Progression Of Vascular Complications Research Articles

Association between changes in pancreatic morphology and vascular complications in subjects with type 2 diabetes mellitus: a retrospective study

Decreased pancreatic volume, increased pancreatic fat mass, and serrated pancreatic margins are characteristic morphological changes of the pancreas in subjects with type 2 diabetes mellitus. This retrospective study aimed to clarify the clinical significance of pancreatic morphological changes in subjects with type 2 diabetes mellitus who underwent abdominal magnetic resonance imaging. The mean age and HbA1c value were 59.1 ± 16.3 years old and 8.9 ± 2.3%, respectively. Pancreatic body mass corrected for body surface area (BSA) in subjects with diabetes mellitus was lower compared to those in normal glucose tolerance (49.4 ± 15.3 cm3 vs. 60.9 ± 7.8 cm3), although it did not reach a statistic significance. There was a negative correlation between BSA-corrected pancreatic volume and age, duration of diabetes, glycoalbumin, mean and max IMT, and there was a positive correlation between BSA-corrected pancreatic volume and HOMA2-β. Serration of the pancreatic limbus was more often observed in subjects with diabetes mellitus compared to those in normal glucose tolerance (74.1% vs. 14.3%). Subjects with serrated changes were older and had higher HbA1c, and visceral fat area was significantly larger in subjects with serrated changes. BSA-corrected pancreatic volume in subjects with serrated changes was significantly smaller, and mean IMT was significantly thicker in subjects with serrulation. Furthermore, advanced diabetic retinopathy and diabetic nephropathy were more often observed in subjects with serrated changes. Taken together, decreased BSA-corrected pancreatic volume and serrated changes were associated with the progression of vascular complications in subjects with type 2 diabetes mellitus.

Cathelicidin as a marker for subclinical cardiac changes and microvascular complications in children and adolescents with type 1 diabetes.

To detect cathelicidin levels in pediatric patients with type 1 diabetes (T1D) as a potential marker for diabetic vascular complications and to assess its relation to diastolic dysfunction as an index for subclinical macrovasculopathy. Totally, 84 patients with T1D were categorized into three groups; newly diagnosed diabetes group (28 patients with a mean age of 12.38±1.99) years, T1D without microvascular complications group (28 patients with a mean age of 13.04±2.27), and T1D with microvascular complications group (28 patients with a mean age of 13.96±2.30). Patients were evaluated using serum cathelicidin levels and echocardiography. Total cholesterol, microalbuminuria, and cathelicidin levels were significantly higher in patients with microvascular complications when compared to the other two groups (p<0.001). Additionally, carotid intima-media thickness (CIMT) echocardiography values and diastolic functions were significantly higher in patients with complications (p<0.001). Cathelicidin was positively correlated to the duration of diabetes (r=0.542, p<0.001), total cholesterol (r=0.346, p=0.001), recurrence of hypoglycemia (r=0.351, p=0.001), recurrence of diabetes ketoacidosis (r=0.365, p=0.001), CIMT (r=0.544, p<0.001), and E/A values (r=0.405, p<0.001). Serum cathelicidin levels can be used as anearly marker for the occurrence and progression of vascular complications in patients with T1D.

The predictive value of Thromboelastography (TEG) parameters in vascular complications in patients with type 2 diabetes mellitus

