目的：通过3年随访观察,研究不同25羟维生素D [25(OH)D]水平对2型糖尿病患者糖尿病肾病(daibetes nephropathy,DN)发病率的影响。方法：选择2009年6月至2012年6月期间在我院内分泌科就诊的尿微量白蛋白正常的2型糖尿病患者共530例,入组时所有患者均需测定空腹血糖、C肽、糖化血红蛋白、25(OH)D、血脂、24 h尿微量白蛋白等。根据基线25(OH)D水平将研究人群分为3组,分别为维生素D（vitamin D,VitD）缺乏组、VitD不足组和VitD正常组,对3组患者进行为期3年的随访,随访结束时再次留取24 h尿检测尿白蛋白排泄率以确诊有无DN,并分析其DN发病率。结果：3年后,VitD缺乏组患者尿白蛋白排泄率显著高于VitD正常组[25.9(3.1~379.6) mg/24 h比18.8（2.5~103.7） mg/24 h,P<0.01],VitD缺乏组较VitD正常组、VitD不足组的DN发生率更高(26.2%比5.3%,26.2%比12.7%,P<0.05)。行回归分析发现,VitD缺乏显著增加了DN发病风险(RR=1.58,95%CI为1.13~2.79),且在控制多重危险因素后这种作用仍然存在（RR=1.23,1.05~2.12）。结论：通过3年的前瞻性队列研究证实,在2型糖尿病患者中VitD缺乏使DN的发病风险显著增加,VitD缺乏可能是DN发生及进展的重要原因。
Objective: To study the effect of 25-hydroxyvitamin D level on incidence of diabetic nephropathy in type 2 diabetic patients by 3-year follow-up study. Methods: From June 2009 to June 2012, a total of 530 type 2 diabetic patients with normal albuminuria were recruited. The fasting blood glucose, C peptide, glycosylated hemoglobin, 25-hydroxyvitamin D, blood lipids and 24 h urinary albumin excretion rate were measured in all the patients at baseline. The study patients were divided into 3 groups based on the baseline 25-hydroxyvitamin D level. All patients were followed up for 3 years. At the end of follow-up, 24 h urine was taken to detect the urinary albumin excretion rate to determine whether there was diabetic nephropathy. The incidence of diabetic nephropathy in the three groups was analyzed at the end of 3-year follow-up. Results: After 3 years, the urinary albumin excretion rate in vitamin D deficiency group was significantly higher than that in vitamin D normal group[25.9(3.1-379.6) mg/24 h vs 18.8（2.5-103.7） mg/24 h, P<0.01]. The incidence of diabetic nephropathy in the vitamin D deficiency group was higher than those in the vitamin D normal group and vitamin D insufficient group (26.2% vs 5.3%, 26.2% vs 12.7% P<0.05). Regression analysis showed that vitamin D deficiency significantly increased the risk of diabetic nephropathy (RR=1.58, 95%CI: 1.13-2.79), and this effect remained after controlling other multiple risk factors (RR=1.23, 1.05-2.12). Conclusions: A 3-year prospective cohort study confirmes that vitamin D deficiency significantly increases the risk of diabetic nephropathy in patients with type 2 diabetes. Vitamin D deficiency is an important factor for the development and progression of diabetic nephropathy.
[1] Chandie Shaw PK, van Es LA, Paul LC, et al. Renal di-sease in relatives of Indo-Asian Type 2 diabetic patients with end-stage diabetic nephropathy[J]. Diabetologia,2003,46(5):618-624.
[2] 中华医学会糖尿病学分会微血管并发症学组. 糖尿病肾病防治专家共识(2014年版)[J]. 中华糖尿病杂志,2014,6(11):792-801.
[3] Sooy K, Schermerhorn T, Noda M, et al.Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines[J]. J Biol Chem,1999,274(48):34343-34349.
[4] 王炜, 邢学农, 叶山东, 等. 2型糖尿病患者血清维生素D3水平和胰岛素抵抗及胰岛B细胞功能的相关性研究[J].中国临床保健杂志,2012,15(5):485-487.
