Progression Of Chronic Complications Research Articles

Protective Factors and the Pathogenesis of Complications in Diabetes.

Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.

Bone mineral density progression following long-term simultaneous pancreas-kidney transplantation in type-1 diabetes

IntroductionSimultaneous pancreas-kidney transplantation (SPKT) has demonstrated favorable impact on the progression of chronic complications in type-1 diabetes (T1D) and terminal chronic kidney disease (CKD). However, some CKD mineral and bone disorders (CKD-MBD) may persist, even after transplantation. There are only a few studies addressing the long-term progression of bone mineral density (BMD) in these patients. Our aim was to assess baseline BMD and long-term progression and consequences in patients with T1D undergoing SPKT. MethodsA retrospective cohort included patients undergoing SPKT in our tertiary center between 2000 and 2017. BMD progression was assessed on dual X-ray absorptiometry (DXA). Only patients with baseline data and a minimum follow-up of 2 years were included. ResultsSeventy-three patients were included, 53.4% male, with a median age at SPKT of 35 years (interquartile range [IQR] 31; 39). At transplantation, the median T-scores for the lumbar spine (LS) and femoral neck (FN) were −1.6 (IQR −2.6; −1.1) and -−2.1 (IQR −2.7; −1.6), respectively. Seventy-five percent of patients presented low BMD (osteopenia or osteoporosis) in the LS and 90% in the FN, with 33% osteoporosis in the LS and 36% in the FN. On multivariate analysis, male gender (odds ratio [OR] 10.82, 95% confidence interval (CI) 2.88–40.70) and low body-mass index (BMI) (OR 0.73, 95% CI 0.55–0.97) were significantly associated with lumbar but not femoral osteoporosis. At long-term follow-up, BMD significantly improved in the LS (ΔT-score +0.41, P<0.001) and FN (ΔT-score +0.29, P=0.01), at a median 4 years after SPKT. Twelve (16.4%) and 9 (12.3%) patients showed persistent FN and LS osteoporosis, respectively. Multivariate linear regression showed that high BMI was predictive of improvement in BMD. ConclusionsThis study demonstrated severe skeletal fragility in T1D patients with terminal CKD undergoing SPKT, more than a quarter of whom showed osteoporosis. The significant improvement in BMD may result from metabolic correction by SPKT and from physiological skeleton mineralization, which continues in this age group. BMD progression was positively associated with BMI, due to improved nutritional balance after transplantation.

Helicobacter pylori infection is associated with increased accumulation of advanced glycation end products in the skin in patients with type 1 diabetes: A preliminary study.

Helicobacter pylori infection (HPI) is more frequently diagnosed in patients with diabetes. Insulin resistance in patients with type 1 diabetes (DMT1) is associated with the accumulation of advanced glycation end products (AGEs) in the skin and progression of chronic complications. Assessment of the relationship between the incidence of HPI and skin AGEs in patients with DMT1. The study included 103 Caucasian patients with a DMT1 duration >5 years. A fast qualitative test was performed to detect the HP antigen in fecal samples (Hedrex). The content of AGEs in the skin was estimated using an AGE Reader device (DiagnOptics). The HP-positive (n = 31) and HP-negative (n = 72) groups did not differ in terms of age, gender, duration of diabetes, fat content, body mass index (BMI) and lipid profile, metabolic control, and inflammatory response markers. The studied groups differed in the amount of AGEs in the skin. The relationship between HPI and increased AGEs in the skin was confirmed in a multifactor regression model taking into account age, gender, DMT1 duration, glycated hemoglobin A1c (HbA1c), BMI, low-density lipoprotein cholesterol (LDL-C) and the presence of hypertension, and tobacco use. The studied groups also differed in serum levels of vitamin D. Increased accumulation of AGEs in the skin of patients with DMT1 with coexisting HPI suggests that eradication of HP may significantly improve DMT1 outcomes.