AimsThe purpose of this research was to explore the association of TEG parameters (Reaction time, R; Clot kinetics, K; Alpha angle, α-angle; Maximum amplitude, MA) with vascular complications of type 2 diabetes mellitus (T2DM), and assess whether TEG parameters could predict T2DM patients with vascular complications. MethodsA total of 68 healthy controls (HC), 57 T2DM patients without vascular complications (NC), 18 T2DM patients with only microvascular complications (MIC), 196 T2DM patients with only macrovascular complications (MAC), and 94 T2DM patients with both microvascular and macrovascular complications (MIC+MAC) were recruited in this study. Participants' clinical information and TEG parameters were recorded. TEG parameters were analyzed by the Jonckheere-Terpstra trend test, assuming the vascular complication was progressing from HC → NC → MIC → MIC+MAC or HC → NC → MAC → MIC+MAC. Receiver operating characteristic (ROC) was performed to explore the diagnostic accuracy of TEG parameters in T2DM with vascular complications. ResultsShorter TEGK, higher TEG-α-angle, and higher TEG-MA were found in T2DM patients with both microvascular and macrovascular complications (MIC+MAC) group compared with healthy controls (HC) group and T2DM patients without vascular complications (NC) group (P < 0.05). Trend analysis showed that TEG-R/K decreased, but TEG-α-angle/MA increased gradually as the vascular complication progressed (P < 0.001). With stratification of urine microalbumin/creatinine ratio (UACR), diabetic nephropathy with macroalbuminuria (grade A3) behaves shorter TEGK, higher TEG-α-angle/MA compared with normal to mildly increased albuminuria (grade A1) and microalbuminuria (grade A2) (P < 0.05). ROC curves implied that TEGK, TEG-α-angle, and TEG-MA have moderate diagnostic values in T2DM without vascular complications (K-AUC: 0.780, α-angle-AUC: 0.773, and MA-AUC: 0.740) as well as T2DM with both microvascular and macrovascular complications (K-AUC: 0.778, α-angle-AUC: 0.757, and MA-AUC: 0.800). ConclusionTEG parameters are associated with the progression of vascular complications in T2DM, and it could be a diagnostic indicator for T2DM without vascular complications or with advanced vascular complications.

[Basic principles of dietary therapy in type 2 diabetes mellitus: focus on antioxidant protection and endothelial dysfunction].

Oxidative stress and endothelial dysfunction have been identified as the most important pathogenetic pathways for the development and progression of vascular complications in type 2 diabetes (T2DM). Objective. To evaluate the effect of individual dietary components on oxidative stress and endothelial dysfunction in patients with T2DM. Material and methods. The search and analysis of publications was carried out using the PubMed, MEDLINE, Web of Science databases, mainly for the last 10 years, using the keywords "type 2 diabetes mellitus", "endothelial dysfunction", "polyphenols", "antioxidants", "diet". Results. It has been shown that despite the progress in the development of drugs for the correction of clinical and metabolic disorders in T2DM, diet therapy is an important therapeutic factor influencing the main mechanisms of development and progression of cardiovascular complications in T2DM, including hyperglycemia, dyslipidemia, arterial hypertension, subclinical inflammation, endothelial dysfunction. Properly organized and built on modern scientific principles, clinical nutrition improves glycemic control, correction of arterial hypertension, dyslipidemia and overweight/obesity. Influencing the mechanisms of development of oxidative stress, therapeutic nutrition can serve as a preventive approach to protect against the occurrence of endothelial dysfunction and subsequent complications, primarily atherosclerotic origin. Conclusion. The review presents current data on the effect of diet therapy on the main clinical and metabolic parameters in T2DM, endothelial function and oxidative stress, as the most significant factors in the development of systemic vascular complications.

Long-term complications of type 1 diabetes: what do we know and what do we need to understand?

Long-term complications of type 1 diabetes (T1D) include microvascular complications and macrovascular disease. Despite the important advances in the treatment of T1D of the last decades, these complications still represent the leading cause of morbidity and mortality in patients with T1D. Extensive evidence indicates that structural and functional alterations of the kidney, retina, nerves and large arteries occur already in the first years after the onset of diabetes. We performed a comprehensive review of the available evidence on screening, diagnosis, prevention and treatment of vascular complications of T1D. In particular, we focused on three major challenges related to long-term complications of T1D: 1) finding of new biomarkers and diagnostic methods able to identify early signs of complications; 2) identifying specific risk factors for the development of these complications; 3) identifying and implementing new therapeutic strategies able to prevent the development and progression of vascular complications.

