A late eating midpoint is associated with increased risk of diabetic kidney disease: a cross-sectional study based on NHANES 2013-2020.

BACKGROUND: Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. METHODS: The National Health and Nutrition Examination Survey (2013-2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were the specific diagnostic criteria for DKD. RESULTS: In total, details of 2194 subjects with diabetes were collected for analysis. The overall population were divided into four subgroups based on the eating midpoint quartiles. The prevalence of DKD varied noticeably (P = 0.037) across the four categories. When comparing subjects in the second and fourth quartiles of eating midpoint to those in the first one, the odds ratios (ORs) of DKD were 1.31 (95% CI, 1.03 to 1.67) and 1.33 (95% CI, 1.05 to 1.70), respectively. And after controlling for potential confounders, the corresponding ORs of DKD in the second and fourth quartiles were 1.42 (95% CI, 1.07 to 1.90) and 1.39 (95% CI, 1.04 to 1.85), respectively. CONCLUSIONS: A strong correlation was found between an earlier eating midpoint and a reduced incidence of DKD. Eating early in the day may potentially improve renal outcomes in patients with diabetes.

Association between the platelet/high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: results from NHANES 2017-2020.

The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) (p < 0.05); however, the OR for hepatic fibrosis was not statistically significant (p > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.

Serum stromal cell-derived factor-1 levels are associated with diabetic kidney disease in type 2 diabetic patients.

The present study was designed to explore whether serum stromal cell-derived factor-1 (SDF-1) levels were associated with diabetic kidney disease (DKD). Serum SDF-1 levels were measured by sandwich ELISA. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g for 3 months were identified as having DKD. Among the recruited type 2 diabetic patients, 18.71% (n = 32) were found to have DKD, and the serum SDF-1 levels of these patients were higher than those of patients without DKD (p < 0.05). Serum SDF-1 levels were positively correlated with cystatin C levels, the UACR and DKD incidence (r = 0.330, 0.183 and 0.186, respectively, p < 0.05) and inversely related to eGFR (r = -0.368, p < 0.001). After adjusting for other clinical covariates by multivariate logistic regression analyses, serum SDF-1 levels were found to be an independent contributor to DKD, and the odds ratio (95% confidence interval) was 1.438 (1.041-1.986). Furthermore, receiver operating characteristic analysis revealed that the optimal SDF-1 cutoff value for indicating DKD was 5.609 ng/mL (its corresponding sensitivity was 82.00%, and specificity was 46.90%). Our results demonstrated that serum SDF-1 levels were closely associated with DKD and could be considered a potent indicator for DKD in patients with T2D.

The bidirectional associations between sarcopenia-related traits and cognitive performance.

While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p < 0.001)] standardized score higher and a 0.07 (SE = 0.01; p < 0.001) standardized score higher cognitive score, whereas a higher hand grip strength was positively associated with a better cognitive performance. Reverse MR assessments also yielded similar findings. These data suggest that lower walking speed, muscle strength, and muscle mass were all closely related to lower cognitive performance irrespective of gender, and that there may be a mutually reinforcing relationship among these variables.

Association between fibrinogen/albumin ratio and arterial stiffness in patients with type 2 diabetes: A cross-sectional study.

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV). Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness. Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness (p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men (p < .01), while they were insignificant in subgroups of elderly and non-elderly women (p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031-1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g. Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.

The Positive Relationship Between the Low-Density Lipoprotein Cholesterol/Apoprotein B Ratio and Bone Turnover Markers in Patients With Type 2 Diabetes.

