【摘要】：目的：糖皮質(zhì)激素（簡稱激素）廣泛應(yīng)用于臨床治療免疫性腎小球疾病，其用藥劑量大、時(shí)間長；激素通過多種途徑引起糖代謝異常，是治療的主要副作用之一。糖耐量正常的腎小球疾病患者應(yīng)用潑尼松(0.8±0.11)mg/(kg·d)治療8~13周,糖代謝異常的發(fā)生率高達(dá)50%，其中25%患者發(fā)生類固醇糖尿病。有研究顯示，血清25（OH）D水平減低，通過干擾胰島素作用、損傷胰島β細(xì)胞分泌胰島素功能，加重系統(tǒng)炎癥反應(yīng)等途徑促進(jìn)2型糖尿病的發(fā)生發(fā)展。低血清25（OH）D水平增加2型糖尿病發(fā)病風(fēng)險(xiǎn)。類固醇糖尿病與2型糖尿病的發(fā)病機(jī)理相似，血清25（OH）D水平對類固醇糖尿病的發(fā)生有無影響，尚不明確。本研究通過觀察腎小球疾病患者應(yīng)用激素前血清25（OH）D水平及其應(yīng)用激素后糖代謝狀況，探討25（OH）D與激素致糖代謝異常的相關(guān)關(guān)系，為類固醇糖尿病的防治提供依據(jù)。 方法：2013年6月至2013年11月順序入選我科住院，經(jīng)臨床及腎活檢確診，首次應(yīng)用潑尼松0.79±0.10mg·kg-1·d-1的腎小球疾病患者61例為病例組，我院體檢中心同期健康體檢者16人為對照組。排除標(biāo)準(zhǔn)：（1）既往有2型糖尿病或本次住院新診斷的2型糖尿病患者。（2）有2型糖尿病家族史者。（3）eGFR≤60ml·Kg-1·1.73m2。（4）近8周內(nèi)曾應(yīng)用維生素D制劑或降鈣素、西那卡塞、雙膦酸鹽或環(huán)孢素等影響血清25（OH）D及糖代謝的藥物。（5）近期有感染、急性腎損傷。（6）慢性肝病、冠心病、心功能不全、內(nèi)分泌系統(tǒng)疾�。ㄈ缂卓骸⒓诇p、甲旁亢、皮質(zhì)醇增多癥）、惡性腫瘤等嚴(yán)重的全身性疾病者。記錄受試者年齡、血壓等一般情況及白蛋白、血鈣、血磷等生化指標(biāo)。采用酶聯(lián)免疫吸附法檢測激素治療前血清25（OH）D（試劑盒由美國ENZO公司提供）。所有研究對象應(yīng)用激素前常規(guī)檢測空腹及三餐后血糖，，并于激素治療前均做簡易OGTT試驗(yàn)（口服50%葡萄糖注射液150ml）。激素治療開始后每隔2-3天間斷測量并記錄空腹及三餐后2小時(shí)血糖，共隨訪6周。隨訪結(jié)束時(shí)據(jù)6周內(nèi)血糖水平分為NGR組、IGR組和SDM組，各組資料進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果： 1患者一般資料：激素治療前對照組白蛋白顯著高于NGR組和IGR組；尿蛋白定量、總膽固醇顯著低于NGR組和IGR組； IGR組餐后2小時(shí)血糖顯著高于對照組和NGR組；對照組血清25（OH）D水平顯著高于NGR組，NGR組顯著高于IGR組（64.09±13.53對50.81±12.44對42.71±8.09，P0.05）。對照組中血清25（OH）D充足者4例（25%），不足者8例（50%），缺乏者占4例（25%）；而在腎小球疾病者中，血清25（OH）D充足者僅4例（6.56%），不足者18例（29.51%），血清25（OH）D缺乏者39例（63.93%）。臨床表現(xiàn)為腎炎組患者年齡顯著高于腎病組（P0.05）；25（OH）D水平顯著高于腎病組（56.94±10.41對45.88±11.55，P0.05）；兩組間類固醇糖尿病發(fā)病率無顯著差異。 2激素治療6周時(shí)糖耐量情況及各組基線資料對比：激素治療6周后，NGR組中15例（34.88%）發(fā)生糖耐量受損，9例（20.93%）發(fā)生類固醇糖尿病，發(fā)生類固醇糖尿病中位時(shí)間為7天；IGR組11例（61.11%）發(fā)生類固醇糖尿病，中位時(shí)間為3天，7例（38.89%）仍為糖耐量受損。IGR組類固醇糖尿病發(fā)生率顯著高于NGR組（P0.05）。據(jù)應(yīng)用激素6周后糖耐量情況，將所有患者分為NGR組19例、IGR組22例和SDM組20例。對照組白蛋白顯著高于其他組，高血壓構(gòu)成比、尿蛋白定量顯著低于其他組； IGR組、SDM組基線水平OGTT2h血糖顯著高于NGR組及對照組,（7.24±1.42、7.84±1.64對5.42±0.99、6.12±0.57，P0.05）；NGR組、 IGR組糖化血紅蛋白顯著低于SDM組（4.94±0.51、5.12±0.50對5.6±0.76，P0.05）；對照組基線25（OH）D水平顯著高于NGR組、IGR組及SDM組。NGR組、IGR組顯著高于SDM組（64.09±13.53對55.68±13.09、48.97±9.91對40.91±7.82，P0.05），NGR組與IGR組之間未見顯著性差異。 3血清25（OH）D水平的影響因素及相關(guān)性：單因素相關(guān)分析顯示，血清25（OH）D水平與血白蛋白呈正相關(guān)，相關(guān)系數(shù)為r=0.455（P=0.00）；與BMI、總膽固醇、OGTT2h血糖及24小時(shí)尿蛋白定量負(fù)相關(guān)，相關(guān)系數(shù)分別為r=-0.302(P0.05)、r=-0.27(P0.05)、r=-0361(P0.05)、r=-0.339(P0.05)；與校正血鈣呈正相關(guān)r=0.317(P0.05)，血25（OH）D與季節(jié)之間存在相關(guān)性，夏季入組者血清25（OH）D水平高于秋季。相關(guān)系數(shù)為-0.308(P0.05)。 4血清25（OH）D水平對類固醇糖尿病的影響：Logistic回歸示：基線血清25(OH)D50nmol/L、HbA1c5.6%發(fā)生SDM的風(fēng)險(xiǎn)分別為50nmol/L、5.6%者的5.6、5.2倍；年齡每增加10歲，胰島素抵抗指數(shù)每增加1，發(fā)生SDM的風(fēng)險(xiǎn)分別增加2.4、2.8倍。 結(jié)論：絕大多數(shù)腎小球疾病患者血清25（OH）D不足或缺乏；低血清25（OH）D水平是激素治療的腎小球疾病患者類固醇糖尿病發(fā)生的主要危險(xiǎn)因素之一。