Association of anthropometric parameters with the risk of developing type 2 diabetes in overweight or obese individuals: cohort prospective study

Background. Type 2 diabetes mellitus (T2DM) is a non-infectious pandemic of the 21st century. The severity and complexity of this disease is associated with the development and progression of chronic complications that begin at the stage of early carbohydrate and fat metabolism disorders.&#x0D; Aim. To identify the leading anthropometric predictors of the development of type 2 diabetes in overweight or obese patients with early carbohydrate metabolism disorders.&#x0D; Materials and methods. The cohort prospective study involved 112 overweight or obese adults (all citizens of Russia, Republic of Tatarstan) aged 22 to 79. The study was carried out from 2016 to 2018 in the City polyclinic №18. R 4.1.0 environment was used for statistical analysis. Univariable and multivariable logistic regression modeling were performed to evaluate association between outcomes and possible predictors, odds ratios with 95% confidence intervals were estimated. Area under the ROC-curve and Nagelkerke pseudo R-squared was used to compare prognostic performance of predictors.&#x0D; Results. During 3 years of follow-up of 112 patients with early carbohydrate metabolism disorders (prediabetes; n=64), without prediabetes (n=48) without medical intervention, new cases of type 2 diabetes in people with prediabetes and obesity amounted to 29% (n=18) compared with 6% (n=3) for patients with normal glucose levels. The ratio of waist circumference to height (WHtR) and the ratio of waist to hip circumference (WHR) had the greatest discriminative ability according to univariate and multifactorial analyses.&#x0D; Discussion. Our study is consistent with previous work indicating a negative impact of visceral adipose tissue on the risk of developing T2DM. WHR and WHtR most accurately reveal the visceral type of obesity. WHR and WHtR are statistically significant parameters for assessing the risk of developing T2DM according to our study.&#x0D; Conclusion. WHR and WHtR can be used as predictors of type 2 diabetes in overweight or obese individuals.

Utility of ambulatory blood pressure monitoring in detection of masked hypertension and risk of hypertension mediated organ damage in normotensive patients with type 2 diabetes mellitus

Purpose In patients with diabetes, unrecognised hypertension is a serious problem risk factor for the development and progression of chronic complications. The study aimed to determine the prevalence of masked hypertension in normotensive diabetic patients, the factors affecting it, and its association with diabetes complications using ambulatory blood pressure monitoring (ABPM). Materials and methods A cross-sectional observational study was conducted on 150 normotensive diabetic patients. Patients were subjected to an interview and clinical examination to record demographic data, epidemiological data, and significant past history. ABPM was performed for each patient. Urine samples, echocardiogram, and ophthalmologic fundoscopy were done to check for diabetes-related complications. Results The mean age of all participants was 56.7 ± 7.8 years. A total of 93 patients (62%) were males. 99 (66%) patients had masked hypertension. A total of 85 (56.7%) were non-dippers, 49 (32.7%) were dippers, 1 (0.7%) was extreme dipper and 15 (10%) were reverse dippers. Non-dipping and reverse dipping were associated with concentric left ventricular hypertrophy LVH (p < .001). Masked hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.008) whereas, nocturnal hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.003). Conclusions A single office blood pressure (BP) reading cannot rule out hypertension in patients with diabetes. Regardless of hypertension, clinicians should have all patients, especially patients with diabetes, undergo ABPM at least once. Masked hypertension, changes in nocturnal dipping and other phenomena that raise the risk of diabetes complications but cannot be measured by office BP can be measured by ABPM, and thus ABPM can provide a good prognostic benefit.

Evaluation of Pulmonary Functions in Children with Type 1 Diabetes Mellitus: A Case-Control Study.

Type 1 diabetes mellitus (T1DM) is one of the most prevalent chronic diseases in children and adolescents with the risk of development and progression of chronic complications. This study evaluates the pulmonary functions with spirometry in children with T1DM in relation with glycemic control. Ninety-six children with T1DM were matched with 102 healthy controls. All the spirometry parameters including FVC, FEV1, FEV1/FVC, PEFR, and MMFR were significantly reduced (p = < 0.001) in T1DM patients when compared with the controls. Compared to the children with fair glycemic control, the children with poor glycemic control were seen to have a significant decrease in FEV1 (p = 0.001) and FVC (p = 0.001) with no significant change in FEV1/FVC ratio (p = 0.9), PEFR (p = 0.4) and MMFR (p = 0.1). Restrictive lung pattern was the most common pulmonary dysfunction in children with T1DM and it worsened with poor glycemic control. This necessitates the need for adequate glycemic control and periodic lung function assessment.

