Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Diabetes mellitus (DM) is a major global health issue, with glycated hemoglobin levels serving as the gold standard for evaluating glucose level control in DM patients. However, it has limitations in reflecting glucose oscillations (i.e. glycemic variability, GV). Increasing evidence suggests that GV is closely related to the progression of diabetes complications and patient prognosis. As people realize the importance of avoiding hypoglycemia while achieving target glycated hemoglobin levels in treatment, the clinical significance of GV becomes more obvious. This article systematically reviewed the concept and connotation of GV, summarized the latest research on its role in the complications of diabetes, and revealed the biochemical and pathophysiological abnormalities caused by excessive glycemic oscillation, aiming to provide a theoretical basis for the risk warning and early intervention of DM patients.
Humans ; Blood Glucose/metabolism* ; Diabetes Complications/physiopathology* ; Glycated Hemoglobin/metabolism* ; Hypoglycemia ; Diabetes Mellitus, Type 2/complications*

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in treating diabetic gastroparesis (DGP) by inhibiting the activation of Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and pyroptosis mediated via NLRP3/cysteinyl aspartate specific proteinase-1 (caspase-1)/gasdermin D (GSDMD) signaling pathway. METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups including the control, DGP model, EA, and MCC950 groups. The DGP model was established by a one-time high-dose intraperitoneal injection of 2% streptozotocin and a high-glucose and high-fat diet for 8 weeks. EA intervention was conducted at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) with sparse-dense wave for 15 min, and was administered for 3 courses of 5 days. After intervention, the blood glucose, urine glucose, gastric emptying, and intestinal propulsive rate were observed. Besides, HE staining was used to observe histopathological changes in gastric antrum tissues, and TUNEL staining was utilized to detect DNA damage. Protein expression levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, caspase-1 and GSDMD were measured by Western blot. Immunofluorescence staining was employed to assess the activity of GSDMD-N. Lactate dehydrogenase (LDH) levels were detected by using a biochemical kit. RESULTS: DGP rats showed persistent hyperglycemia and a significant decrease in gastrointestinal motility (P<0.05 or P<0.01), accompanied by pathological damage in their gastric antrum tissues. Cellular DNA was obviously damaged, and the expressions of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD proteins were significantly elevated, along with enhanced fluorescence signals of GSDMD-N and increased LDH release (P<0.01). EA mitigated hyperglycemia, improved gastrointestinal motility in DGP rats and alleviated their pathological injury (P<0.05). Furthermore, EA reduced cellular DNA damage, lowered the protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD, suppressed GSDMD-N activity, and decreased LDH release (P<0.05 or P<0.01), demonstrating effects comparable to MCC950. CONCLUSION EA promotes gastrointestinal motility and repairs the pathological damage in DGP rats, and its mechanism may be related to the inhibition of NLRP3 inflammasome and pyroptosis mediated by NLRP3/caspase-1/GSDMD pathway.
Animals ; Electroacupuncture ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Gastroparesis/physiopathology* ; Signal Transduction ; Male ; Diabetes Mellitus, Experimental/physiopathology* ; Phosphate-Binding Proteins/metabolism* ; Gastrointestinal Motility ; Rats ; Intracellular Signaling Peptides and Proteins/metabolism* ; Diabetes Complications/physiopathology* ; Gasdermins

Fetuin-B (FETUB) is a glycoprotein mainly synthesized and secreted by the liver. It is involved in many physiological and pathological processes including glucose metabolism, inflammatory response, nonalcoholic fatty liver disease, myocardial infarction, tumor and so on. In recent years, FETUB has also been confirmed to play roles in the female reproductive system. FETUB may affect follicular development and play an important role in in vivo and in vitro fertilization. In addition, serum FETUB level is elevated significantly during pregnancy and labor. FETUB expression is changed in a variety of reproductive diseases (polycystic ovary syndrome, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy). In this review, we summarize FETUB related studies in female reproduction, and focus on the roles of FETUB in female reproductive physiology and pathology, in order to provide information for the pathogenesis of reproductive disorders.
Humans ; Female ; Pregnancy ; Polycystic Ovary Syndrome/physiopathology* ; Fetuin-B/physiology* ; Pregnancy Complications/metabolism* ; Animals ; Diabetes, Gestational/physiopathology* ; Cholestasis, Intrahepatic/metabolism* ; Reproduction/physiology* ; Ovarian Follicle/physiology*

