Discrete Relationships between Spatiotemporal Gait Characteristics and Domain-Specific Neuropsychological Performance in Midlife.

Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline-with the aim of identifying individuals who may benefit from potential preventative interventions.

[Construction of a mouse model of type 2 diabetes induced by high fat diet alone and evaluation of pathological changes].

The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects of HFD on the pathology and function of organs related to glucose and lipid metabolism. C57BL/6 mice were fed with normal diet (NC group) or HFD (HFD group). The time of successful T2DM modeling was evaluated by measuring body weight, fasting blood glucose and glucose tolerance at time points of 0, 4, 8, 12, 16 and 20 weeks. The functional and pathological changes of glucose and lipid metabolism related organs were evaluated by detecting insulin tolerance, plasma lipid levels, vascular function, as well as HE staining of pancreas and liver. The results showed that compared with the NC group, the HFD group had significantly increased body weight after 8 weeks of HFD. After 16 weeks of HFD, the HFD group exhibited impaired fasting glucose tolerance. After 20 weeks of HFD, the HFD group mice reached diabetic state, showing impaired glucose tolerance and insulin resistance, islet volume reduction and vacuolar degeneration; Large number of lipid droplets appeared in liver cells, and the level of AMPK phosphorylation in liver tissue was significantly increased in the HFD groups, compared with the NC group; There was endothelial dependent diastolic dysfunction in the thoracic aorta of the HFD group; Compared with the NC group, the HFD group mice showed a significant increase in urinary protein levels. These results suggest that T2DM mouse model can be successfully established by HFD induction alone for 20 weeks. The model is characterized by insulin resistance, fatty liver, hyperlipidemia, vascular dysfunction, renal dysfunction and pathological changes of islet and liver cells, which are similar to those of T2DM patients. Therefore it can be used as an ideal animal model for T2DM research.

Usefulness of DXA-based bone strain index in postmenopausal women with type 2 diabetes mellitus.

Bone Strain Index (BSI) is a new dual-energy x-ray absorptiometry (DXA)-based index. We retrospectively evaluated data from 153 postmenopausal women with a history of type 2 diabetes mellitus (T2DM). Lumbar spine and femoral Bone Strain Index (BSI) were sensitive to skeletal impairment in postmenopausal women suffering from T2DM. PURPOSE: Bone Strain Index (BSI) is a new dual-energy X-ray absorptiometry (DXA)-based measurement. We evaluated the performance of BSI in predicting the presence of fragility fractures in type 2 diabetes mellitus (T2DM) postmenopausal women. METHODS: We retrospectively evaluated data from a case-control study of 153 postmenopausal women with a history of at least 5 years of T2DM (age from 40 to 90 years). For each subject, we assessed the personal or familiar history of previous fragility fractures and menopause age, and we collected data about bone mineral density (BMD), BSI, and Trabecular Bone Score (TBS) measurements. Statistical analysis was performed having as outcome the history of fragility fractures. RESULTS: Out of a total of 153 subjects, n = 22 (14.4%) presented at least one major fragility fracture. A negative correlation was found between lumbar BSI and lumbar BMD (r = - 0.49, p < 0.001) and between total femur BSI and total femur BMD (r = - 0.49, p < 0.001). A negative correlation was found between femoral neck BSI and femoral neck BMD (r = - 0.22, p < 0.001). Most DXA-based variables were individually able to discriminate between fractured and non-fractured subjects (p < 0.05), and lumbar BSI was the index with the most relative difference between the two populations, followed by femoral BSI. CONCLUSION: Lumbar spine and femoral BSI are sensitive to skeletal impairment in postmenopausal women suffering from T2DM. The use of BSI in conjunction with BMD and TBS can improve fracture risk assessment.

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.

Low-calorie diet-induced weight loss is associated with altered brain connectivity and food desire in obesity.

OBJECTIVE: The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity. METHODS: A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis. RESULTS: After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger. CONCLUSIONS: A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.

Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients.

Objective: The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients. Methods: We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model. Results: For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1µmol/L, Cit higher than 26 µmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR. Conclusion: Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.

Does type 2 diabetes duration influence the effectiveness of an aerobic exercise intervention: Results from the INTENSITY study.

BACKGROUND: Studies suggest that longer durations of T2DM increase the risk of T2DM complications and premature mortality. However, whether T2DM duration impacts the efficacy of an aerobic exercise intervention is unclear. OBJECTIVE: The purpose of this study was: 1) to compare changes in body composition, cardiorespiratory fitness, and glycemia between individuals with short- and long-duration T2DM after aerobic exercise and 2) to determine whether these changes were associated with changes in glycemia by T2DM duration. METHODS: A secondary analysis of the INTENSITY study (NCT03787836), including thirty-four adults (≥19 years) with T2DM who participated in 28 weeks of aerobic exercise training for 150 minutes per week at a moderate-to-vigorous intensity (4.5 to 6.0 metabolic equivalents (METs)). Using pre-established cut-points, participants were categorized into two groups 1) short-duration T2DM (<5 years) or 2) long-duration T2DM (≥5 years). Glycemia was measured by glycated hemoglobin (HbA1c), body composition by BodPod, and cardiorespiratory fitness by a measure of peak oxygen consumption (VO2peak). All measurements were performed at baseline, 16 weeks, and 28 weeks. RESULTS: Participants in the short-duration T2DM group experienced decreases in fat mass (kg) (p = 0.03), HbA1c (p = 0.05), and an increased relative VO2peak (p = 0.01). Those with long-duration T2DM experienced decreases in fat mass (kg) (p = 0.02) and HbA1c (p <0.001) and increased fat-free mass (p = 0.02). No significant differences were observed between groups in any outcomes. Changes in fat mass (r = 0.54, p = 0.02), and body fat percentage (r = 0.50, p = 0.02) were significantly associated with the change in HbA1c in those with a long-duration T2DM only. CONCLUSION: Our results suggest T2DM duration did not differently impact the efficacy of a 28-week aerobic exercise intervention. However, changes in body composition were associated with better glycemia in individuals with longer T2DM duration only.

MARRIAGE: A Randomized Trial of Moxonidine Versus Ramipril or in Combination With Ramipril in Overweight Patients With Hypertension and Impaired Fasting Glucose or Diabetes Mellitus. Impact on Blood Pressure, Heart Rate and Metabolic Parameters.

BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.

Association of high vibration perception threshold with reduced renal function in patients with type 2 diabetes.

Objective: To investigate the correlation between vibration sensory threshold (VPT) and renal function, including glomerulus and renal tubule, in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1274 patients with T2DM who were enrolled in the Department of Endocrinology of the First Affiliated Hospital of Fujian Medical University between January 2017 and June 2020 were included. Patients were grouped according to VPT levels and divided into three groups, including the normal VPT group (VPT<15V), the mild-moderate elevated VPT group (VPT15~25V), and the severely elevated VPT group (VPT≥25 V). Linear correlation analysis was used to analyze the correlation between VPT and renal functions, including glomerulus markers urine microalbumin (MA) and urinary immunoglobulin G (U-IgG), and renal tubule marker α1-microglobulin (α1-MG). Chronic kidney disease (CKD) was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The binary logistic regression of the relation between VPT and CKD, eGFR<60 ml/min, and UACR >30 mg/g were expressed. Results: In the mild-moderate and severely elevated VPT group, injury biomarkers of glomerulus (MA and U-IgG), renal tubule (α1-MG), and the incidence of CKD, eGFR<60 ml/min, and UACR > 30 mg/g were gradually increased compared with the normal VPT group. Furthermore, patients with diabetes and severely elevated VPT had significantly higher levels of MA (ß=197.54, p=0.042) and α1-MG (ß=11.69, p=0.023) compared to those with normal VPT. Also, patients with mild-moderate elevated VPT demonstrate significantly higher levels of MA (ß=229.02, p=0.005). Patients in mild-moderate elevated VPT group (OR=1.463, 95% CI 1.005-2.127; OR=1.816, 95% CI 1.212-2.721) and severely elevated VPT group (OR=1.704, 95% CI 1.113-2.611; OR=2.027, 95% CI 1.248-3.294) are at a higher incidence of CKD and elevated levels of UACR>30mg/g compared to those in the VPT normal group. Moreover, the incidence of positive Upro was notably higher in the severely elevated VPT group (OR=1.738, 95% CI 1.182-2.556). However, this phenomenon was not observed in the incidence of eGFR <60 ml/min. Conclusion: A higher VPT is positively associated with the incidence of CKD in patients with T2DM, particularly with elevated UACR. VPT may serve as a marker for glomerulus and renal tubule injury.