Faster Aspart: a fast-acting insulin analog for an optimal glycemic control

The basal-bolus insulin regimen in the management of diabetes is essential to achieve the recommended glycosylated hemoglobin (HbA1c) to reduce the incidence or the progression of chronic complications. HbA1c is influenced by either fasting plasma glucose and post-prandial hyperglycemia. Faster Aspart is an insulin Aspart with two additional excipients, L-arginine and niacinamide, which provide a faster subcutaneous absorption, the earlier onset of appearance, and consequently the optimization of post-prandial glucose control. Faster Aspart has been widely investigated in the ‘‘onset’’ clinical trials, which show better post-prandial glycemic excursions and noninferiority compared to insulin Aspart with HbA1c reduction. Clinical evidence demonstrates that faster Aspart is a therapeutic option able to provide clinical benefits over the current rapid-acting insulin analogs in terms of improved meal-related glycaemic control in subjects with diabetes. KEY WORDS post-prandial hyperglycemia; cardiovascular disease; insulin treatment; faster-acting insulin; faster aspart.

Can Innovative Technologies Overcome HbA1c Disparity for African-American Youth with Type 1 Diabetes?

Achieving normal or near-normal glycemic control as reflected by HbA1c levels in patients with type 1 diabetes (T1D) is important for preventing the development and progression of chronic complications. Despite delineation and dissemination of HbA1c management targets and advances in insulin pharmacology, insulin delivery systems, and glucose monitoring, the majority of children with T1D do not achieve HbA1c goals. In particular, African Americans are more likely not to reach HbA1c goals and have persistently higher HbA1c than Non-Hispanic Whites. Availability of pumps and other technology has not eliminated the disparity in HbA1c. Multiple factors play a role in the persisting racial disparity in HbA1c outcome. The carefully designed application and deployment of new technology to help the patient/family and facilitate the supportive role of the diabetes management team may be able to overcome racial disparity in glycemic outcome and improve patient quality of life.

«Умные» глюкометры — революция в управлении диабетом

The rapid spread of diabetes mellitus (DM) is one of the global health challenges around the world. In Russia, the number of registered patients reached 5.1 million in 2020 [1]. Today, it does not raise doubts that achieving good glycaemic control prevents or significantly reduces the risk of development and progression of chronic complications in patients with diabetes. With advances in technology, “smart” glucometers have been launched, significantly expanding options in diabetes management [2].

PB2311 COMPARISON BETWEEN THE EFFECTIVENESS OF CHRONIC PARTIAL RED BLOOD CELL EXCHANGE AND AUTOMATED RED BLOOD CELL EXCHANGE TRANSFUSION IN SICKLE CELL DISEASE: THE EXPERIENCE OF A HOSPITAL IN PORTUGAL

