Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus.

Diabetes mellitus is associated with changes in intestinal morphology and the enteric nervous system. We previously reported constipation in Goto-Kakizaki (GK) rats, a non-obese model for type 2 diabetes mellitus. AIM: The morpho-quantitative analysis of myenteric plexus neurons in the small and large intestines of 120-day-old male GK rats was investigated. METHODS: The diabetes was confirmed by high fasting blood glucose levels. The myenteric plexus was evaluated through wholemount immunofluorescence. The morpho-quantitative analyses included evaluating neuronal density (neurons per ganglion) of the total neuronal population, the cholinergic and nitrergic subpopulations, and enteric glial cells per ganglion. The cell body area of 100 neurons per segment per animal was measured. RESULTS: The total neurons and nitrergic subpopulation were unaltered in the GK rats' small and large intestines. The cholinergic subpopulation exhibited decreased density in the three segments of the small intestine and an increased number in the proximal colon of the GK rats. The number of enteric glial cells increased in the ileum of the GK rats, which could indicate enteric gliosis caused by the intestinal inflammatory state. The area of the cell body was increased in the total neuronal population of the jejunum and ileum of the GK rats. Frequency histograms of the cell body area distribution revealed the contribution of cholinergic neurons to larger areas in the jejunum and nitrergic neurons in the ileum. CONCLUSION: The constipation previously reported in GK rats might be explained by the decrease in the density of cholinergic neurons in the small intestine of this animal model.

Smartphone-based evaluation of static balance and mobility in type 2 Diabetes.

It was compared smartphone-based measurements of static balance control and mobility of elderly population with and without type 2 diabetes mellitus (DM2). The present cross-sectional study investigated 73 participants grouped in a control group (n = 36) and a DM2 group (n = 37). Smartphone's built in inertial sensors were used to record inertial changes of the participants during static balance and mobility (Timed Up and Go test - TUG) tasks. The inertial variations as a function of the time were analyzed and compared between groups. Both groups were matched in age, body mass index, male-female proportion, but DM2 group had significant larger fasting glucose than control group. Additionally, DM2 group had worst static balance control with open and closed eyes than the controls (p < 0.05) as well as they also had longer duration to execute the different events of the mobility test than the controls (p < 0.05). DM2 patients had decline of motor functions compared to controls and the use of bult-in sensors of smartphones was feasible to identify these functional impairments. The easy access of smartphones could be improving the screening of functional impairments in DM2 patients.

Ectopic fat in muscle and poor glycemic control are negatively associated with trabecular bone score in type 2 diabetes.

INTRODUCTION: Type 2 Diabetes (T2D) is associated with fractures, despite preserved Bone Mineral Density (BMD). This study aimed to evaluate the relationship between BMD and trabecular bone score (TBS) with the reallocation of fat within muscle in individuals with eutrophy, obesity, and T2D. METHODS: The subjects were divided into three groups: eutrophic controls paired by age and sex with the T2D group (n = 23), controls diagnosed with obesity paired by age, sex, and body mass index with the T2D group (n = 27), and the T2D group (n = 29). BMD and body fat percentage were determined using dual-energy X-Ray absorptiometry. TBS was determined using TBS iNsight software. Intra and extramyocellular lipids in the soleus were measured using proton magnetic resonance spectroscopy. RESULTS: TBS was lower in the T2D group than in the other two groups. Glycated hemoglobin (A1c) was negatively associated with TBS. Body fat percentage was negatively associated with TBS and Total Hip (TH) BMD. TH BMD was positively associated with intramuscular lipids. A trend of negative association was observed between intramuscular lipids and TBS. CONCLUSION: This study showed for the first time that the reallocation of lipids within muscle has a negative association with TBS. Moreover, these results are consistent with previous studies showing a negative association between a parameter related to insulin resistance (intramuscular lipids) and TBS.

Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.

Effects of combined training on nonshivering thermogenic activity of muscles in individuals with overweight and type 2 diabetes.