[5] Pittas AG, Sun Q, Manson JE, et al.Plasma 25-hydroxy-vitamin D concentration and risk of incident type 2 diabetes in women[J]. Diabetes Care,2010,33(9):2021-2023.
[6] Tracy SM, Mazen JH.The role of vitamin D defciency in the pathogenesis of type 2 diabetes mellitus[J]. Clin Nutr and Meta,2010,5(4):e155-e165.
[7] Fernández-Juárez G, Luño J, Barrio V, et al.25 (OH) vitamin D levels and renal disease progression in patients with type 2 diabetic nephropathy and blockade of the renin-angiotensin system[J]. Clin J Am Soc Nephrol,2013, 8(11):1870-1876.
[8] 李冬梅, 张颖, 丁波, 等. 血清25羟维生素D缺乏与糖尿病肾病的关系[J]. 中华内科杂志,2013,52(11):970-974.
[9] Cavalier E, Delanaye P, Souberbielle JC, et al.Vitamin D and type 2 diabetes mellitus: where do we stand?[J]. Diabetes Metab,2011,37(4):265-272.
[10] Kayaniyil S, Retnakaran R, Harris SB, et al.Prospective associations of vitamin D with β-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study[J]. Diabetes,2011,60(11):2947-2953.
[11] Rabinovitch A, Suarez-Pinzon WL, Sooy K, et al.Expression of calbindin-D(28k) in a pancreatic islet beta-cell line protects against cytokine-induced apoptosis and necrosis[J]. Endocrinology,2001,142(8):3649-3655.
[12] Forouhi NG, Luan J, Cooper A, et al.Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000[J]. Diabetes,2008,57(10):2619-2625.
[13] Pannu PK, Piers LS, Soares MJ, et al.Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia[J]. PLoS One,2017,12(6):e0178825.
[14] Sonneveld R, Ferrè S, Hoenderop JG, et al.Vitamin D down-regulates TRPC6 expression in podocyte injury and proteinuric glomerular disease[J]. Am J Pathol,2013,182(4):1196-1204.
[15] Vaidya A, Forman JP.Vitamin D and vascular disease: the current and future status of vitamin D therapy in hypertension and kidney disease[J]. Curr Hypertens Rep,2012,14(2):111-119.
[16] Bouillon R, Carmeliet G, Verlinden L, et al.Vitamin D and human health: lessons from vitamin D receptor null mice[J]. Endocr Rev,2008,29(6):726-776.
[17] Damasiewicz MJ, Magliano DJ, Daly RM, et al.25-Hydroxyvitamin D levels and chronic kidney disease in the AusDiab (Australian Diabetes, Obesity and Lifestyle) study[J]. BMC Nephrol,2012,13:55.
[18] Kim HW, Park H, Cho KH, et al.Parathyroid hormone, vitamin D levels and urine albumin excretion in older persons: the 2011 Korea National Health and Nutrition Examination Survey(KNHANES)[J]. Clin Endocrinol (Oxf),2014,80(1):34-40.
[19] Diaz VA, Mainous AG 3rd, Carek PJ, et al. The association of vitamin D deficiency and insufficiency with diabetic nephropathy: implications for health disparities[J]. J Am Board Fam Med,2009,22(5):521-527.
[20] Huang Y, Yu H, Lu J, et al.Oral supplementation with cholecalciferol 800 IU ameliorates albuminuria in Chinese type 2 diabetic patients with nephropathy[J]. PLoS One,2012,7(11):e50510.
[21] Joergensen C, Hovind P, Schmedes A, et al.Vitamin D levels, microvascular complications, and mortality in type 1 diabetes[J]. Diabetes Care,2011,34(5):1081-1085.
[22] 谷巍, 耿建林, 赵正历, 等. 红景天联合培哚普利治疗糖尿病肾病早期临床观察[J]. 内科理论与实践,2016, 11(2):103-104.