Analysis of time in range depending on the method of assessing the glucose level

Introduction. In recent years, there has been an increase in the prevalence and incidence diabetes type 1. The high-quality glycemic control is critical in reducing the risk of developing and progression of vascular complications and adverse outcomes of diabetes. Self-monitoring blood glucose (SMBG) and professional continuous glucose monitoring (PCGM) provide the data set which must be interpreted using multiple indicators of glycemic control. A number of researchers have demonstrated the relationship between the time in range (TIR) and the risk of developing both micro- and macrovascular complications of diabetes. Considering the insufficient amount of data on TIR differences depending on the glucose level assessment method and the significant potential of using this indicator for the stratification of the risk of both micro- and macrovascular complications of diabetes, the study of TIR differences based on the data of PCGM and SMBG is relevant at present.Aims. To estimate the time range according to professional continuous glucose monitoring and self-monitoring of blood glucose levels in the patients with diabetes type 1 among the adult population to improve the control of the disease course.Materials and methods. An interventional open-label multicenter study in the patients with diabetes type 1 was conducted. The patients with diabetes type 1 aged 18 and older, with the disease duration of more than 1 year receiving the therapy with analog insulin was enrolled into the study. The calculation of the indicators of the time spent in the ranges of glycemia was carried out on the basis of the data of PCGM and SMBG.Results and discussion. We examined 218 patients who met the inclusion criteria and did not have exclusion criteria. The presented differences in the indicators of time in ranges indicate the comparability of the SMBG and PCGM methods.Conclusions. When assessing the indicators of time in the ranges of glycemia obtained on the basis of the data of PCGM and SMBG, clear correlations and linear dependence were demonstrated, which indicates the comparability of these parameters regardless of the measurement method.

Risk factors of the development of vascular and neuropathic complications in patients with type 2 diabetes mellitus and autoimmune thyroiditis

Issues of the formation and progression of late complications of diabetes mellitus remain interesting and foreground today, especially in cases of type 2 diabetes mellitus (dm) combined with other endocrine diseases. The pathogenetic relation between the mechanisms leading to blood vessels and nerves damage against the background of diabetes mellitus, and, for example, mechanisms of autoimmune thyroid abnormality (ait), is far from being unambiguous, but the very fact of its existence cannot be denied.Purpose: to determine the predominant type of comorbidity (trans-syndromal, trans-nosological or chronological) and the level of comorbidity according to the disease rating scale (cirs) in patients with type 2 diabetes and ait, to study the structure of later complications of diabetes mellitus in this group of patients and to assess the contribution of certain factors to increased risk of complications.Methods. 428 patients were examined in a specialized endocrinology department, and two groups were formed: an observation group — 213 people with diagnosed type 2 diabetes and ait, and a comparison group — 215 people with a diagnosis of type 2 diabetes. These groups were comparable in age, the duration of diabetes, body mass index, correction of the disease. The analysis included clinical and laboratory parameters, the results of hormones level studies (tsh, free t4, insulin, c-peptide) and antibodies (at-tpo), thyroid ultrasonography, calculation of the insulin resistance index (homa) and the comorbidity index (cirs — cumulative illness rating scale) followed by a correlation-regression analysis of statistical data. The state of the peripheral nervous system was evaluated with the use of electromyography in patients of both groups, and the severity of diabetic neuropathy was evaluated with the use of the neuropathy disability score and vas (visual analogue scale) scales. The state of the vascular system was studied according to the data of ultrasound examination of the vessels of the lower extremities, echocardiography, and ophthalmoscopy.Results. The obtained data made it possible to determine the factors infl uencing the risk of type 2 diabetes complications developement, and to establish that neuropathic complications begin and progress faster in patients with comorbid endocrine pathology, however, there is no such dependence for vascular complications. According to the linear regression equation of the dependence of total complications on the duration of the disease, it was revealed that the development of vascular complications in patients with combined endocrinopathy occurs even more slowly than in patients with diabetes. The contribution of diabetes compensation and identifi ed risk factors to the progression of diabetic complications was less important for patients with endocrinopathies. As for evaluating the contribution of individual parameters, the most signifi cant were the duration of diabetes mellitus, albuminuria, atherosclerosis of the vessels of the lower extremities.Conclusion. In addition to the known risk factors for the development and progression of vascular complications, in patients with overlapping endocrinopathy, the preservation of residual insulin secretion and renal function (chronic kidney disease, proteinuria) were important. the prevalence of “total” Complications in the group of patients with combined endocrine pathology was lower, however, neuropathic complications in the same group were observed more often,т which indicates the primary eff ect of thyroid dysfunction on the structure of the nervous tissue.

