Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte-endothelial interactions.

Aims/hypothesis: Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients.

The Hybrid Closed-Loop System Tandem t:slim X2™ with Control-IQ Technology: Expert Recommendations for Better Management and Optimization.

Technological advances in the management of diabetes, especially type 1 diabetes (T1D), have played a main role in significantly improving glycemic control of these patients in recent years. Undoubtedly, the most important advance has been the commercialization of hybrid closed-loop systems (HCL). Their effectiveness places them in the different guidelines from scientific societies as the gold standard for the treatment of people with T1D.

Association between gut microbiota and psychiatric disorders: a systematic review.

Introduction: In recent years, it has been described that the dysbiosis of the intestinal microbiota plays a transcendental role in several pathologies. In this sense, the importance of the gut microbiota in the gut-brain axis, with a bidirectional communication, has been demonstrated. Furthermore, the gut microbiota has been linked with mood disorders and neuropsychiatric disorders.

Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes.

Objective: Type 2 diabetes (T2D) is linked to metabolic, mitochondrial and inflammatory alterations, atherosclerosis development and cardiovascular diseases (CVDs). The aim was to investigate the potential therapeutic benefits of GLP-1 receptor agonists (GLP-1 RA) on oxidative stress, mitochondrial respiration, leukocyte-endothelial interactions, inflammation and carotid intima-media thickness (CIMT) in T2D patients.

Research Design And Methods: Type 2 diabetic patients (255) and control subjects (175) were recruited, paired by age and sex, and separated into two groups: without GLP-1 RA treatment (196) and treated with GLP-1 RA (59).

Psychometric properties of a questionnaire to measure adherence to treatment in patients with type 1 diabetes mellitus.

Aim: To validate the psychometric properties of a questionnaire to measure adherence to treatment among people with type 1 diabetes mellitus and to evaluate its relationship with metabolic control.

Design: A cross-sectional study of 167 adult people with type 1 diabetes mellitus recruited from the Endocrinology Service of University Hospital Doctor Peset (Spain).

Methods: The validity of the content, construct and reliability of the instrument were evaluated and the results correlated with levels of glycosylated haemoglobin.

The Role of Mitochondrial Dynamic Dysfunction in Age-Associated Type 2 Diabetes.

Mitochondrial dynamics, such as fusion and fission, play a critical role in maintaining cellular metabolic homeostasis. The molecular mechanisms underlying these processes include fusion proteins (Mitofusin 1 [MFN1], Mitofusin 2 [MFN2], and optic atrophy 1 [OPA1]) and fission mediators (mitochondrial fission 1 [FIS1] and dynamin-related protein 1 [DRP1]), which interact with each other to ensure mitochondrial quality control. Interestingly, defects in these proteins can lead to the loss of mitochondrial DNA (mtDNA) integrity, impairment of mitochondrial function, a severe alteration of mitochondrial morphology, and eventually cell death.

Institutional Experience With New Antidiabetic Drugs in Kidney Transplant.

Background: The recent introduction of new antidiabetic drugs, analogs of glucagon-like peptide-1 (GLP-1) and sodium-glucose cotransporter 2 inhibitors, has shown excellent results in the management of patients with diabetes with chronic kidney disease. However, documented results of these medications in the population that has undergone kidney transplant are sparse. We report our institutional experience with them, including occurrence of side effects and possible interactions with immunosuppressive medications.

Does Empagliflozin Modulate Leukocyte-Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric and endocrine parameters, leukocyte-endothelium interactions, adhesion molecules, ROS production, and NFkB-p65 transcription factor expression.

Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues.

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation.

The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes.

Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Sixty-one T2D patients and 53 controls were included.

Mitochondrial DNA Haplogroup JT is Related to Impaired Glycaemic Control and Renal Function in Type 2 Diabetic Patients.

The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical and metabolic parameters were assessed and mtDNA haplogroup was determined in each individual.

Does Glycemic Control Modulate the Impairment of NLRP3 Inflammasome Activation in Type 2 Diabetes?

