Chronic Microvascular Complications Research Articles

Evaluation of Chitotriosidase and Neopterin as Biomarkers of Microvascular Complications in Patients with Type 1 Diabetes Mellitus.

The chronic complications of diabetes mellitus (DM) are accompanied by inflammatory manifestations. Our study aimed to evaluate a possible association between the inflammatory status (reflected by serum chitotriosidase and neopterin) and the timely evolution and occurrence of chronic microvascular complications in patients with type 1 DM. This observational, cross-sectional study included 82 type 1 DM patients from the Centre for Diabetes, Nutrition and Metabolic Diseases, Cluj-Napoca, Romania. Our results demonstrated a link between the extent of inflammation, evaluated by the enzymatic activity of circulating chitotriosidase, and the onset of microvascular complications, especially diabetic neuropathy and retinopathy. Chitotriosidase enzymatic activity showed an ascending evolution over time. In non-smoking patients, the increase in chitotriosidase activity was correlated with the extent of microalbuminuria and the decline of glomerular filtration rate, while in smokers, only the presence of a positive correlation between chitotriosidase activity and disease progression was noticed. According to our results, the time span between the moment of diagnosis and the onset of microvascular complications was longer in non-smokers than in smokers. These results also imply that increased chitotriosidase activity may be a predictor of endothelial dysfunction in type 1 DM.

Role of Vitamin D and uric acid levels in serum to identify the risk of developing macular edema - A case-control study

Background: Diabetes mellitus is more prevalent in India and also an emerging epidemic across the world. Uncontrolled diabetes mellitus is associated with chronic microvascular complications including diabetic retinopathy. In patients with diabetic retinopathy, macular edema is one of the common causes of vision loss. Vitamin D has inhibitory role against inflammation and angiogenesis and uric acid are found to be associated with microvascular damage. Aim and Objective: Our study was aimed to check the Vitamin D and uric acid levels in serum and its association with patients with macular edema and compare them with age-matched controls. Materials and Methods: It is an observational case–control study. The study group consists of a total of 100 subjects. Among them, there were 50 patients in Group1 and 50 controls (selective age matched) in Group 2 enrolled into the study. Group 1 cases have diagnosed cases of macular edema including both males and females. After taking informed consent, detailed history taken and thorough ophthalmological examination was done, patients in Group 1 underwent optical coherence tomography scan to assess macular edema to detect central retinal thickness. Later, they were advised for Vitamin D and uric acid levels in serum in an advanced biochemistry laboratory. Data were expressed in mean ± SD and Student’s t-test was applied to compare groups. P ≤ 0.05 was considered statistically significant. Results: Uric acid levels were raised and Vitamin D levels were reduced in serum of patients with macular edema when compared to the age-matched controls and were statistically significant (P < 0.001). Conclusion: Decreased Vitamin D levels and increased uric acid levels can be a risk factor for occurrence of macular edema in adults. Hence, serum Vitamin D levels and uric acid levels to be investigated for all patients with macular edema. It remains to be determined whether normalizing the serum Vitamin D and serum uric acid levels could improve visual acuity and prevent the occurrence of macular edema in the other eye.

Quantitative assessment of renal damage in rhesus monkeys with diabetic nephropathy using contrast-enhanced ultrasound.

BackgroundDiabetic nephropathy (DN) is a common chronic microvascular complication of diabetes. Noninvasive diagnosis of DN is difficult. Contrast-enhanced ultrasound (CEUS), as a functional imaging method, provides noninvasive real-time images and quantitative assessment of renal microvascular perfusion. This study investigated the efficacy of CEUS in discriminating between DN and normal kidneys in rhesus monkeys.MethodsA total of 12 male rhesus monkeys (DN model group, n=6; normal control group, n=6) were included in this study. The following parameters were evaluated: (I) blood biochemistry; (II) CEUS; and (III) ultrasound-guided renal biopsy.ResultsPathological and biochemical results showed that all subjects in the lesion group had serious renal damage. There were significant differences in the CEUS parameters, including the area under the curve, the time from peak to one half, and peak intensity between the lesion group and the normal group. The time to peak was slightly delayed in the lesion group. There was no significant difference in the rise time between the two groups.ConclusionsAlthough the precise CEUS parameters that may best predict renal damage still require systematic evaluation, the results of these animal studies suggest that CEUS may be used as a supplemental tool in diagnosing renal damage in rhesus monkeys with DN. We hope these findings can provide insights for the application of CEUS in DN.

Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice.

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player.Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies.Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone.Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

Impact of licochalcone A on the progression of diabetic nephropathy in type 2 diabetes mellitus of C57BL/6 mice.

Diabetic nephropathy (DN) is the most common chronic microvascular complication of diabetes. Therefore, it is of great significance to effectively prevent and treat DN. Licochalcone A (LicA) is a flavonoid found in licorice; previous studies have shown that LicA can reduce blood glucose, blood lipids and improve insulin resistance. There has been no research on whether LicA can prevent and treat DN. In this study, an animal model of type 2 diabetes mellitus (T2DM) mice induced by high fat diet/streptozotocin was established, and the intervention of LicA was applied to investigate the protective effect of LicA on the kidneys of DN mice. After 4 weeks of intervention, LicA could effectively reduce blood glucose and alleviate the phenomenon of weight loss in mice. Meanwhile, the levels of MDA, SOD and GSH-Px in the kidney tissue and serum were recovered to different degrees. Besides, LicA decreased the levels of TC, TG and LDL-C in the kidney tissue and increased the level of HDL-C in the kidney tissue. The 24 h urinary protein, blood urea nitrogen (BUN) and serum creatinine (SCr) levels of mice in the treatment group of LicA were significantly lower than those in the model group. Furthermore, HE staining, PAS staining and Masson staining indicated that LicA improved the pathological damage of kidneys, and the kidney index of mice also decreased. Western blotting results indicated that LicA could significantly down-regulate the protein expression of AGEs/RAGE, TGF-β1, HIF-1α and GLUT1, and up-regulate the protein expression of Nrf2. It provides a theoretical basis for the further development and utilization of LicA.

Protective Effect of Yi Shen Pai Du Formula against Diabetic Kidney Injury via Inhibition of Oxidative Stress, Inflammation, and Epithelial-to-Mesenchymal Transition in db/db Mice.

Objective Diabetic kidney disease (DKD) is one of the most common chronic microvascular complications of diabetes; however, there remains a lack of effective therapeutic strategies. Yi Shen Pai Du Formula (YSPDF), a traditional Chinese medicine preparation, has been clinically used in treating chronic kidney disease (CKD) for more than 20 years. However, whether YSPDF has a therapeutic effect on DKD has not been studied. Methods This study was conducted to investigate the effect of YSPDF administration on db/db mice, a model of type 2 diabetes that develops DKD, and reveal its underlying mechanism of action through a high glucose- (HG-) induced renal injury cell model. Results We found that YSPDF significantly improved numerous biochemical parameters (fasting blood glucose, serum creatinine, blood urea nitrogen, 24 h urine total protein, total cholesterol, and total triglycerides) and ameliorated the abnormal histology and fibrosis of renal tissue. Moreover, the status of oxidative stress and levels of inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) were markedly inhibited by YSPDF treatment. YSPDF treatment significantly mitigated renal fibrosis, with evidence suggesting that this was by inhibiting epithelial-to-mesenchymal transition (EMT) via suppression of the TGF-β1/Smad pathway. Interestingly, the expression of Nrf2, HO-1, and NQO1, proteins known to be associated with oxidative stress, were significantly increased upon administration of YSPDF. The levels of NLRP3 inflammasome proteins, including NLRP3, ASC, caspase-1, and cleaved caspase-1 were decreased in the YSPDF-treated group. Cell experiments showed that YSPDF inhibited EMT and the NLRP3 inflammasome in HG-exposed HK-2 cells, possibly via activation of Nrf2. Conclusion Our study indicates that YSPDF may ameliorate renal damage in db/db mice via inhibition of oxidative stress, inflammation, and EMT, with the mechanism potentially being related to the activation of the Nrf2 pathway.

