, namely thyroid autoimmunity positive group (TPOAb+ or TGAb + ) and thyroid autoimmunity negative group (TPOAb- and TGAb-). Clinical data were collected and BMD was determined by dual-energy X-ray absorptiometry (DXA). SPSS26.0 software was used to data analysis. Model regression was used to analyze the influencing factors of BMD, and ROC curve was used to analyze the optimal cut-off point of thyroid peroxidase antibody (TPOAb) for screening osteoporosis. RESULTS: TPOAb and thyroglobulin antibody (TGAb) were negatively correlated with BMD and T-score (LS, FN and WB) (P < 0.01), and TGAb was negatively correlated with 25(OH)D (P < 0.05). Multiple linear regression analysis showed that TPOAb was an independent influence factor on LS, FN and WB BMD. ROC curve analysis showed that the optimal threshold of TPOAb for predicting osteoporosis was 12.35. CONCLUSIONS: In T2DM patients, TPOAb and TGAb levels are negatively correlated with LS, FN and WB BMD, and TPOAb is an independent influencing factor for diabetic osteoporosis, and TPOAb has a certain predictive value for the occurrence and development of diabetic osteoporosis clinically.

Association of serum trimethylamine N-oxide levels and bone mineral density in type 2 diabetes mellitus.

PURPOSE: The relationship between trimethylamine N-oxide (TMAO) and bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) is unclear. We explore the relationship between TMAO levels and BMD in T2DM. METHODS: This is a cross-sectional study. 254 T2DM patients were enrolled and divided into three groups by TMAO tertiles, and the clinical data were collected. BMD was determined by dual-energy X-ray absorptiometry (DXA) and serum TMAO levels was determined by stable isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). RESULTS: Patients in the highest tertile of TMAO levels (TMAO > 6.72 µmol/L) showed relatively low BMD and a higher number of fracture history, osteoporosis (OP) than those in the lower tertiles. Spearman correlation analysis showed that serum TMAO was negatively correlated with BMD of whole body (WB), lumbar spine (LS) and femoral neck (FN), while TMAO was positive correlated with osteoporotic fracture (p < 0.05). Logistic regression models showed that TMAO was an independent influencing factor of fracture history after adjusting for confounders in TMAO > 6.72 µmol/L group. CONCLUSIONS: There is a significant linear correlation between TMAO levels and BMD in T2DM patients. Especially in TMAO > 6.72 µmol/L group, TMAO was negatively correlated with WB, LS, and FN BMD, and was positive correlated with osteoporotic fracture in T2DM patients. The findings suggest that elevated TMAO levels are associated with OP and osteoporotic fracture in T2DM patients.

Correlation Between Insulin Resistance and Urinary Incontinence in Female Patients with Type 2 Diabetes Mellitus.

INTRODUCTION AND HYPOTHESIS: Patients with type 2 diabetes mellitus (T2DM) are at a high risk of developing urinary incontinence; however, its pathogenesis is unclear. The purpose of this study is to explore the relationship between insulin resistance and urinary incontinence and its severity in female patients with T2DM. METHODS: A total of 366 women with T2DM aged ≥18 years were enrolled in this study. Insulin resistance was evaluated by the homeostasis model insulin resistance (HOMA-IR) index and urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). All subjects were divided into four groups according to HOMA-IR quartiles. Logistic regression analysis was performed to investigate the relationship between insulin resistance and urinary incontinence and its severity. RESULTS: Among the 366 patients, 186 (50.8%) had urinary incontinence. The prevalence of urinary incontinence increased significantly with HOMA-IR quartiles (p < 0.001). Adjusted logistic regression analysis showed that compared with HOMA-IR ≤ 1.76, 2.81 ≤ HOMA-IR ≤ 4.27 was associated with a significantly increased risk of moderate incontinence (OR = 2.197, 95% CI 1.031-4.683, p = 0.041), and HOMA-IR ≥ 4.28 was associated with a significantly increased risk of severe incontinence (OR = 5.699, 95% CI 1.685-19.276, p = 0.005). Binary logistic regression analysis showed that HOMA-IR was the independent risk factor for urinary incontinence (p < 0.001). CONCLUSIONS: Higher levels of insulin resistance are associated with urinary incontinence and its severity in female patients with type 2 diabetes mellitus.

Association of C-peptide level with bone mineral density in type 2 diabetes mellitus.