BACKGROUND: Increased thermogenic activity has shown to be a promising target for treating and preventing obesity and type 2 diabetes (T2DM). Little is known about the muscular influence on nonshivering thermogenesis (NST), and it remains unclear whether physical training and potential metabolic improvements could be associated with changes in this type of thermogenic activity. OBJECTIVE: The present study aimed to assess muscular NST activity in overweight and T2DM before and after a combined training period (strength training followed by aerobic exercise). METHODS: Nonshivering cold-induced 18-fluoroxyglucose positron emission computed tomography (18F-FDG PET/CT) was performed before and after 16 weeks of combined training in 12 individuals with overweight and T2DM. The standard uptake value (SUV) of 18F-FDG was evaluated in skeletal muscles, the heart and the aorta. RESULTS: Muscles in the neck region exhibit higher SUV pre- and posttraining. Furthermore, a decrease in glucose uptake by the muscles of the lower and upper extremities and in the aorta was observed after training when adjusted for brown adipose tissue (BAT). These pre-post effects are accompanied by increased cardiac SUV and occur concurrently with heightened energy expenditure and metabolic improvements. CONCLUSIONS: Muscles in the neck region have greater metabolic activity upon exposure to cold. In addition, combined training appears to induce greater NST, favoring the trunk and neck region compared to limbs based on joint work and adaptations between skeletal muscles and BAT.

Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.

BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.

The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial.

Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual's motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).

The dysfunctional adiposity index is a clinical surrogate of pericardial fat in adults without premature CVD: A sub-analysis of the GEA Mexican study control group.

BACKGROUND AND AIM: The Dysfunctional Adiposity Index (DAI) is a clinical surrogate for evaluating adipose tissue functionality and cardiometabolic health. However, its association with Pericardial Fat Volume (PFV) has not been tested. The aim of this study was to evaluate DAI- PFV association, stratified by type 2 diabetes (T2D) status, and identify DAI thresholds for detecting increased PFV among patients without premature CVD. METHODS AND RESULTS: Participants from the GEA-Mexican study underwent a computed tomography scan to measure PFV. Adjusted logistic regression analyses tested the association between DAI and PFV. AUROC curves evaluated DAI's ability to identify elevated PFV (≥57.57 cm³), and the Youden method determined DAI thresholds, along with diagnostic metrics. The study analyzed 997 participants (women: 55%; mean age: 54 ± 9 years; median PFV: 42 cm³ [IQR: 29-58]), with a 13% prevalence of T2D. DAI was positively associated with elevated PFV (OR: 1.33, 95% CI: 1.07-1.70), which was more pronounced among subjects with T2D (OR: 3.01, 95% CI: 1.41-6.40). DAI thresholds were established for all participants (>1.176), individuals without T2D (>1.003), and with T2D (>1.936), yielding sensitivities of 71%, 81%, and 57%, and specificities of 48%, 38%, and 75%, respectively. The adjusted logistic regression tied DAI thresholds to a 1.68-fold elevation in PFV for all, 2.06-fold for those without T2D, and 6.81-fold for those with T2D. CONCLUSION: DAI was positively associated with increased PFV, particularly among participants with T2D. Established DAI thresholds demonstrated good diagnostic values for detecting increased PFV. DAI could serve as an accessible marker to identify PF in clinical settings.

Cardiorespiratory Fitness Is Impaired in Type 1 and Type 2 Diabetes: A Systematic Review, Meta-Analysis, and Meta-Regression.

INTRODUCTION: Low cardiorespiratory fitness (CRF) increases the risk of cardiovascular disease by up to eightfold and is one of the strongest predictors of mortality. Some studies demonstrate impaired CRF in people living with type 1 and type 2 diabetes compared with those without diabetes, whereas others demonstrate no diabetes-associated impairment in CRF. PURPOSE: We aimed to determine whether diabetes can influence CRF and, if so, identify clinical associations underlying diabetes-associated exercise impairments. METHODS: Sixty-eight studies were included in the quantitative analysis. Standardized mean difference (SMD) was calculated and meta-analyses and meta-regressions were performed by using a random-effects model. RESULTS: Diabetes is associated with a large negative effect on CRF (SMD = -0.80, P < 0.001)-an effect that is partially mitigated, but still significant, in those with high physical activity levels (SMD = -0.50, P = 0.007). A sedentary lifestyle (SMD = -0.83, P = 0.007) and the presence of clinical complications related to diabetes (SMD = -1.66, P < 0.001) predict a greater magnitude of CRF reduction in people with diabetes compared with controls without diabetes. Both type 1 diabetes and type 2 diabetes are independently associated with impaired CRF compared with controls without diabetes; however, the effect is significantly greater in those type 2 diabetes (SMD = -0.97, P < 0.001). Meta-regression analysis demonstrates the effects of diabetes on CRF are primarily associated with HbA1c levels for type 1 diabetes ( B = -0.07, P < 0.001) and body mass index for type 2 diabetes ( B = -0.17, P = 0.005). CONCLUSIONS: These data demonstrate a negative influence of diabetes on the key risk factor of low CRF and provide critical insight into specific clinical markers of low CRF associated with diabetes.

