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Introduction Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1‐Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. Methods In a case‐control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR‐RFLP method, the Keap1 (rs11085735) variants were identified. Results Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. Conclusions Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested., Studying 400 T2DM patients without complication indicated: In T2DM patients without complication, the GPx and TAC levels decreased and the MDA level elevated. T2DM with neuropathy had lower levels of GSH, GPx, and TAC and higher levels of TOS, MDA, and OSI and a higher frequency of Keap1 AA genotype. T2DM with retinopathy had lower levels of GSH and GPx and a higher level of MDA. Obesity‐enhanced oxidative stress was associated with lower GPx activity and higher TOS and Keap1 AA genotype correlated with lower GPx activity. Reduced antioxidant system and Keap1 variants are involved in the pathogenesis of T2DM and its complications of neuropathy and retinopathy.

OBJECTIVES: Diabetic neuropathy (DNP) is a widespread and debilitating complication with complex pathophysiology that is caused by neuronal dysfunction in diabetic patients. Conventional therapeutics for DNP are quite challenging due to their serious adverse effects. Hence, there is a need to investigate novel effective and safe options. The novelty of the present study was to provide available therapeutic approaches, emerging molecular mechanisms, signaling pathways and future directions of DNP as well as polyphenols’ effect, which accordingly, give new insights for paving the way for novel treatments in DNP. EVIDENCE ACQUISITION: A comprehensive review was done in electronic databases including Medline, PubMed, Web of Science, Scopus, national database (Irandoc and SID), and related articles regarding metabolic pathways on the pathogenesis of DNP as well as the polyphenols’ effect. The keywords “diabetic neuropathy” and “diabetes mellitus” in the title/abstract and “polyphenol” in the whole text were used. Data were collected from inception until May 2019. RESULTS: DNP complications is mostly related to a poor glycemic control and metabolic imbalances mainly inflammation and oxidative stress. Several signaling and molecular pathways play key roles in the pathogenesis and progression of DNP. Among natural entities, polyphenols are suggested as multi-target alternatives affecting most of these pathogenesis mechanisms in DNP. CONCLUSION: The findings revealed novel pathogenicity signaling pathways of DNP and affirmed the auspicious role of polyphenols to tackle these destructive pathways in order to prevent, manage, and treat various diseases. [Figure: see text]

Sleep disturbances have been shown to be associated with adverse health outcomes including diabetes mellitus (DM), hypertension, and obesity. However, little is known about the relationship between sleep duration and diabetes complications. The present cross-sectional study aimed to examine the association between sleep duration and nephropathy in a population of type 2 DM patients. Diabetic patients aged ≥ 18 years who visited two outpatient clinics in Kermanshah from February 2014 to February 2015 entered the study. Demographic, anthropometric, and biochemical data, as well as information on sleep duration of participants within the past 4 weeks, were collected by an interviewer. Patients with estimated glomerular filtration rate (eGFR) ≤ 60 ml/24 h were excluded from the study. Proteinuria was defined as excretion of more than 150 mg protein in 24-h urine. Differences in urine protein and related variables were examined between four sleep duration groups (≤ 5, 6, 7, and ≥ 8 h). Linear and logistic regression analyses were employed to assess the association between sleep duration and diabetic nephropathy. Four hundred thirty-two patients (63.8% female) with a mean age of 54.68 ± 9.98 years were analyzed. There were statistically significant differences in age, body mass index, waist circumference, DM duration, HbA1C, total cholesterol, HDL cholesterol, triglyceride, uric acid, and urine protein between sleep duration groups. While adjusted linear regression showed no association between sleep duration and urine protein (p = 0.300), multivariable logistic regression revealed male gender, increased HbA1C, shorter sleep duration, increased DM duration, lower eGFR, higher DBP, decreased HDL-C, and higher uric acid levels to be statistically associated with proteinuria. Short sleep duration is adversely associated with proteinuria in type 2 DM patients with normal and near-normal kidney function.

Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus.All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019.Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications.The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications. Graphical abstract.

We summarized 16 controlled studies and evaluated the correlation of resveratrol supplementation with metabolic parameters such as the body weight, waist circumference (WC), systolic blood pressure (sbp), HDL, total cholesterol, triglyceride and glucose levels. This meta-analysis was carried out to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients. PubMed, Scopus, Cochrane and Google Scholar were searched from inception to December 2018 using relevant keywords. All articles were independently reviewed by two authors using predetermined selection criteria. We have selected the studies that investigated the effects of resveratrol on metabolic parameters. Of 16 studies, 10 were performed on human subjects, and in 6 studies animal models were used. Standard mean difference (SMD) with 95% confidence interval were determined using Der Simonian and Laird random-effects modeling, when there was a significant heterogeneity between studies. Funnel plot and Egger's test were conducted to examine the risk of publication bias. Pooled effect sizes in human studies indicated a significant impact of resveratrol supplementation on glucose level [-1.73 (-2.99, -0.47); p = 0.007)] and WC [-1.73 (-2.79, -0.67); p = 0.001] compared with the control group. Also combining the results of studies on rat samples (n = 6), indicated significant effect of resveratrol on decreasing weight [-22.95 (-44.74, -1.17); p = 0.04], TGs [-6.76 (-11.10, -2.42); p = 0.001], sbp [-7.30 (-12.48, -2.13); p = 0.006], and it can influence significantly on increasing HDL level (4.75 (1.87, 7.63); p = 0.001). However, resveratrol was not significantly effective on total cholesterol in both samples. The results of subgroup analysis of human studies showed that resveratrol has significant effect on metabolic parameters (glucose level and WC) at the dosage of > 500 mg and with long-term interventions ≥ 10 weeks. Administration of resveratrol can meaningfully reduce the BW, WC, TGs, and glucose level, also it can increase HDL, but not total cholesterol.

Background and aims: Diabetes mellitus is a chronic heterogenic disease characterized by the deregulation of the metabolism of insulin and glucose. The aim of this review has been to evaluate the e...