Chronic Microvascular Complications in Prediabetic States-An Overview.

A prediabetic state is a major risk factor for the development of diabetes, and, because of an identical pathophysiological background of both conditions, their prevalence increases parallelly and equally fast. Long-term hyperglycemia is the main cause inducing chronic complications of diabetes, yet the range of glucose levels at which they start has not been yet unequivocally determined. The current data show that chronic microvascular complications of diabetes can be observed in patients with abnormal glucose metabolism in whom glycaemia is higher than optimal but below diagnostic criteria for diabetes. Prediabetes is a heterogenous nosological unit in which particular types are differently characterized and show different correlations with particular kinds of complications. Analysis of the latest research results shows the need to continue studies in a larger population and can imply the need to verify the currently employed criteria of diagnosing diabetes and chronic complications of diabetes in people with prediabetes.

Acupuncture attenuates the development of diabetic peripheral neuralgia by regulating P2X4 expression and inflammation in rat spinal microglia

Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication of diabetes. The purpose of this study is to find the underlying mechanism for the effects of acupuncture in DPN rats. Rats were rendered diabetic with a single injection of 35 mg/kg streptozotocin (STZ). These STZ-diabetic rats were treated with acupuncture for 20 min once daily. The therapeutic efficacy of acupuncture was assessed using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) evaluations. After 14 days treatment, acupuncture markedly reduced the pathological injury in STZ-diabetic rats. Moreover, it significantly down-regulated P2X4 and OX42 expression along with the reduced levels of inflammatory factors (CXCR3, TNF-α, IL-1β, IL-6), GSP and lipid metabolisms in the spinal cord of the DPN rats. Acupuncture could relieve DPN in rats by regulating P2X4 expression and inflammation in spinal microglia.

Ligustilide alleviates podocyte injury via suppressing the SIRT1/NF-κB signaling pathways in rats with diabetic nephropathy.

BackgroundDiabetic nephropathy (DN) is one of the common chronic microvascular complications of diabetes, and podocyte injury and dysfunction are strictly related to the pathogenesis of DN. Studies have shown that ligustilide (LIG) has anti-inflammatory, antioxidant, and anti-apoptotic activities. This study was designed to investigate the therapeutic effect of LIG in DN rats and their mechanisms.MethodsDN rat models (n=10) were induced by streptozotocin (STZ) combined with a high-fat diet. Rats in the LIG group were intragastrically administered with LIG daily for eight weeks, and animals in the positive control group were treated with Losartan potassium. The body weight and blood glucose were checked weekly during the treatment. The pathological changes of kidney tissue were observed with hematoxylin and eosin (HE) staining. Blood lipid profiles and renal function-related markers, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), and serum creatinine (Scr) were monitored using a biochemical analyzer. The protein expression of nephrin was determined by immunohistochemistry and Western blotting. Finally, Western blot was used to determine the protein expression of Sirtuin 1 (SIRT1) and nuclear factor-kappa B (NF-κB).ResultsCompared with the healthy control group, rats in the DN group have slower weight gain, increased blood sugar level, renal lesions, and impaired renal function, along with decreased nephrin expression, abnormally activated NF-κB, and inhibited SIRT1 protein expression. All the above conditions were improved after intervention with either losartan potassium or LIG.ConclusionsLIG attenuates podocyte injury by regulating the SIRT1/NF-κB signaling pathway and thereby exerts its protective effect on renal function in DN rats.

Emotional distress in patients with type 1 diabetes mellitus.

