New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Effect of low dose Semaglutide in people with Type 1 Diabetes and excess weight.

Obesity is a prevalent problem in people living with T1D (PwT1D), and it has been linked to cardiovascular disease in this population. The use of low dose weekly Semaglutide (0,5 mg) was evaluated in a cohort of PwT1D and excess weight.

Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review.

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was "ground-based environment"; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity.

Combination of hyperoxia and a right-shifted HbO2 dissociation curve delays V̇o2 kinetics during maximal contractions in isolated muscle.

Acute enhancement of peripheral O2 diffusion may accelerate skeletal muscle O2 uptake (V̇o2) kinetics and lessen fatigue during transitions from rest to maximal contractions. Surgically isolated canine gastrocnemius muscles in situ (n = 6) were studied during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions at V̇o2peak, in two conditions: normoxia (CTRL) and hyperoxia ([Formula: see text] = 1.00) + administration of a drug (RSR-13), which right shifts the Hb-O2 dissociation curve (Hyperoxia + RSR-13). Before and during contractions, muscles were pump-perfused with blood at constant elevated flow ([Formula: see text]) and infused with the vasodilator adenosine. Arterial ([Formula: see text]) and muscle venous ([Formula: see text]) O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions; V̇o2 was calculated as [Formula: see text]·([Formula: see text] - [Formula: see text]). Po2 at 50% of Hb saturation (standard P50) and mean microvascular Po2 ([Formula: see text]) were calculated by the Hill equation and a numerical integration technique. P50 [42 ± 7 (means ± SD) mmHg vs. 33 ± 2 mmHg, P = 0.02] and [Formula: see text] (218 ± 73 mmHg vs. 49 ± 4 mmHg, P = 0.003) were higher in Hyperoxia + RSR-13. Muscle force and fatigue were not different in the two conditions. V̇o2 kinetics (monoexponential fitting) were unexpectedly slower in Hyperoxia + RSR-13, due to a longer time delay (TD) [9.9 ± 1.7 s vs. 4.4 ± 2.2 s (P = 0.001)], whereas the time constant (τ) was not different [13.7 ± 4.3 s vs. 12.3 ± 1.9 s (P = 0.37)]; the mean response time (TD + τ) was longer in Hyperoxia + RSR-13 [23.6 ± 3.5 s vs. 16.7 ± 3.2 s (P = 0.003)]. Increased O2 availability deriving, in Hyperoxia + RSR-13, from higher [Formula: see text] and from presumably greater intramuscular O2 stores did not accelerate the primary component of the V̇o2 kinetics, and delayed the metabolic activation of oxidative phosphorylation.NEW & NOTEWORTHY In isolated perfused skeletal muscle, during transitions from rest to V̇o2peak, hyperoxia and a right-shifted oxyhemoglobin dissociation curve increased O2 availability by increasing microvascular Po2 and by presumably increasing intramuscular O2 stores. The interventions did not accelerate the primary component of the V̇o2 kinetics (as calculated from blood O2 unloading) and delayed the metabolic activation of oxidative phosphorylation. V̇o2 kinetics appear to be mainly controlled by intramuscular factors related to the use of high-energy "buffers."

Determination of time in range associated with HbA1c ≤ 6.5% in Latin American pregnant women diagnosed with type 1 diabetes mellitus using an automated insulin delivery system.

