Related Risk Factors between Subclinical Carotid Atherosclerosis and Diabetic Retinopathy in Newly Diagnosed Type 2 Diabetes Mellitus in China.

PURPOSE: To analyze the clinical features and related risk factors in diabetic retinopathy (DR) and subclinical atherosclerosis, the micro- and macro-vascular diseases in newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A retrospective study of 435 cases of inpatients with newly diagnosed T2DM from 2013-2017, and compare the 2 types of T2DM related vascular complications. RESULTS: The macro- and microvascular complications are not rare at this stage. Subclinical atherosclerosis was found in 251 subjects (57.7%), which was higher than that of DR (13.1%). In addition, some cases of subclinical atherosclerosis co-existed with DR, suggesting that DR was related with subclinical atherosclerosis (r=0.098, P=0.041). Older age showed a significant association with both subclinical atherosclerosis and DR. Single factor analysis indicated that dyslipidemia was the common risk factor in DR and subclinical atherosclerosis. CONCLUSIONS: It should be paid attention to the screening of both DR and subclinical atherosclerosis in each age group of newly diagnosed T2DM. Except for the control of blood glucose, the control of the dyslipidemia is important in the prevention and treatment of the micro- and macro-vascular diseases.

Association of diabetic nephropathy with the severity of obstructive sleep apnea-hypopnea syndrome in patients with type 2 diabetes mellitus.

This study aimed to analyze the effect of the severity of obstructive sleep apnea-hypopnea syndrome (OSAHS) on diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). A total of 322 patients with T2DM participated in this cross-sectional study. OSAHS was diagnosed according to the apnea-hypopnea index (AHI) and it was categorized as follows: normal, mild, moderate, and severe. Relevant clinical data retrieved from medical charts were cross-analyzed between different groups. The relationship between urinary albumin/creatinine ratio(UACR) and OSAHS parameters, which included AHI, lowest oxygen saturation (L-SaO2), and mean oxygen saturation (M-SaO2), was evaluated by partial correlation analysis. DN stages were classified into a non-DN group, a microalbuminuria group, and a macroalbuminuria group. Multiple factor logistic regression analysis was employed to analyze factors influencing DN. The results showed that mild OSAHS, moderate OSAHS, and severe OSAHS patients had a higher Body mass index (BMI), creatinine (CR) level, UACR, and a longer duration of T2DM (p < 0.05) than the non-OSAHS group. The prevalence of DN in the non-OSAHS, mild OSAHS, moderate OSAHS, and severe OSAHS groups was 18.4%, 19.2%, 34.6%, and 49.4%, respectively (p < 0.05). Multiple factor logistic regression analysis revealed that systolic blood pressure (SBP) (OR = 1.03), AHI (OR = 1.02), and duration of T2DM (OR = 1.04) were correlated with DN (p < 0.05). These findings revealed that OSAHS is highly prevalent in T2DM and AHI is independently associated with the presence of DN.

Modulation of IGF1R Signaling Pathway by GIGYF1 in High Glucose-Induced SHSY-5Y Cells.

Grb10 (growth factor receptor-bound protein 10)-interacting GYF protein 1 (GIGYF1) can modulate insulin-like growth factor 1 receptor (IGF1R) signaling pathway, which plays an important role in regulating diabetes-associated cognitive impairment, by linking to Grb10 adapter. However, it remains unclear whether endogenous GIGYF1 expression is associated with the development of diabetes-related cognitive impairment. In this study, we measured the expression level of GIGYF1, Grb10, phosphorylated IGF1R/IGF1R, phosphorylated AKT serine/threonine protein kinase/protein kinase B (AKT)/AKT, and phosphorylated extracellular signal-regulated kinase (ERK)/ERK in human neuroblastoma SHSY-5Y cells. Meanwhile, we detected cell apoptosis, proliferation, and migration. Our results showed that the percentage of apoptotic cells increased along with the increasing concentrations of glucose (0-200 mM). The expression of GIGYF1 had a significant increase in the presence of 25 mM concentration of glucose in SHSY-5Y cells. In addition, high glucose augmented the expression of IGF1R and Grb10, but decreased the expression of p-IGF1R, p-AKT, and p-ERK. However, GIGYF1 knockdown reversed the decline in the expression of p-IGF1R, p-AKT, and p-ERK. In addition, knocking down GIGYF1 promoted the proliferation and migration of SHSY-5Y cells, but inhibited the apoptosis in SHSY-5Y cells. These results demonstrate that the expression of GIGYF1 can regulate IGF1R signaling pathway in high glucose-induced SHSY-5Y cells.

Relationship between serum adipsin and the first phase of glucose-stimulated insulin secretion in individuals with different glucose tolerance.