Since mitochondrial dysfunction is associated with NOD-like receptor family protein 3 (NLRP3) activation in type 2 diabetes (T2D), which can eventually lead to an impaired immune response, we set out to determine if glycemic control modulates the effects of T2D on the NLRP3 inflammasome. We have studied leukocytes from 61 diabetic patients [25 with glycated hemoglobin (HbA) ≤7% and 36 with HbA ≥8%] and 40 healthy controls. Total and mitochondrial reactive oxygen species (ROS) production was enhanced in T2D patients, and mitochondrial ROS was more pronounced in those with poor glycemic control.

Does Metformin Modulate Endoplasmic Reticulum Stress and Autophagy in Type 2 Diabetic Peripheral Blood Mononuclear Cells?

Since type 2 diabetes (T2D) is associated with oxidative stress and metformin has been shown to exert a protective role against the said stress, we wondered whether metformin treatment might also modulate endoplasmic reticulum (ER) stress and autophagy in leukocytes of T2D patients. We studied 53 T2D patients (37 of whom had been treated with metformin 1700 mg for at least 1 year) and 30 healthy volunteers. Leukocytes from both groups of T2D patients exhibited increased protein levels of 78-kDa glucose-regulated protein (GRP78) with respect to controls, whereas activating transcription factor 6 (ATF6) was enhanced specifically in nonmetformin-treated T2D, and (s-xbp1) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased only in the metformin-treated group.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients.

Type 2 diabetes can increase the risk of skeletal muscle dysfunction and, consequently, that of cardiovascular diseases, including coronary artery disease and stroke. It is also related to a reduced capacity for exercise, but the underlying mechanism is only partially understood. There are several factors that contribute to the development of skeletal muscle dysfunction, of which oxidative stress and mitochondrial dysfunction are among the most important.

Association of metabolic syndrome and its components with hyperuricemia in a Mediterranean population.

Several studies have found an association between hyperuricemia and metabolic syndrome (MS), although there are discrepancies as to which MS components play a pivotal role in this association. We aimed to investigate the association between serum uric acid (SUA) levels and MS in a Mediterranean population (eastern Spain). We performed a case-control study of 71 patients with MS and 122 healthy controls.

Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait.

Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients.

Red blood cell distribution width is not related with inflammatory parameters in morbidly obese patients.

Objective: Red blood cell distribution width (RDW) is a hematological parameter that has been studied in several clinical settings and has been found to be related to both anemia and inflammatory status. As obesity is related to increased inflammatory pattern, we aimed to analyze the RDW in this setting.

Methods: We determined hematological and inflammatory parameters in morbidly obese patients before bariatric surgery (n=142) and normo-weight controls (n=144).

Association of serum retinol binding protein 4 with atherogenic dyslipidemia in morbid obese patients.

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m(2)) were divided in euglycemic, metabolic syndrome or type 2 diabetic.

Homocysteine levels in morbidly obese patients: its association with waist circumference and insulin resistance.

The association between morbid obesity and hyperhomocysteinemia (HH) remains controversial and the nature of this relationship needs to be clarified as several metabolic, lipidic, inflammatory and anthropometric alterations that accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women and 19 men aged 41 ± 12 years and 66 normo-weight subjects, 43 women and 23 men, aged 45 ± 11 years, we determined homocysteine (Hcy) levels along with lipidic, anthropometric, inflammatory and insulin resistance markers. In addition, we investigated the effect of Metabolic Syndrome (MS) and its components on Hcy levels.

Association between hemorheological alterations and metabolic syndrome.

The contribution of hemorheological alterations in the prothrombotic condition in patients with metabolic syndrome (MS) remains a question of debate. We aimed to determine the association between MS and hemorheological parameters by means of a case-control study in 61 MS patients and 89 controls without MS. We determined blood viscosity at 230 s(-1) (Brookfield DVIII viscosimeter); plasma viscosity (Fresenius capillary plasma viscosimeter); erythrocyte aggregation at stasis and 3 s(-1) (MA-1 erythrocyte aggregometer); erythrocyte deformability (Rheodyn SSD at shear stresses of 12, 30 and 60 Pascals) and fibrinogen, along with anthropometric, lipidic and inflammatory parameters.