This study revealed that there was no significant linear relationship between fasting C-peptide (FCP) level and bone mineral density (BMD) or fracture risk in type 2 diabetes mellitus (T2DM) patients. However, in the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with whole body (WB), lumbar spine (LS), and femoral neck (FN) BMD and negatively correlated with fracture risk. PURPOSE: To explore the relationship between C-peptide and BMD and fracture risk in T2DM patients. METHODS: 530 T2DM patients were enrolled and divided into three groups by FCP tertiles, and the clinical data were collected. BMD was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was evaluated by adjusted fracture risk assessment tool (FRAX). RESULTS: In the FCP ≤ 1.14 ng/ml group, FCP level was positively correlated with WB, LS, and FN BMD, while FCP was negatively correlated with fracture risk and osteoporotic fracture history. However, FCP was not correlated with BMD and fracture risk and osteoporotic fracture history in the 1.14 < FCP ≤ 1.73 ng/ml and FCP > 1.73 ng/ml groups. The study has shown that FCP was an independent factor influencing BMD and fracture risk in the FCP ≤ 1.14 ng/ml group. CONCLUSIONS: There is no significant linear relationship between FCP level and BMD or fracture risk in T2DM patients. In the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with WB, LS, and FN BMD and negatively correlated with fracture risk, and FCP is an independent influencing factor of BMD and fracture risk. The findings suggest that FCP may predict the risk of osteoporosis or fracture in some T2DM patients, which has a certain clinical value.

Association of Insulin-Like Growth Factor-1 With Polycystic Ovarian Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: Circulating concentration of insulin-like growth factor (IGF)-1 in patients with polycystic ovary syndrome (PCOS) is still unclear. Therefore, we aimed to investigate the association of IGF-1 with PCOS through this meta-analysis. METHODS: Literature search was conducted through PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (up to July 2022). A manual search was performed on the references of related original research. Then, we applied the random-effects model to evaluate the overall effect size by calculating the standard mean difference and its 95% CI. Subgroup analyses were used to explore the sources of heterogeneity. In addition, a sensitivity analysis was performed and publication bias was assessed. RESULTS: Twenty studies were included in this meta-analysis involving 657 individuals: 362 patients with PCOS and 295 normal controls. The results of meta-analysis showed that serum IGF-1 levels were significantly higher in patients with PCOS than in controls (standard mean difference, 0.89; 95% CI, 0.34-1.45; P = .002). The final pooled data were determined by the random-effects model because a significant high heterogeneity (I2 = 89%) was found. A subgroup analysis based on body mass index showed that elevated IGF-1 level was associated with normal-weight and overweight patients in the PCOS group, but there was no significant association with obesity. The sensitivity analysis indicated that no individual study significantly affected the overall pooled result and no publishing bias was observed. CONCLUSION: These data suggest that elevated serum IGF-1 levels may not be a major cause of PCOS pathogenesis. Body mass index may be a major determinant of serum IGF-1.

Association Between Coronary Artery Calcium Score and Bone Mineral Density in Type 2 Diabetes Mellitus with Different Visceral Fat Area.

Purpose: The relationship between coronary artery calcification and bone mineral density (BMD) in T2DM is still unclear. The aim of this study is to analyze the association between coronary artery calcium score (CACs) and BMD in T2DM with different visceral fat area (VFA), and further to explore the clinical significance of CACs in predicting osteoporosis in T2DM patients. Patients and Methods: A total of 479 T2DM patients aged ≥50 years were included. Agatston was applied to calculate CACs to evaluate the degree of coronary artery calcification. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD. According to VFA, all subjects were divided into VFA <100cm2 and VFA ≥100cm2 group. Adjusted regression analysis was performed to analyze the association between CACs and BMD. ROC curve was used to analyze the optimal cut-off value of CACs for screening osteoporosis. Results: The baseline showed that in VFA ≥100cm2 group, CACs increased significantly than that in VFA <100cm2 group (212.1±195.9 vs 139.3±141.8, p<0.001) and total hip BMD decreased obviously (0.968±0.19 vs 1.021±0.184, p=0.01). After multivariable adjustment, CACs was not significantly associated with BMD in all patients (p>0.05). However, CACs was negatively associated with BMD of total hip and lumbar spine in patients with VFA ≥100cm2 (total hip ß=-0.087 p=0.01; lumbar spine ß=-0.052 p=0.005), but not VFA <100cm2. ROC curve analysis showed that the optimal cut-off value of CACs for screening osteoporosis was 191.505. Conclusion: The present study implied that associations between CACs and BMD varied by the visceral fat deposition. It is critical to evaluate the condition of visceral fat accumulation for exploring the complex interplay of coronary artery calcification and BMD in T2DM patients. It may be of some clinical value for CACs in predicting osteoporosis in T2DM with visceral obesity.

