肾小球疾病患者血清25（OH）D水平对激素致糖代谢异常的影响
发布时间：2018-07-15 14:28
【摘要】：目的：糖皮质激素（简称激素）广泛应用于临床治疗免疫性肾小球疾病，其用药剂量大、时间长；激素通过多种途径引起糖代谢异常，是治疗的主要副作用之一。糖耐量正常的肾小球疾病患者应用泼尼松(0.8±0.11)mg/(kg·d)治疗8~13周,糖代谢异常的发生率高达50%，其中25%患者发生类固醇糖尿病。有研究显示，血清25（OH）D水平减低，通过干扰胰岛素作用、损伤胰岛β细胞分泌胰岛素功能，加重系统炎症反应等途径促进2型糖尿病的发生发展。低血清25（OH）D水平增加2型糖尿病发病风险。类固醇糖尿病与2型糖尿病的发病机理相似，血清25（OH）D水平对类固醇糖尿病的发生有无影响，尚不明确。本研究通过观察肾小球疾病患者应用激素前血清25（OH）D水平及其应用激素后糖代谢状况，探讨25（OH）D与激素致糖代谢异常的相关关系，为类固醇糖尿病的防治提供依据。 方法：2013年6月至2013年11月顺序入选我科住院，经临床及肾活检确诊，首次应用泼尼松0.79±0.10mg·kg-1·d-1的肾小球疾病患者61例为病例组，我院体检中心同期健康体检者16人为对照组。排除标准：（1）既往有2型糖尿病或本次住院新诊断的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周内曾应用维生素D制剂或降钙素、西那卡塞、双膦酸盐或环孢素等影响血清25（OH）D及糖代谢的药物。（5）近期有感染、急性肾损伤。（6）慢性肝病、冠心病、心功能不全、内分泌系统疾病（如甲亢、甲减、甲旁亢、皮质醇增多症）、恶性肿瘤等严重的全身性疾病者。记录受试者年龄、血压等一般情况及白蛋白、血钙、血磷等生化指标。采用酶联免疫吸附法检测激素治疗前血清25（OH）D（试剂盒由美国ENZO公司提供）。所有研究对象应用激素前常规检测空腹及三餐后血糖，，并于激素治疗前均做简易OGTT试验（口服50%葡萄糖注射液150ml）。激素治疗开始后每隔2-3天间断测量并记录空腹及三餐后2小时血糖，共随访6周。随访结束时据6周内血糖水平分为NGR组、IGR组和SDM组，各组资料进行统计学分析。 结果： 1患者一般资料：激素治疗前对照组白蛋白显著高于NGR组和IGR组；尿蛋白定量、总胆固醇显著低于NGR组和IGR组； IGR组餐后2小时血糖显著高于对照组和NGR组；对照组血清25（OH）D水平显著高于NGR组，NGR组显著高于IGR组（64.09±13.53对50.81±12.44对42.71±8.09，P0.05）。对照组中血清25（OH）D充足者4例（25%），不足者8例（50%），缺乏者占4例（25%）；而在肾小球疾病者中，血清25（OH）D充足者仅4例（6.56%），不足者18例（29.51%），血清25（OH）D缺乏者39例（63.93%）。临床表现为肾炎组患者年龄显著高于肾病组（P0.05）；25（OH）D水平显著高于肾病组（56.94±10.41对45.88±11.55，P0.05）；两组间类固醇糖尿病发病率无显著差异。 2激素治疗6周时糖耐量情况及各组基线资料对比：激素治疗6周后，NGR组中15例（34.88%）发生糖耐量受损，9例（20.93%）发生类固醇糖尿病，发生类固醇糖尿病中位时间为7天；IGR组11例（61.11%）发生类固醇糖尿病，中位时间为3天，7例（38.89%）仍为糖耐量受损。IGR组类固醇糖尿病发生率显著高于NGR组（P0.05）。据应用激素6周后糖耐量情况，将所有患者分为NGR组19例、IGR组22例和SDM组20例。对照组白蛋白显著高于其他组，高血压构成比、尿蛋白定量显著低于其他组； IGR组、SDM组基线水平OGTT2h血糖显著高于NGR组及对照组,（7.24±1.42、7.84±1.64对5.42±0.99、6.12±0.57，P0.05）；NGR组、 IGR组糖化血红蛋白显著低于SDM组（4.94±0.51、5.12±0.50对5.6±0.76，P0.05）；对照组基线25（OH）D水平显著高于NGR组、IGR组及SDM组。NGR组、IGR组显著高于SDM组（64.09±13.53对55.68±13.09、48.97±9.91对40.91±7.82，P0.05），NGR组与IGR组之间未见显著性差异。 3血清25（OH）D水平的影响因素及相关性：单因素相关分析显示，血清25（OH）D水平与血白蛋白呈正相关，相关系数为r=0.455（P=0.00）；与BMI、总胆固醇、OGTT2h血糖及24小时尿蛋白定量负相关，相关系数分别为r=-0.302(P0.05)、r=-0.27(P0.05)、r=-0361(P0.05)、r=-0.339(P0.05)；与校正血钙呈正相关r=0.317(P0.05)，血25（OH）D与季节之间存在相关性，夏季入组者血清25（OH）D水平高于秋季。相关系数为-0.308(P0.05)。 4血清25（OH）D水平对类固醇糖尿病的影响：Logistic回归示：基线血清25(OH)D50nmol/L、HbA1c5.6%发生SDM的风险分别为50nmol/L、5.6%者的5.6、5.2倍；年龄每增加10岁，胰岛素抵抗指数每增加1，发生SDM的风险分别增加2.4、2.8倍。 结论：绝大多数肾小球疾病患者血清25（OH）D不足或缺乏；低血清25（OH）D水平是激素治疗的肾小球疾病患者类固醇糖尿病发生的主要危险因素之一。
[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.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.6
[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.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.6
【参考文献】
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