Diabetes mellitus (DM) is a complex metabolic disease with many specifically related complications. Early diagnosis of this disease could prevent the progression to overt disease and its related complications. There are several limitations to using existing biomarkers, and between 24% and 62% of people with diabetes remain undiagnosed and untreated, suggesting a large gap in current diagnostic practices. Early detection of the percentage of insulin-producing cells preceding loss of function would allow for effective therapeutic interventions that could delay or slow down the onset of diabetes. MicroRNAs (miRNAs) could be used for early diagnosis, as well as for following the progression and the severity of the disease, due to the fact of their pancreatic specific expression and stability in various body fluids. Thus, many studies have focused on the identification and validation of such groups or “signatures of miRNAs” that may prove useful in diagnosing or treating patients. Here, we summarize the findings on miRNAs as biomarkers in diabetes and those associated with direct cellular reprogramming strategies, as well as the relevance of miRNAs that act as a bidirectional switch for cell therapy of damaged pancreatic tissue and the studies that have measured and tracked miRNAs as biomarkers in insulin resistance are addressed.

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The aim of this study was to correlate anthropometric, biochemical and oxidative stress parameters in newly diagnosed (ND) T2DM patients and to investigate the role of oxidative stress in T2DM associated with obesity. A group of 115 ND- T2DM patients was compared to a group of 32 healthy subjects in terms of clinical, anthropometric, biochemical and oxidative stress parameters. ND-T2DM patients had significantly lower adiponectin, glutathione (GSH) and gluthatione peroxidase (GPx) and elevated insulin, proinsulin, HOMA-IR index, proinsulin/insulin (P/I) and proinsulin/adiponectin (P/A) ratio, fructosamine, and total oxidant status (TOS). The total body fat mass was positively correlated with total oxidant status (TOS). Positive correlations were found between TOS and glycated hemoglobin (HbA1c), and between TOS and glycaemia. Negative correlations were identified between: GPx and glycaemia, GPx and HbA1c, and also between GSH and fructosamine. The total antioxidant status was negatively correlated with the respiratory burst. The identified correlations suggest the existence of a complex interplay between diabetes, obesity and oxidative stress.

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection and the caused disease ‑ coronavirus disease 2019 (COVID‑19), has affected so far >6,000,000 people worldwide, with variable grades of severity, and has already inflicted >350,000 deaths. SARS‑CoV‑2 infection seems severely affected by background diseases such as diabetes mellitus and its related complications, that seem to be favoring the most severe manifestations of SARS‑CoV‑2 and, therefore, require special attention in clinical care units. The present literature review focus on addressing several hypotheses explaining why diabetic patients could develop multi‑organ failure in severe acute respiratory syndrome coronavirus (SARS‑CoV) infections. Undoubtedly, as diabetes related complications are present it is expected to emphasize the severity of the COVID‑19. Dermatological complications can occur and worsen in diabetic patients, and diseases such as acanthosis nigricans and psoriasis are prone to more severe manifestations of COVID‑19. Approaches to treat SARS‑CoV‑2 infected patients, based on different solutions i.e. plasma therapy, use of antiviral compounds, development of vaccines or new therapeutic agents are ongoing.

Oxidative stress is associated with scleroderma (systemic sclerosis) and is supposed to favor disease progression by complex effects on the vascular endothelium and on fibroblasts.Plasma oxidative process marker, thiobarbituric acid-reactive substances, and several markers of antioxidant defense capacity (plasma total antioxidant activity, serum albumin, uric acid and glutathione, superoxide dismutase and catalase) were evaluated by spectrophotometric methods using blood samples collected from 23 scleroderma patients and 21 healthy controls.In scleroderma patients, thiobarbituric acid-reactive substances levels (mmol/L plasma) were significantly elevated (29.3+/-5.8) compared with healthy controls (16.6+/-3.1, p<0.001). Total antioxidant activity (mmol Trolox/L) was significantly lower in scleroderma patients than in controls (1.29+/-0.13 vs. 1.55+/-0.23, p<0.001), as well as the antioxidant gap (mmol Trolox/L) (0.57+/-0.18 vs. 0.92+/-0.22, p<0.001). Superoxide dismutase activity (IU/g hemoglobin) was markedly decreased in patients as compared with controls (395+/-184 vs. 659+/-211, p<0.001).Lower plasma total antioxidant activity and plasma antioxidant gap in scleroderma patients show that plasma antioxidant defense is deficient in scleroderma patients. As previous studies on this issue are controversial, the decreased erythrocyte superoxide dismutase activity found in the patients in this study needs further investigation.

Pancreatic beta cells produce and secrete insulin as a response to rises in blood glucose. Despite the advances in understanding glucose-regulated insulin transcription and translation the mechanisms triggering the synthesis of new insulin molecules are still incompletely described. In this report, we identify EDEM1 as a new modulator of insulin synthesis and secretion. In the presence of EDEM1, INS-1E cells secrete significantly more insulin upon glucose stimulation compared to control cells. We found that overexpression of EDEM1 inhibited the IRE1/JNK/c-Jun pathway, leading to an increase in the insulin mRNA level. Similarly, EDEM1 transduced human islets secreted significantly more insulin upon stimulation. Furthermore, EDEM1 improved insulin secretion restoring normoglycemia and glucose tolerance in diabetic rats. We propose EDEM1 as a regulator of the UPR via IRE1/XBP1s and IRE1/JNK/c-Jun signaling cascades and insulin transcription in pancreatic β-cells, supporting EDEM1 as a potential target for the treatment of diabetes.

Background/Aims: Since peritoneal membrane is more compatible and residual renal function better preserved during peritoneal dialysis, we questioned whether the oxidative burden in chronic kidney disease (CKD) is influenced by dialysis modality. Methods: 49 stable CKD patients, 17 on continuous ambulatory peritoneal dialysis (CAPD), 16 on hemodialysis (HD), and 16 non-dialyzed, and 13 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS; nmol/g protein), serum total antioxidant activity (TAA), total plasma-free thiols (Pt-SH; µmol/g protein), albumin and uric acid were measured by spectrophotometry. Serum residual antioxidant activity (RAA) was calculated. Results: TBARS were higher in HD (78.3 ± 20.3) versus both non-dialyzed (53.1 ± 27.9, p = 0.007) and CAPD groups (58.3 ± 19.8, p = 0.008). Pt-SH was reduced in CKD patients, but showed comparable values between dialysis groups. TAA and RAA were similarly increased in HD and CAPD patients than in the other two groups. Conclusion: Oxidative stress occurs in all CKD patients and worsens as renal function declines. Lipid peroxidation seems more augmented during chronic HD as compared to CAPD, but the plasma antioxidant status did not differ between the investigated dialysis methods. Therefore, dialysis modality appears to influence lipid peroxidation without changing the extracellular antioxidant defense of CKD patients.