Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice

Background  

Oxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs) to control the hyperglycemic conditions in streptozotocin induced diabetic mice.     

Sexual dysfunctions in patients with diabetes: a study from Iran

Background  

Diabetes mellitus is a chronic disease that causes short and long-term complications. This study aimed to investigate the prevalence of sexual dysfunctions (SD) among diabetic patients in Iran and to examine whether glycemic control has a role in SD.     

Quantitative iTRAQ-Based Proteomic Identification of Candidate Biomarkers for Diabetic Nephropathy in Plasma of Type 1 Diabetic Patients

Introduction  

As part of a clinical proteomics programme focused on diabetes and its complications, it was our goal to investigate the proteome of plasma in order to find improved candidate biomarkers to predict diabetic nephropathy.     

A case study of type 2 diabetes self-management

Background  

It has been established that careful diabetes self-management is essential in avoiding chronic complications that compromise health. Disciplined diet control and regular exercise are the keys for the type 2 diabetes self-management. An ability to maintain one's blood glucose at a relatively flat level, not fluctuating wildly with meals and hypoglycemic medical intervention, would be the goal for self-management. Hemoglobin A1c (HbA1c or simply A1c) is a measure of a long-term blood plasma glucose average, a reliable index to reflect one's diabetic condition. A simple regimen that could reduce the elevated A1c levels without altering much of type 2 diabetic patients' daily routine denotes a successful self-management strategy.     

Les dysfonctions érectiles chez le diabétique: Rôle des facteurs neurologiques

Objective

To assess the etiological factors of erectile dysfunction in male diabetics.

Material and methods

We have performed a prospective evaluation including 69 diabetic patients suffering from erectile dysfunction. Studied parameters including age, type and duration of diabetes, complications, treatments and associated risk factors were analysed. Comparison was done with a control group of 138 diabetic patients without erectile dysfunction.

Results

There was a significant difference between the diabetic with neurologic complications and the others without neuropathy (p=0.0004). The duration of the diabete was was another risk factor of erectile dysfunction (p=0.049)

Conclusion

We confirm various authors who demonstrated that diabetic impotence seems to be mainly neuropathic in etiology even though it was a multifactorial discomfort.     

Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic development and oxidative stress

Background  

The tissue accumulation of protein-bound advanced glycation endproducts (AGE) may be involved in the etiology of diabetic chronic complications, including osteopenia. The aim of this study was to investigate the effect of an AGE-modified type I collagen substratum on the adhesion, spreading, proliferation and differentiation of rat osteosarcoma UMR106 and mouse non-transformed MC3T3E1 osteoblastic cells. We also studied the role of reactive oxygen species (ROS) and nitric oxide synthase (NOS) expression on these AGE-collagen mediated effects.     

Lower Rate of Cardiovascular Complications in Patients on Bolus Insulin Analogues: A Retrospective Population-Based Cohort Study

Background

Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases.

Methods

A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients’ characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups.

Results

A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58–0.92) for any diabetes-related complication and HRs of 0.73 (0.55–0.93) and 0.55 (0.32–0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications.

Conclusions

Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use.     

Analyzing M-CSF dependent monocyte/macrophage differentiation: Expression modes and meta-modes derived from an independent component analysis

Background  

The analysis of high-throughput gene expression data sets derived from microarray experiments still is a field of extensive investigation. Although new approaches and algorithms are published continuously, mostly conventional methods like hierarchical clustering algorithms or variance analysis tools are used. Here we take a closer look at independent component analysis (ICA) which is already discussed widely as a new analysis approach. However, deep exploration of its applicability and relevance to concrete biological problems is still missing. In this study, we investigate the relevance of ICA in gaining new insights into well characterized regulatory mechanisms of M-CSF dependent macrophage differentiation.     

Silent coronary artery disease in type 2 diabetes mellitus: the role of Lipoprotein(a), homocysteine and apo(a) polymorphism

Background  

There is little data on the relationship between novel cardiovascular risk factors and silent coronary artery disease (CAD) in diabetic patients. We investigated whether Lipoprotein(a), homocysteine and apolipoprotein(a) polymorphism are associated with angiographically assessed asymptomatic coronary artery disease (CAD) in diabetic patients.     