Background:In sickle cell disease (SCD), red blood cell (RBC) transfusion has an important role in the management of emergency and elective settings. In both settings, transfusion may be administered by simple transfusion or by exchange transfusion, manual exchange transfusion or automated Exchange transfusion (AET). Chronic Transfusion Program (CTP) remains the gold standard therapy for stroke prevention and for patients with a severe disease who have inadequate response to hydroxyurea treatment.Aims:To evaluate the safety, efficacy and cost between the patients that underwent both AET and partial manual exchange transfusion (pMET) procedures.Methods:Retrospective observational cohort study of patients with SCD on CTP that have switched between pMET and AET. This study was carried out from 01/01/2017 to 31/12/2018 in a Tertiary Hospital in Portugal. Data on patient history, biological values, duration of the procedure, intervals between them, adverse events as well as the cost of material and human needs were collected and compared between both proceduresResults:A total of 6 patients met the inclusion criteria described. However, 1 patient was excluded from our study because of the lack of attendance to the CTP. During the study, we recorded 88 exchange procedures (42 pMET and 46 AET), both on peripherical venous access. From all those procedures the major concern was the poor venous access, which was the reason why 2 patients had returned to pMET. No major complication or alloimmunization was observed. The indications for CTP were cerebral vasculopathy (N = 2), stroke (N = 1) and recurrent vaso‐occlusive crisis with multiorgan failure (N = 2). For both procedures, target values were to obtain a pre‐exchange HbS level ≤30% for stroke and cerebral vasculopathy and ≤50‐60% for other indications. We documented in 11,4% of patients a higher HbS level prior to the next procedure (N = 10). Despite that all patients remained stable without any SCD related event. Both procedures were well tolerated and iron overload was well controlled. The duration of the exchange procedure was longer and the intervals between procedures were shorter with pMET. Annual RBC requirements per procedure were superior and the overall costs related with AET were 2,2 times higher – 18.180,93€ and 8.174,79€ AET and pMET, respectively (estimated cost per session AET: 790,48€ and pMET:389,28€). Since in our cohort we did not observe the interruption of chelation due to the switch, we did not include the cost for chelation.Summary/Conclusion:Our study shows, as described in literature, that AET allows a faster decrease in the HbS level immediately after exchange transfusion than pMET. Nonetheless, the HbS level before both procedures, performed during the same interval, were similar. We verified that pMET has a comparable efficacy with AET in terms of preventing the development or progression of chronic complications and that the cost per procedure is significantly higher with AET. However, in a clinical situation where it is important to rapidly reduce the HbS level, and/or where the control of the target HbS is stricter so that the patients are clinically controlled without an increase in hospital visits, AET is preferred. We conclude that AET is more effective in the rapid reduction of HbS and ferritin levels, as well as being less time consuming. Despite this, for the reasons described above, it is more cost‐effective to maintain both AET and pMET procedures.

Clinical inertia in insulin prescription for patients with type 2 diabetes mellitus at a primary health care institution of Cartagena, Colombia

Introduction: Evidence has demonstrated clinical or prescriptive inertia along with an increased prescription of insulin, causing a delay in the change of prescription.Objective: To determine the prescription pattern and clinical inertia of insulin use in the treatment of patients with type 2 diabetes mellitus (DM2) enrolled in a diabetes program at a primary health care institution of Cartagena, Colombia.Materials and methods: Pharmacoepidemiology study that addresses drug utilization based on data collected through a review of medical records of 331 patients with DM2, aged 18 and older, who had at least 6 months of control.Results: 64.4% of patients were treated with long-acting insulin analogues and 18.4% used insulin; 52.7% of the patients in which insuline use was required did not have a prescription of this drug.Conclusions: There is clinical inertia related to insulin prescription. Strategies should be implemented to overcome prescriptive inertia for people with DM2 in order to achieve therapeutic goals earlier and effectively prevent the development and progression of chronic complications.

HIPOGLUCEMIAS EN PACIENTES CON ENFERMEDAD RENAL CRÓNICA

El control glucémico estricto demostró disminuir la incidencia y progresión de las complicaciones crónicas, con el consecuente incremento del riesgo de hipoglucemias. Actualmente la Asociación Americana de Diabetes clasifica: Nivel 1: alarma de hipoglucemia &lt;70 mg/dl; Nivel 2: hipoglucemia clínicamente significativa &lt;54 mg/dl; Nivel 3: hipoglucemia severa en la cual, sin especificar el valor de glucemia, se requiere la ayuda de terceros o se presentan alteraciones cognitivas. La hipoglucemia suele ser menos frecuente en pacientes con diabetes tipo 2 que en diabetes tipo 1; se relaciona con alta morbilidad y mortalidad, y representa frecuentemente una de las principales barreras para lograr un óptimo control glucémico. Los pacientes con filtrado glomerular (FG) disminuido (&lt;60 ml/min/1,73 m2) frecuentemente presentan menores requerimientos de insulina y disminución de la degradación de la insulina en los tejidos periféricos, los cuales son factores de riesgo para el desarrollo de hipoglucemia severa.

Glycaemic control in type 1 diabetes mellitus among children and adolescents in a resource limited setting in Dar es Salaam - Tanzania.