Background: Dyslipidemia may contribute to low bone turnover in patients with type 2 diabetes (T2D) through mediating oxidative stress and atherosclerosis. The low-density lipoprotein cholesterol/apoprotein B (LDL-C/Apo B) ratio is a surrogate marker of small and density low-density lipoprotein cholesterol (sd-LDL-C), a most harmful group of LDL-Cs. The present study aimed to investigate the association between the LDL-C/Apo B ratio and bone turnover in patients with T2D. Methods: This study was a cross-sectional study enrolled patients with T2D from January 2021 to December 2021. Each participant was assessed for lipid profiles, bone turnover markers (BTMs), lumbar spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip. Results: A total of 335 patients with T2D were enrolled in the study, and the LDL-C/Apo B ratio ranged from 0.78 to 4.00. Along with the LDL-C/Apo B ratio tertile ascending, osteocalcin (OC), C-terminal telopeptide (CTx) and N-terminal propeptide of type-I procollagen (PINP) levels gradually increased (all p < 0.05). There were no differences in lumbar spine and hip T-score, proportion of osteoporosis (all p > 0.05) among the three subgroups. The LDL-C/Apo B ratio was positively correlated with lnOC (r = 0.244, p < 0.001), lnCTx (r = 0.226, p < 0.01) and lnPINP (r = 0.211, p < 0.001). These significant positive correlations persisted even when divided into male and female subgroups. Furthermore, three multiple linear regression analyses were constructed to investigate the independent association of the LDL-C/Apo B ratio with the BTMs levels. After adjusting for other clinical parameters, the LDL-C/Apo B ratio was still significantly associated with OC level (ß = 0.199, t = 3.348, p < 0.01), CTx level (ß = 0.238, t = 4.084, p < 0.001) and PINP level (ß = 0.162, t = 2.741, p < 0.01). Conclusion: The LDL-C/Apo B ratio was significantly and positively associated with BTMs in patients with T2D. In clinical practice, more attention should be paid to the patients with T2D whose LDL-C/Apo B ratio is relatively low for the purpose of maintaining bone health.

Comparisons of the Relationships Between Multiple Lipid Indices and Diabetic Kidney Disease in Patients With Type 2 Diabetes: A Cross-Sectional Study.

Background: Dyslipidemia is a well-recognized risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Growing evidences have shown that compared with the traditional lipid parameters, some lipid ratios may provide additional information of lipid metabolism. Thus, the present study aimed to investigate which lipid index was most related to DKD. Methods: This study was a cross-sectional study that enrolled patients with T2D from January 2021 to October 2021. Each participant was screened for DKD, and the diagnostic criterion for DKD is estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months. Fasting blood was collected to determine lipid profiles by an automatic biochemical analyzer, and lipid ratios were calculated based on corresponding lipid parameters. Spearman's correlation analyses were conducted to assess the correlations between lipid indices and kidney injury indices, and binary logistic regression analyses were conducted to explore the relationship between lipid indices and the risk of DKD. Results: A total of 936 patients with T2D were enrolled in the study, 144 (15.38%) of whom had DKD. The LDL-C/Apo B ratios were positively correlated with eGFR (r = 0.146, p < 0.05) and inversely correlated to cystatin C and UACR (r = -0.237 and -0.120, both p < 0.001). Multiple logistic regression demonstrated that even after adjusting for other clinical covariates, the LDL-C/Apo B ratios were negatively related to DKD, and the odds ratio (95% confidence interval) was 0.481 (0.275-0.843). Furthermore, subgroup analyses revealed that compared with patients with normal lipid profiles and a high LDL-C/Apo B ratio, the odds ratio of DKD in patients with normal lipid metabolism and a low LDL-C/Apo B ratio was 2.205 (1.136-4.280) after adjusting for other clinical covariates. Conclusion: In patients with T2D, the LDL-c/Apo B ratio was most closely associated with DKD among various lipid indices, and a lower LDL-C/Apo B ratio was associated with increased risks of DKD among patients with T2D.

Association of serum stromal cell-derived factor 1 levels with EZSCAN score and its derived indicators in patients with type 2 diabetes.

