Evaluation of bi-directional causal association between obstructive sleep apnoea syndrome and diabetic microangiopathy: a Mendelian randomization study.

Background: The relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial. Objective: This study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy. Methods: First, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses. Results: In the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors. Conclusion: Our results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy.

SIRT3: A Potential Target of Different Types of Osteoporosis.

Osteoporosis (OP) is a common age-related disease. OP is mainly a decrease in bone density and mass caused by the destruction of bone microstructure, which leads to an increase in bone fragility. SIRT3 is a mitochondrial deacetylase that plays critical roles in mitochondrial homeostasis, metabolic regulation, gene transcription, stress response, and gene stability. Studies have shown that the higher expression levels of SIRT3 are associated with decreased levels of oxidative stress in the body and may play important roles in the prevention of age-related diseases. SIRTs can enhance the osteogenic potential and osteoblastic activity of bone marrow mesenchymal stromal cells not only by enhancing PGC-1α, FOXO3, SOD2, and oxidative phosphorylation, but also by anti-aging and reducing mitochondrial autophagy. SIRT3 is able to upregulate antioxidant enzymes to exert an inhibitory effect on osteoclasts, however, it has been shown that the inflammatory cascade response can in turn increase SIRT3 and inhibit osteoclast differentiation through the AMPK-PGC-1ß pathway. SIRT3 plays an important role in different types of osteoporosis by affecting osteoblasts, osteoclasts, and bone marrow mesenchymal cells. In this review, we discuss the classification and physiological functions of SIRTs, the effects of SIRT3 on OCs osteoblasts, and BMSCs, and the roles and mechanisms of SIRT3 in different types of OP, such as diabetic OP, glucocorticoid-induced OP, postmenopausal OP, and senile OP.

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.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Aim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM. Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.

The BRAFV600E mutation maintains the aggressiveness of papillary thyroid cancers requiring downregulation of primary cilia.

Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.

Codonopsis pilosula polysaccharides promote osteogenic differentiation and inhibit lipogenic differentiation of rat bone marrow stem cells by activating ß-catenin.

Aberrant bone marrow mesenchymal stem cell (BMSC) lineage differentiation leads to osteoporosis. Codonopsis pilosula polysaccharides (CPPs) have been widely used in traditional Chinese medicines, due to their multiple pharmacological actions. However, little is known regarding their effects on BMSC differentiation. This study aimed to identify the effects and mechanisms of CPPs on osteogenic and adipogenic differentiation in rat BMSCs. An osteoporosis model was established in Sprague-Dawley (SD) rats through bilateral ovariectomy (OVX), and be applied to observe the effect of CPPs on osteoporosis in vivo. The ability of CPPs to affect rBMSC proliferation was determined using the CCK-8 assay, and the osteogenic differentiation of rBMSCs measured by ALP and Alizarin Red S staining. The adipogenic differentiation of rBMSCs was measured by Oil Red O staining. The mRNA and protein levels related to osteogenesis and adipogenic differentiation of rBMSCs were measured using qRT-PCR and western blotting, respectively. Cellular immunofluorescence was used to detect cytokine expression and localisation in rBMSCs. We observed that CPPs ameliorated bone loss in OVX rats. CPPs considerably enhanced osteogenic differentiation by increasing ALP activity and the prevalence of mineralised nodules and promoting the mRNA and protein expression of osteogenic differentiation markers (RUNX2, COL I, ALP, and OPN). Furthermore, it inhibited the accumulation of lipid vesicles in the cytoplasm and the mRNA and protein expression levels of adipogenic differentiation markers (PPARγ and C/EBPα) in a concentration-dependent manner. Meanwhile, CPPs notably increased the mRNA and protein expression of ß-catenin, the core protein of the Wnt/ß-catenin signaling pathway, in a concentration-dependent manner. Adding DKK1, a mature inhibitor of the Wnt/ß-catenin signaling pathway, partially suppressed CPP-stimulated ß-catenin activation, and reversed the acceleration of osteogenic differentiation and the inhibition of lipogenic differentiation. Our observations demonstrated CPPs ameliorate bone loss in OVX rats in vivo, and favour osteogenic differentiation while inhibit adipogenic differentiation of rBMSCs in vitro. The findings suggested that CPPs could serve as functional foods for bone health, and have great potential for the prevention and treatment of osteoporosis.