Eight Weeks of Intermittent Exercise in Hypoxia, with or without a Low-Carbohydrate Diet, Improves Bone Mass and Functional and Physiological Capacity in Older Adults with Type 2 Diabetes.

In an increasingly aging and overweight population, osteoporosis and type 2 diabetes (T2DM) are major public health concerns. T2DM patients experience prejudicial effects on their bone health, affecting their physical capacity. Exercise in hypoxia (EH) and a low-carbohydrate diet (LCD) have been suggested for therapeutic benefits in T2DM, improving bone mineral content (BMC) and glycemic control. This study investigated the effects of EH combined with an LCD on body composition and functional and physiologic capacity in T2DM patients. Older T2DM patients (n = 42) were randomly assigned to the following groups: (1) control group: control diet + exercise in normoxia; (2) EH group: control diet + EH; (3) intervention group: LCD + EH. Cardiopulmonary tests (BRUCE protocol), body composition (DEXA), and functional capacity (6MWT, handgrip strength) were evaluated. Body mass index (kg/m2) and body fat (%) decreased in all groups (p < 0.001). BMC (kg) increased in all groups (p < 0.001) and was significantly higher in the EH and EH + LCD groups (p < 0.001). VO2peak improved in all groups (p < 0.001), but more so in the hypoxia groups (p = 0.019). Functional capacity was increased in all groups (p < 0.001), but more so in the EH group in 6MWT (p = 0.030). EH with and without an LCD is a therapeutic strategy for improving bone mass in T2DM, which is associated with cardiorespiratory and functional improvements.

Impact of oxidative stress on myocardial performance in patients with diabetes: a focus on subclinical left ventricular dysfunction.

INTRODUCTION: Oxidative stress is known to affect left ventricular functions negatively. There is a strong bidirectional connection between diabetes mellitus (DM) and oxidative stress. In parallel, left ventricular dysfunction is observed more frequently, even in patients with DM without other risk factors. In this context, the objective of this study is to comparatively investigate the potential relationship between oxidative stress and subclinical left ventricular dysfunction (SCLVD) assessed by Myocardial Performance Index (MPI) in patients with and without DM. RESEARCH DESIGN AND METHODS: The sample of this observational cross-sectional single-center study consisted of 151 patients who were evaluated for oxidative stress and SCLVD by tissue Doppler echocardiography. Patients' total oxidant status (TOS), total antioxidant status (TAS), and Oxidative Stress Index (OSI) values were calculated. The effects of oxidative stress and DM on MPI were analyzed. RESULTS: There were 81 patients with DM (mean age: 46.17±10.33 years) and 70 healthy individuals (mean age: 45.72±9.04 years). Mean TOS and OSI values of the DM group were higher than healthy individuals (5.72±0.55 vs 5.31±0.50, p = <0.001; and 4.92±1.93 vs 1.79±0.39, p = <0.001; respectively). The mean TAS value of the DM group was significantly lower than the healthy group (1.21±0.40 vs 3.23±0.51, p = <0.001). There was a significant correlation between OSI and MPI mitral in the DM group (R 0.554, p = <0.001) but not in the healthy group (R -0.069, p=0.249). CONCLUSIONS: Both oxidative stress and myocardial dysfunction were found to be more common in patients with DM. The study's findings indicated the negative effect of oxidative stress on myocardial functions. Accordingly, increased oxidative stress caused more significant deterioration in MPI in patients with DM compared with healthy individuals.

