血清25-羟基维生素D水平与2型糖尿病患者下肢动脉血管病变的关联性研究
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摘要
目的探讨25-羟基维生素D[25(OH)D]血清浓度与2型糖尿病(T2DM)患者下肢动脉血管病变(LEAD)之间的联系以及LEAD的早期影响因素。方法选取226例T2DM患者为糖尿病组,其中新发无并发症者82例为DM1组,合并LEAD者144例为DM2组,66名健康人为对照组。用酶联免疫法测定糖尿病组和对照组血清25(OH)D、肿瘤坏死因子-α(TNF-α)及视黄醇结合蛋白(RBP4)水平。结果 DM2组血清25(OH)D水平显著低于对照组[(12.63±7.83) ng/ml vs (24.77±5.92) ng/ml,P <0.01],DM1组略低于对照组。DM2组TNF-α、RBP4水平较对照组明显升高[TNF-α:(2.67±0.75) pg/ml vs (0.43±0.22) pg/ml;RBP4:(39.00±2.10)μg/ml vs (14.82±1.84)μg/ml,P <0.01]。25(OH)D水平与TNF-α(r=-0.267,P=0.045)、RBP4(r=-0.538,P=0.015)水平呈负相关。结论 25(OH)D水平降低与T2DM患者LEAD的发生有明显相关性,LEAD的早期变化亦与细胞炎性因子及内皮损伤有关。
Objective To explore the relationship between serum levels of 25-hydroxyvitamin D[25(OH)D and lower-extremity arterial disease(LEAD) in type 2 diabetes mellitus(T2DM) patients and the early influencing factors of LEAD.Methods Two hundred and twenty-six cases of T2DM were collected as diabetic group,including DM1 group(82 new diagnostic T2DM patients without complications) and DM2 group(144 diabetic patients with LEAD),and 66 cases of healthy subjects were collected as normal control group.The serum levels of 25(OH)D,tumor necrosis factor-α(TNF-α) and retinol-binding protein 4(RBP4) were determined by enzyme-linked immunosorbent assay.Results The levels of 25(OH)D in the DM2 group were significantly lower than those in the control group[(12.63 ± 7.83) ng/ml vs(24.77 ± 5.92) ng/ml,P < 0.01].The levels of 25(OH)D in the DM1 group were slightly lower than those in the control group.The levels of TNF-α and RBP4 in the DM2 group were significantly higher than those in the control group[TNF-α:(2.67 ± 0.75) pg/ml vs(0.43 ± 0.22) pg/ml; RBP4:(39.00 ±2.10) μg/ml vs(14.82 ± 1.84) μg/ml,P < 0.01].There were significantly negative correlations between the levels of 25(OH)D and TNF-α(r =-0.267,P = 0.045) and RBP4(r =-0.538,P = 0.015).Conclusion Low level of 25(OH)D is significantly associated with the occurrence of T2DM complicated with LEAD,and the factors that contribute to LEAD include inflammatory cytokines and the damadge of vascular endothecium.
Objective To explore the relationship between serum levels of 25-hydroxyvitamin D[25(OH)D and lower-extremity arterial disease(LEAD) in type 2 diabetes mellitus(T2DM) patients and the early influencing factors of LEAD.Methods Two hundred and twenty-six cases of T2DM were collected as diabetic group,including DM1 group(82 new diagnostic T2DM patients without complications) and DM2 group(144 diabetic patients with LEAD),and 66 cases of healthy subjects were collected as normal control group.The serum levels of 25(OH)D,tumor necrosis factor-α(TNF-α) and retinol-binding protein 4(RBP4) were determined by enzyme-linked immunosorbent assay.Results The levels of 25(OH)D in the DM2 group were significantly lower than those in the control group[(12.63 ± 7.83) ng/ml vs(24.77 ± 5.92) ng/ml,P < 0.01].The levels of 25(OH)D in the DM1 group were slightly lower than those in the control group.The levels of TNF-α and RBP4 in the DM2 group were significantly higher than those in the control group[TNF-α:(2.67 ± 0.75) pg/ml vs(0.43 ± 0.22) pg/ml; RBP4:(39.00 ±2.10) μg/ml vs(14.82 ± 1.84) μg/ml,P < 0.01].There were significantly negative correlations between the levels of 25(OH)D and TNF-α(r =-0.267,P = 0.045) and RBP4(r =-0.538,P = 0.015).Conclusion Low level of 25(OH)D is significantly associated with the occurrence of T2DM complicated with LEAD,and the factors that contribute to LEAD include inflammatory cytokines and the damadge of vascular endothecium.
