To understand the large inter-species variations in drug effects on repolarization, the properties of the rapid (I_Kr) and the slow (I_Ks) components of the delayed rectifier potassium currents were compared in myocytes isolated from undiseased human donor (HM), dog (DM), rabbit (RM) and guinea pig (GM) ventricles by applying the patch clamp and conventional microelectrode techniques at 37 °C. The amplitude of the E-4031-sensitive I_Kr tail current measured at −40 mV after a 1 s long test pulse of 20 mV, which was very similar in HM and DM but significant larger in RM and GM. The L-735,821-sensitive I_Ks tail current was considerably larger in GM than in RM. In HM, the I_Ks tail was even smaller than in DM. At 30 mV, the I_Kr component was activated extremely rapidly and monoexponentially in each studied species. The deactivation of the I_Kr component in HM, DM, and RM measured at −40 mV. After a 30 mV pulse, it was slow and biexponential, while in GM, the I_Kr tail current was best fitted triexponentially. At 30 mV, the I_Ks component activated slowly and had an apparent monoxponential time course in HM, DM, and RM. In contrast, in GM, the activation was clearly biexponential. In HM, DM, and RM, I_Ks component deactivation measured at −40 mV was fast and monoexponential, while in GM, in addition to the fast component, another slower component was also revealed. These results suggest that the I_K in HM resembles that measured in DM and RM and considerably differs from that observed in GM. These findings suggest that the dog and rabbit are more appropriate species than the guinea pig for preclinical evaluation of new potential drugs expected to affect cardiac repolarization.

Introduction: The earliest signs of cognitive decline include deficits in temporal (time-based) speech characteristics. Type 2 diabetes mellitus (T2DM) patients are more prone to mild cognitive impairment (MCI). The aim of this study was to compare the temporal speech characteristics of elderly (above 50 y) T2DM patients with age-matched nondiabetic subjects. Materials and Methods: A total of 160 individuals were screened, 100 of whom were eligible (T2DM: n=51; nondiabetic: n=49). Participants were classified either as having healthy cognition (HC) or showing signs of MCI. Speech recordings were collected through a phone call. Based on automatic speech recognition, 15 temporal parameters were calculated. Results: The HC with T2DM group showed significantly shorter utterance length, higher duration rate of silent pause and total pause, and higher average duration of silent pause and total pause compared with the HC without T2DM group. Regarding the MCI participants, parameters were similar between the T2DM and the nondiabetic subgroups. Conclusions: Temporal speech characteristics of T2DM patients showed early signs of altered cognitive functioning, whereas neuropsychological tests did not detect deterioration. This method is useful for identifying the T2DM patients most at risk for manifest MCI, and could serve as a remote cognitive screening tool.

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease that necessitates individualized therapeutic strategies focusing on both glycemic control and the mitigation of comorbidities. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of modern treatment due to their unique renal mechanism of action. This review summarizes the metabolic mechanisms, pleiotropic effects, and clinical significance of SGLT2 inhibitors in the management of T2DM. This review provides an updated overview of the metabolic and systemic effects of SGLT2 inhibition. By promoting glycosuria, SGLT2 inhibitors induce a negative energy balance that contributes to modest weight loss, improved body composition, and beneficial alterations in lipid metabolism. Beyond their metabolic effects, accumulating preclinical evidence suggests that SGLT2 inhibitors exert anti-inflammatory and antifibrotic actions, partly through modulation of macrophage polarization and attenuation of oxidative stress. The clinical utility of SGLT2 inhibitors is highlighted through the review of major cardiovascular and renal outcome trials, which confirm significant benefits in reducing heart failure hospitalizations and slowing the progression of chronic kidney disease. Finally, we integrate these findings into the context of the latest international guidelines while addressing safety profiles, the rationale for combination therapies, and the transition toward a personalized, risk-based management approach in T2DM.

Acromegaly is an uncommon systematic endocrine disease caused by the hypersecretion of human growth hormone and, consequently, of insulin-like growth factor-1 during adulthood. Acromegaly could cause a typical cardiomyopathy characterized by left ventricular hypertrophy associated with diastolic dysfunction, which later could progress to systolic dysfunction. Moreover, some valvular and vascular abnormalities are also associated with acromegaly. This present review aims to summarize available information regarding acromegaly-associated abnormalities in myocardial, valvular, and vascular structural and functional properties and their relationship to disease activity and treatment options.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14–4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Background/Objectives: The aortic valve has a prominent role in regulating blood flow and is of exceptional importance in clinical cardiological practice, as it can be affected by numerous abnormalities, so any clinical study that examines its physiological properties may be of significance. It is known that the dimensions of the aortic valve annulus (AVA) not only change during the cardiac cycle, but also undergo spatial displacement. Considering this, the question arises as to whether the AVA’s dimensions and their spatial displacement, represented by aortic annular plane systolic excursion (AAPSE), are related or not. Therefore, these parameters were simultaneously assessed using three-dimensional speckle-tracking echocardiography (3DSTE) in healthy adults. Methods: The present study’s cohort consisted of 148 healthy adults (mean age: 34.8 ± 12.4 years, 80 men). In all cases, two-dimensional Doppler echocardiography and 3DSTE were performed, the latter being used to assess the aortic valve. Results: In all subjects, end-diastolic and end-systolic AVA dimensions showed no association with an increase in AAPSE. In subjects with a greater end-diastolic AVA area (AVA-A), end-systolic AVA dimensions tended to decrease with increasing AAPSE; this trend reached statistical significance for end-systolic minimum AVA diameter, when comparing participants with AAPSE below versus above the mean. With increasing end-diastolic AVA-A, all other AVA parameters increased accordingly in all subjects and regardless of which AVA-A proved to be greater. In all subjects, and in those with a greater end-systolic AVA-A, the AAPSE proved to be similar regardless of the size of the end-diastolic AVA-A. In cases with a greater end-diastolic AVA-A, only one subject showed a very small end-diastolic AVA-A. With increasing end-systolic AVA-A, all other AVA dimensions were increased in all subjects and in cases with a greater end-diastolic or end-systolic AVA-A. AAPSE showed no significant differences between the subgroups examined, although it tended to be lower in cases with a greater end-diastolic AVA-A and the largest end-systolic AVA-A, and in subjects with a greater end-systolic AVA-A and the smallest end-systolic AVA-A. Moreover, individuals with a greater end-diastolic AVA-A and the smallest end-systolic AVA-A had a tendency for increased AAPSE. No correlations were present between AVA dimensions and AAPSE. Conclusions: 3DSTE-derived AVA dimensions showed no obvious associations with AAPSE in the same healthy adults.