LADA患者血清胰岛素原水平及其意义

目的 探讨成人隐匿性自身免疫性糖尿病(LADA)患者血清胰岛素原(PI)的分泌特征及其意义.方法 36例LADA患者、37例2型糖尿病患者和43名正常对照者均行口服糖耐量试验(OGTT),检测空腹和2 h血糖、胰岛素原(FPI和PPI)和C肽(FCP和PCP)水平,放射配体法测定谷氨酸脱羧酶抗体(GAD-Ab).结果 (1)LADA组FPI和PPI均低于2型糖尿病组(均P<0.05),但均较对照组升高(P<0.05或P<0.01);FPI/FCP和PPI/PCP(%)较2型糖尿病和正常对照均增高(P<0.05或P<0.01);(2)LADA-1型(GAD-Ab≥0.3)的PI低于LADA-2型(0.05≤GAD-Ab<0.3)(P<0.05或P<0.01),而PI/C肽均高于LADA-2型(均P<0.05);而LADA-2型与2型糖尿病差异无统计学意义;(3)LADA患者的GAD-Ab滴度与FPI和PPI呈显著负相关(r为-0.236和-0.268,均P<0.05),与PPI/PCP呈显著正相关(r=0.254,P=0.030);(4)FPI/FCP"不成比例"增高者占LADA、2型糖尿病和正常组的百分比分别为77.8%、62.2%和2.3%,PPI/PCP增高者为83.3%、51.4%和2.3%.结论 LADA患者和2型糖尿病患者一样,亦存在高PI血症,且"不成比例"PI异常增多在LADA更为显著,可能与免疫凶素有关.

Serum proinsulin levels in LADA patients

Objective To explore the characteristics of proinsulin secretion in latent autoimmune diabetes in adults (LADA). Methods Fasting and 2 h sera in oral glucose tolerance test from 36 LADA patients, 37 type 2 diabetic patients and 43 healthy controls were collected to test glucose, proinsulin (PI) and C-peptide (CP) by radioimmune assay. Glutamie acid decarboxylase antibodies (GAD-Ab) were determined by radioligand assay.Results (1) Fasting proinsulin (FPI) and 2 h proinsulin (PPI) level in LADA patients were lower than those in type 2 diabetic patients (P<0.05), being both significantly inereasad compared with healthy controls (P<0.05 or P<0.01); The ratios of FPI/FCP and PPI/PCP (%) in LADA were beth significantly higer than those of type 2 diabetes mellitus and controls (P<0.05 or P<0.01); (2) LADA type-1 (GAD-Abe>0.3) patients showed lower PI levels(P<0.05 or P<0.01) and higher PI/CP ratio (all P<0.05) than LADA type-2 (0.05≤GAD-Ab<0.3); Meanwhile, there were no significant differences in above parameters between LADA type-2 and type 2 diabetes meUitus (P>0.05). (3) GAD-Ab index was negatively correlated with FPI and PPI in LADA group (r=-0.236 and-0.268, both P<0.05), and positively correlated with PPI/PCP (r=0.254, P=0.030).Meanwhile BMI was positively correlated with FPI, PPI and PI/CP in type 2 diabetes mellitus (all P<0.01). No factor entered the multiple regression analysis for predieting the hyperproinsulinemia and dispropriately elevated proinsulin levels in LADA patients. (4) According to the 99.5 th percentile of proinsulinemia in the healthy controls, which is defined as the cutoff point dispropriately elevated proinsulin levels, the proportion of subjects with fasting dispropriately elevated proinsulin levels (FPI/FCP) were 77.8%, 62.2% and 2.3% in LADA, type 2 diabetes meUitus and controls respectively, and PPI/PCP 83.3%, 51.4% and 2.3% respectively. Conclusion LADA patients, as well as type 2 diabetic patients, all showed hyperproinsulinemia and disproportionately elevated proiasulin levels that were one of characteristics of defective β-cell function. Moreover, disproportionately elevated nproinsulin level is more evident in LADA patients than that in type 2 diabetics and this may be related to humoral immunity.