BackgroundType 1 Diabetes Mellitus is a rapidly growing problem in Tanzania. Children and adolescents with type 1 diabetes have previously been found to have poor glycaemic control and high prevalence of complications. Strict glycaemic control reduces the incidence and progression of chronic complications. The aim of this study was to identify the factors associated with glycaemic control among children and adolescents.MethodsA cross sectional study was done at the diabetes clinic for children and adolescents. Data on socioeconomic, demographic and diabetes specific variables including adherence, diabetes knowledge, caregivers knowledge and their involvement in the care of the child was obtained. Glycaemic control was assessed by measuring glycosylated hemoglobin. (HbA1C). Linear regression analysis was done to determine factors associated with glycaemic controlResultsSeventy-five participants were recruited into the study (51 % males). The mean HbA1c was 11.1 ± 2.1 %. Children aged <10 years were found to have a significantly better glycaemic control (9.8 %) as compared to 10–14 year olds (11.5 %) and >14 year olds (11.4 %) (P value = 0.022). Sixty-eight percent of patients had good adherence to insulin while adherence to blood glucose monitoring regimen was 48 % and to diet control was 28 %.Younger age, having the mother as the primary caregiver, better caregiver knowledge of diabetes, better adherence to blood glucose monitoring regimen and diabetes duration of less than 1 year were associated with better glycaemic control.In multivariate analysis, age, adherence to blood glucose monitoring regimen and the mother as the primary caregiver were found to independently predict glycaemic control (R2 = 0.332, p value = 0.00).ConclusionsChildren and adolescents with type 1 diabetes in Dar es Salaam have poor glycaemic control. In order to improve metabolic control, adherence to blood glucose monitoring should be encouraged and caregivers encouraged to participate in care of their children especially the adolescents.

Glycated albumin as a marker of glycemia in diabetes and its vascular complications

Effective glycemic control is very important to prevent the onset and the progression of chronic complications in diabetic patients. It is known that glycation of various proteins is increased in diabetic patients compared with non-diabetics. Among these glycated proteins, glycated hemoglobin (HbA1c) is commonly used as a gold standard index of glycemic control in the clinical setting. However, it can be unreliable in conditions affecting the lifespan of erythrocytes (120 days) as well as in the clinical state in which glycemic control alleviates or deteriorates in a short period. By overcoming the shortcomings of HbA1c, glycated albumin (GA) has gained interest as a useful index for an intermediate glycation period (2 weeks) and pathogenic protein. After giving a brief overview of the key role of HbA1c as a long-term glycemic marker, this review focuses on (a) glycation of human albumin and its main properties, (b) methods of GA determination, (c) the recent clinical status of GA as a glycemic index in diabetic patients and its association with vascular complications. Finally, conditions with a possible inaccurate GA level are also mentioned.

Human islet transplantation

that achieves insulin-independent, constant normoglycemic state and avoidance of hypoglycemic episodes is the replacement of a patient’s islet of Langerhans either by pancreas transplantation or by isolated islet transplantation. The cost of this benefit, however, is the need for immunosupressive treatment of the recipient with all its potential risks. Currently, only vascularized pancreas transplantation can re-establish long-term normoglycemia however this has been associate with significant morbidity and mortality. Approximately 25.000 patients worldwide underwent this procedure and it has been shown to improve quality of life and even reverse some secondary complications of diabetes.4 Simultaneous pancreas and kidney transplantation are presently considered the standard of care for selected patients with type I diabetes with end-stage renal failure.5 Diabetes is a major burden to healthcare economies despite the use of exogenous insulin injections. Type I diabetes mellitus is a chronic metabolic disorder that currently afflicts 5 million individuals in the world. It results from auto-immune mediated destruction of insulin secreting beta cells in islet of Langerhans of the pancreas.1 Long-term studies strongly suggest that tight control of blood glucose achieved by conventional or intensive insulin treatment, self blood glucose monitoring, and patient education can significantly prevent developing and retard the progression of chronic complications of this disease.2 On the other hand, the cost of this benefit was a threefold increase in the number of severe hypoglycemic episodes, a significant increase of body weight and dietary and other lifestyle restrictions affecting the quality of life.3 The only treatment for Type I diabetes mellitus Human islet transplantation

THE FORMATION OF CHRONIC COMPLICATIONS OF TYPE 1 DIABETES IN DEPENDENCE OF THE DISEASE FEATURES (literary review and own data)

In the review is present the literature data devoted to the peculiarities the flow of type 1 diabetes in adults (analyzed a number of studies), provides examples of our own observations. In view of inconsistency of existing points of view about the development and progression of chronic complications of the disease in the adult patient population is justified need for further study of this problem.