Oxidative stress and increasing antioxidant defence in type 2 diabetes

The article discusses topical issues reflecting the high prevalence of diabetes mellitus (DM), the continuing trend towards an increase in the number of patients, the high incidence of vascular complications that lead to early disability and high mortality. The review presents current data on the role of oxidative stress in the development and progression of vascular complications in patients with type 2 diabetes, as well as the mechanisms underlying the imbalance between prooxidants and the antioxidant defense system in this disease. The article presents the role of a balanced diet in achieving metabolic goals and increasing antioxidant protection in type 2 diabetes. The review provides data on the role of vitamins in the correction of metabolic disorders in type 2 diabetes. The increased need for antioxidant vitamins in diabetes is due to impaired glucose metabolism in this category of patients. Food products, which contain polyphenolic compounds, have a pronounced antioxidant and antithrombotic activity, which favorably affect metabolic parameters that contribute to weight loss. Thus, one of the ways to optimize the therapeutic nutrition of patients with type 2 diabetes is the inclusion in the standard hypocaloric diet of specialized food products containing antioxidant vitamins and minor biologically active substances with pronounced antioxidant properties.

Association of Hemoglobin A1c, 1,5-Anhydro-D-Glucitol and Glycated Albumin with Oxidative Stress in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

IntroductionOxidative stress plays a central role in the development and progression of vascular complications in patients with type 2 diabetes mellitus (T2DM). We have previously shown that markers of glucose variability evaluated by continuous glucose monitoring (CGM) are positively associated with oxidative stress in patients with T2DM. However, the evaluation of the glycemic variability by CGM remains a time- and money-consuming procedure. Therefore, this study investigated the independent correlates of oxidative stress among various other clinical markers routinely measured in primary care.MethodsThis was a retrospective cross-sectional study with 234 T2DM patients to examine which clinical variables, including 1,5-anhydro-D-glucitol (1,5-AG) and glycated albumin (GA), were independently associated with oxidative stress. Oxidative stress was measured using the diacron-reactive oxygen metabolites (d-ROMs) test. The relationships between d–ROMs and clinical factors, such as blood glucose, glycated hemoglobin (HbA1c), 1,5-AG, GA, lipid parameters, and blood pressure, were examined.ResultsMultiple stepwise regression analysis revealed that 1,5-AG (inversely), GA, triglycerides, use of metformin and being female were independently associated with d-ROMs. When patients with T2DM were stratified into two groups with HbA1c < 8.0% and HbA1c ≥ 8.0%, 1,5-AG (inversely), HbA1c, use of metformin and being female were independently associated with d-ROMs in diabetes patients with HbA1c < 8.0%, whereas GA, fasting plasma glucose and being female were independently associated with d-ROMs in patients with HbA1c ≥ 8.0%.ConclusionOur present study suggests that 1,5-AG and GA are the strongest correlates of oxidative stress in patients with well and poorly controlled T2DM, respectively.

P707Endothelial function and testosterone deficiency in men with type 2 diabetes mellitus

Abstract Background To date, the currently available data aboutthe effect of testosterone (T) on the cardiovascular system of men are highly controversial. The particular interest is its effect on the endothelium in men with type 2 diabetes mellitus (T2DM) having a high risk of vascular complications. The purpose of this work was to evaluate the effect of endogenous T on function of endothelium in men with T2DM. Methods The study included 204 men, aged 40–65 years, with T2DM. Patients underwent clinical examinations, analysis of carbohydrate metabolism, evaluation of biochemical parameters of endothelial function such as nitric oxide (NO), endothelial synthase type 3 (eNOS3), VCAM-1, ICAM-1, p- and e-selectins, endothelin. The ultrasound assessment of flow-mediated dilatation of the brachial artery (FMD-BA) and intima-media thickness (IMT) of brachial arteries were performed. Patients were divided into 2 groups: 1 – 93 men with late onset hypogonadism established according to EAU 2015 criteria and 2 – 111 men having normal level of endogenous T and absence of clinical symptoms of hypogonadism. Statistical analysis of the data was carried out using the Mann-Whitney U-test (STATISTICA 10 software package). Results The parameters of carbohydrate metabolism and the duration of T2DM were comparable in two groups. The concentrations of NO (85.0 [60.4; 210.4] vs 137.5 [87.8; 281.5] μmol/l, p=0.001) and eNOS3 (192.2 [109.6; 407.3] vs 293.3 [117.1; 686.2] pg/ml, p=0.03) were lower in the 1st group compared to the 2nd one. There was an increase in the levels of VCAM-1 by 32.6% and ICAM-1 by 43% (p&lt;0.0001), p-selectin by 19.5% (p=0.003) in the 1st group compared to the 2nd group. The endothelium-dependent FMD-BA was less pronounced (9.4 [6.9; 13.0] vs 12.2 [10.0; 16.7] %, p=0.0007) and had a delay in time of dilation by 33.3% in patients with hypogonadism compared to eugonadal men. There was an increase in IMT (1.0 [0.9; 1.2] vs 0.9 [0.7; 1.1] mm, p=0.03) in the 1st group compared to the 2nd. Conclusion T deficiency in men with T2DM leads to endothelial dysfunction, decreasing secretory and vasomotor function of endothelium. This indicates the raise of cardiovascular risk and predicts progression of vascular complications in men with T2DM and late onset hypogonadism. Acknowledgement/Funding Supported by Russian Science Foundation, grant #14-25-00052.