引文
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11 Siragy HM,Awad A,Abadir P,et al.The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-αin diabetic rats[J].Endocrinology,2003,144(6):2229-2233.
12 Di Petrillo K,Gesek FA.Pentoxifylline ameliorates renal tumor necrosis factor expression,sodium retention,and renal hypertrophy in diabetic rats[J].Am J Nephrol,2004,24(3):352-359.
13 Metheniti D,Sakka S,Dracopoulou M,et al.Decreased circu-lating 25-(OH)Vitamin D concentrations in obese female children and adolescents:positive associations with Retinol Binding Protein-4and Neutrophil Gelatinase-associated Lipocalin[J].Hormones(Athens),2013,12(3):397-404.
14 Mc Carty MF,Thomas CA.PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium,vitamin D,and alcohol on body weight[J].Med Hypotheses,2003,61(5-6):535-542.
2 Mosekilde L.Vitamin D requirement and setting recommen-dation levels:long-term perspectives[J].Nutr Rev,2008,66(10 Suppl 2):S170-S177.
3 Kayaniyil S,Vieth R,Retnakaran R,et al.Association of vitamin Dwith insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes[J].Diabetes Care,2010,33(6):1379-1381.
4 Makariou S,Liberopoulos EN,Elisaf M,et al.Novel roles of vitamin D in disease:what is new in 2011?[J].Eur J Intern Med,2011,22(4):355-362.
5 Fahrleitner-Pammer A,Obernosterer A,Pilger E,et al.Hypovitaminosis D,impaired bone turnover and low bone mass are common in patients with peripheral arterial disease[J].Osteoporos Int,2005,16(3):319-324.
6 Dunlop TW,Vaisanen S,Frank C,et al.he human peroxisome proliferator-activated receptor?gene is a primary target of 1?,25-dihydroxyvitamin D3 and its nuclear receptor[J].J Molecular Biology,2005,349(2):248-260.
7 Lee V,Rekhi E,Kam JH,et al.Vitamin D rejuvenates aging eyes by reducing inlammation,clearing amyloid beta and improving visual function[J].Neurobiol Aging,2012,33(10):2382-2389.
8 Rueda S,Fernandez-Fernandez C,Romero F,et al.Vitamin D,PTH,and the metabolic syndrome in severely obese subjects[J].Obes Surg,2008,18(2):151-154.
9 Graham TE,Yang Q,Bluher M,et al.Retinol-binding protein 4 and insulin resistance in lean,obese,and diabetic subjects[J].N Engl JMed,2006,354(24):2552-2563.
10 CabréA,Lazaro I,Girona J,et al.Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease in Type 2 diabetes[J].J Intern Med,2007,262(4):496-503.
11 Siragy HM,Awad A,Abadir P,et al.The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-αin diabetic rats[J].Endocrinology,2003,144(6):2229-2233.
12 Di Petrillo K,Gesek FA.Pentoxifylline ameliorates renal tumor necrosis factor expression,sodium retention,and renal hypertrophy in diabetic rats[J].Am J Nephrol,2004,24(3):352-359.
13 Metheniti D,Sakka S,Dracopoulou M,et al.Decreased circu-lating 25-(OH)Vitamin D concentrations in obese female children and adolescents:positive associations with Retinol Binding Protein-4and Neutrophil Gelatinase-associated Lipocalin[J].Hormones(Athens),2013,12(3):397-404.
14 Mc Carty MF,Thomas CA.PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium,vitamin D,and alcohol on body weight[J].Med Hypotheses,2003,61(5-6):535-542.