初诊2型糖尿病胰岛功能的影响因素及胰岛素干预策略的研究

发布时间：2018-05-29 22:35

本文选题：2型糖尿病 + 葡萄糖耐量试验　；参考：《华中科技大学》2016年硕士论文

【摘要】：目的:探索初诊2型糖尿病患者胰岛功能与空腹血糖水平的关系以及可能与其独立相关的因素。方法:收集2013年至2015年我院内分泌科门诊或住院的初诊2型糖尿病患者,按照FPG水平将患者分为1组(FPG7mmol/l)、2组(7mmol/l≤FPG8.2mmol/l)、3组(8.2mmol/l≤FPG11.1mmol/l)、4组(11.1mmol/l≤FPG),所有患者均行口服葡萄糖耐量(OGTT)及胰岛素释放(IRT)试验。计算HOMA-IR、HOMA-β,糖负荷后30min胰岛素和葡萄糖增加的比值(ΔI30/ΔG30)、胰岛素曲线下面积AUCI,各组相关结果进行统计学分析。记录年龄、性别、血压、体重指数(BMI)以及Hb A1c、TC、TG、LDL-C、HDL-C、肌酐(Cr)等指标,建立多重线性回归分析模型探索胰岛β细胞功能的独立相关因素及各因素与胰岛功能的相关强度。用EPIDATA软件进行数据录入,spss20.0统计软件进行统计学分析,正态分布资料以均数±方差(?x±s)表示,多组计量资料比较用单因素方差分析,建立多重线性回归分析模型探索胰岛β细胞功能独立相关因素,P值小于0.05被认为具有统计学意义。结果:1、共收集初诊T2DM患者176例,各组性别构成、收缩压、舒张压无显著差异,各组总胆固醇、肌酐无显著差异。FPG越高的组,平均年龄越大,甘油三脂、LDL越高,HDL-C越低。1~3组BMI无显著差异,4组BMI均值较其他三组明显下降。2、各组FIns、Fc、AUCI比较,相邻两组差异无统计学意义,其余各组间比较有显著差异。HOMA-β3组与4组比较无明显差异,其余各组两两比较有显著差异。随着FPG升高,FINS、Fc、HOMA-β、AUCI逐渐下降。3、HOMA-IR 1、2、3组间两两比较差异无统计学意义,4组与1、2、3组分别比较有显著差异。随着FPG升高,HOMA-IR有逐渐增强的趋势。ΔI 30/ΔG30均值2组1组3组4组,随着FPG升高,胰岛素早相分泌量有逐渐升高然后下降的趋势,但组间两两比较差异无统计学意义。4、各组AUC曲线下面积1组2组3组4组。1组胰岛素分泌高峰延迟,胰岛素早相、晚相分泌明显高于其他组。2组胰岛素分泌高峰延迟,胰岛素早相分泌量没有明显下降,晚相分泌量略有减少。3组胰岛素早相分泌和晚相分泌均明显下降,分泌高峰延迟,峰值不明显。4组呈现胰岛素分泌的低平曲线,早相分泌及晚相分泌明显下降,无胰岛素分泌高峰。5、线性回归分析示年龄、Hb A1c、甘油三脂、LDL-C、FPG、2h PG、HOMA-IR与HOMA-β显著负相关,HDL-C、FIns与HOMA-β显著正相关。年龄、FIns、HOMA-IR为HOMA-β独立相关因素。年龄、甘油三脂、LDL-C、FIns、FPG、2h PG与HOMA-IR显著正相关,HDL-C与HOMA-IR显著负相关。FIns、FPG、甘油三脂为HOMA-IR独立相关因素。结论:2型糖尿病发病有年轻化、高发化趋势,应加强2型糖尿病高危人群的筛查。FPG是评估胰岛功能的简易、经济指标,对初步评价患者胰岛功能、指导临床治疗具有重要意义,初诊FPG越高的患者,其基础和总体胰岛素分泌功能越差。FPG 8.2mmol/l为胰岛素第一相分泌的转折点,FPG8.2mmol/l时胰岛素第一相分泌代偿性增加,FPG8.2mmol/l时,胰岛素第一相分泌下降。FPG11.1mmol/l为胰岛素抵抗的转折点,FPG11.1mmol/l时胰岛素抵抗骤然加重。年龄、FIns、HOMA-IR为胰岛素分泌功能的独立相关因素;FIns、FPG、甘油三脂为HOMA-IR的独立相关因素。严重高血糖使BMI与胰岛功能的相关性减弱。FIns可能是一个评价胰岛功能较FPG更准确的指标。同时,糖脂代谢存在相互影响,因此T2DM的治疗应提倡综合管理,控制血糖的同时积极控制血脂,尤其是LDL-C和HDL-C达标。2型糖尿病患者在其诊断之初,胰岛素基础及总体分泌功能已严重受损,特别是FPG≥11.1mmol/l的患者,对此类患者行早期胰岛素强化治疗,迅速降低血糖,阻断“糖毒性”对胰岛β细胞的进一步损伤,保护残余胰岛功能,可能会有较大的获益。目的:探讨不同胰岛素干预方案对初诊2型糖尿病患者胰岛β细胞功能的影响。方法:选取2013年至2015年我院内分泌科门诊或住院,FPG≥11.1mmol/l或Hb A1c9%,且自愿接受胰岛素治疗的初诊2型糖尿病患者,将患者按照入选先后顺序编号,采用随机数字表法,随机归入预混胰岛素类似物每日2次注射组或基础+餐时胰岛素每日4次注射组或基础胰岛素+口服降糖药组,随访半年,教育患者进行日常空腹和餐后2h血糖自我监测并记录低血糖发生次数,每三月监测一次Hb A1c,半年复查OGTT+IRT试验,检测不同胰岛素治疗方案血糖及Hb A1C下降程度、血糖控制达标时间、糖化血红蛋白达标比率、最大胰岛素用量、低血糖发生次数等指标。采取前后自身对照及组间比较,依据两次OGTT+IRT结果,探索不同胰岛素干预方案改善胰岛β细胞功能的差异,尤其是对胰岛素第一相分泌的影响。观察数据包括FPG、2h PG、FIns、Fc、Hb A1c、HOMA-IR、HOMA-β、ΔI30/ΔG30、AUCI。用EPIDATA软件进行数据录入,spss20.0统计软件进行统计学分析,正态分布资料以均数±方差(?x±s)表示,用单因素方差分析进行多组计量资料的比较,采用配对t检验进行治疗前后数据比较,P0.05被认为具有统计学意义。结果:1、选取重症初诊2型糖尿病患者共30例,共有27例完成随访,不同干预方式组性别构成、年龄、BMI、Hb A1c、甘油三脂、LDL-C、HDL-C无显著差异。治疗后24周FPG、2h PG、Hb A1c、HOMA-IR显著下降,FIns、Fc、HOMA-β、ΔI30/ΔG30、AUCI显著增加,具有统计学意义。绘制Pre组和Aft组AUC曲线,治疗后胰岛素总体分泌量明显增加,胰岛素分泌峰值升高,胰岛素第一相分泌明显增加。2、各组治疗前后Hb A1c、FPG、2h PG、FIns、Fc、ΔI30/ΔG30、AUCI、HOMA-IR、HOMA-β差值比较,基础胰岛素+口服药物组与基础+餐时胰岛素组间Δ(ΔI30/ΔG30)差异有统计学意义,其余指标组间比较均无统计学意义。3、随访24周,所有患者Hb A1c平均下降2.58%,不同干预方式组降低Hb A1c的能力无明显差异。所有患者体重均明显增加,其中基础胰岛素+口服降糖药物组体重平均增加1.8kg,预混胰岛素组体重平均增加2.6kg,基础+餐时胰岛素组体重平均增加3.1kg。低血糖评分,基础胰岛素+口服药物组最低,基础+餐时胰岛素组明显高于基础胰岛素+口服药物组,预混胰岛素组最高并有一例患者曾发生夜间严重低血糖。