Morphological changes induced by advanced glycation endproducts in osteoblastic cells: Effects of co-incubation with alendronate

Advanced glycation endproducts (AGEs) accumulate with age in various tissues, and are further increased in patients with Diabetes mellitus, in which they are believed to contribute to the development and progression of chronic complications that include a decrease in bone quality. Bisphosphonates are anti-osteoporotic drugs that have been used for the treatment of patients with diabetic bone alterations, although with contradictory results. In the present study, we have evaluated the in vitro alterations on osteoblastic morphology by environmental scanning electron microscopy, in actin cytoskeleton and apoptosis induced by AGEs, as well as the modulation of these effects by alendronate (an N-containing bisphosphonate). Our present results provide evidence for disruption induced by AGEs of the osteoblastic actin cytoskeleton (geodesic domes) and significant alterations in cell morphology with a decrease in cell-substratum interactions leading to an increase in apoptosis of osteoblasts and a decrease in osteoblastic proliferation. High concentrations of alendronate (10−5M, such as could be expected in an osteoclastic lacuna) further increase osteoblastic morphological and cytoskeletal alterations. However, low doses of alendronate (10−8M, compatible with extracellular fluid levels to which an osteoblast could be exposed for most of its life cycle) do not affect cell morphology, and in addition are able to prevent AGEs-induced alterations and consequently apoptosis of osteoblasts.

Effect of C7 Modifications on Benzothiadiazine‐1,1‐dioxide Derivatives on Their Inhibitory Activity and Selectivity toward Aldose Reductase

The development and progression of chronic complications in diabetic patients, such as retinopathy, nephropathy, neuropathy, cataracts, and stroke, are related to the activation and/or overexpression of aldose reductase (ALR2), which is a member of the aldo-keto reductase superfamily. A structure-activity relationship study focused on the C7 position of 1,2,4-benzothiadiazine-1,1-dioxide derivatives was pursued in an attempt to discover ALR2 inhibitors with enhanced potency and selectivity. These studies led to a series of new C7-substituted compounds, which were evaluated for their inhibitory activity against ALR2; they exhibited IC(50) values in the range of 2.80-45.13 nM. Two compounds with a C7-dimethylcarbamoyl and a C7-diethylcarbamoyl substituent, respectively, were found to be the most active and presented excellent selectivity for ALR2 over aldehyde reductase (ALR1). The structure-activity relationship analyses and molecular modeling studies presented herein highlight the importance of hydrophobic and bulky groups at the C7 position for inhibitory activity and selectivity toward ALR2.