Elevated Vascular Endothelial Growth Factor Level in Association with Mean Platelet Volume Are Emerging Risk Factors for Vascular Complications in T2DM Patients

Increasing evidence in both experimental and clinical studies suggests oxidative stress (OS) plays a major role in the pathogenesis of type 2 diabetes mellitus and its complications. In a physiological condition, appropriate levels of ROS, generated either in restricted amounts or transient fashion, are required to promote physiological angiogenesis and homeostatic maintenance of healthy vasculature. Uncontrolled continuous ROS production will ultimately contribute to pathology and cause tissue damage. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF) which plays a key role in diabetic endothelial dysfunction, which ultimately leads to pathogenesis of vascular complications. As VEGF is released by activated platelets, hence platelet activation could be the source of VEGF in plasma samples. Increased platelet activity is emphasized to play a role in the development of vascular complications in T2DM patients and platelet volume, a marker of the platelet function and activation, is measured as mean platelet volume (MPV). Therefore, we aimed to investigate the association between plasma VEGF levels and MPV levels that may lead to vascular complications. A case-control study of one hundred patients with T2DM (n = 100) and thirty control subjects (n = 30) were screened from different areas of West Bengal. All procedures were done with the informed consent of participants. Elevated VEGF level was found in T2DM patients (526.8 ± 34.3 pg/ml) compared to healthy controls (317.9 ± 12.9 pg/ml) which was statistically significant. T2DM patients had higher MPV (12.5 ± 0.2 fl) compared to controls (11.4 ± 0.2 fl). Thus the present study showed a significant association between VEGF level in plasma and MPV indicating the severity of vascular complications. Hence, in conclusion, it suggested that VEGF levels along with MPV are a reliable biomarker for evaluating the development and progression of vascular complications.

Treatment approach to type 2 diabetes: Past, present and future.

Type 2 diabetes mellitus (DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health (fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known “ominous triumvirate” to “ominous octet” indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention.

Effect of Testosterone Therapy on Renal and Endothelial Functions in Men with Type 2 Diabetes Mellitus

Recently, the attention of researchers is attracted to the problem of testosterone (T) deficiency in men. Its negative effect on the cardiovascular system has been established, but the data about the effect of T deficiency on the renal function in patients with type 2 diabetes mellitus (T2DM) haven’t been studied yet. Aim: Evaluate the effect of T therapy on glycemic control, the renal function and the biochemical parameters of endothelial function in men with T2DM having an androgen deficiency. Materials and Methods: The study included 80 men (mean age 51.5±6.3 years), with T2DM and T deficiency. Patients were randomized into 2 groups: the 1st-40 men receiving transdermal T (Androgel 50 mg/day) during 9 months and the 2nd group - 40 men who were not assigned to T. Patients underwent a clinical examination, analysis of biochemical parameters of carbohydrate metabolism (fasting glycemia, HbA1c), renal (creatinin, glomerular filtration rate (GFR)) and endothelial functions (p-, e-selectins, ICAM-1, VCAM-1). Statistical analysis was performed with Mann-Whitney and Wilcoxon tests using the Statistica 10 software package. Results: T therapy in men with T2DM, along with a decrease in body weight by 5.02±0.99 kg (p=0.003) and waist circumference by 6.5±1.6 sm, led to an improvement in carbohydrate metabolism - fasting glycemia by 22.2% and HbA1c by 1% (p=0.00001). At the same time, a statistically significant decrease in the creatinine concentration and an increase in the GFR by 12.5% ​​(p=0.01), as well as a decrease in the levels of endothelial dysfunction markers (ICAM-1 by 56% and p -selectin by 7.7 times (p=0.01)) were found. No significant changes in the 2nd group were found. Conclusion: T therapy in men with T2DM and androgen deficiency leads not only to a decrease of visceral obesity and an improvement in carbohydrate metabolism, but also ameliorates the renal and endothelial functions, which could reduce the rate of progression of vascular complications of diabetes. Disclosure I.A. Khripun: None. E.V. Bova: None. S.V. Vorobyev: None.