4、预混胰岛素组控制血糖达标时间最长,24周Hb A1c个体化目标达标率、无低血糖Hb A1c个体化目标达标率最低;基础胰岛素+口服药物组最大胰岛素用量最少,24周无低血糖Hb A1c个体化目标达标率最高;基础+餐时胰岛素组控制血糖达标时间最短,胰岛素用量最大,24周Hb A1c个体化目标达标率最高。结论:综上所述,初诊T2DM患者行胰岛素治疗均可明显改善胰岛素抵抗和胰岛素分泌功能,尤其是胰岛素第一相分泌功能,不同胰岛素干预方式改善胰岛素抵抗和胰岛素总体分泌功能的能力并无差别,但基础+餐时胰岛素方案改善胰岛素第一相分泌能力的功能较基础+口服药方式更好。对具体的患者,以改善胰岛素抵抗为主还是以改善胰岛β细胞分泌功能为主存在个体差异,可能与遗传背景或血糖恶化的环境因素相关。随访24周,所有患者Hb A1c平均下降2.58%,此数据较既往研究Hb A1c下降1.5%~2.1%的结论明显升高,考虑与入选人群基础Hb A1c较高、且样本量小有关。不同治疗方案的Hb A1c改善程度并无差别。预混胰岛素方案因其低血糖发生率高,且有严重低血糖风险,降低患者治疗满意度和依从性,对于生活不规律、依从性及其自我管理能力差的患者不推荐此治疗方式。基础胰岛素+口服降糖药物组低血糖发生率低、体重增加少,是一种安全有效的起始胰岛素治疗方式,但控制血糖和Hb A1c达标时间长,可能不适用于初诊FPG严重升高、胰岛素抵抗重的患者。基础+餐时胰岛素治疗方案可迅速控制血糖、Hb A1c达标,对于初诊FPG较高的患者适用,但注射次数多降低患者的接受程度,且体重增加明显、低血糖发生风险较高,控制血糖平稳后逐渐减少胰岛素剂量或更改为基础胰岛素+口服药物方案可能更合适。总而言之,胰岛素干预方案的选择应充分考虑机体异质性,制定个体化治疗方案。
[Abstract]:Objective: To explore the relationship between pancreatic islet function and fasting blood glucose level in newly diagnosed type 2 diabetic patients and the factors that may be related to their independence. Methods: the patients with type 2 diabetes in the Department of endocrinology of our hospital from 2013 to 2015 were collected, and the patients were divided into 1 groups (FPG7mmol/l) according to the FPG level, group 2 (7mmol/l < FPG8.2mmol/l), and 3 groups (8.2mmo L/l < < FPG11.1mmol/l), 4 groups (11.1mmol/l < FPG), all patients were treated with oral glucose tolerance (OGTT) and insulin release (IRT) test. The ratio of HOMA-IR, HOMA- beta, the ratio of 30min insulin to glucose after sugar load (delta I30/ Delta G30), the area AUCI under insulin curve, statistical analysis of the related results of each group. Blood pressure, body mass index (BMI) and Hb A1c, TC, TG, LDL-C, HDL-C, creatinine (Cr) and so on, establish the multiple linear regression analysis model to explore the independent factors of islet beta cell function and the correlation between the factors and the islet function. The data are recorded with EPIDATA software, the spss20.0 statistics software is statistically analyzed, normal distribution data are used. The mean variance (? X + s) indicated that the multiple linear regression analysis was used to establish a multiple linear regression analysis model to explore the independent factors of islet beta cell function. The P value was less than 0.05 and was considered to be statistically significant. Results: 1, 176 cases of primary T2DM were collected, and there was no significant difference in sex composition, systolic pressure and diastolic pressure in each group. There was no significant difference in total cholesterol and creatinine in the group with higher.FPG, the greater the average age, the higher the glycerol three, the higher the LDL, the lower the BMI in the.1~3 group, but the BMI mean of the 4 groups was significantly lower than that of the other three groups. There was no significant difference between the groups of FIns, Fc and AUCI in each group, and there was a significant difference between the.HOMA- beta 3 groups and the 4 groups in the other groups. There was no significant difference in the 