Vascular Stem and Progenitor Cells in Diabetic Complications

Hyperglycemia and its associated biochemical abnormalities damage vascular wall cells, especially the endothelium, leading to an increased risk of cardiovascular events and disease, as well as microangiopathy and end-organ complications. In the last decade, accumulating data suggest that vascular repair mechanisms are important to maintain normal homeostasis of the arterial wall and to prevent development of pathologic processes, such as atherosclerosis, restenosis, and microvascular disease. Diabetes mellitus, through the impairment of vascular stem and progenitor cells, entails a defective repair of the injured endothelium. The biochemical and cellular mechanisms that account for reduced or functionally impaired vascular progenitor cells in diabetes are not fully elucidated, and this is an intense area of research. Additionally, therapeutic approaches to modulate the endogenous reparative/regenerative processes are of particular interest in the setting of experimental and clinical diabetes research. For this special issue of Experimental Diabetes Research, we invited investigators to contribute with original research articles and review articles that stimulate the continuing efforts to understand the molecular and cellular aspects underlying defective vascular repair by means of stem/progenitor cells in diabetes, as well as the development of interventions to reverse it. The journal has received a variety of valuable submissions spanning the pathophysiological and therapeutic implications of vascular stem/progenitor cells. The pathophysiological implications are herein described in the setting of both diabetes and the metabolic syndrome. S. Devaraj and I. Jialal report how number and/or functionality of endothelial progenitor cells (EPCs) could emerge as a novel cellular biomarker of endothelial/vascular dysfunction and cardiovascular disease (CVD) risk in patients with the metabolic syndrome. In the setting of diabetes, a focus review highlights the central contribution played by bone-marrow-derived progenitor cells in the development and progression of chronic complications. Not only are EPCs reduced and dysfunctional in diabetes, but they also appear to have a deranged differentiation capacity, which is shifted toward a procalcific phenotype that may have a negative impact on ectopic calcification and atherosclerosis. Of note, circulating progenitor cell phenotypes are not limited to EPC, but may include a variety of lineage-committed cells relevant for the pathobiology of diabetic complications. As an example, the level of pericyte progenitor cells (PPCs) in type 2 diabetes appears to be related to microangiopathy in response to glucose-lowering therapy. Among disparate complications, retinopathy has received a special attention: while G. Tremolada and colleagues provide a comprehensive analysis of the mechanisms of neoangiogenesis in the diabetic retina, R. Longeras et al. show how pigment-epithelium-derived-factor- (PEDF-) 34 attenuates EPC mobilization from the bone marrow into the bloodstream during retinal neovascularization. This therapeutic approach can now be considered part of the armamentarium available to reverse microangiopathy, through regenerative cells. In parallel, S. Bernardi et al. provided an analysis of cell-based strategies to counter diabetic complications that have been so far devised and applied in the experimental and clinical settings. Besides cell therapies, several other pharmacologic and nonpharmacologic approaches have shown ability to reverse EPCs dysfunction in diabetes. In conclusion, this special issue provides a series of updated reviews on vascular stem/progenitor cell defects in diabetes and on the therapeutic approaches to reverse them and counter diabetic complications. Original contributions help us to dissect the complexity of vascular stem/progenitor cell biology and trace the way for future studies in this field. Amazingly, circulating progenitor cells are uncovering an entirely new scenario in diabetology research: it is all in the blood! Gian Paolo Fadini Paolo Madeddu Johannes Waltenberger Paolo Fiorina

Impacto de la actividad física sobre el control metabólico y el desarrollo de complicaciones crónicas en pacientes con diabetes mellitus tipo 1

La realización de actividad física regular constituye, junto con la dieta equilibrada, uno de los pilares básicos del tratamiento de la diabetes mellitus (DM). La práctica de actividad física en personas con DM, teóricamente, ofrece las mismas ventajas que sobre la población general, y además ciertos efectos beneficiosos, en cuanto al control metabólico de la enfermedad, como mejorar los niveles de glucemia y aumentar la acción o sensibilidad a la insulina. En la presente revisión se analizan los principales estudios clínicos publicados hasta la actualidad que evalúan el impacto de la actividad física sobre el control metabólico o el desarrollo de complicaciones crónicas en pacientes con diabetes mellitus tipo 1. A modo de conclusión podemos afirmar que la mayoría de los estudios evaluados evidencian que la práctica de actividad física regular afecta favorablemente al control metabólico de la DM (o al menos no lo empeora), existiendo insuficiente información al respecto del impacto de la actividad física sobre el desarrollo y la progresión de complicaciones crónicas. Together with a balanced diet, regular physical activity is one of the pillars of diabetes mellitus (DM) management. Physical activity theoretically provides the same advantages in people with DM as in the general population and also has some beneficial effects in controlling metabolic factors, such as improving blood glucose levels and insulin sensitivity. In this article, we analyze the main clinical studies published to date that evaluate the impact of physical activity on metabolic control or the development of chronic complications in patients with type 1 diabetes mellitus. In conclusion, most of the evaluated studies show that regular physical activity favorably affects metabolic control in DM (or at least does not have adverse effects). However, there is insufficient information about the impact of physical activity on the development and progression of chronic complications.