AIMS/INTRODUCTION: To detect serum adipsin levels in individuals with different glucose tolerance, and investigate the relationship between adipsisn and the first phase of insulin secretion. MATERIALS AND METHODS: A total of 56 patients with newly diagnosed type 2 diabetes mellitus, 36 patients with impaired glucose tolerance (IGT) and 45 individuals with normal glucose tolerance were enrolled. Intravenous glucose tolerance tests were carried out to evaluate pancreatic ß-cell function. The serum levels of adipsin, interleukin-1ß and high-sensitivity C-reactive protein were assayed. RESULTS: Serum adipsin levels were significantly lower in the type 2 diabetes mellitus and the IGT patients than those in the normal glucose tolerance group (P < 0.05). The acute insulin response and area under the curve showed a progressive decrease in the normal glucose tolerance and IGT groups, and decreased to the lowest levels in the type 2 diabetes mellitus group (P < 0.05). Adipsin was found to be negatively correlated with waist-to-hip ratio, free fatty acid, fasting plasma glucose, 2-h postprandial plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, interleukin-1ß and high-sensitivity C-reactive protein (P < 0.05 or P < 0.001), and positively correlated with homeostasis model assessment of ß-cell function, high-density lipoprotein cholesterol, the area under the curve of the first phase insulin secretion and acute insulin response (P < 0.05 or P < 0.001). Stepwise multiple regression analysis showed that homeostasis model assessment for ß-cell function and acute insulin response were independently related to adipsin (P < 0.05). CONCLUSIONS: Serum adipsin levels were lower in type 2 diabetes mellitus and IGT patients, and correlated with the first phase of insulin secretion. Adipsin might be involved in the pathology of type 2 diabetes mellitus.

Early Assessment of the Risk Factors for Diabetic Retinopathy Can Reduce the Risk of Peripheral Arterial and Cardiovascular Diseases in Type 2 Diabetes.

BACKGROUNDS: There is still a lack of consensus about how to assess the risk of peripheral arterial disease (PAD) and cardiovascular disease (CVD) in patients with diabetic retinopathy (DR). AIMS: We investigated the risk factors for DR and their association with PAD and CVD in patients with type 2 diabetes (T2D). METHODS: A total of 1,421 patients diagnosed with T2D participated in this study. DR stages were classified as non-DR, nonproliferative DR (NPDR), or proliferative DR (PDR). Logistic regression analysis was employed to analyze risk factors associated with DR. RESULTS: NPDR and PDR patients had higher systolic blood pressure (SBP) and higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than the non-DR group (p < 0.05). The prevalence of abnormal ankle-brachial index (ABI) in the non-DR, NPDR, and PDR groups was 7.00, 10.80, and 13.96%, respectively (p < 0.05) and the prevalence of peripheral arterial plaques was 68.48, 81.38, and 80.56%, respectively (p < 0.001). Logistic regression analysis showed that DR (vs. non-DR) was associated with peripheral arterial plaques (OR = 2.07), SBP ≥130 mm Hg (OR = 1.53) and levels of hemoglobin (Hb)A1c (OR = 2.11) and TC (OR = 1.42). CONCLUSION: PAD is commonly associated with NPDR and PDR. Hypercholesterolemia is an important risk factor for the development of PAD and CVD in patients with DR. Our results suggest that a routine ABI test, duplex ultrasonography, and obtaining a lipid profile for DR patients may help to reduce the occurrence of PAD and CVD.

Amelioration of Diabetic Mouse Nephropathy by Catalpol Correlates with Down-Regulation of Grb10 Expression and Activation of Insulin-Like Growth Factor 1 / Insulin-Like Growth Factor 1 Receptor Signaling.

Growth factor receptor-bound protein 10 (Grb10) is an adaptor protein that can negatively regulate the insulin-like growth factor 1 receptor (IGF-1R). The IGF1-1R pathway is critical for cell growth and apoptosis and has been implicated in kidney diseases; however, it is still unknown whether Grb10 expression is up-regulated and plays a role in diabetic nephropathy. Catalpol, a major active ingredient of a traditional Chinese medicine, Rehmannia, has been reported to possess anti-inflammatory and anti-aging activities and then used to treat diabetes. Herein, we aimed to assess the therapeutic effect of catalpol on a mouse model diabetic nephropathy and the potential role of Grb10 in the pathogenesis of this diabetes-associated complication. Our results showed that catalpol treatment improved diabetes-associated impaired renal functions and ameliorated pathological changes in kidneys of diabetic mice. We also found that Grb10 expression was significantly elevated in kidneys of diabetic mice as compared with that in non-diabetic mice, while treatment with catalpol significantly abrogated the elevated Grb10 expression in diabetic kidneys. On the contrary, IGF-1 mRNA levels and IGF-1R phosphorylation were significantly higher in kidneys of catalpol-treated diabetic mice than those in non-treated diabetic mice. Our results suggest that elevated Grb10 expression may play an important role in the pathogenesis of diabetic nephropathy through suppressing IGF-1/IGF-1R signaling pathway, which might be a potential molecular target of catalpol for the treatment of this diabetic complication.

Negative regulation of Grb10 Interacting GYF Protein 2 on insulin-like growth factor-1 receptor signaling pathway caused diabetic mice cognitive impairment.

