The Clinical Analysis And Circulating Levels Of MiR-25、miR-146a、miR-21、miR-181a In Autoimmune Diabetes

Objective:To analyze the clinical characteristics of 261 cases of hospitalizing patients with type 1 diabetes mellitus(T1DM) and 78 case of latent autoimmune diabetes in adults(LADA) in Peking Union Medical College(PUMCH). To observe the expression of the serum mi R-25、mi R-146a、mi R-21、mi R-181 a of the autoimmune diabetes、T2DM、healthy control. Methods:The clinical characteristics of T1DM: Clinical documents of 261 cases of hospitalizing patient with T1 DM in the department of endocrinology at PUMCH from Jan 2007 to Dec 2014 were analyzed retrospectively. Subjects were divided into adult onset group and non-adult onset group according to the onset age of T1DM; and were divided into T1 DM antibodies positive group and negative group, respectively. The effects of hospitalized admission times on the treatment in T1 DM were compared.The clinical characteristics of LADA and adult-onset T1DM: The clinical documents of 78 hospitalized patients with LADA and 110 patients with adult-onset T1 DM in the department of endocrinology at PUMCH from Jan 2007 to Dec 2014 were analyzed retrospectively. Subjects were divided into 2 groups according to disease duration : ≦ 5 years group and > 5 years group, to explore the clinical features and complications of the LADA patients and adult-onset T1 DM patients. In order to understand the treatment features of LADA, we investigated the differences between LADA and adult-onset T1 DM in insulin dosage and oral administration.The clinical analysis and circulating levels of mi R-25、mi R-146a、mi R-21、mi R-181 a in autoimmune diabetes: The subject of this study include 33 case of T1 DM patients, 25 cases of LADA Patients, 35 cases of T2 DM patients and 30 cases of healthy peo Ple. We use PCR(Real Time q RT-PCR)method to determine the serum mi RNA level expression between patients and healthy subjects.Results:a) Analysis of the clinical characteristics of T1DM:There are 261 cases in this study and the age of set was 26.6±15.4 years, the average duration of disease was 49 months(1 ~480 months), the positive rate of GAD antibody was 58.8%. 123 newly diagnosed patients were included in the study, 65 in non-adult onset group and 58 in adult onset group. The 2h postprandial C peptide, and the positive rate of T1 DM antibodies in non-adult onset group were higher than that in adult onset group(non-adult onset group vs adult onset group: 2h postprandial C peptide: 0.98(0~2.59) ng/ml vs 0.52(0~2.43) ng/ml, P < 0.05; positive rate of T1 DM antibodies: 80.4% vs 62.5%, P < 0.05). The age of onset in the T1 DM antibodies positive group was smaller than that in the antibodies negative group(19.7±11.4 years vs 24.7±15.6years,P<0.05), the incidence of ketosis was higher in the antibodies positive group(48.3% vs 34.2%,P<0.05). With the progress of the disease, the fasting C peptide level of the antibodies positive group decreased more rapidly. Compared with the single time hospitalized patients, multiple hospitalized patients have a lower incidence of diabetic retinopathy(8.2% vs 22.4%,P<0.05), a lower Hb A1 c level(8.04%±2.1% vs 9.56%±2.64%,P<0.05)and fasting blood plasma level(8.7±3.07mmol/l vs 10.9±4.2mmol/l,P<0.05).b) Analysis of the clinical characteristics of LADA and adult-onset T1DM:There are 78 patients with LADA and 110 patients with adult-onset T1 DM in this study. Compared with adult-onset T1 DM, the onset age LADA was older, the average of Hb A1 c was lower, the positive rate of GAD antibody was higher. In the disease duration ≦ 5 years group, compared with adult-onset T1 DM Patients, the fasting C peptide levels of LADA patients were higher, the insulin dosage in LADA patients was less. In the disease duration > 5 years group, although the C peptide of LADA were higher than adult-onset T1 DM, the islet function of LADA and adult-onset T1 DM were both worse. There was no significant difference in the prevalence of diabetic complications in LADA and adult-onset T1 DM. Compared with adult-onset T1 DM, more LADA patients were in the therapy of combination with oral hypoglycemic drugs(almost use α-glucosidase inhibitors).c) The clinical analysis and circulating levels of mi R-25、mi R-146a、mi R-21、mi R-181 a in autoimmune diabetesThere are 33 cases of T1 DM patients, average of age is 23.4±9.2 years, the course of disease is 36.3±48.5 months, average of BMI is 21.3±3.9 Kg/m2; 25 cases of LADA patients, average of age is 51.8±10.1 years, the course of disease is 46.3±9.8 months, average of BMI is 21.52±2.54 Kg/m2; 35 cases of T2 DM patients, average of age is 45.48±7.45 years, the course of disease is 6.4±14. months, average of BMI is 23.09±2.68 Kg/m2; 30 cases of healthy control, average of age is 28.7±4.7 years, average of BMI is 23.1±3.6 Kg/m2.We demonstrated that the serum mi R-25 and mi R-181 a had significant decreased levels in LADA,T1 DM,T2DM patients compared with healthy subjects(P<0.05),the serum mi R-146 a and mi R-21 had significant decreased levels in LADA,T1 DM patients compared with healthy subjects(P<0.05),and compared with LADA patients the serum mi R-146 a had significant decreased levels in T1 DM patients.Conclusion:1. Compare with non-adult onset T1 DM patients,the islet function of adult onset patients was even worse. In T1 DM antibodies positive patients, the islet βcell function decreased more rapidly, so the antibodies can not only clarify the diagnosis of T1 DM and also could predict prognosis of the isletβcell function. In the management of T1 DM patients, regular hospital revisits help to get better glycemic control and reduce the occurrence of diabetic complications.2. Compared with adult-onset T1 DM, the onset age of LADA patients was older, Ketoacidosis tendency was not obvious, and the positive rates of GAD-Ab and IAA-Ab were higher. The islet β cell function of LADA decreased more slowly. In the treatment of LADA, combination with oral hypoglycemic drugs can keep a more stable condition of blood glucoses.3. Compared with healthy subjects the serum mi R-25、mi R-146a、mi R-21、mi R-181 a expression decreased in autoimmune diabetes, the serum mi R-25、mi R-181 a had significant decreased levels in T2 DM patients. The serum mi R-146 a and mi R-181 a regulating the proliferation and differentiation of immune cell, participating in the occurrence of pancreatic inflammation, we demonstrated that maybe the serum mi R-146 a mediated the immune response in T1 DM patients more serious compared with LADA patients. The research shown the expression of serum mi RNA maybe affected by the age、BMI and course of disease of patients, so as a biomarker is still not suitable, a large number of studies are needed to validate it.