Therapeutic Interventions to Improve Static Balance in Type 2 DiabetesMellitus: A Systematic Review and Meta-Analysis.

INTRODUCTION: Diabetes mellitus (DM) is a metabolic disorder characterized by an abnormal increase in blood glucose levels resulting from insulin secretion and/or dysfunctional activity that can lead to several serious complications in addition to decreased postural balance. OBJECTIVE: This study aimed to identify and analyze the main interventions used to improve static balance in patients with DM. METHODS: For the selection of articles, a bibliographic search was performed using PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Only clinical trials that investigated the effect of training on static balance in adults with type 2 DM were selected, and 34 studies were included. RESULTS: The search resulted in the identification of 2681 articles, and of these, 31 were eligible for the study. The identified interventions were proprioceptive, aerobic, resistance training on platforms, in virtual reality, and Tai Chi. The main results obtained were an increase in time in the one-leg stance, Romberg test, and tandem position, a significant increase in the Berg Balance Scale score and balance index, and a reduction in the variables of postural sway. CONCLUSION: There are a variety of effective training methods for improving static balance, and the choice of intervention to be applied goes beyond proven effectiveness, depending on reproducibility and/or financial cost.

Impacto del SARS-CoV2 en el control de pacientes diabéticos del CESFAM Las Américas, Talca / Impact of SARS-CoV2 on the control of diabetic patients CESFAM Las Américas, Talca

INTRODUCTION: Type 2 diabetes mellitus is a metabolic disorder that affects all aspects of the life and family of the person who suffers from it. The SARS-COV-2 infection pandemic has generated an immense problem at the health system level, causing a significant overload and a complexity of the services to attend to the infection. The foregoing has led many people to lose their chronic controls and cannot take care of themselves properly. OBJECTIVES: To measure the impact of the SARS-COV2 pandemic on the control of diabetic patients at CESFAM Las Américas, Talca city. METHODS: Observational, descriptive/analytical study of the Cardiovascular Health Program at CESFAM Las Américas in the city of Talca, of type 2 diabetic patients, enrolled under control, evaluated between December 2019 and September 2021. Information cutoffs will be 12 months and 15 months RESULTS: In a comparative analysis, we found significant differences with an increase in the indicators BMI, Glycemia, HAb1c and Triglycerides during the time of the Pandemic. However, clinically modest.

Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia.

Type 2 diabetes (T2D) is a complex multifactorial disease that emerges from the combination of genetic and environmental factors, and obesity, lifestyle, and aging are the most relevant risk factors. Hyperglycemia is the main metabolic feature of T2D as a consequence of insulin resistance and ß-cell dysfunction. Among the cellular alterations induced by hyperglycemia, the overproduction of reactive oxygen species (ROS) and consequently oxidative stress, accompanied by a reduced antioxidant response and impaired DNA repair pathways, represent essential mechanisms underlying the pathophysiology of T2D and the development of late complications. Mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation are also closely correlated with insulin resistance and ß-cell dysfunction. This review focus on the mechanisms by which oxidative stress, mitochondrial dysfunction, ER stress, and inflammation are involved in the pathophysiology of T2D, highlighting the importance of the antioxidant response and DNA repair mechanisms counteracting the development of the disease. Moreover, we indicate evidence on how nutritional interventions effectively improve diabetes care. Additionally, we address key molecular characteristics and signaling pathways shared between T2D and Alzheimer's disease (AD), which might probably be implicated in the risk of T2D patients to develop AD.

Alterations of tibialis anterior muscle activation pattern in subjects with type 2 diabetes and diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is associated with loss of motor units (MUs), which can cause changes in the activation pattern of muscle fibres. This study investigated the pattern of muscle activation using high-density surface electromyography (HD-sEMG) signals from subjects with type 2 diabetes mellitus (T2DM) and DPN. Thirty-five adults participated in the study: 12 healthy subjects (HV), 12 patients with T2DM without DPN (No-DPN) and 11 patients with T2DM with DPN (DPN). HD-sEMG signals were recorded in the tibialis anterior muscle during an isometric contraction of ankle dorsiflexion at 50% of the maximum voluntary isometric contraction (MVIC) during 30-s. The calculated HD-sEMG signals parameters were the normalised root mean square (RMS), normalised median frequency (MDF), coefficient of variation (CoV) and modified entropy (ME). The RMS increased significantly (p = 0.001) with time only for the DPN group, while the MDF decreased significantly (p < 0.01) with time for the three groups. Moreover, the ME was significantly lower (p = 0.005), and CoV was significantly higher (p = 0.003) for the DPN group than the HV group. Using HD-sEMG, we have demonstrated a reduction in the number of MU recruited by individuals with DPN. This study provides proof of concept for the clinical utility of this technique for identifying neuromuscular impairment caused by DPN.

Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.

OBJECTIVE: The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS: Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS: L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION: L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.

Cognitive screening and depressive symptoms in hypertensive and diabetic women

Abstract Aim: The objective of this study was to compare the global cognitive function and depressive symptoms in hypertensive and/or diabetic middle-aged and elderly women (52-76 years old). Methods: Sixteen participants with hypertension (HT) and 12 with hypertension and type 2 diabetes mellitus (HT+DM) were included; sociodemographic data, anthropometric measurements, and blood pressure were analyzed, and questionnaires for cognitive screening (Mini-Mental State Examination - MMSE) and depressive symptoms (Geriatric Depression Scale - GDS-30) were administered. For statistical analysis, independent Student's t-test, chi-square test (dichotomous variables), and the Mann-Whitney test (ordinal variables) were used and p < 0.05 was adopted. Results: Results indicate that there were no significant differences pertaining to depressive symptoms (HT = 7.4 ± 5.5; HT+DM = 10.2 ± 4.6 points; p = 0.1658) and global cognitive function (HT = 22.3 ± 4.2; HT+DM = 21.0 ± 3.2 points; p = 0.4015) between hypertensive women and hypertensive and diabetic women, contradicting the hypothesis that the presence of two comorbidities would intensify cognitive impairment and mental health. However, clinically relevant cognitive decline (HT = 63%; HT+DM = 75%; χ2 = 0.4834) and depressive symptoms (HT = 38%; HT+DM = 33%; χ2 = 0.8199) were found in both groups. Conclusion: It has been shown that the presence of two comorbidities: type 2 diabetes mellitus and hypertension, does not intensify cognitive impairment and mental health when compared to hypertension alone in middle-aged and elderly women.

Aerobic Physical Exercise Improves Exercise Tolerance and Fasting Glycemia Independent of Body Weight Change in Obese Females.

Obesity is associated with increased risk of several chronic diseases and the loss of disease-free years, which has increased the focus of much research for the discovery of therapy to combat it. Under healthy conditions, women tend to store more fat in subcutaneous deposits. However, this sexual dimorphism tends to be lost in the presence of comorbidities, such as type 2 diabetes mellitus (T2DM). Aerobic physical exercise (APE) has been applied in the management of obesity, however, is still necessary to better understand the effects of APE in obese female. Thus, we investigated the effect of APE on body weight, adiposity, exercise tolerance and glucose metabolism in female ob/ob mice. Eight-weeks-old female wild-type C57BL/6J and leptin-deficient ob/ob mice (Lepob) were distributed into three groups: wild-type sedentary group (Wt; n = 6), leptin-deficient sedentary group (LepobS; n = 5) and leptin-deficient trained group (LepobT; n = 8). The LepobT mice were subjected to 8 weeks of aerobic physical exercise (APE) at 60% of the maximum velocity achieved in the running capacity test. The APE had no effect in attenuating body weight gain, and did not reduce subcutaneous and retroperitoneal white adipose tissue (SC-WAT and RP-WAT, respectively) and interscapular brown adipose tissue (iBAT) weights. The APE neither improved glucose intolerance nor insulin resistance in the LepobT group. Also, the APE did not reduce the diameter or the area of RP-WAT adipocytes, but the APE reduced the diameter and the area of SC-WAT adipocytes, which was associated with lower fasting glycemia and islet/pancreas area ratio in the LepobT group. In addition, the APE increased exercise tolerance and this response was also associated with lower fasting glycemia in the LepobT group. In conclusion, starting APE at a later age with a more severe degree of obesity did not attenuate the excessive body weight gain, however the APE promoted benefits that can improve the female health, and for this reason it should be recommended as a non-pharmacological therapy for obesity.

High Fasting Glycemia Predicts Impairment of Cardiac Autonomic Control in Adults With Type 2 Diabetes: A Case-Control Study.

Introduction: Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes. Objective: To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements. Materials and Methods: This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR. Results: At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D. Conclusion: Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.