AIMS: To determine the correlation between %TIR and HbA1c in pregnant women with type 1 diabetes mellitus (DM1). METHODS: Diagnostic test study in a prospective cohort of pregnant patients with DM1 using automated insulin delivery system (AID)in Colombia and Chile. RESULTS: Fifty-two patients were included [mean age 31.8 ± 6.2 years, pregestational HbA1c 7.2% [interquartile range (IQR), 6.5-8.2]. During follow-up, we found a better metabolic control during the second (HbA1c 6.40%, IQR 5.9,7.1) and third trimesters (HbA1c 6.25%;IQR 5.9,6.8). A weak and negative correlation between %TIR and HbA1c was found for all the gestation (Spearman's rank correlation coefficient:-0.22, p:0.0329), and in the second (r:-0.13, p: 0.38) and third trimesters (r:-0.26, p = 0.08). %TIR had poor discriminating capacity for predicting HbA1c < 6% (area under the curve [AUC], 0.59; 95% confidence interval [CI],0.46-0.72) and for predicting HbA1c < 6.5% (AUC, 0.57;95% CI,0.44-0.70). The optimal cutoff points for %TIR were > 66.1% for predicting HbA1c < 6% (65% sensitivity, 62% specificity) and %TIR > 61.1% for HbA1c < 6.5% (59% sensitivity, 54% specificity). CONCLUSION: The correlation between HbA1c and %TIR during pregnancy was weak. The optimal cutoff points for identifying patients with HbA1c < 6.0% and < 6.5% were %TIR > 66.1% and > 61.1%, respectively, with moderate sensitivity and specificity.

In Cardiac Patients ß-Blockers Attenuate the Decrease in Work Rate during Exercise at a Constant Submaximal Heart Rate.

PURPOSE: Exercise prescription based on fixed heart rate (HR) values is not associated with a specific work rate (WR) during prolonged exercise. This phenomenon has never been evaluated in cardiac patients and might be associated with a slow component of HR kinetics and ß-adrenergic activity. The aims were to quantify, in cardiac patients, the WR decrease at a fixed HR and to test if it would be attenuated by ß-blockers. METHODS: Seventeen patients with coronary artery disease in stable conditions (69 ± 9 yr) were divided into two groups according to the presence (BB) or absence (no-BB) of a therapy with ß-blockers, and performed on a cycle ergometer: an incremental exercise (INCR) and a 15-min "HR CLAMPED " exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to the gas exchange threshold +15%. HR was determined by the ECG signal, and pulmonary gas exchange was assessed breath-by-breath. RESULTS: During INCR, HR peak was lower in BB versus no-BB ( P < 0.05), whereas no differences were observed for other variables. During HR CLAMPED , the decrease in WR needed to maintain HR constant was less pronounced in BB versus no-BB (-16% ± 10% vs -27 ± 10, P = 0.04) and was accompanied by a decreased V̇O 2 only in no-BB (-13% ± 6%, P < 0.001). CONCLUSIONS: The decrease in WR during a 15-min exercise at a fixed HR (slightly higher than that at gas exchange threshold) was attenuated in BB, suggesting a potential role by ß-adrenergic stimulation. The phenomenon may represent, also in this population, a sign of impaired exercise tolerance and interferes with aerobic exercise prescription.

Sarcopenia parameters in active older adults - an eight-year longitudinal study.

BACKGROUD: Sarcopenia is a common skeletal muscle syndrome that is common in older adults but can be mitigated by adequate and regular physical activity. The development and severity of sarcopenia is favored by several factors, the most influential of which are a sedentary lifestyle and physical inactivity. The aim of this observational longitudinal cohort study was to evaluate changes in sarcopenia parameters, based on the EWGSOP2 definition in a population of active older adults after eight years. It was hypothesized that selected active older adults would perform better on sarcopenia tests than the average population. METHODS: The 52 active older adults (22 men and 30 women, mean age: 68.4 ± 5.6 years at the time of their first evaluation) participated in the study at two time points eight-years apart. Three sarcopenia parameters were assessed at both time points: Muscle strength (handgrip test), skeletal muscle mass index, and physical performance (gait speed), these parameters were used to diagnose sarcop0enia according to the EWGSOP2 definition. Additional motor tests were also performed at follow-up measurements to assess participants' overall fitness. Participants self-reported physical activity and sedentary behavior using General Physical Activity Questionnaire at baseline and at follow-up measurements. RESULTS: In the first measurements we did not detect signs of sarcopenia in any individual, but after 8 years, we detected signs of sarcopenia in 7 participants. After eight years, we detected decline in ; muscle strength (-10.2%; p < .001), muscle mass index (-5.4%; p < .001), and physical performance measured with gait speed (-28.6%; p < .001). Similarly, self-reported physical activity and sedentary behavior declined, too (-25.0%; p = .030 and - 48.5%; p < .001, respectively). CONCLUSIONS: Despite expected lower scores on tests of sarcopenia parameters due to age-related decline, participants performed better on motor tests than reported in similar studies. Nevertheless, the prevalence of sarcopenia was consistent with most of the published literature. TRIAL REGISTRATION: The clinical trial protocol was registered on ClinicalTrials.gov, identifier: NCT04899531.