BACKGROUND: Weight gain during pregnancy reflects the mother's nutritional status. However, it may be affected by nutritional therapy and exercise interventions used to control blood sugar in gestational diabetes mellitus (GDM). This study aimed to evaluate weight gain during gestation and pregnancy outcomes among women with GDM. METHODS: A retrospective study involving 1523 women with GDM was conducted between July 2013 and July 2016. Demographic data, gestational weight gain (GWG), blood glucose, glycated-hemoglobin level, and maternal and fetal outcomes were extracted from medical records. Relationships between GWG and pregnancy outcomes were investigated using multivariate logistic regression. RESULTS: In total, 451 (29.6%) women showed insufficient GWG and 484 (31.8%) showed excessive GWG. Excessive GWG was independently associated with macrosomia (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.50-3.52, P < 0.001), large for gestational age (aOR 2.06, 95% CI 1.44-2.93, P < 0.001), small for gestational age (aOR 0.49, 95% CI 0.25-0.97, P = 0.040), neonatal hypoglycemia (aOR 3.80, 95% CI 1.20-12.00, P = 0.023), preterm birth (aOR 0.45, 95% CI 0.21-0.96, P = 0.040), and cesarean delivery (aOR 1.45, 95% CI 1.13-1.87, P = 0.004). Insufficient GWG increased the incidence of preterm birth (aOR 3.53, 95% CI 1.96-6.37, P < 0.001). CONCLUSIONS Both excessive and insufficient weight gain require attention in women with GDM. Nutritional therapy and exercise interventions to control blood glucose should also be used to control reasonable weight gain during pregnancy to decrease adverse pregnancy outcomes.
Adult ; Body Mass Index ; Diabetes, Gestational ; pathology ; physiopathology ; Female ; Fetal Macrosomia ; pathology ; physiopathology ; Gestational Age ; Humans ; Logistic Models ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Retrospective Studies ; Weight Gain ; physiology

Obstructive sleep apnoea (OSA) and Type 2 diabetes mellitus (T2DM) are common diseases. The global prevalence of OSA is between 2% and 7% in general population cohorts. The worldwide prevalence of T2DM among adults (aged 20-79 years) was estimated to be 6.4%. The concurrent presence of OSA and T2DM can be expected in the same patient, given their high prevalence and similar predisposition. We reviewed the overlapping pathophysiology of OSA and T2DM in this article.
Adult ; Aged ; Continuous Positive Airway Pressure ; Diabetes Mellitus, Type 2 ; complications ; epidemiology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; complications ; epidemiology ; physiopathology ; therapy ; Young Adult

The incidence and mortality rates of diabetes with cardiovascular complications are continually rising, and diabetic cardiovascular disease is becoming a major public health issue that threatens human health. Acute endothelial dysfunction and chronic cellular damage caused by diabetes are important risk factors for diabetic cardiovascular disease and related mortality. Adiponectin is an adipocyte-derived molecule with significant cytoprotective effects, including the protection against diabetes-induced vascular endothelial injury. Here we review the mechanisms of adiponectin protective effects on acute vascular endothelial dysfunction and chronic structural damage induced by diabetes.
Adiponectin ; physiology ; Cardiovascular Diseases ; complications ; Diabetes Mellitus ; pathology ; Endothelium, Vascular ; physiopathology ; Humans

Penile erectile dysfunction (ED) is ascribed to the contraction-relaxation imbalance of smooth muscle cells (SMC), the weakening of their diastolic function and the strengthening of their systolic function. The contraction-related signaling pathways, cell membrane ion channels and SMC phenotypes all participate in the regulation of their contraction and its malfunction may cause a variety of SMC-related diseases. The signaling pathways RhoA/Rock and Raf/MEK/ERK1/2 interact with each other, suppressing the expression of the RhoA protein or reducing the level of Rock2 phosphorylation, which may contribute to the treatment of ED. The poor performance of VDCC or TRPC is reckoned to be an important cause of hypertension- or diabetes-related ED. The expressions of CaV1.2, TRPC1 and TRPC4 can be upregulated by many pathological factors, which may enhance the contraction of SMCs. The pathogenesis of ED may be associated with the differentiation of the phenotypes corpus cavernosal SMCs. This review focuses on the recent progress in the studies of the relationship between SMC contraction and ED.
Animals ; Diabetes Complications ; etiology ; physiopathology ; Erectile Dysfunction ; etiology ; physiopathology ; Humans ; Hypertension ; complications ; Ion Channels ; metabolism ; Male ; Mitogen-Activated Protein Kinase 3 ; Muscle Contraction ; physiology ; Myocytes, Smooth Muscle ; physiology ; Penile Erection ; physiology ; Phosphorylation ; Signal Transduction ; physiology

