Background Vitamin D deficiency was reported to be associated with diabetic peripheral neuropathy. But the association in Chinese population and the screening value of vitamin D deficiency for diabetic peripheral neuropathy were unknown.

BackgroundFibroblast growth factor 21 (FGF21) is an emerging metabolic regulator associated with glucose and lipid metabolism, and it is still unclear whether FGF21 is related to atherosclerosis. Here, we explored the potential link between FGF21 and lower extremity atherosclerotic disease (LEAD) in type 2 diabetic patients.MethodsA cross-sectional study was conducted on 504 type 2 diabetic patients (283 men, 221 women). LEAD was defined by Ankle-brachial index (ABI) <0.9 and lower extremity arterial plaque evaluated by color Doppler ultrasound. Serum FGF21 concentrations were quantified by a sandwich enzyme-linked immunosorbent assay.ResultsThe total FGF21 levels of male and female patients had no significant differenence ((299.14(177.31-534.49) vs 362.50(214.01-578.73), P=0.516). Serum FGF21 levels in LEAD group were significantly higher than non-LEAD group in females (385.34(243.89-661.54) vs 313.13(156.38-485.79), P=0.006), while not in male patients (295.52(177.09-549.64) vs 342.09 (198.70-549.87), P=0.613). In diabetic women, subjects with LEAD had significantly higher serum FGF21 regardless of non-alcoholic fatty liver disease (NAFLD) (P < 0.05). And serum FGF21 levels were positively correlated with waist circumference and systolic blood pressure after adjusted for age and BMI (r=0.198, P=0.004; r=0.152, P=0.027; respectively). Moreover, FGF21 was independently tied to femoral intima-media thickness (FIMT) (β=0.208, P=0.031). After adjusted for other LEAD risk factors, FGF21 was demonstrated to be an independent risk factor for LEAD in type 2 diabetic women (OR, 1.106; 95%CI 1.008-1.223; P=0.028). In addition, FGF21 was negatively correlated with estradiol in premenopausal diabetic women (r=−0.368, P=0.009). After adjusted for estradiol, serum FGF21 levels were still positively associated with FIMT in premenopausal diabetic women (r=0.381, P=0.007). In diabetic men, serum FGF21 levels were correlated with triglyceride and C-reactive protein even after adjusted for age and BMI (r=0.204, P=0.001; r=0.312, P < 0.001; respectively). However, serum FGF21 was not an independent impact factor for LEAD in men (P > 0.05).ConclusionsSerum FGF21 level independently and positively links LEAD in Chinese women with type 2 diabetes. The gender difference may be due to different estrogen levels.

Endoplasmic reticulum (ER) stress plays an important role in metabolic diseases like obesity and type 2 diabetes mellitus (T2DM), although the underlying mechanisms and regulatory pathways remain to be elucidated. Here, we induced chronic low-grade ER stress in lean mice to levels similar to those in high-fat diet (HFD)–fed obese mice and found that it promoted hyperglycemia due to enhanced hepatic gluconeogenesis. Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14), which increased the stability and levels of 3′,5′-cyclic monophosphate–responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis. Exogenous overexpression of USP14 in the liver significantly increased hepatic glucose output. Consistent with this, liver-specific knockdown of USP14 abrogated the effects of ER stress on glucose metabolism, and also improved hyperglycemia and glucose intolerance in obese mice. In conclusion, our findings show a mechanism underlying ER stress-induced disruption of glucose homeostasis, and present USP14 as a potential therapeutic target against T2DM.

Objective: Serum cystatin C (CysC) is a sensitive marker of kidney function and recent studies have shown that CysC plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study was to explore the relationship between serum CysC and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. Methods: In total, 937 type 2 diabetic patients were enrolled in this cross-sectional study. Serum CysC concentration was measured by immunoturbidimetry. DPN was evaluated by neurological symptoms, neurological signs, neurothesiometer, and electromyogram. Results: Serum CysC levels were significantly higher in DPN patients (1.3 (1.1-1.5) mg/l) compared with patients with signs of DPN (1.1 (0.9-1.3) mg/l, P!0.001) and non-DPN patients (1.0 (0.9-1.3) mg/l, P!0.001). Multiple regression analysis revealed that DPN was associated with age, diabetes duration, HbA1c, and serum CysC. Spearman's correlation analysis showed that serum CysC was closely related with age, sex, diabetes duration, hypertension, glomerular infiltration rate, and serum creatinine (Cr) level. The patients were divided into quartiles according to the serum CysC levels. Compared with quartile 1 (referent), the risk of DPN was significantly higher in quartile 2 (odds ratio (OR), 1.753; 95% CI, 1.055-2.912; P!0.05), quartile 3 (OR, 2.463; 95% CI, 1.445-4.917; P!0.01), and quartile 4 (OR, 5.867; 95% CI, 2.075-16.589; P!0.01). Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum CysC to indicate DPN was 1.25 mg/l in male patients and 1.05 mg/l in female patients. High serum CysC level indicated a onefold higher risk of DPN. Conclusions: High serum CysC level is closely associated with DPN and may be a potential biomarker for DPN in type 2 diabetic patients.

Lower ficolin-3 level is independently associated with DPN, and it may be a potential biomarker for DPN.

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There was a close association between vibration perception threshold and the severity of diabetic retinopathy. vibration perception threshold was a potential screening method for diabetic retinopathy, and its optimal cut-off for prompting high risk of sight-threatening retinopathy was 18 V.

BackgroundDespite advances in the treatment of acute promyelocytic leukemia (APL) with all‐trans‐retinoic acid (ATRA), its underlying mechanism has not been fully elucidated. The oncogenic microRNA cluster miR‐17‐92 modulates multiple cellular processes, including survival, proliferation, and apoptosis. However, the role of miR‐17‐92 and its regulation has not yet been documented for APL.MethodsWe analyzed miR‐17‐92 expression in APL samples and cell lines by qRT‐PCR. The expression of c‐Myc was measured by western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis.ResultsWe observed that miR‐17‐92 was upregulated in APL compared with healthy donors. Furthermore, we demonstrated that expressions of c‐Myc and miR‐17‐92 are markedly suppressed during ATRA‐induced NB4 cell differentiation. Importantly, we also demonstrated that miR‐17‐92 is directly regulated by c‐Myc during the granulocytic differentiation of APL cells. Finally, the overexpression of miR‐17‐5p blocks ATRA‐induced differentiation.ConclusionsWe report abnormal expression of the miR‐17‐92 cluster in APL cells, which is responsible for the differentiation block in blast cells in APL. In addition, we identified miR‐17‐92 as a target gene of c‐Myc during ATRA‐induced granulocytic differentiation.