Relationship between vitamin D status and cardiac autonomic neuropathy in prediabetes.

BACKGROUND AND OBJECTIVES: Studies have suggested that vitamin D deficiency is associated with impaired cardiac autonomic nerve function. This study explores the correlation between serum vitamin D and cardiac autonomic neuropathy (CAN) in prediabetes and reveals the protective effect of vitamin D against CAN. METHODS AND STUDY DESIGN: In total, 113 patients with prediabetes and definite CAN and 180 with prediabetes but without CAN were enrolled on the basis of their standard cardiovascular autonomic reflex test results. Chemiluminescence was used to measure 25(OH)D, the patients with CAN were divided into four groups, and the heart rate variability (HRV) of the study groups were compared. RESULTS: Relative to the 50≤25(OH)D<75-nmol/L group, the 25≤25(OH)D<50-nmol/L and 25(OH)D<25-nmol/L groups exhibited significant differences in the time and frequency domains of HRV (p< 0.05). Furthermore, we discovered that 25(OH)D is positively correlated with standard deviation of normal-to-normal RR intervals (SDNN) (ß=0.566, p<0.05) and negatively correlated with low-to-high frequency ratio (LF/HF) (ß=-0.199, p<0.05). A logistic regression reveals that CAN in prediabetes is significantly correlated with the 25(OH)D concentrations of <25 nmol/L (OR, 2.380 [1.208-4.691]; p<0.05) and 25≤25(OH)D<50 nmol/L (OR, 1.875 [1.064-3.751]; p<0.05). CONCLUSIONS: Serum 25(OH)D is significantly correlated with CAN in prediabetes, especially in the 25(OH)D <25-nmol/L group. Therefore, vitamin D deficiency may be related to the occurrence of CAN in prediabetes, and appropriate supplementation may provide protection against CAN.

Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis.

OBJECTIVE: The relationship between Toll like receptor 4(TLR4) gene Asp299Gly polymorphism and diabetic microvascular complications (DMI) is unclear. Therefore, the aim of this meta analysis was to explore the relationship between TLR4 Asp299Gly polymorphism and DMI. METHODS: System search PubMed, Web of science, Springer, Cochrane library, ELSEVIER, Wanfang database, VIP, CNKI, a case-control study of the correlation between TLR4 gene Asp299Gly polymorphism and DMI published before June 2020 was collected. RESULTS: We included 6 articles, a total of 11 studies involving patients with type 2 diabetes mellitus (T2DM) complicated by microvascular complications 1834 cases, without corresponding microvascular complications 4069 cases. TLR4 gene Asp299Gly polymorphism increased the risk of microvascular complications in T2DM (dominant model OR = 1.52, 95% CI 1.10-2.09, p = 0.01; allelic model OR = 1.42, 95% CI 1.02-1.96, p = 0.04). Subgroup analysis by race and different type of microvascular complications, we found that TLR4 gene Asp299Gly polymorphism was associated with increased risk of microvascular complications in the Caucasian population (dominant model OR = 1.69, 95% CI 1.22-2.35, P = 0.002; allelic model OR = 1.56, 95% CI 1.10-2.21, P = 0.01) and increased the risk of retinopathy in patients with T2DM(dominant model OR = 1.81, 95% CI 1.04-3.14, P = 0.03; allelic model OR = 1.77, 95% CI 1.05-2.98, P = 0.03). CONCLUSION: TLR4 gene Asp299Gly polymorphism was associated with increased risk of microvascular complications in patients with T2DM, especially diabetic retinopathy (DR).

Impaired Vascular Endothelial Function is Associated with Peripheral Neuropathy in Patients with Type 2 Diabetes.