Impact of a Combined High Cholesterol Diet and High Glucose Environment on Vasculature

Aims

Vascular complications are the leading cause of mortality and morbidity in patients with diabetes. However, proper animal models of diabetic vasculopathy that recapitulate the accelerated progression of vascular lesions in human are unavailable. In the present study, we developed a zebrafish model of diabetic vascular complications and the methodology for quantifying vascular lesion formation real-time in the living diabetic zebrafish.

Methods and Results

Wild type zebrafish (AB) and transgenic zebrafish lines of fli1:EGFP, lyz:EGFP, gata1:dsRed, double transgenic zebrafish of gata1:dsRed/fli1:EGFP were exposed to high cholesterol diet and 3% glucose (HCD-HG) for 10 days. The zebrafish model with HCD-HG treatment was characterized by significantly increased tissue levels of insulin, glucagon, glucose, total triglyceride and cholesterol. Confocal microscopic analysis further revealed that the diabetic larvae developed clearly thickened endothelial layers, distinct perivascular lipid depositions, substantial accumulations of inflammatory cells in the injured vasculature, and a decreased velocity of blood flow. Moreover, the vascular abnormalities were improved by the treatment of pioglitazone and metformin.

Conclusion

A combination of high cholesterol diet and high glucose exposure induces a rapid onset of vascular complications in zebrafish similar to the early atherosclerotic vascular injuries in mammalian diabetic models, suggesting that zebrafish may be used as a novel animal model for diabetic vasculopathy.     

The True Value of HbA1c as a Predictor of Diabetic Complications: Simulations of HbA1c Variables

Aim

The updated mean HbA1c has been used in risk estimates of diabetic complications, but it does not take into account the temporal relationship between HbA1c and diabetic complications. We studied whether the updated mean HbA1c underestimated the risk of diabetic complications.

Method

Continuous HbA1c curves for 10,000 hypothetical diabetes patients were simulated over an average of 7 years. Simulations were based on HbA1c values encountered in clinical practice. We assumed that each short time interval of the continuous HbA1c curves had a long-lasting effect on diabetic complications, as evidenced by earlier studies. We tested several different HbA1c variables including various profiles, e.g. different duration, of such a long-lasting effect. The predictive power of these variables was compared with that of the updated mean HbA1c.

Results

The predictive power of the constructed HbA1c variables differed considerably compared to that of the updated mean HbA1c. The risk increase per standard deviation could be almost 100% higher for a constructed predictor than the updated mean HbA1c.

Conclusions

The importance of good glycemic control in preventing diabetic complications could have been underestimated in earlier hallmark studies by not taking the time-dependent effect of HbA1c into account.     

Plasma proteome analysis of patients with type 1 diabetes with diabetic nephropathy

Background  

As part of a clinical proteomics program focused on diabetes and its complications we are looking for new and better protein biomarkers for diabetic nephropathy. The search for new and better biomarkers for diabetic nephropathy has, with a few exceptions, previously focused on either hypothesis-driven studies or urinary based investigations. To date only two studies have investigated the proteome of blood in search for new biomarkers, and these studies were conducted in sera from patients with type 2 diabetes. This is the first reported in depth proteomic study where plasma from type 1 diabetic patients was investigated with the goal of finding improved candidate biomarkers to predict diabetic nephropathy. In order to reach lower concentration proteins in plasma a pre-fractionation step, either hexapeptide bead-based libraries or anion exchange chromatography, was performed prior to surface enhanced laser desorption/ionization time-of-flight mass spectrometry analysis.     

Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice

   

Pancreatic islet transplantation is considered an appropriate treatment to achieve insulin independence in type I diabetic patients. However, islet isolation and transplantation-induced oxidative stress and autoimmune-mediated destruction are still the major obstacles to the long-term survival of graft islets in this potential therapy. To protect islet grafts from inflammatory damage and prolong their survival, we transduced islets with an antioxidative gene thioredoxin (TRX) using a lentiviral vector before transplantation. We hypothesized that the overexpression of TRX in islets would prolong islet graft survival when transplanted into diabetic non-obese diabetic (NOD) mice.     

Hyperuricemia as an Independent Predictor of Vascular Complications and Mortality in Type 2 Diabetes Patients: A Meta-Analysis

Background

Recent data have suggested that serum uric acid (SUA) level is positively associated with the development of type 2 diabetes (T2DM). Whether SUA is also independently associated with the development of vascular complications and mortality in T2DM is controversial.

