Purpose To examine the prevalence of different microvascular complications and investigate the association between thyroid hormones (THs) and these complications in euthyroid patients with type 2 diabetes mellitus (T2DM). Methods A total of 248 T2DM patients were analyzed retrospectively for the study. All patients received a detailed and standard assessment to identify diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), and diabetic retinopathy (DR). Multivariate logistic regression was carried out to analyze the association between THs and diabetic microvascular complications. Results The study found the prevalence of any microangiopathy to be 72.18% (n = 179). At the same time, the prevalence of DPN was 54.84% (n=136), while that of DN was 31.85% (n=79). Likewise, the prevalence of DR was 35.48% (n=88). The odds ratios (ORs) for free triiodothyronine (FT3) developing any microangiopathy, DPN, DN and DR were 0.200, 0.361, 0.310, and 0.588 (P<0.05), respectively. Also, the ORs for free thyroxine (FT4) developing any microangiopathy, DPN, DN and DR were 0.643, 0.800, 0.702 and 0.726 (P<0.05), respectively. Lastly, the ORs for thyroid-stimulating hormone (TSH) developing DPN was 1.57 (95% CI: 1.148–2.137, P=0.005). Conclusion The study concludes that serum FT3 and FT4 levels are negatively associated with any microangiopathy, DPN, DN and DR in euthyroid patients with T2DM, independent of traditional risk factors. However, the TSH levels are positively associated with DPN. Future larger sample-size studies are needed to confirm the relationship between thyroid hormone levels and microvascular complications in euthyroid patients with T2DM.

Background Epithelial–mesenchymal transition (EMT) plays an important role in interstitial matrix deposition and renal fibrosis in diabetic kidney disease (DKD). It has been verified that Astragaloside IV (AS-IV) is beneficial for ameliorating DKD. However, the underlying mechanisms of AS-IV on regulating EMT in DKD are yet to be established. Accumulated evidence has suggested that C-X3-C motif ligand 1 (CX3CL1) plays a significant role in the progression of EMT. Purpose We aimed to investigate whether AS-IV could alleviate EMT by regulating CX3CL1 in DKD and reveal its underlying mechanisms. Methods For the in vivo study, mice were divided into the following five groups (n=10): db/m+vehicle, db/db+vehicle, db/db+AS-IV-L (10mg/kg/d), db/db+AS-IV-M (20mg/kg/d), db/db+AS-IV-H (40mg/kg/d). After 12 weeks of treatment, the renal injuries were assessed based on the related parameters of urine, blood and histopathological examination. Immunohistochemistry and Western blotting were used to detect relative proteins levels. Then in HK-2 cells, the molecular mechanism of AS-IV attenuating the EMT in mice with DKD through the CX3CL1-RAF/MEK/ERK pathway was studied. Results In the present study, we found that AS-IV reduced urinary protein levels and improved renal pathological damage in DKD mice. Moreover, AS-IV ameliorated the renal tubular EMT induced by hyperglycemia or high glucose (HG), and decreased the expression of CX3CL1 and inhibited the activation of the RAF/MEK/ERK pathway in vivo and in vitro. In HK-2 cells, downregulation of CX3CL1 suppressed the stimulation of the RAF/MEK/ERK pathway and EMT induced by HG. However, CX3CL1 overexpression eliminated the benefits of AS-IV on the RAF/MEK/ERK pathway and EMT. Conclusion In summary, we indicated that AS-IV alleviates renal tubular EMT through the CX3CL1-RAF/MEK/ERK signaling pathway, indicating that CX3CL1 could be a potential therapeutic target of AS-IV in DKD.