This study aimed to analyze the association between emotional distress and glycated hemoglobin (HbA1c) values in adolescents and young adults with type 1 diabetes mellitus (T1DM), with respect to dental anxiety, microvascular diabetes chronic complications, demographic conditions. The cross-sectional study design included 100 adolescents and young adults with T1DM, from regional diabetes reference center. The clinical and laboratory data were obtained from medical records. Distress and dental anxiety scales were produced from questionnaires that were validated for emotional distress (DDS) and dental anxiety (Corah Scale). Multiple analyses estimated odds ratios and their respective 95% confidence intervals using a binary logistic regression model (P<.05). The mean participants age was 20.7±5.5 years, and 52% were female. Of the patients, 19% presented with chronic microvascular diabetes complications (nephropathy, retinopathy, neuropathy). Regarding the distress scale, 53% of the patients presented with high DDS and 83% had little to slight anxiety with dental procedures. There were statistically significant differences when variables were adjusted in the model, such as that of microvascular diabetes chronic complications and female gender with emotional distress. Our results showed that female sex and microvascular diabetes chronic complications are associated with greater emotional distress in patients with T1DM.

UPLC-MS-based urine nontargeted metabolic profiling identifies dysregulation of pantothenate and CoA biosynthesis pathway in diabetic kidney disease

AimsDiabetic kidney disease (DKD) is a major prevalent chronic microvascular complication of type 2 diabetes (T2D). However, the present diagnostic indicators have limitations in the early diagnosis of DKD. This study concentrated on the sensitive and specific biomarkers in early diagnosis of DKD by metabolomics. Materials and methodsIn this cross-sectional study, we performed a UPLC-MS based nontargeted metabolomics assay to profile the urinary metabolites in patients with DKD. Principal Component Analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) were used for screening out the metabolomic variables. Key findingsA total of 147 urinary metabolites were identified and 5 metabolic pathways were correlated with DKD pathophysiology. Pantothenate and coenzyme A biosynthesis pathway alteration was found the most prominent in DKD subjects. 4 metabolites, including dihydrouracil, ureidopropionic acid, pantothenic acid (PA), and adenosine 3′,5′-diphosphate involved in pantothenate and CoA biosynthesis were significantly down-regulated. SignificanceOur finding indicates that PA would be served as a novel predictive biomarker associated with DKD development and progression. Furthermore, our results provide a promising prospect that PA and CoA biosynthesis pathway can be potential therapeutic targets for DKD treatment.

BUERGER ALLEN EXERCISE REVIEW ON PERIPHERAL CIRCULATION IN DIABETES MELLITUS PATIENTS: A LITERATURE REVIEW

Introduction : Diabetes mellitus is metabolic dysfunction that increasing the number of blood glucose with enhancement incidences. Increasing blood glucose levels for a long time causes chronic microvascular and neuropathic complications, and impaired peripheral circulation of the lower extremities. The actions that can be done in form of leg exercise, such as Buerger Allen exercise. Objectives: the study aim is to find out the effect of the Buerger Allen exercise on peripheral circulation of the lower extremity in patients with diabetes mellitus. Method: descriptive qualitative design with a literature review approach. The databases used are PubMed, Pro-Quest, DOAJ, and Google Scholar. Result: 86 articles were found. After the identification, screening, and eligibility process, 12 articles were obtained . The indicators are ABI values (9 articles), HbO2 and HbT concentrations (2 articles), a nd capillary refill time (1 article). Conclusion : Buerger Allen exercise significantly increases the level of peripheral perfusion pressure due to postural changes, modulation of gravity, and the application of muscle pump that increases the ABI values, increases HbO2 and HbT concentrations, and decreases the capillary refill time. Further study can examine the frequency and duration that is most appropriate in providing intervention, comparing Buerger Allen exercise with other foot exercise methods, and using a randomized control trial research method.

Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice.

BACKGROUNDType 1 diabetes (T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity. The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2 (SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIMTo determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODSThe SGLT2 inhibitors empagliflozin or dapagliflozin (25 mg/kg/d) or vehicle dimethylsulfoxide (DMSO) were administered to C57BL/6J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid (SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTSDue to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57BL/6J and Kimba mice. Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin. In non-diabetic C57BL/6J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSIONThe inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1D and its complications.

Pyrroloquinoline Quinone Inhibits Oxidative Stress in Rats with Diabetic Nephropathy.