22 other groups. With the increase of FPG, FINS, Fc, HOMA- beta and AUCI gradually decreased.3, and there was no significant difference between the 22 groups of HOMA-IR 1,2,3 groups. The 4 groups were significantly different from the 1,2,3 groups. As FPG increased, HOMA-IR had a trend to increase gradually. PG increased, the early secretion of insulin increased and then decreased, but there was no significant difference between 22 groups, but there was no statistically significant difference between the groups of 1 groups and 2 groups under the AUC curve. The insulin secretion peak was delayed in the 3 groups, 3 groups and 4 groups, and the early phase and late secretion of insulin were significantly higher than those of the other group.2 group. There was no obvious decrease in the secretion of early phase and late secretion of insulin in.3 group, the secretion peak was delayed, the peak was delayed, the peak was not obvious in the.4 group, the early secretory and late secretory decreased obviously, the insulin secretion peak was.5, the linear regression analysis showed age, Hb A1c, glycerin three fat, LDL-C FPG, 2h PG, HOMA-IR and HOMA- beta are negatively correlated, HDL-C and FIns are positively correlated with HOMA- beta. Age, FIns, HOMA-IR are HOMA- beta independent correlation factors. Age, glycerol three fat, LDL-C, three fat are independent related factors. Conclusion: type 2 diabetes mellitus The disease has the tendency of young and high incidence. The screening of.FPG in the high-risk group of type 2 diabetes should be a simple and easy way to evaluate the function of islet. The economic index is of great significance to the preliminary evaluation of the function of the islet and guiding clinical treatment. The more patients with higher FPG at first visit, the less.FPG 8.2mmol/l is the first phase of insulin in the base and the overall secretion function of islet. At the turning point of the secretion, the first phase of insulin secretion increased compensatory at FPG8.2mmol/l, when FPG8.2mmol/l, the insulin first secretory decreased.FPG11.1mmol/l as the turning point of insulin resistance, and the insulin resistance suddenly aggravated when FPG11.1mmol/l. Age, FIns, HOMA-IR were independent factors of insulin secreting function; FIns, FPG, glycerol three fat were H The independent related factors of OMA-IR. Severe hyperglycemia may weaken the correlation between BMI and islet function..FIns may be a more accurate indicator of islet function than FPG. At the same time, there is a mutual influence on glycemic metabolism. Therefore, the treatment of T2DM should promote comprehensive management, control blood glucose and control blood lipids, especially the LDL-C and HDL-C standard.2 type. At the beginning of the diagnosis of diabetes, the insulin base and the overall secretory function of the patients have been severely damaged, especially in patients with FPG > 11.1mmol/l. The early intensive insulin therapy for such patients, the rapid