BACKGROUND Increased blood urea nitrogen (BUN) levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes (T2D), potentially playing a role in the development of diabetic complications, including diabetic peripheral neuropathy. AIM To examine the relationship between BUN levels and peripheral nerve function in patients with T2D. METHODS This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured. Electromyography was used to assess peripheral motor and sensory nerve function in all patients, and overall composite Z -scores were subsequently calculated for nerve latency, amplitude, and conduction velocity (NCV) across the median, ulnar, common peroneal, posterior tibial, superficial peroneal, and sural nerves. RESULTS Across the quartiles of BUN levels, the overall composite Z -score for latency (F = 38.996, P for trend < 0.001) showed a significant increasing trend, whereas the overall composite Z -scores for amplitude (F = 50.972, P for trend < 0.001) and NCV (F = 30.636, P for trend < 0.001) exhibited a significant decreasing trend. Moreover, the BUN levels were closely correlated with the latency, amplitude, and NCV of each peripheral nerve. Furthermore, multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite Z -score for latency (β = 0.166, t = 3.864, P < 0.001) and lower overall composite Z-scores for amplitude (β = -0.184, t = -4.577, P < 0.001) and NCV (β = -0.117, t = -2.787, P = 0.006) independent of the estimated glomerular filtration rate and other clinical covariates. Additionally, when the analysis was restricted to sensory or motor nerves, elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction. CONCLUSION Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.

Increased glucagon levels are now recognized as a pathophysiological adaptation to counteract overnutrition in type 2 diabetes (T2D). This study aimed to elucidate the role of glucagon in peripheral nerve function in patients with T2D with different body mass indices (BMIs). We consecutively enrolled 174 individuals with T2D and obesity (T2D/OB, BMI ≥ 28 kg/m2), and 480 individuals with T2D and nonobesity (T2D/non-OB, BMI < 28 kg/m2), all of whom underwent oral glucose tolerance tests to determine the area under the curve for glucagon (AUCgla). Electromyography was utilized to assess overall composite Z-scores for latency, amplitude, and nerve conduction velocity (NCV) across all peripheral nerves, specifically examining the median, ulnar, common peroneal, posterior tibial, superficial peroneal, and sural nerves. In the T2D/OB group, the AUCgla exhibited a significant correlation with the latency, amplitude and NCV of each peripheral nerve, as well as with the overall composite Z-scores for latency (r = –0.283, p < 0.001), amplitude (r = 0.295, p < 0.001), and NCV (r = 0.362, p < 0.001). In contrast, the T2D/non-OB group did not exhibit obvious correlations between the AUCgla and the overall composite Z-scores for latency (r = –0.088, p = 0.056), amplitude (r = 0.054, p = 0.251), and NCV (r = 0.116, p = 0.012). Furthermore, multivariate linear regression analyses indicated that elevated AUCgla was independently associated with a lower overall composite Z-score for latency (β = –0.304, t = –3.391, p = 0.001), as well as higher overall composite Z-scores for amplitude (β = 0.256, t = 2.630, p = 0.010) and NCV (β = 0.286, t = 3.503, p = 0.001), after adjusting for other clinical covariates within the T2D/OB group. Increased glucagon levels may be a potential protective factor against peripheral nerve compromise in patients with T2D and obesity.

This study investigated the correlation between glucose time-in-range (TIR) and hepatic steatosis severity or liver fibrosis risk in Chinese adults with type 2 diabetes mellitus (T2DM) comorbid with metabolic dysfunction-associated steatotic liver disease (MASLD). Participants with T2DM were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. TIR was calculated based on data from a retrospective continuous glucose monitoring system. A total of 184 T2DM patients with MASLD were enrolled. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) decreased with increasing TIR (p < 0.05). Spearman correlation showed negative correlations between CAP, LSM, and TIR (r = -0.824 and − 0.842, p < 0.05) and positive correlations with basal insulin resistance (HOMA-IR) (r = 0.205 and 0.208, p < 0.01). Multiple linear regression revealed TIR and HOMA-IR independently correlated with CAP (std. regression coefficients = -0.695 and 0.103, p < 0.05) and LSM (std. regression coefficients = -0.735 and 0.083, p < 0.05), wit0.34 h TIR having a stronger impact. Binary logistic regression showed TIR Groups 3 (70

