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.

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.

The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD.

PURPOSE: To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. RESULTS: The BMD levels of the L4, and L1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L4, and L1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L4, and L1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L4 in males, and the BMD level of L4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. CONCLUSION: The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.

Ferroptosis: roles and molecular mechanisms in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a serious complication of type 1 and type 2 diabetes, which leads to the aggravation of myocardial fibrosis, disorders involving systolic and diastolic functions, and increased mortality of patients with diabetes through mechanisms such as glycolipid toxicity, inflammatory response, and oxidative stress. Ferroptosis is a form of iron-dependent regulatory cell death that is attributed to the accumulation of lipid peroxides and an imbalance in redox regulation. Increased production of lipid reactive oxygen species (ROS) during ferroptosis promotes oxidative stress and damages myocardial cells, leading to myocardial systolic and diastolic dysfunction. Overproduction of ROS is an important bridge between ferroptosis and DCM, and ferroptosis inhibitors may provide new targets for the treatment of patients with DCM.

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.

Serum ferritin is correlated with non-alcoholic fatty liver disease in middle-aged and older patients with type 2 diabetes.

OBJECTIVE: Previous studies have shown the correlations between serum ferritin and non-alcoholic fatty liver disease (NAFLD) or diabetes. However, this relationship remains unclear in patients with type 2 diabetes (T2DM) with NAFLD. Therefore, this study aimed to elaborate the relationship between serum ferritin levels and NAFLD in middle-aged and older patients with T2DM and further explored the biomarkers for NAFLD in T2DM. METHODS: A total of 805 middle-aged and older patients with T2DM were divided into NAFLD and non-NAFLD groups, and their serum ferritin levels were compared. Next, NAFLD group were divided into five subgroups according to the quintile levels of serum ferritin, and the differences in the constituent ratios of NAFLD were analyzed. A logistic regression analysis was performed to determine the risk factors for NAFLD in patients with T2DM. RESULTS: The serum ferritin levels were significantly higher in T2DM patients with NAFLD (168.47 (103.78, 248.00) ng/mL) than in the non-NAFLD patients (121.19 (76.97, 208.39) ng/mL). The constituent ratios of NAFLD were significantly higher in the F5 and F4 groups than in the F2 or F1 groups (22.70 and 22.70% vs. 15.90 and 16.90%, respectively; P < 0.05). Binary logistic regression analysis showed that serum ferritin (P = 0.001) was an independent risk factor for NAFLD in patients with T2DM. CONCLUSIONS: Serum ferritin levels were significantly increased in T2DM with NAFLD, and the constituent ratios of NAFLD increased gradually along with the increased levels of serum ferritin. Thus, serum ferritin is an independent risk factor for NAFLD in patients with T2DM.