Real-world performance of the MiniMed 780G advanced hybrid closed loop system in Latin America: Substantial improvement in glycaemic control with each technology iteration of the MiniMed automated insulin delivery system.

AIM: We studied real-world performance of MiniMed (MM) 780G system users from Argentina, Brazil, Colombia and Chile (geographical analysis), and the effect of each technology iteration of the MM system on glycaemic control (technology iteration analysis). MATERIALS AND METHODS: CareLink data from August 2020 to September 2022 were extracted. Endpoints included continuous glucose monitoring metrics. For the geographical analysis, aggregated endpoints for MM780G system users were calculated. For the technology iteration analysis, MM780G system user outcomes were compared with outcomes when the same individuals were still using the MM640G or MM670G system. RESULTS: On average, 1025 MM780G system users from the geographical analysis were followed for 136 (SD 135) days, spent 91.5 (14.3)% in advanced hybrid closed loop, showed a glucose management indicator (GMI) of 6.7 (0.3)%, a time in range between 70 and 180 mg/dl (TIR) of 76.5 (9.0)%, and a time below range 70 mg/dl (TBR) of 2.7 (2.1)%. The percentage of users reaching targets of GMI <7%, TIR >70% and TBR <4% was 80.8%, 78.1% and 80.1%, respectively. The technology iteration analysis on users transitioning from MM640G to MM780G system (N = 381) showed 0.4% decrease in GMI (7.1% to 6.7%, p < .0001), 10.7% increase in TIR (65.9% to 76.6%, p < .0001), while TBR remained. The percentage of insulin delivered automatically increased as well (47.5%-57.7%, p < .0001). Users transitioning from MM670G system (N = 78) showed a similar but less pronounced pattern. CONCLUSIONS: Real-world Latin American MM780G users on average showed good glucose control, achieving international targets. Glycaemic control increased with every technology iteration of the MM system, providing more automation each time.

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.

OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases.

Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present with fatigue and multi-system disorders, are often lean, and die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients with mitochondrial diseases (n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism. We examine this phenomenon longitudinally in patient-derived fibroblasts from multiple donors. Genetically or pharmacologically disrupting OxPhos approximately doubles cellular energy expenditure. This cell-autonomous state of hypermetabolism occurs despite near-normal OxPhos coupling efficiency, excluding uncoupling as a general mechanism. Instead, hypermetabolism is associated with mitochondrial DNA instability, activation of the integrated stress response (ISR), and increased extracellular secretion of age-related cytokines and metabokines including GDF15. In parallel, OxPhos defects accelerate telomere erosion and epigenetic aging per cell division, consistent with evidence that excess energy expenditure accelerates biological aging. To explore potential mechanisms for these effects, we generate a longitudinal RNASeq and DNA methylation resource dataset, which reveals conserved, energetically demanding, genome-wide recalibrations. Taken together, these findings highlight the need to understand how OxPhos defects influence the energetic cost of living, and the link between hypermetabolism and aging in cells and patients with mitochondrial diseases.

The impact of body composition on mortality of COVID-19 hospitalized patients: A prospective study on abdominal fat, obesity paradox and sarcopenia.