Heat waves accelerate the spread of infectious diseases.

COVID-19 pandemic appeared summer surge in 2022 worldwide and this contradicts its seasonal fluctuations. Even as high temperature and intense ultraviolet radiation can inhibit viral activity, the number of new cases worldwide has increased to >78% in only 1 month since the summer of 2022 under unchanged virus mutation influence and control policies. Using the attribution analysis based on the theoretical infectious diseases model simulation, we found the mechanism of the severe COVID-19 outbreak in the summer of 2022 and identified the amplification effect of heat wave events on its magnitude. The results suggest that approximately 69.3% of COVID-19 cases this summer could have been avoided if there is no heat waves. The collision between the pandemic and the heatwave is not an accident. Climate change is leading to more frequent extreme climate events and an increasing number of infectious diseases, posing an urgent threat to human health and life. Therefore, public health authorities must quickly develop coordinated management plans to deal with the simultaneous occurrence of extreme climate events and infectious diseases.

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.

The prevalence of subclinical hypothyroidism in a pre-diabetes population and an analysis of related factors.

BACKGROUND: To investigate the prevalence and related influencing factors of subclinical hypothyroidism (SCH) in a pre-diabetes (PreDM) population. PATIENTS AND METHODS: A multi-stage stratified cluster random sampling method was used to select the adult Han population in Gansu Province for investigation. General data and related biochemical indices were recorded and SPSS software was used for statistical analyses. RESULTS: This study selected 2876 patients, including 548 with SCH and 433 with PreDM. In the PreDM population, the levels of thyroid stimulating hormone (TSH), serum phosphorus, TPOAb and TgAb in the SCH group were higher than those in the euthyroid group (P < 0.05). The level of TPOAb in females of SCH group was higher than that in males (P < 0.05). The positive rates of TPOAb and TgAb in females were higher than those in males in the total population and SCH population. The prevalence of SCH in the PreDM group under 60 was significantly higher than that in the normal glucose tolerance (NGT) group (26.02% vs. 20.40%, χ2 = 5.150, P < 0.05). We defined SCH as a TSH level of >4.20 mIU/L. Using this criterion, the prevalence of SCH in the total population of PreDM was higher than that in the NGT population (χ2 = 8.611, P < 0.05), the prevalence of SCH in the PreDM population generally showed an upward trend. However, we performed a separate analysis considering the accepted impact of age on TSH redefining SCH as TSH >8.86 mIU/L (for individuals over age 65). However, allowing for the expected rise in TSH levels in individuals over age 65, the prevalence of SCH in the elderly over 65 years of age decreased significantly (NGT population from 27.48% to 9.16%, PreDM population from 34.18% to 6.33%, P < 0.05). Logistic regression analysis showed that the risk factors for SCH in the PreDM population were female gender, fasting plasma glucose and TSH (all P < 0.05). Risk factors for SCH in the impaired fasting glucose (IFG) population were female gender, OGTT 2 h, TSH and TPOAb (all P < 0.05). CONCLUSION: The prevalence of SCH in the PreDM population not considering the known physiological increase in age related TSH was relatively high and was significant in female and the IFG population. However, the effect of age on these findings needs to attract more attention.

The prevalence of subclinical hypothyroidism (SCH) in the pre-diabetic population was analysed by cross-sectional survey. There is a great deviation in the diagnosis of SCH in the elderly with physiologically increased thyroid stimulating hormone, which needs to be redefined.

Targeting the NLRP3 inflammasome in diabetic retinopathy: From pathogenesis to therapeutic strategies.

