Relationship between vitamin D status and cardiac autonomic neuropathy in prediabetes.

BACKGROUND AND OBJECTIVES: Studies have suggested that vitamin D deficiency is associated with impaired cardiac autonomic nerve function. This study explores the correlation between serum vitamin D and cardiac autonomic neuropathy (CAN) in prediabetes and reveals the protective effect of vitamin D against CAN. METHODS AND STUDY DESIGN: In total, 113 patients with prediabetes and definite CAN and 180 with prediabetes but without CAN were enrolled on the basis of their standard cardiovascular autonomic reflex test results. Chemiluminescence was used to measure 25(OH)D, the patients with CAN were divided into four groups, and the heart rate variability (HRV) of the study groups were compared. RESULTS: Relative to the 50≤25(OH)D<75-nmol/L group, the 25≤25(OH)D<50-nmol/L and 25(OH)D<25-nmol/L groups exhibited significant differences in the time and frequency domains of HRV (p< 0.05). Furthermore, we discovered that 25(OH)D is positively correlated with standard deviation of normal-to-normal RR intervals (SDNN) (ß=0.566, p<0.05) and negatively correlated with low-to-high frequency ratio (LF/HF) (ß=-0.199, p<0.05). A logistic regression reveals that CAN in prediabetes is significantly correlated with the 25(OH)D concentrations of <25 nmol/L (OR, 2.380 [1.208-4.691]; p<0.05) and 25≤25(OH)D<50 nmol/L (OR, 1.875 [1.064-3.751]; p<0.05). CONCLUSIONS: Serum 25(OH)D is significantly correlated with CAN in prediabetes, especially in the 25(OH)D <25-nmol/L group. Therefore, vitamin D deficiency may be related to the occurrence of CAN in prediabetes, and appropriate supplementation may provide protection against CAN.

Clinical characteristics and gene mutation analysis of an adult patient with ETFDH­related multiple acyl­CoA dehydrogenase deficiency.

Multiple acyl­CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder of fatty acid metabolism caused by defects in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). These defects are mainly classified into the neonatal and late­onset types, based on their clinical manifestations. ETFDH gene mutations are generally considered to be associated with the late­onset type. The present study reported an adult woman with late­onset MADD accompanied with biochemical and muscle biopsy findings indicating metabolic disorders. Gene sequencing analysis showed that the c.1514T>C homozygous mutation in the region of the 12th exon of the ETFDH gene, which led to the amino acid substitution p.I505T (isoleucine > threonine), resulting in defective ETFDH protein function. The results of family verification revealed that the homozygous mutation originated from her parents. The female patient was treated with a large dose of vitamin B2, L­carnitine and coenzyme Q10, and the symptoms were significantly relieved. The c.1514T>C mutation in the ETFDH gene, was considered as a novel pathogenic mutation that had not been previously reported. Therefore, it was hypothesized that this mutation was responsible for the clinical characteristics of the adult female patient. Overall, this novel mutation could expand the spectrum of the ETFDH gene mutation and provide the basis for the etiological and prenatal diagnosis of MADD.

Analysis of angiographic characteristics and intervention of vitamin D in type 2 diabetes mellitus complicated with lower extremity arterial disease.

AIMS: Previous studies have suggested that type 2 diabetes mellitus with lower extremity arterial disease is related to 25-hydroxyvitamin D deficiency. The purpose of this study is to explore the relation between vitamin D supplementation and the characteristics of type 2 diabetes mellitus complicated with lower extremity arterial disease. METHODS: The clinical data of 514 patients and 148 healthy subjects treated in the First Hospital of Lanzhou University from January 2012 to June 2019 were collected, including the clinical data, ankle-brachial index, and medical records of lower limb artery angiography. We divided the patients into control group (NC group), type 2 diabetes mellitus group (DM group), lower extremity artery disease in type 2 diabetes mellitus without vitamin D supplement group (DM1 group) and lower extremity artery disease in type 2 diabetes mellitus with vitamin D supplement group (DM2 group). The level of serum 25(OH)D was analyzed and the characteristics of arterial lesions of lower extremities were compared by DSA arteriography in DM1 and DM2 group, respectively. RESULTS: Compared with the NC group, serum 25(OH)D level decreased in DM group (25.39 ± 4.94 ng/mL vs 19.43 ± 5.98 ng/mL) and significantly decreased in DM1 and DM2 group (14.22 ± 5.64 ng/mL vs 17.36 ± 6.25 ng/mL). However, the level of serum 25(OH)D in the DM2 group was higher than that in the DM1 group. Compared with the DM1 group, the disease rate of the inferior knee artery (65% vs 39.3%) and occlusion rate (11.5% vs 3.7%)were decreased in the DM2 group (P < 0.05). Logistic stepwise regression analysis showed that serum 25(OH)D level was a risk factor for lower extremity arterial disease in patients with type 2 diabetes mellitus (OR = 0.898,95%CI = 0.856-0.942). CONCLUSIONS: The serum level of 25(OH)D in patients with type 2 diabetes mellitus complicated with lower extremity arterial disease is decreased, and level of 25 (OH) D is related to stenosis and occlusion rate, especially in inferior genicular artery in T2DM complicated with LEAD. A high level of 25(OH)D may be a protective factor in type 2 diabetes with lower extremity arterial disease.

Puerarin enhances proliferation and osteoblastic differentiation of human bone marrow stromal cells via a nitric oxide/cyclic guanosine monophosphate signaling pathway.

Puerarin, a major active isoflavone extracted from the Traditional Chinese Medicine Radix Puerariae, has been studied for its comprehensive biological effects. However, to date, its effect on bone formation and the underlying mechanism of action have not been well investigated. The present study investigated the effect of puerarin on cell proliferation and osteoblastic maturation in cultured human bone marrow stromal cells (hBMSC) in vitro. Puerarin (2.5-100 µM) increased hBMSC growth in a dose-dependent manner, as indicated by an MTT assay, and stimulated osteoblastic maturation as indicated by assessment of alkaline phosphatase (ALP) activity, as well as calcium deposition into the extracellular matrix detected by alizarin red S staining. Furthermore, polymerase chain reaction analysis showed that the expression of osteoblastic markers, including Runt-related transcription factor 2/core-binding factor alpha 1, osterix and osteocalcin, were increased in hBMSCs following incubation with puerarin. Further experiments indicated that puerarin increased the nitric oxide (NO) production and cyclic guanosine monophosphate (cGMP) content in hBMSCs. The effects of puerarin were mimicked by 17ß-estrodiol (10(-8) M) and were abolished in the presence of estrogen receptor antagonist ICI182780 (10(-7) M). A NO synthase inhibitor, Nx-nitro-L-arginine methylester (6 x 10(-3) M), significantly attenuated puerarin-induced increases in NO production and cGMP content, in parallel with a reduction of cell proliferation and osteoblastic differentiation as well as the expression of osteoblastic markers. These results suggested that puerarin may prevent osteoporosis by exerting stimulatory effects on bone formation and the NO/cGMP pathway, which has an important role in puerarin-induced hBMSC proliferation and osteoblastic differentiation.