Background Accompanying islet α- and β-cell dysregulation in type 2 diabetes (T2D) at the microscopic scale, alterations in body composition at the macroscopic scale may affect the pathogenesis of T2D. However, the connections between body composition and islet α-cell and β-cell functions in T2D have not been thoroughly explored. Methods For this cross-sectional study, we recruited a total of 729 Chinese Han patients with T2D in a consecutive manner. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition, which included total bone-free mass, total fat and lean mass, trunk fat and lean mass and limb fat and lean mass. Every patient underwent an oral glucose tolerance test to simultaneously detect glucose, C-peptide and glucagon. The indices of islet α-cell function included fasting glucagon levels and the area under the curve of glucagon after a challenge (AUC glucagon ), while the indices of β-cell function included the insulin sensitivity index derived from C-peptide (ISI C-peptide ) and the area under the curve of C-peptide after a challenge (AUC C-peptide ). Results Among all patients, fat mass, especially trunk fat mass, was significantly correlated with ISI C-peptide and AUC C-peptide levels ( r = − 0.330 and 0.317, respectively, p < 0.001), while lean mass, especially limb lean mass, was significantly correlated with fasting glucagon and AUC glucagon levels ( r = − 0.196 and − 0.214, respectively, p < 0.001). Moreover, after adjusting for other relevant variables via multivariate linear regression analysis, increased trunk fat mass was independently associated with decreased ISI C-peptide ( β = − 0.247, t = − 3.628, p < 0.001, partial R 2 = 10.9%) and increased AUC C-peptide ( β = 0.229, t = 3.581, p < 0.001, partial R 2 = 8.2%), while decreased limb lean mass was independently associated with increased fasting glucagon ( β = − 0.226, t = − 2.127, p = 0.034, partial R 2 = 3.8%) and increased AUC glucagon ( β = − 0.218, t = − 2.050, p = 0.041, partial R 2 = 2.3%). Additionally, when separate analyses were performed with the same concept for both sexes, we found that increased trunk fat mass was still independently associated with decreased ISI C-peptide and increased AUC C-peptide , while decreased limb lean mass was still independently associated with increased fasting glucagon and AUC glucagon . Conclusions Increased trunk fat mass may partly account for decreased insulin sensitivity and increased insulin secretion, while decreased limb lean mass may be connected to increased fasting glucagon and postprandial glucagon secretion.

Abstract Background Impaired thyroid hormone sensitivity has been associated with type 2 diabetes (T2D), obesity, and metabolic syndrome, which can lead to alterations of body composition. However, impaired thyroid sensitivity to exacerbate alterations of body composition remains unconfirmed. This study aimed to ascertain impaired thyroid hormone sensitivity association with body composition in euthyroid T2D. Methods A total of 634 individuals with normothyroid T2D were enrolled. Each participant underwent a dual-energy X-ray absorptiometry (DXA) scan to assess body composition, including measurements of body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD), and total BMD (T-BMD). Thyroid hormone resistance indices were assessed by calculating serum thyrotropin (TSH) index (TSHI), thyrotrophin T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric TFQI (PTFQI). Relevant clinical data was also collected. Results Among the recruited patients, females (n = 265) had higher indicators of thyroid hormone resistance and fat distribution than males (n = 369) (all P < 0.05). Across the entire population, indicators of thyroid hormone resistance exhibited positive correlations with fat distribution (all P < 0.01), while most indicators displayed negative associations with skeletal muscle mass. These findings were consistent solely among male participants. Furthermore, even after adjusting for basic characteristics, linear regression analysis revealed that these correlations remained statistically significant (all P < 0.05). Conclusions In males with euthyroid T2D, impaired thyroid hormone sensitivity correlates with fat distribution independent of conventional risk factors.

BACKGROUND:This study aims to examine the alterations and clinical significance of CD8+ regulatory T cell subsets in the peripheral blood of individuals with type 1 diabetes mellitus (T1DM). METHODS:From January 2020 to December 2023, a study was conducted involving 40 individuals with T1DM, who visited the Department of Endocrinology at the First Affiliated Hospital of Nanjing Medical University (T1DM group). For comparison, 40 healthy individuals who underwent routine physical examinations at the same hospital during this period were selected as the control group. Peripheral blood mononuclear cells were isolated, and CD8+ T cells were labeled with CD3, CD25 and FoxP3 to analyze their subset frequencies using flow cytometry. The study examined differences in subset frequencies between the two groups and explored correlations between subset frequency, disease duration, and age of onset. RESULTS:The frequencies of CD8+ CD25+, CD8+ FoxP3+, CD8+ CD25+ CD3+ and CD8+ FoxP3+ CD3+ subsets in peripheral blood mononuclear cells did not significantly differ between the healthy control group and the T1DM group (P > 0.05). In the T1DM group, the expression level of CD25 on CD8+ T cells showed no correlation with the age of onset or disease duration, and FoxP3 levels were also unrelated to the age of onset, with no statistical differences (P > 0.05). However, within the T1DM group, FoxP3 levels progressively decreased with longer disease duration, demonstrating a statistically significant negative correlation (Pearson r = -0.331, P < 0.05). In the T1DM group, the level of CD3+ CD8+ T cells expressed CD25, and there was no correlation between Foxp 3 level and age of onset, not statistically significant (P > 0.05), but the level of Foxp 3 in the T1DM group decreased with the duration of the disease, (Pearson r= - 0.363, P < 0.05). CONCLUSION:The levels of CD8+FoxP3+ regulatory T cells in peripheral blood mononuclear cells of patients with T1DM show a significant correlation with disease duration, suggesting that these cells may play a critical role in the progression of T1DM.