Dinámica no lineal de la regulación autonómica cardiovascular durante la prueba del peso sostenido en pacientes con diabetes mellitus tipo 2 / Nonlinear dynamics of cardiovascular autonomic regulation during the sustained weight test in patients with type 2 diabetes mellitus

Resumen Introducción: La dinámica no lineal de la regulación autonómica cardiovascular a partir de la variabilidad de la frecuencia cardiaca no ha sido previamente estudiada en pacientes con diabetes mellitus tipo 2 mediante la prueba del peso sostenido como inductor de hiperreactividad cardiovascular. Objetivo: Determinar las variaciones en la dinámica no lineal de la regulación autonómica cardiovascular durante la prueba del peso sostenido en pacientes con diabetes mellitus tipo 2. Método: Estudio cuasiexperimental, antes-después, con grupo control, realizado en junio-agosto de 2018 en la Facultad No. 1 de Medicina de Santiago de Cuba. Se trabajó con 15 pacientes que padecían diabetes mellitus tipo 2 sin otra enfermedad asociada y 15 sujetos sanos, a quienes se les aplicó la prueba del peso sostenido. Resultados: En los pacientes con diabetes mellitus, al realizar la prueba del peso sostenido se produjo un aumento significativo en la presión arterial sistólica, diastólica y media, y en la frecuencia cardiaca. En la entropía muestral, parámetro que evalúa la adaptabilidad de los sistemas, se produjo una disminución significativa (2.28 ± 0.33 vs. 1.83 ± 0.47 ms; p = 0.003143). El valor del estadístico C de la entropía muestral en estado basal quedó establecido en 0.973, siendo la variable con mayor capacidad predictiva. Conclusiones: Durante la prueba del peso sostenido en los pacientes con diabetes mellitus tipo 2 se produjo una disminución de la complejidad de la regulación autonómica cardiovascular; la entropía muestral basal constituyó el indicador de mayor eficacia en la identificación de alteraciones autonómicas cardiovasculares.

Abstract Introduction: The analysis of non-linear dynamics of cardiovascular autonomic regulation based on heart rate variability has not been previously studied in patients with type 2 diabetes mellitus using the sustained weight test as an inducer of cardiovascular hyperreactivity. Objective: To determine the variations in the non-linear dynamics of cardiovascular autonomic regulation during the sustained weight test in patients with type 2 diabetes mellitus. Method: A quasi-experimental, before-after study with a control group, from June-August 2018, at the No. 1 School of Medicine in Santiago de Cuba. We worked with 15 patients suffering from type 2 diabetes mellitus without other associated disease and 15 healthy subjects, to whom the sustained weight test was applied. Results: In patients with diabetes mellitus, when performing the sustained weight test, there was a significant increase in the hemodynamic parameters TAS, TAD, TAM and FC. In the sample entropy, a parameter that evaluates the adaptability of the systems, there is a significant decrease (2.28 ± 0.33 vs. 1.83 ± 0.47 ms; p = 0.003143). The value of the C statistic of the sample entropy at baseline was established at 0.973, being the variable with the highest predictive capacity. Conclusions: In patients with type 2 diabetes mellitus during the sustained weight test, there was a decrease in the complexity of cardiovascular autonomic regulation, the basal sample entropy was the indicator of greater efficacy in the identification of cardiovascular autonomic alterations.

Effect of diabetic kidney disease on therapeutic strategies for coronary artery disease: ten year follow-up.

BACKGROUND: The best treatment for coronary artery disease (CAD) in patients with type 2 diabetes (DM2) and chronic kidney disease is unknown. METHODS: This retrospective study included MASS registry patients with DM2 and multivessel CAD, stratified by kidney function. Primary endpoint was combined of mortality, myocardial infarction, or additional revascularization. RESULTS: Median follow-up was 9.5 years. Primary endpoint occurrences among strata 1 and 2 were 53.4% and 40.7%, respectively (P=.020). Mortality rates were 37.4% and 24.6% in strata 1 and 2, respectively (P<.001). We observed a lower rate of major adverse cardiovascular events (MACE) (P=.027 for stratum 1 and P<.001 for stratum 2) and additional revascularization (P=.001 for stratum 1 and P<.001 for stratum 2) for those in the surgical group. In a multivariate analysis, eGFR was an independent predictor of MACE (P=.034) and mortality (P=.020). CONCLUSIONS: Among subjects with DM2 and CAD the presence of lower eGFR rate was associated with higher rates of MACE and mortality, irrespective of treatment choice. CABG was associated with lower rates of MACE in both renal function strata. eGFR was an independent predictor of MACE and mortality in a 10-year follow-up.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.

PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.