The effect of SGLT2 inhibitors and GLP1 receptor agonists on arterial stiffness: A meta-analysis of randomized controlled trials.

BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We evaluated the effect of sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) on arterial stiffness indices. METHODS: We searched PubMed (up to January 2024) for RCTs assessing the effect of SGLT2i or GLP1-RA on arterial stiffness with reporting outcomes PWV and AIx. Effect sizes of the included studies were expressed as weighted mean difference (WMD) and 95 % confidence interval. Subgroup analyses were performed based on comparator (placebo vs. active comparator), design (RCT vs. crossover), population (diabetic vs. all) and blindness (yes vs. no). RESULTS: A total of 19 studies (SGLT2i, 12 studies; GLP1-RA, 5 studies; SGLT2i/GLP1-RA combination, 2 studies) assessing 1212 participants were included. We did not find any statistically significant association between GLP1-RA or SGLT2i and PWV or AIx. None of the subgroup analyses showed any statistically significant result. CONCLUSION: No evidence of a favorable change in arterial stiffness indices (PWV, AIx) was found following the administration of SGLT2i or GLP1-RA.

BMI, weight change, appetite reduction and cognitive impairment of elderly patients with diabetes.

Body weight is related to both diabetes and cognitive impairment; however, the associations between body mass index (BMI) and cognitive impairment have been reported less frequently among diabetes patients. A total of 1355 patients with type 2 diabetes aged ≥ 60 years were included in this study. The Montreal Cognitive Assessment (MoCA) was administered to assess participants' cognitive status. We collected self-reported body weight, weight loss and appetite loss data using questionnaires. Associations between body weight status (in childhood, midlife age, and late life), weight loss, appetite changes and cognitive impairment were explored using logistic regression. Among the participants, 41.7% exhibited cognitive impairment. Overweight in childhood and late life was associated with cognitive impairment among diabetes patients (OR 2.63, 95% CI 1.52-4.55; OR 1.32, 95% CI 1.03-1.69). Diabetes patients with cognitive impairment were more likely to report a body weight decline and appetite reduction in the past three months (OR 4.18, 95% CI 2.61-6.71; OR 4.41, 95% CI 2.67-7.29). Higher BMI, weight loss, and appetite reduction were positively correlated with cognitive impairment. Given the risk of cognitive impairment, we suggest that body weight and BMI decline should be monitored in patients with diabetes.

Impact of pretransplant T2DM on left ventricular deformation and myocardial perfusion in heart transplanted recipients: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. METHODS: We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM-)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman's analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. RESULTS: In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM-) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM-) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = - 0.399; radial, r = - 0.362; circumferential, r = - 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (ß = longitudinal, - 0.508; radial, - 0.370; circumferential, - 0.371) (all P < 0.05). CONCLUSION: In heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.

Effect of blood flow-restrictive resistance training on metabolic disorder and body composition in older adults with type 2 diabetes: a randomized controlled study.