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.

Background Increased serum cystatin C (CysC) can predict the onset of type 2 diabetes (T2D). Meanwhile, impaired pancreatic α- and β-cell functions get involved in the pathophysiological processes of T2D. So this study was to explore the relationships between serum CysC levels and pancreatic α- and β-cell functions in T2D. Methods In this cross-sectional observational study, a total of 2634 patients with T2D were consecutively recruited. Each recruited patient received a serum CysC test and oral glucose tolerance test for synchronous detection of serum C-peptide and plasma glucagon. As components of pancreatic β-cell function, insulin secretion and sensitivity indices were evaluated by C-peptide area under the curve (AUC-CP) and C-peptide-substituted Matsuda’s index (Matsuda-CP), respectively. Fasting glucagon (F-GLA) and post-challenge glucagon calculated by glucagon area under the curve (AUC-GLA) were used to assess pancreatic α-cell function. These skewed indices and were further natural log-transformed (ln). Results With quartiles of serum CysC levels ascending, AUC-CP, F-GLA and AUC-GLA were increased, while Matsuda-CP was decreased (P for trend <0.001). Moreover, serum CysC levels were positively related to lnAUC-CP, lnF-GLA and lnAUC-GLA (r= 0.241, 0.131 and 0.208, respectively, P < 0.001), and inversely related to lnMatsuda-CP (r= –0.195, P  < 0.001). Furthermore, after controlling for other relevant variables via multivariable linear regression analysis, serum CysC levels were identified to account for lnAUC-CP (β= 0.178, t= 10.518, P  < 0.001), lnMatsuda-CP (β= –0.137, t= –7.118, P  < 0.001), lnF-GLA (β= 0.049, t= 2.263, P = 0.024) and lnAUC-GLA (β= 0.121, t= 5.730, P  < 0.001). Conclusions Increased serum CysC levels may be partly responsible for increased insulin secretion from β-cells, decreased systemic insulin sensitivity, and elevated fasting and postprandial glucagon secretion from α-cells in T2D.

BackgroundIncreased plasma D-dimer levels have been reported to be associated with a range of adverse health outcomes. This study aimed to determine whether plasma D-dimer is connected to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsThis study was part of a series exploring the potential risks for DPN. All patients were questioned for neurologic symptoms, examined for neurologic signs, and received nerve conduction studies to collect nerve action potential onset latency, amplitude, and nerve conduction velocity (NCV). Composite Z scores of latency, amplitude, and NCV were calculated. DPN was confirmed as both at least a neurologic symptom/sign and an abnormality of nerve conduction studies. Coagulation function indices, such as plasma D-dimer levels, were also synchronously detected.ResultsWe finally recruited 393 eligible patients for this study, of whom 24.7% (n = 97) were determined to have DPN. The plasma D-dimer level was found to be closely associated with the composite Z score of latency, amplitude, and NCV after adjusting for other coagulation function indices and clinical covariates (latency: β = 0.134, t = 2.299, p = 0.022; amplitude: β = –0.138, t = –2.286, p = 0.023; NCV: β = –0.139, t = –2.433, p = 0.016). Moreover, the prevalence of DPN in the first, second, third, and fourth quartiles (Q1, Q2, Q3, and Q4) of the D-dimer level was 15.2%, 15.9%, 26.4%, and 42.7%, respectively (p for trend < 0.001). The corresponding adjusted odds ratios and 95% CIs for DPN in D-dimer quartiles were 1, 0.79 (0.21–2.99), 1.75 (0.49–6.26), and 5.17 (1.38–19.42), respectively. Furthermore, the optimal cutoff value of the plasma D-dimer level to discriminate DPN was ≥0.22 mg/L (sensitivity = 67.01%, specificity = 58.78%, and Youden index = 0.26) after analysis by the receiver operating characteristic curve.ConclusionsIncreased plasma D-dimer levels may be a promising indicator for DPN in patients with T2D.

