FSH may mediate the association between HbA1c and bone turnover markers in postmenopausal women with type 2 diabetes.

INTRODUCTION: Recent studies in postmenopausal women have found associations of follicle-stimulating hormone (FSH) levels with both glucose metabolism and bone turnover. The objective of the study was to investigate whether FSH may contribute to suppressed bone turnover markers (BTMs) in postmenopausal women with type 2 diabetes (T2D). MATERIALS AND METHODS: 888 postmenopausal women with T2D, 352 nondiabetes (prediabetes plus normoglycemia) were included from the METAL study. HbA1c, sex hormones, 25-hydroxy vitamin D (25(OH)D), serum procollagen type I N-terminal propeptide (P1NP), and ß-C-terminal telopeptide (ß-CTX) were measured. RESULTS: P1NP and ß-CTX decreased in postmenopausal T2D women compared with nondiabetes controls (both p < 0.001). The major factors responsible for the changes in P1NP were HbA1c (ß = - 0.050, p < 0.001), 25(OH)D (ß = - 0.003, p = 0.006), FSH (ß = 0.001, p = 0.044) and metformin (ß = - 0.109, p < 0.001), for ß-CTX were HbA1c (ß = - 0.049, p < 0.001), body mass index (BMI) (ß = - 0.011, p = 0.005), 25(OH)D (ß = - 0.003, p = 0.003), FSH (ß = 0.002, p = 0.022) and metformin (ß = - 0.091, p = 0.001) in postmenopausal T2D women based on multivariate regression analysis. With the increase in HbA1c, FSH decreased significantly (p for trend < 0.001). Mediation analysis demonstrated that FSH partly mediated the suppression of LnP1NP and Lnß-CTX by HbA1c (ß = - 0.009 and - 0.010, respectively), and Lnß-CTX by BMI (ß = - 0.015) when multiple confounders were considered (all p < 0.05). CONCLUSION: HbA1c was the crucial determinant contributing to the suppression of BTMs. FSH might play a novel mediation role in BTM suppression due to HbA1c or BMI.

Effect of triptolide on expression of oxidative carbonyl protein in renal cortex of rats with diabetic nephropathy.

The traditional Chinese medicine (Tripterygium wilfordiiHook.f., TWH) has been clinically used to treat primary and secondary renal diseases and proteinuria for nearly 40 years. However, there is a rare literature about the effect of triptolide (the main active ingredient of TWH) on the expression of oxidative carbonyl protein (OCP) in diabetic nephropathy (DN). This study aimed to provide experimental evidence for triptolide treatment on DN through its effect on the expression of OCP, in order to investigate the effects of triptolide on the expression of OCP in rats with DN. Sixty SD rats were randomly divided into five groups: control group, high-dose triptolide (Th) group, low-dose triptolide (Tl) group, DN model group, and positive control (benazepril) group. The DN model was established using streptozotocin. Urinary protein excretion, fasting blood glucose (FBG), superoxide dismutase (SOD) in renal homogenate, malondialdehyde (MDA) in renal homogenate and renal nitrotyrosine by immunohistochemistry, and the expression of OCP by oxyblotimmune blotting were detected. In the DN model group, rat urinary protein excretion and renal MDA were significantly increased, while renal SOD significantly decreased and nitrotyrosine expression was obviously upregulated in the kidney. After triptolide treatment, 24-h urinary protein excretion (61.96±19.00 vs. 18.32±4.78 mg/day, P<0.001), renal MDA (8.09±0.79 vs. 5.45±0.68 nmol/L, P<0.001), and nitrotyrosine expression were decreased. Furthermore, renal OCP significantly decreased, while renal SOD (82.50±19.10 vs. 124.00±20.52 U/L, P<0.001) was elevated. This study revealed that triptolide can down-regulate the expression of OCP in the renal cortex of DN rats.

Effects and clinical significance of pentoxifylline on the oxidative stress of rats with diabetic nephropathy.

Diabetic nephropathy (DN) is a common and serious clinical complication of diabetes and presently there are no effective ways to prevent its occurrence and progression. Recent studies show that pentoxifylline (PTX) can improve renal hemodynamics, reduce urinary protein excretion, and alleviate or delay renal failure in DN patients. In this study, we focused on the anti-oxidative stress effect of PTX on alleviating renal damages of DN using rat models. DN rats were established with injection of streptozotocin. Blood glucose, urinary protein excretion, serum cystatin C, renal biopsy, superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and renal homogenate and renal nitrotyrosine levels were analyzed before and 12 weeks after the treatment of PTX. Before treatment, all the DN rats had elevated blood glucose, increased urinary protein excretion and elevated serum cystatin C. Morphologically, DN rats exhibited renal tissue damages, including swelling and fusions of foot processes of podocytes under electron microscope. Masson staining revealed blue collagen deposition in glomeruli and renal interstitium. With treatment of PTX, symptoms and renal pathological changes of DN rats were alleviated. Furthermore, the MDA levels were increased and the SOD levels were decreased in the serum and kidneys of DN rats, and these changes were reversed by PTX. The expression of nitrotyrosine was up-regulated in DN rat model and down-regulated by PTX, indicating that PTX was able to inhibit oxidative reactions in DN rats. PTX could alleviate renal damage in DN, which may be attributable to its anti-oxidative stress activity.