Background Components of the RAAS may influence bone metabolism. Different roles of the RAAS are found in patients with primary aldosteronism (PA), Gitelman syndrome (GS) and Bartter syndrome (BS). We collected inpatient medical records including 20 patients with Gitelman syndrome (GS group), 17 patients with Bartter syndrome (BS group) and 20 age-matched patients with primary aldosteronism (PA group). We found the following results. (1) PA patients had significantly higher serum magnesium, potassium, plasma aldosterone, serum parathyroid hormone, urinary calcium and BMI (p<0.05) while significantly lower serum calcium and phosphorus (P < 0.05) than GS and BS patients. (2) Total hip and femoral neck bone mineral density (BMD) in PA patients were significantly lower than those in GS and BS patients (P<0.05). (3) GS patients had lower serum magnesium and urinary calcium than BS patients (P < 0.05). (4) Compared with BS patients, the vertebral BMD in GS patients were significantly higher (P < 0.05). So we believe higher aldosterone and PTH levels may be the reason that PA patients have lower hip BMD. Lower urinary calcium and inactivation of the NCC gene (Na-Cl cotransporter) in GS patients may have protective effects on vertebral bone mineral density. Conclusions With persistence disordered RAAS, PA patients have lower BMD, especially hip BMD as compared with GS and BS patients. We presumed the lower renin and higher aldosterone level may be the reason. With the same level of renin and aldosterone, BS patients have lower vertebrate BMD than GS patients. Decreased urinary calcium excretion may be the reason.

Diabetic foot ulcers (DFUs) are a multifactorial complication of diabetes mellitus associated with impaired angiogenesis. Potentially effective treatments for such wounds are currently unknown. Cross-talk between pericyte and endothelial cell exosomes has been reported as a therapeutic strategy for treating DFUs. By regulating pericyte-endotheliocyte exosomes crosstalk, Angelica dahurica (AD) promoted angiogenesis and accelerated diabetic wound healing in this study. AD stimulated the migration and angiogenic tubule formation of human umbilical vein endothelial cells (HUVECs) by stimulating exosomes derived from human cerebrovascular pericytes (HBVPs), which was accompanied by increased protein expressions of Wnt4, β-catenin, and cyclinD1. In addition, the Wnt/β-catenin pathway inhibitor XAV939 reversed the activation of the Wnt4/β-catenin signalling pathway in HUVECs by AD. In the STZ-induced cutaneous wound rat model, AD enhanced angiogenesis and collagen deposition in vivo, resulting in a faster wound healing rate and a smaller wound area. AD concurrently promoted capillary formation by activating the Wnt4/β-catenin signalling pathway. AD promoted angiogenesis of HUVECs in vitro by regulating HBVPs-derived exosomes via the Wnt4/β-catenin signal pathway, thereby enhancing vascularization in regenerated tissue and promoting wound healing in vivo. The research indicated that AD could be used as a treatment for enhancing angiogenesis in diabetic wound healing.

Background Primary hyperparathyroidism (PHPT) is a common endocrinopathy that may increase fracture risk and decrease bone mineral density (BMD). Some patients develop distal renal tubular acidification dysfunction under conditions of hyperchloraemia or hyperchloraemic acidosis. To examine whether this dysfunction influences the clinical outcome, we explored the distal renal tubular acidification function in patients with PHPT and its effects on the clinical manifestations of the disease. Methods We retrospectively analysed 75 PHPT patients with regard to renal tubular acidification and blood gas analysis. The patients were divided into two groups, the renal tubular acidification dysfunction group and normal function group. Results Serum phosphate level and total hip bone density were significantly decreased and 25OHD level was significantly increased in the renal tubular acidification dysfunction group in comparison to the normal function group. Female patients in the renal tubular acidification dysfunction group showed significantly decreased femoral neck and total hip BMD and increased susceptibility to fracture. However, there were no such differences in male patients between the two groups. Conclusions About 54.6 % of PHPT patients in our study population had abnormal distal renal tubular acidification. PHPT patients with abnormal distal renal tubular acidification may have lower hip bone density. Female PHPT patients with abnormal distal renal tubular acidification showed increased susceptibility to fractures and the development of osteoporosis.