reduction of blood sugar, the interruption of the further damage of the "sugar toxicity" to the islet beta cells and the protection of the residual islet function may have great benefit. Objective: To investigate the effect of different insulin intervention programs on pancreatic islet beta cell function in patients with newly diagnosed type 2 diabetes. Methods: from 2013 to 2015, the patients with type 2 diabetes, FPG more than 11.1mmol/l or Hb A1c9%, who were voluntarily accepted by insulin, were selected in the Department of endocrinology of our hospital. The patients were numbered according to the sequence of admission and were randomly selected. The digital table method was randomly assigned to a daily 2 injection group of premixed insulin analogues or 4 times daily insulin injection group or basal insulin + oral hypoglycemic group. The patients were followed up for half a year. The patients were monitored for daily fasting and postprandial 2H blood glucose self-monitoring and recorded hypoglycemia, and each March was monitored at a Hb A1c, and OGTT+I was reviewed for half a year. RT test was used to detect the decrease of blood sugar and Hb A1C, the time of blood glucose control, the standard of glycemic hemoglobin, the maximum insulin dosage, the frequency of hypoglycemia, and so on, to explore the different insulin intervention programs to improve the islet beta cells according to the two OGTT+IRT results before and after the comparison. The difference in function, especially the effect on the secretion of insulin first phase. The observation data include FPG, 2h PG, FIns, Fc, Hb A1c, HOMA-IR, HOMA- beta, and delta I30/ Delta G30. Comparison of group measurement data, using paired t test to compare the data before and after treatment, P0.05 was considered to have statistical significance. Results: 1, 30 cases of type 2 diabetic patients with severe initial diagnosis were selected, and 27 cases were followed up. There were no significant differences in sex composition, age, BMI, Hb A1c, glycerin three fat, LDL-C, HDL-C in different intervention groups. 24 weeks after treatment, FPG 2H PG, Hb A1c, HOMA-IR decreased significantly, FIns, Fc, HOMA- beta, Delta I30/ Delta G30, AUCI significantly increased, and had statistical significance. The difference of AUCI, HOMA-IR and HOMA- beta was statistically significant between basal insulin + oral medication group and basal + meal insulin group Delta (delta I30/ Delta G30), and there was no statistically significant difference between the rest of the groups and.3. All patients were followed up for 24 weeks, and the average Hb A1c decreased by 2.58%. There was no significant difference in the ability to reduce Hb A1c in the intervention group. The weight of the group increased significantly, the average weight of the basal insulin + oral hypoglycemic drug group increased by 1.8kg, the average weight of the premixed insulin group increased by 2.6kg, the average weight of the basal + meal insulin