BackgroundDiabetic nephropathy (DN) is one of the chronic microvascular complications of diabetes. This study focused on the protective effects of pyrroloquinoline quinone (PQQ) on oxidative stress (OS) in DN.Material/MethodsThirty Sprague Dawley rats were randomly selected for this study; 10 rats were randomly selected as the control group. The other 20 rats were established for the DN model. After establishment of the successful model, the DN model rats were randomly divided into a DN group and a PQQ group. The PQQ group was fed with a PQQ diet. Blood urea nitrogen (BUN), serum creatinine (SCr), and blood glucose levels were measured in each group, and OS-related protein expression and AMPK pathway were detected by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). At the same time, we constructed a DN model by culturing NRK-52E cells with high glucose to detect the molecular mechanisms.ResultsThe kidney function of the DN group was significantly decreased, SCr and BUN levels were significantly increased, and the renal structure under the microscope was disordered, and interstitial edema was obvious. The expression of SOD1, SOD2, GPX1, and GPX3 were significantly decreased, and the level of reactive oxygen species (ROS) was significantly increased. PQQ treatment can effectively alleviate renal function, improve structural damage, and inhibit OS. In vivo, PQQ can effectively inhibit high glucose-induced OS damage and activate the AMPK/FOXO3a signaling pathway.ConclusionsPQQ improves renal structural damage and functional damage, and protects kidney cells in DN by inhibiting OS, which may be related to activating the AMPK/FOXO3a pathway.

Correlation between High Serum Uric Acid Levels with Occurrence of Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes

Background: Diabetic Peripheral Neuropathy is a chronic microvascular complication of type 2 diabetes mellitus (T2DM) leads to increased risk of foot ulceration and morbidity.The increased serum uric acid (SUA) levels have been linked to macro vascular disease in T2DM. We found that the correlation between SUA levels and diabetic peripheral neuropathy has not been investigated. Objective: To determine the correlation between high serum uric acid levels and diabetic peripheral neuropathy. Method: The case-control design was used in this study and the sampling was done consecutively by following the inclusion and the exclusion criteria. The diabetic peripheral neuropathy was evaluated using EMNG and the serum were taken for uric acid levels examination. Chi square test was used for data analysis. Results: Thirty subjects were enrolled and divided into an experimental group of 15 subjects and a control group of 15 subjects as well. We found that the diabetic peripheral neuropathy did not show a significant correlation with high serum uric acid levels, p=0,136 and OR 3,143 (CI 95% 0,681-14,503). Conclusion: High serum uric acid levels did not have correlation with diabetic peripheral neuropathy.

Albumin excretion rate among patients with diabetic retinopathy.

Background:Chronic microvascular complications consist of diabetic nephropathy (DN), diabetic retinopathy (DR), and diabetic neuropathy. Diabetic nephropathy is assessed through albuminuria, and diabetic retinopathy is assessed through fundoscopy. Several studies have assessed the albuminuria in diabetic retinopathy but have found inconclusive results. This study aims to investigate the albumin excretion rate in patients with diabetic retinopathy.Methods:A cross sectional design was applied in this study. The diagnosis of type 2 diabetes mellitus was determined based on the anamnesis and laboratory examinations. The study was conducted at Dr. Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital in Makassar during November 2018 until April 2019. The stages of diabetic retinopathy were based on funduscopic examinations. In addition, the blood pressure, BMI, albumin excretion rate, lipid profile, and HbA1C were also examined. Chi Square and Kappa tests were performed in the statistical analysis.Results:120 subjects with type 2 diabetes mellitus were observed. Of the total subjects, the number of females within the age of 36-79 years made up the biggest fraction. There was a significant relation between hypertension comorbidity with the albumin excretion rate and grading diabetic retinopathy where the A3 and proliferative diabetic retinopathy (PDR) percentages were higher in the hypertension group at 68.8% and 54.5%. There was also a significant correlation between incidence of albuminuria with diabetic retinopathy. Particularly, proliferative diabetic retinopathy (PDR) remained associated with albuminuria, while non-proliferative diabetic retinopathy (NPDR) was related to non-albuminuria.Conclusion:Albuminuria incidence confirms association with diabetic retinopathy grading.

