Unravelling the Inflammatory Processes in the Early Stages of Diabetic Nephropathy and the Potential Effect of (Ss)-DS-ONJ.

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic (Ss)-DS-ONJ is able to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of (Ss)-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation. The (Ss)-DS-ONJ treatment is able to inhibit the epithelial-to-mesenchymal transition (EMT) progression, but only when the IL18 levels are reduced by the treatment. These findings suggest that (Ss)-DS-ONJ could be a novel, and multifactorial treatment for DN.

Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (SS,1R)-1-docecylsulfiny-5N,6O-oxomethylidenenojirimycin ((Ss)-DS-ONJ), a member of the sp2-iminosugar glycolipid (sp2-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (Ss)-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of (SS)-DS-ONJ in microglia. (SS)-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR.

Quality-of-life and treatment satisfaction in actual clinical practice of patients with Type 1 diabetes mellitus (T1DM) and hypoglycemia treated with insulin degludec.

OBJECTIVE: The frequency of hypoglycemia in patients with T1DM is high and results in a poorer quality-of-life and low treatment satisfaction. The aim of this study is to demonstrate the effect of changing the basal insulin (glargine or detemir) to insulin degludec. METHODS: An observational analytical study was conducted on a cohort of 110 patients with T1DM. The patients were administered three questionnaires to assess treatment satisfaction (DTSQ-s), fear of hypoglycemia (HFS-II) and quality-of-life (EQ-5D), before the change and at 6 months. A statistical analysis was performed for repeated measures. RESULTS: The 110 patients with T1DM had a mean diabetes duration of 19.1 (11.6) years, 53.6% were men, the mean age was 43.4 (15.4) years, and the mean BMI was 25.2 (4.2) kg/m2. After 6 months, there was a significant reduction in baseline fasting plasma glucose (from 159.1 [68.6] to 132.9 [56.6] mg/dL; p < .001) and HbA1c levels (from 7.82% [1.2] to 7.6% [1.2]; p = .002). A reduction in the number of severe hypoglycemic episodes (0.17 [0.5] vs 0.05 [0.2]; p = .03) was observed. At 6 months, an improvement in the DTSQ-s (from 24.3 [5.5] to 27.3 [5.4]; p < .001) was observed. There was a decrease in the mean number of perceived hypoglycemia (from 2.9 [1.4] to 2.3 [1.4]; p = .003) and hyperglycemia (from 3.5 [1.3] to 2.7 [1.4]; p < .001). There was also a decrease in the mean HFS-II score (from 24.1 [14.0] to 20.0 [13.0]; p < .001). There were no significant differences in the EQ-5D index (from 0.91 [0.14] to 0.89 [0.16]; p = .13). However, there was significant improvement in the EQ-5D as measured by VAS (from 70.5 [16.5] to 73.6 [14.4]; p = .04). CONCLUSIONS: The change to insulin degludec in patients with T1DM improved their metabolic control, increased their satisfaction with the insulin therapy, and offered them improved quality-of-life.