Diabetic retinopathy (DR) is a common diabetic microvascular complication and the main cause of vision loss in working-aged people. The NLRP3 inflammasome is a cytosolic multimeric complex that plays a significant role in innate immunity. After sensing injury, the NLRP3 inflammasome induces inflammatory mediator secretion and triggers a form of inflammatory cell death known as pyroptosis. Studies over the past five years have shown increased expression of NLRP3 and related inflammatory mediators in vitreous samples from DR patients at different clinical stages. Many NLRP3-targeted inhibitors have shown great antiangiogenic and anti-inflammatory effects in diabetes mellitus models, suggesting that the NLRP3 inflammasome is involved in the progression of DR. This review covers the molecular mechanisms of NLRP3 inflammasome activation. Furthermore, we discuss the implications of the NLRP3 inflammasome in DR, including the induction of pyroptosis and inflammation and the promotion of microangiopathy and retinal neurodegeneration. We also summarize the research progress on targeting the NLRP3 inflammasome in DR therapeutics with the expectation of providing new insights into DR progression and treatment.

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.

Role of Pyroptosis in Intervertebral Disc Degeneration and Its Therapeutic Implications.

Intervertebral disc degeneration (IDD), a progressive and multifactorial pathological process, is predominantly associated with low back pain and permanent disability. Pyroptosis is a type of lytic programmed cell death triggered by the activation of inflammasomes and caspases. Unlike apoptosis, pyroptosis is characterized by the rupture of the plasma membrane and the release of inflammatory mediators, accelerating the destruction of the extracellular matrix (ECM). Recent studies have shown that pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis in nucleus pulposus (NP) cells is activated in the progression of IDD. Furthermore, targeting pyroptosis in IDD demonstrates the excellent capacity of ECM remodeling and its anti-inflammatory properties, suggesting that pyroptosis is involved in the IDD process. In this review, we briefly summarize the molecular mechanism of pyroptosis and the pathogenesis of IDD. We also focus on the role of pyroptosis in the pathological progress of IDD and its targeted therapeutic application.

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.

Aromatase deficiency caused by mutation of CYP19A1 gene: A case report. / CYP19A1åŸºå› çªå˜è‡´èŠ³é¦™åŒ–é ¶ç¼ºä¹ç—‡1例.

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.

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).

Relationship between prevalence and risk of osteoporosis or osteoporotic fracture with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The aim of this study was to investigate the relationship between prevalence and risks of osteoporosis or osteoporotic fracture and NAFLD. Patients with NAFLD should be monitored regularly for bone mineral density and bone metabolism indicators to prevent osteoporosis or osteoporotic fractures. OBJECTIVES: The aim of this meta-analysis was to investigate the relationship between prevalence and risks of osteoporosis or osteoporotic fracture and non-alcoholic fatty liver disease (NAFLD). METHODS: Five databases, including PubMed, Web of Science, Embase, Scopus and Cochrane Library, were searched since the conception of these databases until December 2021. The cohort studies, cross-sectional analyses or case-control studies evaluating the relationship between osteoporosis or osteoporotic fracture and NAFLD were retrieved from these databases. Relevant data were extracted from the included studies, and a meta-analysis was performed. RESULTS: A total of seven studies were included. The prevalence of osteoporosis or osteoporotic fractures was higher in the NAFLD group than in the non-NAFLD group [OR = 1.17, 95%CI(1.04,1.31)], while the prevalence of osteoporosis was higher in the NAFLD group than in the non-NAFLD group [OR = 1.46, 95%CI (1.21,1.77) and OR = 1.48, 95%CI (1.31,1.68), respectively] in men and women. The risk of osteoporosis or osteoporotic fractures was higher in the NAFLD group than in the non-NAFLD group [OR = 1.33,95%CI (1.24,1.44) and OR = 1.57,95%CI (1.08,2.29), respectively]. The risk of osteoporosis or osteoporotic fractures was higher in male and female NAFLD groups than that in the non-NAFLD group [OR = 1.29, 95%CI(1.14,1.47) and OR = 1.36, 95%CI (1.25,1.48), respectively]. After parameter adjustment, the risk of osteoporosis or osteoporotic fracture was higher in the male NAFLD group than in the non-NAFLD group [OR = 2.10, 95%CI(1.36,3.25)], while no significant difference was found among women [OR = 1.13, 95%CI (0.86,1.48)]. CONCLUSIONS: The prevalence and risk of osteoporosis or osteoporotic fractures were significantly associated with NAFLD in men and women. TRIAL REGISTRATION: PROSPERO 2022 CRD42022304708.