Protective effect of vanillin on diabetic nephropathy by decreasing advanced glycation end products in rats

AimsDiabetic nephropathy (DN) is a common chronic microvascular complication of both types of diabetes mellitus, which leads to renal dysfunction and subsequent need of dialysis and organ transplantation. Advanced glycation end products (AGEs) are metabolic consequence of hyperglycemia and are main contributory factor in the DN pathogenesis through mediating establishment of oxidative status and chronic inflammatory milieu. This study aimed to explore the impact of vanillin on preventing the progression of DN. Main methodsExperimental DN model was established in rats utilizing streptozotocin. Serum concentration of AGEs and Interleukin-6 (IL-6) and transforming growth factor β1 (TGFβ1) levels in kidney homogenate were assessed using ELISA technique. Also, we evaluated the expression of nuclear factor kappa B (NF-κB) using immunohistochemistry. Key findingsTreatment with vanillin for 8 weeks significantly ameliorated DN. Vanillin significantly decreased hyperglycemia and improved kidney function reflected by decreased serum levels of blood urea nitrogen, creatinine, and decreased proteinuria. Also, vanillin significantly decreased malondialdehyde content and elevated superoxide dismutase activity in renal tissues. Moreover, vanillin decreased renal expression of NF-κB and renal concentrations of IL-6, TGFβ1 and collagen. In addition, vanillin significantly decreased serum AGEs concentration. Also, vanillin attenuated histological abnormalities in kidney architecture. SignificanceVanillin, which is a cheap and abundant natural product, exhibited anti-AGEs, antioxidant, anti-inflammatory and anti-fibrotic activities. These activities might be helpful and potent mechanisms in preventing the progression of DN.

Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes.

Objective Type 2 diabetes (T2DM) is a global epidemic and increases mortality due to its vascular complications. Chemerin has been found to exert a major role in glucose and lipid metabolism. The aim of this study was to explore the correlation between plasma chemerin levels and microangiopathy in patients with T2DM. Methods A total of 598 T2DM patients were classified into two groups: with and without microvascular complications. Anthropometric parameters and blood pressure were taken. The amounts of glycosylated hemoglobin, glucose, lipid profiles, creatinine, and chemerin concentrations in the blood were determined. The presence and severity of nephropathy, retinopathy, and neuropathy were also evaluated by specific tests. Results Plasma levels of chemerin in diabetic subjects with microvascular complications were markedly elevated compared to those without. The number of microvascular complications increased with high plasma chemerin levels. Patients with high chemerin levels had an increased incidence of nephropathy and retinopathy. Furthermore, the chemerin plasma concentrations increased with the progression of diabetic nephropathy with highest values in macroalbuminuria groups. In contrast, no significant difference was observed in plasma chemerin levels between subjects with and without peripheral neuropathy. Pearson correlation analysis showed that plasma chemerin levels were positively related to duration of diabetes, serum creatinine, and 24-hour urine albumin excretion, even after multiple adjustments. Using logistic regression analysis, plasma chemerin concentrations were independently associated with the presence of nephropathy and retinopathy, not neuropathy. Conclusion This study elucidated a positive correlation between increased chemerin levels and the development of some subtypes of diabetic microangiopathy.

Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes

IntroductionNon-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications. MethodsA matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D. ResultsConsidering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05–0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04–0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12–0.98], p value = 0.048). ConclusionDiagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.

Alterations in postural control, gait pattern, and muscle function in diabetes mellitus: does it matter in children and adolescents with type 1 diabetes?

Diabetes mellitus (DM) is associated with chronic microvascular complications such as neuropathy. The most frequent is diabetic pe-ripheral neuropathy (DPN) which is related to chronic disability and decrease in quality of life. Alterations in postural control, gait per-formance, and muscle function are widely described in the literature. However, the role of other non-neuropathic factors in these altera-tions remains unclear. Although neuropathy is rather rare in children and adolescents with type 1 DM, there is evidence that early chang-es and symptoms might have their onset in the early stages of the disease. On the other hand, there is no evidence on functional changes related to neuromuscular status in the paediatric population with type 1 DM.