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Insulin and liraglutide have been demonstrated to control blood glucose and exert neuroprotective effects. However, the impact of liraglutide or insulin alone or in combination on brain pathology in type 1 diabetes mellitus (T1DM) and their underlying mechanisms are unclear. In the present study, diabetes mellitus (DM) was induced via intraperitoneal injection of streptozotocin in mice and subsequently mice were treated with insulin, liraglutide, a combination of the two drugs or saline. Changes in body weight and blood glucose were assessed weekly. The pathological changes in the brain tissue and the apoptosis of neurons were assessed using H&E staining and TUNEL staining. The mRNA and protein expression levels of apoptosis-related proteins were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. Moreover, Ki67 protein expression was analyzed using immunohistochemistry and the mRNA and protein expression levels of Wnt/β-catenin signaling pathway-related proteins were examined using RT-qPCR and western blotting, respectively. The results of the present study suggested that DM mice developed hyperglycemia and weight loss and also exhibited significantly increased neural cell apoptosis and significantly reduced numbers of Ki67-positive cells. Liraglutide significantly decreased blood glucose levels in DM mice, whereas both insulin and the combination of the two drugs failed to control blood glucose well. Insulin, liraglutide and their combination also failed to control body weight well, but significantly attenuated brain pathological changes and activation of the pro-apoptotic proteins Caspase-3 and Bax, which may have resulted in the significant increase in the expression levels of Wnt/β-catenin signaling pathway-associated molecules such as Wnt3a and S9-pGSK-3β. Liraglutide also promoted the protein expression of the neurogenesis marker of Ki67 and the antiapoptotic factor Bcl-2. These results suggested that insulin and liraglutide may improve brain damage via upregulation of the Wnt/β-catenin signaling pathway and could be of therapeutic relevance for improvement of cognitive impairment in patients with DM. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical characteristics of different subtypes of type 1 diabetes mellitus(T1DM) patients and to analyze the risk of macrovascular diseases in different subtypes of T1DM patients. Methods The clinical data among 79 T1DM patients who treated in the Endocrinology Department of Beijing Puren Hospital from March 2002 to July 2021 were retrospectively analyzed. There were 21 patients with idiopathic T1DM and 58 patients with autoimmune T1DM. Excluding 14 patients because of data missing, 65 patients were divided into macrovascular disease group (n=13) and non-macrovascular disease group (n=52). Results 1)Patients with idiopathic T1DM manifested a longer diabetic course,a higher high density lipoprotein cholesterol(HDL-c)level, a lower body mass index(BMI), hemoglobin A1c(HbA1c) and fasting C peptide(FC-P)level. 2)Compared with the group non-macrovascular disease, the macrovascular disease group was elder with higher prevalence of idiopathic T1DM and lower estimated glomerular filtration rate(eGFR) level and incidence of diabetic ketoacidosis(DKA) at the beginning of disease. 3)Macrovascular lesions were positively correlated with age(r=0.432) and diabetic course (r=0.245)(P＜0.05), were negatively correlated with eGFR(r=-0.392), positive islet autoantibody (r=-0.268) and DKA incidence at the beginning of disease(r=-0.313)(P＜0.05). 4)Multivariate regression analysis showed that negative auto-antibody finding was a risk factor for macrovascular disease (OR=0.03, 95% CI:0.001-0.858, P＜0.05) after age, diabetic course, BMI, eGFR, HDL-c and incidence of DKA at onset were adjusted. Conclusions Patients with idiopathic T1DM show a higher risk of macrovascular disease risk than those with autoimmune T1DM.

Abstract: Background: The purpose was to characterize the clinical, biochemical, and immunological features of newly diagnosed adult-onset nonobese diabetic patients in China. Methods: Newly diagnosed diabetic patients aged 18–45 years with body mass index<23 kg/m2 were included. Excluding one mitochondrial diabetes patient, there were 102 diabetic patients enrolled in this study. Clinical and biochemical data were collected and analyzed. Radioimmunoassay was used to detect islet autoantibodies. Results: Among the 102 study participants, 68.6% had type 1 diabetes (T1DM), 20.6% had type 2 diabetes (T2DM), and 10.8% had latent autoimmune diabetes in adults (LADA). About 92% of the T1DM patients presented hyperglycemic symptoms. The corresponding number in T2DM and LADA patients was 13% and 38%, respectively (P<.01). C-peptide in T2DM patients (1.4±0.7 ng/ml) was significantly higher than that in T1DM (0.4±0.3 ng/ml) and LADA (0.4±0.2 ng/ml) patients (P<.01). The prevalence of glutamic acid decarboxylase antibody (GADA) (64.3%) in T1DM patients was higher than that of insulin autoantibody (17.1%) (P<.05). GADA and islet cell antibody (ICA) combination was positive in 75.7% of T1DM patients. Conclusion: T1DM patients accounted for majority of the study sample. In addition, the clinical symptoms of T1DM patients were more severe compared with T2DM patients. GADA is the most sensitive autoantibody marker for adult-onset T1DM and LADA. GADA and ICA are the best test combination for adult-onset autoimmune diabetes. Specific types of diabetes should be in mind when diabetes presents itself with special transmission mode or with other extrapancreatic manifestations. [Copyright &y& Elsevier]