[Abstract]:Objective: Glucocorticoid (corticosteroid) is widely used in the clinical treatment of immune glomerular disease. The dosage of glucocorticoid is large and the time is long. Hormone is one of the main side effects. It is one of the main side effects. The patients with normal glucose tolerance should be treated with prednisone (0.8 + 0.11) mg/ (kg. D) for 8~13 weeks and glucose metabolism The incidence of abnormal incidence was as high as 50%, of which 25% patients had steroid diabetes. Some studies showed that the level of serum 25 (OH) D decreased, and the development of type 2 diabetes was promoted by interfering the action of insulin, injure the insulin function of islet beta cells and aggravate the systemic inflammatory response. The level of low serum 25 (OH) D increased the onset of type 2 diabetes. Corticosteroid diabetes is similar to the pathogenesis of type 2 diabetes. Serum 25 (OH) D level has no influence on the occurrence of steroid diabetes. This study is to explore the correlation between 25 (OH) D and glucocorticoid induced metabolic abnormalities by observing the level of pre hormone serum 25 (OH) D and its application hormone glucose metabolism in patients with glomerular disease. This relationship provides a basis for the prevention and treatment of steroid diabetes.
Methods: from June 2013 to November 2013, we were hospitalized in order to be hospitalized. 61 cases of glomerular disease with prednisone 0.79 + 0.10mg / kg-1 D-1 were used for the first time by clinical and renal biopsy. 16 people in the medical check-up center of our hospital were compared with 16 people in the same period. (1) 2 of type 2 diabetes or 2 of the new diagnosis in this hospital. Patients with type diabetes. (2) a family history of type 2 diabetes. (3) eGFR < 60ml / Kg-1 / 1.73m2. (4) had used vitamin D preparation or calcitonin, ciccacus, bisphosphonates, or cyclosporin in serum 25 (OH) D and carbohydrate metabolism. (5) recent infection, acute renal injury. (6) chronic liver disease, coronary heart disease, cardiac insufficiency, endocrinology Patients with systemic diseases (such as hyperthyroidism, hypothyroidism, hyperthyroidism, cortisol), malignant tumor, and other serious systemic diseases. Record the subjects' age, blood pressure and other biochemical indexes, such as albumin, blood calcium, and blood phosphorus. The serum 25 (OH) D (kit provided by ENZO, USA) was detected by enzyme linked immunosorbent assay before treatment of hormone. A simple OGTT test (oral 50% Glucose Injection 150ml) was performed before hormone treatment before hormone treatment (50% Glucose Injection 150ml). After hormone therapy, the fasting and 2 hour blood glucose were recorded every 2-3 days and followed up for 6 weeks. The blood sugar levels were divided into NGR group, IGR group and SDM during the 6 weeks of follow-up. Group, the data of each group were analyzed statistically.