Purpose: It is believed that vascular endothelial dysfunction is involved in the occurrence of cardiovascular disease (CVD), and diabetic peripheral neuropathy (DPN) is associated with flow-mediated dilation (FMD), however, the correlation is still unclear. Aims of the present study is to explore the relationship between DPN parameters and FMD, providing a new approach for the prevention of CVD. Patients and Methods: A total of 272 patients with T2DM from the Department of Endocrinology of The First Hospital of Lanzhou University according to the grading criteria were selected. FMD was measured by a new vascular ultrasound system and patients were divided into FMD>7%, 4%≤FMD≤7%, and FMD<4% groups. The Toronto Clinical Scoring System (TCSS) was used to assess the severity of DPN. The nerve conduction studies (NCS) assessed large fibre neuropathy by nerve conduction velocity (CV), compound muscle action potential (CMAP) amplitude (Amp), and distal motor latency (DML). SPSS 25.0 was used for statistical analysis. Results: TCSS evaluation revealed that the percentage of patients with severe nerve injury was significantly higher in FMD<4% (70%) compared to FMD>7% (2%). Among the TCSS indicators of all subjects, the proportion of temperature disturbance was the most (73%), and joint position disturbance was the least (0). TCSS scores were negatively correlated with FMD (r=-0.756, p<0.001). More interesting, in FMD<4% group, CV and Amp were positively correlated with FMD, while DML was negatively correlated (p<0.05). Linear regression analysis model showed that different systolic blood pressure (SBP), triglyceride (TG), TCSS and CV had statistically different effects on FMD. Conclusion: High TCSS score and decreased CV of common peroneal and tibial nerves are risk factors of FMD injury, which provide potential value for timely prevention and treatment of cardiovascular diseases.

Birth weight and the risk of overall breast cancer, premenopausal and postmenopausal breast cancer in adulthood: a dose-response meta-analysis of observational studies.

IMPORTANCE: The effect of birth weight on breast cancer across different menopausal states remains unknown. OBJECTIVE: The aim of this study was to systematically evaluate the association of birth weight with the risk of overall breast cancer (OBC) and premenopausal and postmenopausal breast cancer during adulthood. In parallel, the dose-response analyses were performed. EVIDENCE REVIEW: Relevant studies were systematically searched from the PubMed, Embase, and the Cochrane Library databases from the inception to May 25, 2021, without language restrictions. All the results were pooled according to risk ratios (RRs). FINDINGS: In total, 21 cohort studies comprising 1,139,032 participants were included. An increase in the birth weight was not associated with the risk of OBC and premenopausal and postmenopausal breast cancer. Compared with women having normal weight at birth, those with a high birth weight are likely to have an increased risk of invasive breast cancer (RR: 1.19, 95% confidence intervals: 1.03-1.38; I2: 28.6%). The dose-response analyses showed that the risk of premenopausal breast cancer increased significantly in unknown singleton status with birth weight over 2850 g (RR: 1.14 [1.02-1.30]). Similarly, postmenopausal breast cancer risk was increased in singleton births with birth weight over 3750 g (RR: 1.21 [1.00-1.47]). CONCLUSIONS AND RELEVANCE: High weight at birth might be not significantly associated with the risk of OBC, premenopausal and postmenopausal breast cancer and ER+ and ER- breast cancer but is positively associated with the risk of invasive breast cancer, regardless of parity. Furthermore, with an increase in birth weight, the risk of postmenopausal breast cancer is likely to increase in the singleton births, whereas the risk of premenopausal breast cancer is likely to increase in unknown singleton status.

Elevated TPOAb is a Strong Predictor of Autoimmune Development in Patients of Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Case-Control Study.

OBJECTIVE: The aim of this study was to assess the prevalence of thyroid autoimmunity in T2DM with NAFLD, furthermore explore the relationship between elevated TPOAb titer and the severity of NAFLD. METHODS: A total of 400 patients with T2DM were divided into two groups according to NAFLD. Thyroid function and other metabolic indicators were measured. RESULTS: There were more TPOAb-positive patients in both groups, and the prevalence of TPOAb positive was significantly different in two groups (17% vs 6.9%, p< 0.01). FT4 was significantly lower in patients with T2DM with NAFLD (median FT4 0.89 vs 1.08, p < 0.001), while TSH was increased (median TSH 2.85 vs 2.28, p < 0.05). In patients with T2DM with NAFLD, the proportion of women in the thyroid autoimmune-positive group was significantly higher than the negative (71.1% vs 46%, p < 0.01). Similarly, thyroid autoimmune-positive T2DM and NAFLD patients had lower FT4 levels (median FT4 0.59 vs 0.92, p < 0.001), higher TSH levels (median TSH 3.65 vs 2.67, p < 0.001), and much higher TPOAb/TGAb (median TPOAb/TGAb 6.8 vs 1.46, p < 0.001). The increase of TPOAb was significantly correlated with the severity of fatty liver. HbA1c, TC, TG, TSH, TPOAb/TGAb and severity of fatty liver were risk factors of thyroid autoimmunity. CONCLUSION: Autoimmune thyroid disease is more common in patients with T2DM complicated with NAFLD. Elevated TPOAb titer is closely related to fatty liver, suggesting that elevated TPOAb titer is a predictor of autoimmune development in T2DM with NAFLD.