Heterozygous Gigyf2⁺/⁻ mice exhibits histopathological evidence of neurodegeneration such as motor dysfunction. Several lines of evidence have demonstrated the important role of insulin-like growth factor-1 receptor (IGF1R) signaling pathway in the neuropathogenic process of cognitive impairment, while decreased Grb10-Interacting GYF Protein 2 (GIGYF2) expression can alter IGF1R trafficking and its downstream signaling pathways. Growth factor receptor-bound protein 10 (Grb10), a suppressor of IGF1R pathway, has been shown to play a critical role in regulating diabetes-associated cognitive impairment. It remains unknown whether endogenous GIGYF2 expression contributes to the development of diabetes-associated cognitive impairment. Using streptozotocin (STZ)-induced diabetic mice model, we first demonstrated that a significantly increased level of GIGYF2 expression was correlated with a significant decrease in the expression of phosphorylated IGF1R as well as the phosphorylation of AKT and ERK1/2, two signaling pathways downstream of IGF1R, in the hippocampus of diabetic mice. On the contrary, in situ knockdown of GIGYF2 expression in hippocampus resulted in increased expression of phosphorylated IGF1R expression and correspondingly reversed the down-regulation of ERK1/2 phsophorylation but had no obvious effect on Grb10 expression. Functionally, knockdown of GIGYF2 expression markedly ameliorated diabetes-associated cognitive dysfunction as well as the ultrastructural pathology and abnormal neurobehavioral changes. These results suggest that increased expression of GIGYF2 might contribute to the development of diabetes-associated cognitive disorder via negatively regulating IGF1R signaling pathway. Therefore, down-regulation of GIGYF2 expression may provide a potential novel approach to treat diabetes-associated cognitive impairment caused by aberrant IGF1R signaling pathway.

Comparative efficacies of fluoxetine and paroxetine in major depression across varying acute-phase treatment periods: a meta-analysis.

INTRODUCTION: Previous studies have shown that varying acute-phase treatment periods of fluoxetine and paroxetine can result in varying antidepressive effects. We therefore did a meta-analysis to ascertain the efficacy of fluoxetine versus paroxetine for depression by varying acute-phase treatment periods. METHODS: PubMed, CCTR, Web of Science, Embase, CBM-disc, and CNKI were searched up to March 2013. The key search terms were "depression," "paroxetine," and "fluoxetine." No language restriction was imposed. RESULTS: We included 17 studies with 3,110 patients. Three treatment period subgroups were created: 6, 8/10, and 12 weeks. In the 6-week subgroup, paroxetine was more efficacious than fluoxetine (odds ratio [OR]: 0.74; P < 0.05). In the 8/10-week subgroup, two drugs displayed comparative efficacy (OR, 0.85; P > 0.05). In the 12-week subgroup, fluoxetine was more efficacious than paroxetine (OR: 1.25; P < 0.05). There were no significant differences in acceptability. Significant heterogeneity and potential publication bias did not exist. CONCLUSIONS: Patients' economic conditions, individual preference, and side effects of fluoxetine and paroxetine can be obstacles of successful treatment. Inappropriate acute-phase treatment, such as inadequate treatment periods, may result in pseudoresistance. Clinicians should take these information into consideration when prescribe fluoxetine or paroxetine for patients. Our results can aid clinicians in making an optimal treatment plan to increase odds of response.

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a meta-analysis of stimulus parameter effects.

BACKGROUND: Studies comparing the antidepressant effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) have reported mixed results, as the choice of rTMS stimulus parameters is essential to its antidepressive effect. This meta-analysis aimed at assessing how rTMS stimulus parameters influence the efficacy of rTMS relative to ECT in treating major depression. METHODS: A comprehensive literature search (including PubMed, CCTR, Web of Science, Embase, EAGLE, NTIS, CBM-disc, CNKI, Current Controlled Trials, Clinical Trials, International Clinical Trials Registry, and Internet Stroke Center) was conducted dating until December 2012. After exclusion of low-quality studies, the key search terms ('depressive', 'depression', 'transcranial magnetic stimulation', 'TMS', 'repetitive TMS', 'electroconvulsive therapy', and 'ECT') produced nine high-quality randomized controlled trials (RCTs) of rTMS versus ECT. RESULTS: These nine studies, composed of 395 patients, were meta-analyzed through assessment of odds of remission, response, and drop-out. Two rTMS subgroups displayed non-significant superiority to ECT: 20 Hz (odds ratio (OR) = 1·20; P > 0·05) and ≥ 1200 daily stimuli (OR = 1·06; P > 0·05). One rTMS subgroup displayed non-significant inferiority to ECT: four-week treatment period (OR = 0·65; P > 0·05). The other rTMS subgroups were significantly inferior to ECT. Repetitive transcranial magnetic stimulation was associated with a 30% relative reduction in the odds of drop-out, however non-significantly (95% confidence interval (CI), 0·36-1·39). DISCUSSION: The results indicate that the efficacy of rTMS is tied to its stimulus parameters. Varying stimulus parameters can result in varying antidepressive effects. Consequently, future research on rTMS or rTMS versus ECT should take the influence of rTMS stimulus parameters into consideration.