group increased by 3.1kg. low blood sugar score, the basal insulin + oral medicine group was the lowest, and the basal + time insulin group was significantly higher than the basic insulin + oral administration. In the group, the premixed insulin group was the highest and there was a patient with severe hypoglycemia.4 at night, the premixed insulin group had the longest blood glucose control time, 24 weeks Hb A1c individualized target target rate, the low blood sugar Hb A1c individualized target target rate was the lowest, the basic insulin + oral medicine group had the least amount of insulin and no hypoglycemic Hb A1c. The rate of individualized target was the highest, the insulin group was the shortest, the insulin dosage was the shortest, the insulin dosage was the highest, the 24 week Hb A1c individualized target reached the highest standard rate. Conclusion: In conclusion, the insulin treatment in the first diagnosis T2DM patients can obviously improve the insulin resistance and islet secretion function, especially the first phase secreting work of insulin. Yes, there is no difference in the ability of insulin intervention to improve insulin resistance and the overall secretory function of insulin, but the function of the basic + meal insulin program to improve the insulin first secretory ability is better than that in the basic + oral administration. To the specific patients, the improvement of insulin resistance is mainly to improve the islet beta cell secretory work. The individual differences could be related to the environmental factors of genetic background or blood glucose deterioration. The average Hb A1c decreased by 2.58% in all patients after 24 weeks of follow-up. This data was significantly higher than the previous study of Hb A1c decreasing 1.5%~2.1%. The higher Hb A1c and smaller sample size of the selected population were related. The Hb A1c improvement of different treatments. There is no difference in degree. The premixed insulin regimen is high in hypoglycemia, and has a severe hypoglycemia risk, lower patient satisfaction and compliance. Patients with poor life, compliance, and poor self management are not recommended for this treatment. The incidence of hypoglycemia in the basic insulin + oral hypoglycemic group is low, and the weight gain is less. It is a safe and effective way of starting insulin treatment, but the control of blood sugar and the long time of Hb A1c may not be suitable for patients with severe early diagnosis of FPG and heavy insulin resistance. Basic + meal insulin therapy can quickly control blood sugar, Hb A1c reaches the standard, it is suitable for patients with higher initial diagnosis of FPG, but the number of injections reduces the patient more. In a word, the choice of insulin intervention should take full account of the heterogeneity of the body and make individualized treatment plans.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1

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