Background: The aim of the study was to explore whether plasma stromal cell-derived factor 1 (SDF-1) levels are associated with the EZSCAN score and its derived indicators in patients with type 2 diabetes (T2D). Methods: From July 2020 to December 2020, a total of 253 patients with T2D were consecutively recruited. Serum SDF-1 levels were measured by sandwich ELISA. EZSCAN test was applied to evaluate the sudomotor function of each patient, and based on the results, EZSCAN score, cardiac autonomic neuropathy risk score (CANRS) and cardiovascular risk score (CVDRS) were calculated by particular algorithms. In addition, other relevant clinical data were also collected. Results: With increasing tertiles of serum SDF-1 levels, the CANRS and CVDRS significantly increased (both Pfor trend <0.001), while the EZSCAN score significantly decreased (Pfor trend <0.001). Moreover, serum SDF-1 levels were significantly and positively correlated with the CANRS and CVDRS (r = 0.496 and 0.510, respectively, both P < 0.001), and negatively correlated with the EZSCAN score (r = -0.391, P < 0.001). Furthermore, multivariate linear regression analyses were constructed, and after adjusting for other clinical covariates, serum SDF-1 levels were independently responsible for EZSCAN score (ß = -0.273, t = -3.679, P < 0.001), CANRS (ß = 0.334, t = 5.110, P < 0.001) and CVDRS (ß = 0.191, t = 4.983, P = 0.003). Conclusions: SDF-1 levels in serum were independently associated with the EZSCAN score and its derived indicators, such as CANRS and CVDRS in patients with T2D.

Corrigendum: The association between normal serum sodium levels and bone turnover in patients with type 2 diabetes.

[This corrects the article DOI: 10.3389/fendo.2022.927223.].

The association between normal serum sodium levels and bone turnover in patients with type 2 diabetes.

Background: Sodium is a critically important component of bones, and hyponatremia has firmly been established as a risk factor associated with the incidence of fragility fractures. However, researches have also revealed that lower serum sodium are linked to reductions in muscle mass and a higher risk of cardiovascular disease even when these levels are within the normal range. Accordingly, this study was developed to examine the relationships between normal serum sodium concentrations and bone turnover in patients with type 2 diabetes (T2D). Methods: Patients with T2D were enrolled in the present study from January 2021 to April 2022. All patients underwent analyses of serum sodium levels, oral glucose tolerance testing (OGTT), bone turnover markers (BTMs), and dual-energy X-ray absorptiometry (DXA) scanning. BTMs included bone formation markers osteocalcin (OC) and N-terminal propeptide of type-I procollagen (PINP), and bone resorption marker C-terminal telopeptide (CTx). Patients were stratified into three subgroups based on the tertiles of their serum sodium concentrations. Results: In total, 372 patients with T2D and sodium levels in the normal range were enrolled in this study. Serum OC and PINP levels were increased from subgroup with the low sodium tertile to that with the high sodium tertile (p for trend < 0.05), whereas CTx level was comparable among the subgroups. A positive correlation was detected between serum sodium levels and both lnOC (r = 0.210, p < 0.001) and lnPINP (r = 0.196, p < 0.001), with these relationships remaining significant even following adjustment for age, sex, body mass index (BMI), and HbA1c. Only after adjusting for these four factors a positive correlation was detected between serum sodium levels and CTx levels (r = 0.108, p < 0.05). Linear regression analyses revealed that following adjustment for potential covariates, serum sodium level was and positively significantly associated with lnOC level (ß = 0.134, t = 2.281, p < 0.05) and PINP level (ß = 0.179, t = 3.023, p < 0.01). Conclusion: These results highlight a significant association between low-normal serum sodium levels and low bone turnover.

Serum adenosine deaminase levels are associated with diabetic kidney disease in type 2 diabetic patients.

The aim of the present study was to evaluate the association between adenosine deaminase (ADA) levels and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). In this study, patients with T2D who had been screened for DKD were recruited. Patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months were identified as having DKD. The prevalence of DKD was 13.3%, and the range of serum ADA levels was 4-37 U/L. Serum ADA levels were positively associated with cystatin C levels and UACR (r = 0.295 and r = 0.302, respectively, both P < 0.05) and negatively associated with eGFR (r = -0.342, P < 0.05). The proportion of participants with DKD increased significantly from 3.8% in the first tertile (T1) to 13.6% in the second tertile (T2) and 25.9% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for clinical risk factors for DKD via multiple logistic regression, the corresponding odds ratios (ORs) of DKD for the participants in T2 and T3 vs those in T1 of ADA were 5.123 (1.282-20.474) and 10.098 (1.660-61.431), respectively. Receiver operating characteristic (ROC) analysis revealed that the optimal cutoff value of ADA to indicate DKD was 10 U/L. Its corresponding sensitivity and specificity were 75.5 and 56.4%, respectively. Our results demonstrated that serum ADA levels were closely associated with DKD and partly reflect the risk of DKD in patients with T2D.

Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes.

OBJECTIVE: Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D. METHODS: This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected. RESULTS: It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = - 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (ß = - 0.125, t = - 5.397, p < 0.001, adjusted R2 = 0.459). CONCLUSIONS: Serum ADA levels are independently associated with islet beta cell function in patients with T2D.

The association between serum adenosine deaminase levels and Graves' disease.

BACKGROUND: Adenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves' disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD. METHODS: A total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography. RESULTS: Serum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels. CONCLUSIONS: Our results demonstrated that serum ADA levels were closely associated with GD.

The relationship between adenosine deaminase and heart rate-corrected QT interval in type 2 diabetic patients.

BACKGROUND: Prolonged heart rate-corrected QT (QTc) interval may reflect poor prognosis of patients with type 2 diabetes (T2D). Serum adenosine deaminase (ADA) levels are related to hyperglycemia, insulin resistance (IR) and inflammation, which may participate in diabetic complications. We investigated the association of serum ADA levels with prolonged QTc interval in a large-scale sample of patients with T2D. METHODS: In this cross-sectional study, a total of 492 patients with T2D were recruited. Serum ADA levels were determined by venous blood during fasting. QTc interval was estimated from resting 12-lead ECGs, and prolonged QTc interval was defined as QTc > 440 ms. RESULTS: In this study, the prevalence of prolonged QTc interval was 22.8%. Serum ADA levels were positively associated with QTc interval (r = 0.324, P < 0.0001). The proportion of participants with prolonged QTc interval increased significantly from 9.2% in the first tertile (T1) to 24.7% in the second tertile (T2) and 39.0% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for other possible risk factors by multiple linear regression analysis, serum ADA level was still significantly associated with QTc interval (ß = 0.217, t = 3.400, P < 0.01). Multivariate logistic regression analysis showed that female (OR 5.084, CI 2.379-10.864, P < 0.001), insulin-sensitizers treatment (OR 4.229, CI 1.290-13.860, P = 0.017) and ADA (OR 1.212, CI 1.094-1.343, P < 0.001) were independent contributors to prolonged QTc interval. CONCLUSIONS: Serum ADA levels were independently associated with prolonged QTc interval in patients with T2D.

Association of serum fibroblast growth factor 19 levels with arteriosclerosis parameters assessed by arterial stiffness and atherogenic index of plasma in patients with type 2 diabetes.

BACKGROUND: The role of serum fibroblast growth factor 19 (FGF19) in arteriosclerosis is not well known. In the present study, we aimed to explore whether serum FGF19 levels were related to arteriosclerosis parameters, including arterial stiffness and atherogenic index of plasma (AIP), in patients with type 2 diabetes (T2D). METHODS: A total of 200 patients with type 2 diabetes and 50 healthy controls were recruited for this study from Apr 2017 to Oct 2018. Serum FGF19 levels, arterial stiffness assessed by brachial ankle pulse wave velocity (baPWV), and AIP assessed by the triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio were measured in those subjects. In addition, other relevant clinical data were also collected. RESULTS: Serum FGF19 levels in T2D patients were significantly lower than those in healthy controls (p < 0.05). The arteriosclerosis parameters, including baPWV and AIP, significantly decreased across ascending tertiles of serum FGF19 levels (all p for trend < 0.001). Moreover, the baPWV and AIP were all inversely correlated with serum FGF19 levels (r = - 0.351 and - 0.303, respectively, p < 0.001). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the serum FGF19 levels were independently associated with baPWV (ß = - 0.20, t = - 2.23, p = 0.029) and AIP (ß = - 0.28, t = - 2.66, p = 0.010). CONCLUSIONS: The serum FGF19 levels were independently and inversely associated with baPWV and AIP, which indicate that serum FGF19 may have a protective role in atherosclerosis in patients with T2D.