Result:
1 general data: before hormone treatment, albumin was significantly higher in the control group than in the NGR group and the IGR group; the urine protein quantitative, total cholesterol was significantly lower than the NGR group and the IGR group; the 2 hour postprandial blood glucose in IGR group was significantly higher than the control group and the NGR group; the level of serum 25 (OH) D in the control group was significantly higher than that in the NGR group, and the NGR group was significantly higher than the IGR group (64.09 + 13.53 pairs 50.81 + 12.). 44 pairs of 42.71 + 8.09, P0.05). 25 (OH) D sufficient in the control group 4 cases (25%), 8 cases (50%) and 4 patients with deficiency (25%), and among the glomerular diseases, the serum 25 (OH) D sufficient persons were only 4 cases (6.56%), the deficiency of the serum (OH) D deficiency was significantly higher than that of the nephrotic group (P0.05). ; 25 (OH) D level was significantly higher than that in the nephrotic group (56.94 + 10.41 to 45.88 + 11.55, P0.05); there was no significant difference in the incidence of steroid diabetes between the two groups.
2 glucocorticoid treatment at 6 weeks of glucose tolerance and comparison of baseline data: after 6 weeks of hormone therapy, 15 cases (34.88%) had impaired glucose tolerance, 9 (20.93%) had steroid diabetes, and steroid diabetes had a median time of 7 days; 11 patients in group IGR (61.11%) had steroid diabetes, median time was 3 days, 7 cases (38.89%) were still sugar. The incidence of steroid diabetes in the.IGR group was significantly higher than that in the NGR group (P0.05). According to the glucose tolerance of 6 weeks after the use of the hormone, all the patients were divided into 19 cases, 22 cases in group IGR and 20 in group SDM. The albumin in the control group was significantly higher than that in the other groups, the ratio of hypertension was significantly lower than that of the other groups; the IGR group and the baseline level of SDM group were OGTT2h. The blood sugar was significantly higher than that of the NGR group and the control group (7.24 + 1.42,7.84 + 1.64 versus 5.42 + 0.99,6.12 + 0.57, P0.05), and in group NGR, the glycated hemoglobin was significantly lower than that in the SDM group (4.94 + 0.51,5.12 + 0.50 versus 5.6 + 0.76, P0.05), and the baseline of the control group was significantly higher than that of the NGR group, the group and the group (64.09 + 13.53 against 55). .68 + 13.09,48.97 + 9.91 to 40.91 + 7.82, P0.05). There was no significant difference between NGR group and IGR group.
3 the influence factors and correlation of serum level 25 (OH) D: single factor correlation analysis showed that serum level of 25 (OH) D was positively correlated with serum albumin, and the correlation coefficient was r=0.455 (P=0.00); it was negatively correlated with BMI, total cholesterol, OGTT2h blood sugar and 24 hour urine protein, and the correlation coefficients were r=-0.302 (P0.05), r=-0.27 (P0.05), respectively. 39 (P0.05); positive correlation with the correction of blood calcium r=0.317 (P0.05), blood 25 (OH) D and the correlation between the seasons, the level of serum 25 (OH) D in the summer group was higher than that in the autumn. The correlation coefficient was -0.308 (P0.05).
4 the effect of serum 25 (OH) D level on steroid diabetes: Logistic regression: the baseline serum 25 (OH) D50nmol/L, the risk of SDM in HbA1c5.6% is 50nmol/L, 5.6% times respectively; the age of 10 years of age increases, the insulin resistance index increases by 1, and the risk of SDM is increased 2.4,2.8 times.
Conclusion: the serum 25 (OH) D in most patients with glomerular disease is deficient or deficient, and the level of low serum 25 (OH) D is one of the major risk factors for steroid diabetes in patients with glomerular disease treated by hormone therapy.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R692.6

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 傅淑霞;張春霞;閆U

本文編號：2124379