Introduction: To explore whether blood flow-restrictive resistance exercise (BFRE) can be used as an alternative strategy to moderate-intensity resistance training (RT) to improve metabolic disorder and body composition in older adults with type 2 diabetes (T2DM). Methods: This is a single-blind, randomized, controlled trial. Ninety-eight older adults with T2DM were randomly divided into three groups: BFRE group (n = 34), RT group (n = 31) and control group (n = 33). Two exercise groups received supervised collective training for a period of six months, each lasting 50 min, three times a week. The primary outcomes included fasting plasma glucose (FPG), Glycosylated hemoglobin (HbA1c), blood lipids, blood pressure, and body composition. The secondary outcome was muscle performance. Results: After six months of intervention, the FPG, HbA1c, blood lipids, diastolic blood pressure, body composition, and muscle performance of the two exercise groups were significantly improved relative to the control group and baseline measurements (P < 0.05). There was no significant increase in lean mass between the two exercise groups compared to the control group and baseline (p > 0.05). There was no significant decrease in systolic blood pressure between the two exercise groups compared to the control group (p > 0.05), but it was significantly lower than their baseline (P < 0.05). There was no significant difference in all indicators between the two exercise groups at the baseline, third and sixth months of intervention (p > 0.05). Discussion: BFRE can safely and effectively improve the metabolic disorder and body composition of older adults with T2DM. For elderly exercise beginners, BFRE can be used as an alternative strategy to moderate-intensity resistance training. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.

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.

Comparative Determination of Glomerular Filtration Rate Estimation Formulae in Type 2 Diabetic Patients: An Observational Study.

Assessing glomerular filtration rate (GFR) involves collecting timed urine samples for 24 hours, requiring significant time and resources in the clinical setting. Using predictive GFR formulae to assess renal function may be a better alternative. Our goal was to determine which predictive GFR formula had the highest level of concordance with the GFR that has been measured in a resource-poor setting. This is an observational study. We selected fifty (50) individuals diagnosed with type 2 diabetes (T2DM) in Kumasi, Ghana. The sociodemographic and clinical characteristics were obtained using a structured questionnaire. Urine was obtained from each subject over 24 hours. The levels of glucose (FBG) and creatinine in patients' blood, as well as the levels of creatinine in their urine, were measured after the patients had fasted overnight. Participants had a mean age of 57.4 ± 10.7 (years), BMI of 27.8 ± 4.1 (kg/m2), FBG of 9.0 ± 3.1 (mmol/L), and creatinine concentrations of 95.6 ± 29.1 (µmol/L). A Krouwer plot was used to compare the measured GFR with three formulae: Chronic Kidney Disease Epidemiology (CKD-EPI), Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault (CG) for GFR prediction. Among the 3 estimates, CG showed nonsignificance (p > 0.05) with the measured GFR. The primary finding was that the GFR calculated using the CG formula was not different from the GFR measured, suggesting that CG is the most appropriate alternative GFR estimate among a cross-section of T2DM patients in Ghana.

Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.

Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the ß-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting ß-cells and reducing T2DM-associated complications, among others.

Multiple urinary peptides are associated with hypertension: a link to molecular pathophysiology.

OBJECTIVES: Hypertension is a common condition worldwide; however, its underlying mechanisms remain largely unknown. This study aimed to identify urinary peptides associated with hypertension to further explore the relevant molecular pathophysiology. METHODS: Peptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database, belonging to general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic blood pressure (SBP) and diastolic BP (DBP) into hypertensive (SBP ≥140 mmHg and/or DBP ≥90 mmHg) and normotensive (SBP <120 mmHg and DBP <80 mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort ( n  = 420) of participants without end-organ damage, matched for age, BMI, eGFR, sex, and the presence of diabetes. Furthermore, the association of the peptides with BP as a continuous variable was investigated. The findings were compared with peptide biomarkers of chronic diseases and bioinformatic analyses were conducted to highlight the underlying molecular mechanisms. RESULTS: Between hypertensive and normotensive individuals, 96 (mostly COL1A1 and COL3A1) peptides were found to be significantly different in both the discovery (adjusted) and validation (nominal significance) cohorts, with consistent regulation. Of these, 83 were consistently regulated in the matched cohort. A weak, yet significant, association between their abundance and standardized BP was also observed. CONCLUSION: Hypertension is associated with an altered urinary peptide profile with evident differential regulation of collagen-derived peptides. Peptides related to vascular calcification and sodium regulation were also affected. Whether these modifications reflect the pathophysiology of hypertension and/or early subclinical organ damage requires further investigation.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.