Relationship between iron metabolism and gestational diabetes mellitus: A systemic review and meta analysis.

BACKGROUND AND OBJECTIVES: To investigate the relationship between serum iron metabolism indexes and gestational diabetes mellitus (GDM) using a meta-analysis. METHODS AND STUDY DESIGN: Databases including PubMed, Web of Science, Embase, and Cochrane Library were searched. Prospective cohort or case-control studies evaluating the relationships between serum iron metabolism indexes and GDM were retrieved from these data-bases. The outcome indicators, such as mean ± standard deviation, relative risk (RR), or odds ratio (OR) were extracted. The RR or OR, standard mean difference (SMD), and 95% confidence interval (CI) were used to calculate the combined effect sizes. RESULTS: A total of 32 studies on the relationships between serum iron metabolic indexes and GDM were included. The serum iron [SMD=0.40 mg/dL, 95% CI (0.16, 0.64), p=0.001], ferritin [SMD=0.58 ng/mL, 95% CI (0.35, 0.81), p˂0.001], hemoglobin [SMD=0.48 g/dL, 95% CI (0.28, 0.67), p˂0.001], transferrin saturation [SMD=0.83%, 95% CI (0.15, 1.52), p=0.000], and hepcidin [SMD=0.63 ng/mL, 95% CI (0.09, 1.18), p=0.023] levels were higher in the GDM group than in the non-GDM group, whereas total iron binding ability [SMD = -0.53 µg/dL, 95% CI (-1.05, -0.02), p=0.001] was lower in the GDM group than in the non-GDM group. High serum ferritin [OR=1.92, 95% CI (1.59, 2.32), p˂0.001] and hemoglobin levels [OR=1.30, 95% CI (1.04,1.63), p=0.023] were associated with GDM risk. CONCLUSIONS: Serum iron, ferritin, transferrin saturation, hepcidin, and hemoglobin levels were higher and total iron binding ability was lower in GDM patients than in those without GDM. High serum ferritin and hemoglobin levels were associated with GDM risk.

Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.

Association Between the Risk of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

Objective: To explore the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1168 patients with T2DM were divided into the non-CKD and CKD groups, and the difference in the prevalence of NAFLD was compared. The differences in serum creatinine (SCr) and urine albumin-to-creatinine ratio (UACR) levels were compared between the non-NAFLD and NAFLD groups. Patients with T2DM were divided into three groups according to their UACR levels (UACR < 30 mg/g [U1 group]; UACR ≤ 30 mg/g to < 300 mg/g [U2 group]; and UACR ≥ 300 mg/g [U3 group]) or estimated glomerular filtration rate (eGFR) levels (≥ 90 mL/min [G1 group]; eGFR ≤ 60 mL/min to < 90 mL/min [G2 group]; and eGFR < 60 mL/min (G3 group]). The difference in the prevalence and risks of NAFLD in the different UACR or eGFR level groups was analyzed. Results: The prevalence of NAFLD in the CKD group was higher than that in the non-CKD group (63.5% vs 50.5%, p < 0.001). The SCr and UACR levels in the NAFLD group were higher than those in the non-NAFLD group (both p<0.05). The prevalence of NAFLD in the U3 group (75.6%) was higher than that in the U1 (50.5%, p < 0.05) and U2 (60.1%, p < 0.05) groups, and the prevalence of NAFLD in the U2 group (60.1%) was higher than that in the U1 group (50.5%, p < 0.05). The risk of NAFLD in the U3 group was higher than that in the U2 group (odds ratio [OR] = 3.032 and 1.473). Despite adjusting the parameters further, the NAFLD risk in the U3 group remained higher than that in the U2 group (OR = 1.660 and 2.342). Conclusion: The risk of NAFLD in patients with T2DM is closely related to CKD.