BACKGROUNDHyperglycemia is associated with adverse pregnancy outcomes. However, the relationships between them remain ambiguous. This study aimed to analyze the effect of different oral glucose tolerance test (OGTT) results on adverse perinatal outcomes.

METHODSThis retrospective cohort study included data from 15 hospitals in Beijing from June 20, 2013 to November 30, 2013. Women with gestational diabetes mellitus (GDM) were categorized according to the number and distribution of abnormal OGTT values, and the characteristics of adverse pregnancy outcomes were evaluated. Chi-square test and logistic regression analysis were used to determine the associations.

RESULTSIn total, 14,741 pregnant women were included in the study population, 2927 (19.86%) of whom had GDM. As the number of hyperglycemic values in the OGTT increased, the risk of cesarean delivery, preterm births, large-for-gestational age (LGA), macrosomia, and neonatal complications significantly increased. Fasting hyperglycemia had clear associations with macrosomia (odds ratios [OR s]:1.84, 95% confidence intervals [CI s]: 1.39-2.42,P < 0.001), LGA (OR: 1.70, 95% CI: 1.29-2.25,P < 0.001), and cesarean delivery (OR: 1.33, 95% CI: 1.15-1.55,P < 0.001). The associations were stronger as fasting glucose increased. GDM diagnosed by hyperglycemia at OGTT-2 h was more likely to lead to preterm birth (OR: 1.50, 95% CI: 1.11-2.03,P < 0.01).

CONCLUSIONSVarious characteristics of OGTTs are associated with different adverse outcomes. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT characteristics is needed.

Birth Weight ; physiology ; Blood Glucose ; metabolism ; Body Mass Index ; Cesarean Section ; Chi-Square Distribution ; Diabetes, Gestational ; blood ; physiopathology ; Female ; Fetal Macrosomia ; blood ; physiopathology ; Glucose Tolerance Test ; methods ; Humans ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Premature Birth ; blood ; physiopathology ; Retrospective Studies

OBJECTIVETo investigate the effect of Musa sapientum L. (MS) bark juice in diabetic gastroparesis and its effect on pharmacokinetic of metformin (MET).

METHODSDiabetes was induced in rats by administering alloxan (120 mg/kg) saline solution and maintained for 8 week. All the 18 Sprague-Dawley rats were divided into three groups (n =6 in each group): normal control, diabetic control and MS bark juice. Assessment of diabetes was done by glucose oxidase-peroxidase method on the 3rd day of alloxan administration. The effects of MS bark juice (100 mL/kg) on gastric emptying time, intestinal transit time, contractility of fundus and pylorus as well as gastric acid secretion in chronic diabetic rats were observed after 8 weeks of alloxan administration. The effect of MS bark juice on the pharmacokinetic of orally administered single dose of MET (350 mg/kg) was evaluated on the 57th day of protocol. Any drugs that may reduce the blood glucose level or influence the fibrinolytic system were not used in this study.

RESULTSThe MS bark juice significantly reduced the blood glucose level in the diabetic rats (P<0.01). There was significant decrease in the pylorus motility and increase in the gastric emptying time, intestinal transit time, contractility of fundus, gastric acid secretion in the MS bark juice treated group (P<0.01). There was significant decrease in the time at which drug at a maximum concentration, half life of drug and increase in the maximum concentration of drug in the plasma of MET in MS bark juice treated group as compared to diabetic control group (P<0.01).

CONCLUSIONMS bark juice effectively manages diabetic gastroparesis and thereby improves the bioavailabilty of MET when administered with MS bark juice.

Alloxan ; Animals ; Blood Glucose ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; blood ; complications ; drug therapy ; physiopathology ; Gastroparesis ; blood ; complications ; drug therapy ; physiopathology ; Male ; Metformin ; blood ; pharmacokinetics ; therapeutic use ; Musa ; chemistry ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Sprague-Dawley