BACKGROUND & AIMS: Obesity has been described as a predisposing risk factor to severe forms of COVID-19, but conflicting results are emerging on its real impact on the mortality of COVID-19. We aimed to compare clinical outcomes and mortality among COVID-19 patients according to obesity, metabolic syndrome and adiposity distribution. METHODS: We conducted a prospective observational study of all consecutive adult patients with a confirmed diagnosis of SARS-CoV-2 infection admitted to the Infectious Diseases Clinic at Udine Hospital, Italy, from January 2021 to February 2021. At admission, the study population was submitted to specific anthropometric, laboratory and bioimpedance analysis (BIA) measurements and divided into five groups according to: 1) BMI < or >30 kg/m2; 2) waist circumference (WC) < or >98 cm for women, < or >102 cm for men; 3) presence or absence of metabolic syndrome (MS); 4) visceral adipose tissue (VAT) distribution; and 5) presence or absence of sarcopenia (SP) both based on BIA. We then compared clinical outcomes (ventilatory support, intensive care unit (ICU) admission, ICU length of stay, total hospital length of stay and mortality), immune and inflammatory makers and infectious and non-infectious acute complications within the five groups. RESULTS: A total of 195 patients were enrolled in the study. The mean age of patients was 71 years (IQR 61-80) and 64.6% (126) were male. The most common comorbidities were hypertension (55.9%) and MS (55.4%). Overall mortality was 19.5%. Abdominal adiposity, measured both with WC and with BIA, and SP were significantly associated with need for increased ventilator support (p = 0.013 for WC; p = 0.037, 0.027 and 0.009 for VAT; p = 0.004 and 0.036 for FMI; and p = 0.051 for SP), but not with ICU admission (WC p = 0.627, VAT p = 0.153, FMI p = 0.519 and SP p = 0.938), length of stay (WC p = 0.345, VAT p = 0.650, FMI p = 0.159 and SP p = 0.992) and mortality (WC p = 0.277, VAT p = 0.533, FMI p = 0.957 and SP p = 0.211). Obesity and MS did not discriminate for the intensity of ventilatory outcome (p = 0.142 and p = 0.198, respectively), ICU admission (p = 0.802 and p = 0.947, respectively), length of stay (p = 0.471 and p = 0.768, respectively) and mortality (p = 0.495 and p = 0.268, respectively). We did not find significant differences in inflammatory markers and secondary complications within the five groups. CONCLUSIONS: In patients admitted with COVID-19, increased WC, visceral abdominal fat and SP are associated with higher need for ventilatory support. However, obesity, MS, SP and abdominal adiposity are not sensitive predictive factors for mortality.

Perfiles de hipoglicemiantes e insulinas en pacientes con diabetes mellitus tipo 2 y su efecto en control metabólico, hipoglicemia y otros efectos adversos / Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus

BACKGROUND: The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. AIM: To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. MATERIAL AND METHODS: Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. RESULTS: The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. CONCLUSIONS: The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk.

The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans.

The final steps of the O2 cascade during exercise depend on the product of the microvascular-to-intramyocyte P O 2 ${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non-invasive methods to determine D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW ), and hypothesized that: (i) k in well oxygenated muscle (kHIGH ) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH  - kLOW ) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s-1  mg-1 (∼5.8 ml min-1  100 g-1 ). CD ranged 348 to 586 mm-2 . kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min-1 , P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = -0.10, P = 0.755). Δk ranged -0.26 to -2.55 min-1 , and correlated with CD (r = -0.68, P = 0.015). m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity. KEY POINTS: We determined post-exercise recovery kinetics of quadriceps muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) measured by near-infrared spectroscopy (NIRS) in humans under conditions of both non-limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables. The m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH ) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = -0.68) of biopsy samples. NIRS provides non-invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.