Autonomic neuropathy in the development and progression of vascular complications of diabetes mellitus

Autonomic neuropathy in the development and progression of vascular complications of diabetes mellitus

Beta 2-adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications

Macrophage activation is increased in diabetes and correlated with the onset and progression of vascular complications. To identify drugs that could inhibit macrophage activation, we developed a cell-based assay and screened a 1,040 compound library for anti-inflammatory effects. Beta2-adrenergic receptor (β2AR) agonists were identified as the most potent inhibitors of phorbol myristate acetate-induced tumor necrosis factor-α production in rat bone marrow macrophages. In peripheral blood mononuclear cells isolated from streptozotocin-induced diabetic rats, β2AR agonists inhibited diabetes-induced tumor necrosis factor-α production, which was prevented by co-treatment with a selective β2AR blocker. To clarify the underlying mechanisms, THP-1 cells and bone marrow macrophages were exposed to high glucose. High glucose reduced β-arrestin2, a negative regulator of NF-κB activation, and its interaction with IκBα. This subsequently enhanced phosphorylation of IκBα and activation of NF-κB. The β2AR agonists enhanced β-arrestin2 and its interaction with IκBα, leading to downregulation of NF-κB. A siRNA specific for β-arrestin2 reversed β2AR agonist-mediated inhibition of NF-κB activation and inflammatory cytokine production. Treatment of Zucker diabetic fatty rats with a β2AR agonist for 12 weeks attenuated monocyte activation as well as pro-inflammatory and pro-fibrotic responses in the kidneys and heart. Thus, β2AR agonists might have protective effects against diabetic renal and cardiovascular complications.

A Study on Antioxidants and Iron nutritional status in Type 2 Diabetes Mellitus with and without Coronary Heart Disease

Background: Diabetes mellitus is an endocrinal disorder. Patients with type 2 diabetes are at high risk for several cardiovascular disorders: coronary heart disease, stroke, peripheral arterial disease, cardiomyopathy and congestive heart failure. Materials & Methods: This, case control study was conducted on 60 subjects. Among them 20 were controls, 20 were known Type 2 Diabetes Mellitus patients and 20 were Type 2 Diabetes Mellitus patients with coronary heart disease. A laboratory investigations consisting of glucose, total cholesterol, triglycerides, HDLC, LDLC, Vitamin E, MDA, Ceruloplasmin, Ferritin, Iron, TIBC and Transferrin were carried out on fasting blood sample of subjects selected for this study. Results: In the present study, FBS, PPBS, total cholesterol, LDL-Cholesterol, VLDL-Cholesterol and antioxidant parameters such as MDA, Ceruloplasmin and ferritin were significantly increased in T2DM patients and T2DM patients with coronary heart disease when compared to controls. Vitamin E and HDL cholesterol was significantly decreased. Iron, TIBC and Transferrin did not show significant difference. ( p value <0.05). Conclusion: The findings of this study is in accordance to earlier studies, that there is dyslipidemia, increased lipid peroxidation, inflammation and oxidative stress in diabetics compared to non diabetics; and the oxidative stress further increases as diabetes to cardiovascular diseases. These observations suggest that supportive therapy aimed at the reduction of dyslipidemia and oxidative stress may prevent the development and progression of vascular complications, responsible for the increased mortality and morbidity associated with type 2 diabetes mellitus. Future large prospective studies are recommended.

