High-normal serum uric acid predicts macrovascular events in patients with type 2 diabetes mellitus without hyperuricemia based on a 10-year cohort.

BACKGROUND AND AIMS: The upper limits of normal serum uric acid (SUA) or the lower limits of hyperuricemia were frequently set at 420 or 360 µmol/L (7.0 or 6.0 mg/dL). We aimed to explore the association between high-normal SUA (360 ≤ SUA≤420 µmol/L) and incidence of macrovascular and renal events based on a 10-year cohort with type 2 diabetes mellitus (T2DM) to explore which cut-off was more appropriate. METHODS AND RESULTS: A total of 2988 patients with T2DM without hyperuricemia (SUA≤420 µmol/L) were included and followed up. Cox proportional hazards models and restricted cubic spline regression were used to evaluate the relationship between baseline SUA (as continuous and categorical variable) and macrovascular and renal events. Patients were grouped as low-normal (SUA<360 µmol/L) and high-normal groups based on baseline SUA, and the latter group had higher incidence of macrovascular events. Multivariate Cox regression analysis indicated that baseline levels of SUA were significantly associated with cardiovascular (HR = 1.385, 95%CI:1.190-1.613, P < 0.001) and peripheral vascular events (HR = 1.266, 95%CI:1.018-1.574, P = 0.034), and the linear association existed. Moreover, fully adjusted multivariable Cox analyses indicated high-normal SUA increased the risks of cardiovascular (HR = 1.835, 95%CI:1.319-2.554, P < 0.001) and peripheral vascular events (HR = 1.661, 95%CI:1.000-2.760, P = 0.050) compared to low-normal SUA. CONCLUSIONS: Baseline SUA levels were positively associated with cardiovascular and peripheral vascular events, and high-normal SUA increased the risks of these events in patients with T2DM even without hyperuricemia. A threshold value for SUA of 360 µmol/L should be more appropriate in terms of predicting macrovascular events risks compared to the value of 420 µmol/L.

OX40 promotes obesity-induced adipose inflammation and insulin resistance.

Adaptive immunity plays a critical role in IR and T2DM development; however, the biological mechanisms linking T cell costimulation and glucose metabolism have not been fully elucidated. In this study, we demonstrated that the costimulatory molecule OX40 controls T cell activation and IR development. Inflammatory cell accumulation and enhanced proinflammatory gene expression, as well as high OX40 expression levels on CD4+ T cells, were observed in the adipose tissues of mice with diet-induced obesity. OX40-KO mice exhibited significantly less weight gain and lower fasting glucose levels than those of WT mice, without obvious adipose tissue inflammation. The effects of OX40 on IR are mechanistically linked to the promotion of T cell activation, Th1 cell differentiation and proliferation-as well as the attenuation of Treg suppressive activity and the enhancement of proinflammatory cytokine production-in adipose tissues. Furthermore, OX40 expression on T cells was positively associated with obesity in humans, suggesting that our findings are clinically relevant. In summary, our study revealed that OX40 in CD4+ T cells is crucial for adipose tissue inflammation and IR development. Therefore, the OX40 signaling pathway may be a new target for preventing or treating obesity-related IR and T2DM.

Metabolic profiling of acromegaly using a GC-MS-based nontargeted metabolomic approach.

PURPOSE: Acromegaly is a rare disease caused by chronic hypersecretion of growth hormone, which leads to multiple comorbidities and reduced life expectancy. The objective of this study was to characterize the serum metabolic profiles of acromegaly patients and identify metabolic biomarkers using metabolomics. METHODS: Twenty-nine active acromegaly patients and age- and sex-matched normal controls were recruited. Serum samples were collected, and serum metabolites were analyzed using gas chromatography-mass spectrometry coupled with a series of multivariate statistical analyses. RESULTS: The orthogonal projections to latent structures-discriminate analysis (OPLS-DA) model identified and validated significant metabolic differences between individuals with acromegaly and normal controls (R2Y = 0.908 and Q2Y = 0.601). Compared with normal controls, acromegaly patients had elevated levels of 5-aminovaleric acid, glyceric acid, L-dithiothreitol, dihydrocoumarin, N-acetyl-L-glutamic acid, gluconic acid, and monoolein (P < 0.05) and reduced serum levels of D-erythronolactone, taurine, carbamoyl-aspartic acid, and mucic acid (P < 0.01). Furthermore, glyceric acid and taurine possessed higher area under the receiver operating characteristic curve values (AUC values, 0.914 and 0.931, respectively), suggesting an excellent clinical ability to distinguish acromegaly patients from normal controls. Pathway analysis revealed that the pentose phosphate pathway and the taurine and hypotaurine metabolic pathway are significant pathways (P = 0.002 and 0.004, respectively). CONCLUSIONS: Metabolic activity is significantly altered in the serum of individuals with active acromegaly. Glyceric acid and taurine may be considered potential biomarkers for distinguishing acromegaly patients from normal controls.

MRI chemical shift imaging of the fat content of the pancreas and liver of patients with type 2 diabetes mellitus.

The present study aimed to investigate the association between the content and distribution of fat in the pancreas and liver in patients with type 2 diabetes mellitus (T2DM). A total of 70 patients newly diagnosed with T2DM (T2DM group) and 30 healthy volunteers (normal control group) were enrolled in the present study. Dual-echo magnetic resonance (MR) chemical shift imaging was used to measure the fat content of the liver and the head, body and tail regions of the pancreas. In addition, the distribution of fat in the various regions of the pancreas, as well as the average fat content of the pancreas versus the liver, were compared. The fat content of the pancreatic head, body and tail regions of the T2DM group were 5.59±4.70, 4.80±3.75 and 4.89±3.86%, respectively. The fat content of these regions in the normal control group were 3.89±2.47, 3.30±2.11 and 3.23±2.23%, respectively. The average fat content of the pancreas was 5.19±3.75% for the T2DM group and 3.47±2.00% for the normal control group. The average fat content of the liver was 9.87±3.19% for the T2DM group and 7.24±2.38% for the normal control group. Therefore, the results from MR chemical shift imaging suggested that there were no significant differences in the distribution of fat between the pancreas of patients newly diagnosed with T2DM and that from the healthy population; however, the average fat content in the pancreas of the T2DM group was significantly higher (F=3.597; P<0.05), as compared with the normal control group. In addition, there was no correlation between the fat contents in the pancreas and liver in patients newly diagnosed with T2DM and the healthy population.