Abstract Background Plasma 1,5-anhydro-d-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia. Methods We recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c < 8.0%) for this cross-sectional study, with plasma 1,5-AG synchronously detected. All patients were questioned for neurologic symptoms, examined for neurologic signs and screened for peripheral nerve function. Nerve function included the latency, amplitude and nerve conduction velocity (NCV) of limbs nerves (median, ulnar nerve, common peroneal, superficial peroneal, tibial and sural nerve). Besides, composite Z-score of latency, amplitude and NCV were calculated. DPN was identified as both at least a neurologic symptom/sign and an abnormality of peripheral nerve function. Results Among the recruited patients, 23.9% (n = 137) were identified to be with DPN, and the prevalence of DPN decreased from 36.6%, 24.5%, 21.2%, 13.3% from first (Q1), second (Q2), and third (Q3) to fourth quartile (Q4) of 1,5-AG. Moreover, multivariable linear regression analysis showed 1,5-AG was associated with composite Z-score of nerve latency (β = − 0.18, t = − 3.84, p < 0.001), amplitude(β = 0.26, t = 5.35, p < 0.001) and NCV (β = 0.24, t = 5.61, p < 0.001), respectively. Furthermore, compared to Q4 of 1,5-AG as reference, the adjusted odds ratios and 95% CIs for DPN of Q3, Q2, and Q1 were 1.29(0.59–2.81), 1.85(0.87–3.97), and 2.72(1.16–6.34), respectively. Additionally, receiver operating characteristic analysis revealed that optimal cutoff value of 1,5-AG to indicate DPN was ≤ 30.8 μmol/L, with sensitivity of 56.20% and specificity of 66.36%. Conclusions Low plasma 1,5-AG is closely associated with impaired peripheral nerve function and DPN in T2D patients under mild-to-moderate hyperglycemia.

Background Increased serum adenosine deaminase (ADA) levels have been shown to be involved in metabolic abnormalities and immune disequilibrium, which may in turn contribute to inflammatory diseases. This study aimed to determine whether increased serum ADA levels are related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods This study was part of a series exploring the potential risks for DPN. All patients received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate the composite Z score of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum ADA levels were also synchronously detected. Results A total of 384 eligible patients with T2D were recruited for this study, and 24.5% (n=94) were determined to have DPN. Increases in serum ADA levels were closely associated with increases in composite Z score of latency ( β =0.263, t =5.273, p <0.001) and decreases in composite Z score of amplitude ( β =–0.126, t =–2.352, p =0.019) and NCV ( β =–0.201, t =–3.841, p <0.001) after adjusting for other clinical covariates. Moreover, each 5 U/L increase in serum ADA levels was associated with a 1.781-fold increased adjusted odds ratio of having DPN (95% confidence interval: 1.271–2.495). Furthermore, the optimal cut-off value of serum ADA levels to discriminate DPN was ≥14.2 U/L (sensitivity=59.57%, specificity=75.52% and Youden index=0.351) after analysis by receiver operating characteristic curve. Conclusions Increased serum ADA levels may be a potential risk factor for DPN in patients with T2D.

Background Deterioration of sleep quality has been reported to contribute to the incidence of diabetes and may be responsible for glycemic status in diabetes. The present study explored the relationship between sleep quality and glycemic variability in patients with type 2 diabetes (T2D). Methods We recruited 111 patients with T2D for this cross-sectional study. Each patient underwent flash glucose monitoring for 14 days to obtain glycemic variability parameters, such as standard deviation of glucose (SD), coefficient of variation of glucose (CV), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and time in glucose range of 3.9–10 mmol/L (TIR 3.9–10 ). After 14 days of flash glucose monitoring, each patient received a questionnaire on the Pittsburgh Sleep Quality Index (PSQI) to evaluate subjective sleep quality. HbA1c was also collected to assess average glucose. Results HbA1c was comparable among the subgroups of PSQI score tertiles. Across ascending tertiles of PSQI scores, SD, CV and MAGE were increased, while TIR 3.9–10 was decreased ( p for trend < 0.05), but not MODD ( p for trend = 0.090). Moreover, PSQI scores were positively correlated with SD, CV, MODD and MAGE ( r = 0.322, 0.361, 0.308 and 0.354, respectively, p < 0.001) and were inversely correlated with TIR 3.9–10 ( r = − 0.386, p < 0.001). After adjusting for other relevant data by multivariate linear regression analyses, PSQI scores were independently responsible for SD ( β = 0.251, t = 2.112, p = 0.041), CV ( β = 0.286, t = 2.207, p = 0.033), MAGE ( β = 0.323, t = 2.489, p = 0.018), and TIR 3.9–10 ( β = − 0.401, t = − 3.930, p < 0.001) but not for MODD ( β = 0.188, t = 1.374, p = 0.177). Conclusions Increased glycemic variability assessed by flash glucose monitoring was closely associated with poor subjective sleep quality evaluated by the PSQI in patients with T2D.