Chronic Kidney Disease and Endothelium

The endothelial cell layer is responsible for molecular traffic between the blood and surrounding tissue, and endothelial integrity plays a pivotal role in many aspects of vascular function. Cardiovascular disease (CVD) is the main cause of death in patients with chronic kidney disease (CKD) and its incidence and severity increase in direct proportion with kidney function decline. Non-traditional risk factors for CVDs, including endothelial dysfunction (ED), are highly prevalent in this population and play an important role in cardiovascular (CV) events. ED is the first step in the development of atherosclerosis and its severity has prognostic value for CV events. Several risk markers have been associated with ED. Reduced bioavailability of nitric oxide plays a central role, linking kidney disease to ED, atherosclerosis, and CV events. Inflammation, loss of residual renal function, and insulin resistance are closely related to ED in CKD. ED may be followed by structural damage and remodelling that can precipitate both bleeding and thrombotic events. The endothelium plays a main role in vascular tone and metabolic pathways. ED is the first, yet potentially reversible step in the development of atherosclerosis and its severity has prognostic value for CV events. Therefore, evaluation of ED may have major clinical diagnostic and therapeutic implications. In patients with CKD, many risk factors are strongly interrelated and play a major role in the initiation and progression of vascular complications that lead to the high mortality rate due to CVD.

Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications.

The vascular complications of diabetes significantly impact the quality of life and mortality in diabetic patients. Extensive evidence from various human clinical trials has clearly established that a period of poor glycemic control early in the disease process carries negative consequences, such as an increase in the development and progression of vascular complications that becomes evident many years later. Importantly, intensive glycemic control established later in the disease process cannot reverse or slow down the onset or progression of diabetic vasculopathy. This has been named the glycemic memory phenomenon. Scientists have successfully modelled glycemic memory using various in vitro and in vivo systems. This review emphasizes that oxidative stress and accumulation of advanced glycation end products are key factors driving glycemic memory in endothelial cells. Furthermore, various epigenetic marks have been proposed to closely associate with vascular glycemic memory. In addition, we comment on the importance of endothelial progenitors and their role as endogenous vasoreparative cells that are negatively impacted by the diabetic milieu and may constitute a “carrier” of glycemic memory. Considering the potential of endothelial progenitor-based cytotherapies, future studies on their glycemic memory are warranted to develop epigenetics-based therapeutics targeting diabetic vascular complications.

Modern insulin therapy with insulin analogues detemir and aspart in children and adolescents: The problems and solutions

DCCT (Diabetes Control and Complications Trial) study showed that intensified insulin therapy associates with significant reduction both of development and progression of vascular complications compared to conventional insulin therapy in type 1 diabetic patients. Modern algorithms of diabetes treatment in children and adolescents reflect the need to achieve and maintenance of glycemic control as closely as possible to normal level. Insulin analogues have improved pharmacokinetic and pharmacodynamic properties, and also have less variability than human insulin. So they have more physiologic and predictable profile actions and, therefore, provide the possibility to achieve optimal glycemic control with low risk of hypoglycemia. Current review demonstrates the benefits of basal-bolus therapy with insulin analogues detemir (Levemir) and aspart (NovoRapid) and advantages of insulin NovoRapid in the continuous subcutaneous insulin infusion (CSII) compared with human insulin in children and adolescents with type 1 diabetes mellitus.

The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus

The aim of the study was to investigate the association of the extracellular inhibitors of Wnt/β-catenin signalling sclerostin and Dickkopf-1 (Dkk-1) with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM). We performed a cross-sectional study including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured by B-mode ultrasound. Serum sclerostin and Dkk-1 were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Serum sclerostin and Dkk-1 concentrations were significantly higher in T2DM group than in controls. There was a significant negative correlation between sclerostin and Dkk-1 and CIMT in T2DM (p = 0.0063 and p = 0.0017, respectively). After adjustment for potential confounders, associations remained significant only for sclerostin. These data suggest that sclerostin, an established modulator of the canonical Wnt signalling, may protect against progression of vascular complications in diabetic patients, possibly by attenuating upregulation of β-catenin activity in the vascular cells.