Methods

A computerized literature search of MEDLINE, Embase and PubMed database was conducted and the odds ratio (OR) or hazard ratio (HR) for per 0.1mmol/l increase in SUA in each study was calculated. Cochrane’s Q and I² statistics were used to evaluate heterogeneity among studies and pooling OR and HR with 95% confidence intervals (CIs) were calculated using random-effects models and fixed-effects models. The pooled analysis was performed using Stata 10.0.

Results

Our search yielded 9 eligible articles (16 ORs and HRs) including 20,891 T2DM patients. Pooled estimates for the relationship suggested that each 0.1 mmol/l increase in SUA resulted in a 28% increase in the risk of diabetic vascular complications and a 9% increase in the risk of diabetic mortality. In stratification-analysis, the positive relationship between SUA and vascular complications remained significant irrespective of mean age, adjustment for metabolic variables and medications. However, it was inconsistent in different populations (significantly positive in the Asian but not in Australian and Italian population) and sample sizes (significantly positive in the relatively large sample size [≥1000] but non-significant in the small sample size [<1000]).

Conclusions

Results of this meta-analysis supported elevated SUA as an independent predictor of vascular complications and mortality in T2DM patients. SUA-lowering therapies might be helpful for prevention and treatment of vascular complications in this population.     

Monocyte matrix metalloproteinase production in Type 2 diabetes and controls – a cross sectional study

Background

Even mild hyperglycemia is associated with future acute and chronic complications. Nevertheless, many cases of diabetes in the community go unrecognized. The aim of the study was to determine if national electronic patient records could be used to identify patients with diabetes in a health management organization.

Methods

The central district databases of Israel's largest health management organization were reviewed for all patients over 20 years old with a documented diagnosis of diabetes mellitus (DM) in the chronic disease register or patient file (identified diabetic patients) or a fasting serum glucose level of >126 mg/100 ml according to the central laboratory records (suspected diabetic patients). The family physicians of the patients with suspected diabetes were asked for a report on their current diabetic status.

Results

The searches yielded 1,694 suspected diabetic patients; replies from the family physicians were received for 1,486. Of these, 575 (38.7%) were confirmed to have diabetes mellitus. Their addition to the identified patient group raised the relative rate of diabetic patients in the district by 3.2%.

Conclusion

Cross-referencing existing databases is an efficient, low-cost method for identifying hyperglycemic patients with unrecognized diabetes who require preventive treatment and follow-up. This model can be used to advantage in other clinical sites in Israel and elsewhere with fully computerized databases.     

Using dynamic pupillometry as a simple screening tool to detect autonomic neuropathy in patients with diabetes: a pilot study

Background  

Autonomic neuropathy is a common and serious complication of diabetes. Early detection is essential to enable appropriate interventional therapy and management. Dynamic pupillometry has been proposed as a simpler and more sensitive tool to detect subclinical autonomic dysfunction. The aim of this study was to investigate pupil responsiveness in diabetic subjects with and without cardiovascular autonomic neuropathy (CAN) using dynamic pupillometry in two sets of experiments.     

Efficacy and safety of pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: A double-blind placebo-controlled trial

Background  

Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy (DPN). We evaluated the efficacy of pregabalin 600 mg/d (300 mg dosed BID) versus placebo for relieving DPN-associated neuropathic pain, and assessed its safety using objective measures of nerve conduction (NC).     

The Potential Association between Obstructive Sleep Apnea and Diabetic Retinopathy in Severe Obesity—The Role of Hypoxemia

Background

Obstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications.

Methods

To investigate the association between OSA, hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m²) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA−).

Results

Forty-six patients were OSA+: median (95% CI) AHI = 37(23–74)/hour and 47 were OSA–ve (AHI = 7(4–11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA_1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA− groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65–0.95; p<0.05), after adjustment.

Conclusions

The presence of OSA, as determined by AHI, was not associated with diabetic retinal complications. In contrast, severity of hypoxemia during sleep (minimum oxygen saturations) may be an important factor. The importance of hypoxia in the development of retinal complications in patients with OSA remains unclear and further studies assessing the pathogenesis of hypoxemia in patients with OSA and diabetic retinal disease are warranted.