Clinical characteristics and gene mutation analysis of an adult patient with ETFDH­related multiple acyl­CoA dehydrogenase deficiency.

Multiple acyl­CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder of fatty acid metabolism caused by defects in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). These defects are mainly classified into the neonatal and late­onset types, based on their clinical manifestations. ETFDH gene mutations are generally considered to be associated with the late­onset type. The present study reported an adult woman with late­onset MADD accompanied with biochemical and muscle biopsy findings indicating metabolic disorders. Gene sequencing analysis showed that the c.1514T>C homozygous mutation in the region of the 12th exon of the ETFDH gene, which led to the amino acid substitution p.I505T (isoleucine > threonine), resulting in defective ETFDH protein function. The results of family verification revealed that the homozygous mutation originated from her parents. The female patient was treated with a large dose of vitamin B2, L­carnitine and coenzyme Q10, and the symptoms were significantly relieved. The c.1514T>C mutation in the ETFDH gene, was considered as a novel pathogenic mutation that had not been previously reported. Therefore, it was hypothesized that this mutation was responsible for the clinical characteristics of the adult female patient. Overall, this novel mutation could expand the spectrum of the ETFDH gene mutation and provide the basis for the etiological and prenatal diagnosis of MADD.

Analysis of angiographic characteristics and intervention of vitamin D in type 2 diabetes mellitus complicated with lower extremity arterial disease.

AIMS: Previous studies have suggested that type 2 diabetes mellitus with lower extremity arterial disease is related to 25-hydroxyvitamin D deficiency. The purpose of this study is to explore the relation between vitamin D supplementation and the characteristics of type 2 diabetes mellitus complicated with lower extremity arterial disease. METHODS: The clinical data of 514 patients and 148 healthy subjects treated in the First Hospital of Lanzhou University from January 2012 to June 2019 were collected, including the clinical data, ankle-brachial index, and medical records of lower limb artery angiography. We divided the patients into control group (NC group), type 2 diabetes mellitus group (DM group), lower extremity artery disease in type 2 diabetes mellitus without vitamin D supplement group (DM1 group) and lower extremity artery disease in type 2 diabetes mellitus with vitamin D supplement group (DM2 group). The level of serum 25(OH)D was analyzed and the characteristics of arterial lesions of lower extremities were compared by DSA arteriography in DM1 and DM2 group, respectively. RESULTS: Compared with the NC group, serum 25(OH)D level decreased in DM group (25.39 ± 4.94 ng/mL vs 19.43 ± 5.98 ng/mL) and significantly decreased in DM1 and DM2 group (14.22 ± 5.64 ng/mL vs 17.36 ± 6.25 ng/mL). However, the level of serum 25(OH)D in the DM2 group was higher than that in the DM1 group. Compared with the DM1 group, the disease rate of the inferior knee artery (65% vs 39.3%) and occlusion rate (11.5% vs 3.7%)were decreased in the DM2 group (P < 0.05). Logistic stepwise regression analysis showed that serum 25(OH)D level was a risk factor for lower extremity arterial disease in patients with type 2 diabetes mellitus (OR = 0.898,95%CI = 0.856-0.942). CONCLUSIONS: The serum level of 25(OH)D in patients with type 2 diabetes mellitus complicated with lower extremity arterial disease is decreased, and level of 25 (OH) D is related to stenosis and occlusion rate, especially in inferior genicular artery in T2DM complicated with LEAD. A high level of 25(OH)D may be a protective factor in type 2 diabetes with lower extremity arterial disease.

Association between diabetic neuropathy and osteoporosis in patients: a systematic review and meta-analysis.

OBJECTIVES: Many studies have explored the association between neuropathy and osteoporosis in patients with diabetes mellitus. However, the results still remain inconsistent and controversial. We aimed to estimate the association between diabetic neuropathy and osteoporosis. METHODS: Databases, including PubMed, Embase, Web of Science, the Cochrane library, Chinese Biomedical Literature Database (CBM), and Wanfang, were screened from inception to 30 March 2020. Studies were selected and data were extracted by two independent reviewers. Study characteristics and quality sections were reviewed independently. Pooled ORs and 95% CIs were calculated using random effects model when evidence of heterogeneity was present; otherwise, fixed effects model was used. Meta-regression and subgroup analyses were performed to explore the source of heterogeneity. Sensitivity analysis and publication bias were also tested. RESULTS: A total of 11 studies with 27,585 participants were included in this analysis which indicated that there was an increased odd between diabetic neuropathy and osteoporosis (overall OR 2.20, 95% CI 1.71-2.83). In the subgroup analyses and meta-regression, diabetic neuropathy has no significant difference in osteoporosis or fracture (p = 0.532). And osteoporosis also has no significant difference in type 1 or type 2 diabetic neuropathy (p = 0.668). CONCLUSIONS: This meta-analysis suggests that patients with diabetic neuropathy have a significantly increased chance of developing osteoporosis, even fragility fracture. The clinicians should pay more attention to the patients with diabetic neuropathy. Further studies were still needed to explore the confounding factors among studies and to elucidate the underlying biological mechanisms.

Effect of thyrotropin suppressive therapy on heart rate variability and QT dispersion in patients with differentiated thyroid cancer.

The effects of thyrotropin (TSH) suppressive therapy on autonomic regulation and ventricular repolarization in patients with differentiated thyroid cancer (DTC) have not been elucidated. The aim of present study was to evaluate variation in heart rate variability (HRV) and QT dispersion after TSH suppressive therapy in patients with DTC.Cases, defined as 271 patients with DTC within 1 year of exogenous levothyroxine, and all patients underwent a full history, physical examination, including standard 12 lead electrocardiogram (ECG), and 24 h ambulatory ECG monitoring (Holter) with normal free thyroxine (FT4) and free triiodothyronine (FT3) with levothyroxine. To evaluate effects of TSH suppressive therapy on HRV and QT dispersion, patients were divided into three groups according to different levels of TSH: TSH < 0.1 mIU/L group and 0.1 ≤ TSH < 0.5 mIU/L group were as TSH suppression groups, and 0.5 ≤ TSH < 2.0 mIU/L group was as TSH replacement group.Comparing with 0.5 ≤ TSH < 2.0 mIU/L group, significant changes in both time and frequency domain of HRV and QT dispersion were observed in TSH < 0.1 mIU/L group (P < .001: SDNN, SDANN, HF, LF/HF, QTd, and QTcd; P < .05: rMSSD) and 0.1 ≤ TSH < 0.5 mIU/L group (P < .001: SDNN, HF, LF/HF, QTd, and QTcd), and especially were more pronounced in TSH < 0.1 mIU/L group. Moreover, we found that TSH level was proportional to SDNN (ß = 15.829, P < .001), but inversely proportional to LF/HF (ß = -0.671, P < .001), QTd (ß = -16.674, P < .001) and QTcd (ß = -18.314, P < .001) in DTC patients with exogenous levothyroxine.Compared with euthyroid state, patients with suppressed serum TSH have increased sympathetic activity in the presence of diminished vagal tone, ultimately showed sympathovagal imbalance and with an increased inhomogeneity of ventricular recovery times. These findings revealed that TSH suppression therapy had a significant impact on cardiovascular system and had certain guiding role in the treatment and management of patients with DTC.

Identification of a novel mutation in the thyroid hormone receptor ß gene that causes thyroid hormone resistance syndrome: A case report.

Thyroid hormone resistance syndrome is a rare disease in which the level of thyroid hormone is elevated and the level of thyroid stimulating hormone is not suppressed. Mutations in the thyroid hormone receptor ß (THRß) gene are thought to be the primary cause of pathogenesis. In the present study, a Chinese boy of 4 years and 8 months, who had been pre­diagnosed with resistance to thyroid hormone, was assessed for mutations. The clinical features and thyroid function of the proband and his parents were collected and gene mutations were analyzed using DNA sequencing. Gene sequencing showed that the THRß genes in the parents of the proband were consistent with the standard sequence, however, in the proband there was a mutation in the tenth exon of the THRß gene (c. 824 T>C). This is a newly identified mutation site and, to the best of our knowledge, there have been no previous reports of this mutation site. Therefore, it is hypothesized that this mutation is the cause of the pathology in the proband.

Efficacy and safety of dapagliflozin as monotherapy in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

BACKGROUND: Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs. METHODS: We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software. RESULTS: Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: -0.60%; 95% confidence interval [CI]: -0.67%, -0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: -1.30 mmol/L; 95% CI: -1.52, -1.08; P < .00001), and body weight (WMD: -1.50 kg; 95% CI: -1.67, -1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001). CONCLUSIONS: Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.