Insulin settings and their association with time in range in patients with type 1 diabetes users of predictive low glucose suspend (PLGS) augmented insulin pumps in Santiago, Chile.

AIMS: Sensor augmented insulin pumps have become a powerful tool for managing type 1 diabetes (T1D). This study aimed to analyze the insulin pump configuration in users of predictive insulin suspension technology (PLGS). METHODS: T1D patients on insulin pumps with PLGS (Medtronic 640G®) were enrolled. Data was obtained from medical records and pump data was downloaded for 30 days. Basal insulin, bolus calculator parameters, and PLGS operation parameters were analyzed and compared with Time in Range, Time Below Range, and Time Above Range. RESULTS: 112 patients were included, with average TIR of 73,96 % and HbA1c 7,0 % and 25 months of follow-up. Basal insulin remained similar to initial doses, with an increase of 27 % for the Dawn phenomenon. The Carbohydrate ratio was slightly more aggressive. Insulin sensitivity was 17 % less stringent than initially programmed. No differences were observed in Time in Rage according to the number of basal, ratio, and sensitivity segments. Time of insulin suspension correlated directly with Time Bellow Range. CONCLUSIONS: Patients with good metabolic control have basal insulin programming similar to their initiation doses with less aggressive sensitivity factors. Excessive suspension time determined by PLGS could be an expression of excess insulin and increased hypoglycemia risk.

Decrease in work rate in order to keep a constant heart rate: biomarker of exercise intolerance following a 10-day bed rest.

Aerobic exercise prescription is often set at specific heart rate (HR) values. Previous studies demonstrated that during exercise carried out at a HR slightly above that corresponding to the gas exchange threshold (GET), work rate (WR) has to decrease in order to maintain HR constant. We hypothesized a greater WR decrease at a fixed HR after simulated microgravity/inactivity (bed rest, BR). Ten male volunteers (23 ± 5 yr) were tested before (PRE) and after (POST) a 10-day horizontal BR and performed on a cycle ergometer 1) incremental exercise; b) 15-min HRCLAMPED exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to that at 120% of GET determined in PRE; 3) two moderate-intensity constant WR (MOD) exercises. Breath-by-breath O2 uptake (V̇o2), HR, and other variables were determined. After BR, peak V̇o2 (V̇o2peak) and GET significantly decreased, by ∼10%. During HRCLAMPED (145 ± 11 beats·min-1), the decrease in WR needed to maintain a constant HR was greater in POST versus PRE (-39 ± 10% vs. -29 ± 14%, P < 0.01). In six subjects the decreased WR switched from the heavy- to the moderate-intensity domain. The decrease in WR during HRCLAMPED, in PRE versus POST, was significantly correlated with the V̇o2peak decrease (R2 = 0.52; P = 0.02). A greater amplitude of the slow component of the HR kinetics was observed during MOD following BR. Exercise at a fixed HR is not associated with a specific WR or WR domain; the problem, affecting exercise evaluation and prescription, is greater after BR. The WR decrease during HRCLAMPED is a biomarker of exercise intolerance after BR.NEW & NOTEWORTHY During a 15-min exercise carried out at a heart rate (HR) slightly above that corresponding to the gas exchange threshold, to keep HR constant work rate significantly decreased; the decrease was more pronounced after a 10-day horizontal bed rest. The work rate decrease at a fixed HR can be considered a systemic biomarker of exercise intolerance during microgravity/inactivity and could also be easily and reliably determined during spaceflights or in patients.

[Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus]. / Perfiles de hipoglicemiantes e insulinas en pacientes con diabetes mellitus tipo 2 y su efecto en control metabólico, hipoglicemia y otros efectos adversos.

BACKGROUND: The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. AIM: To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. MATERIAL AND METHODS: Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. RESULTS: The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. CONCLUSIONS: The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

Reduced burnout and higher mindfulness in medical students after a self-care program during the COVID-19 pandemic.

BACKGROUND: Medical students experience high levels of psychological stress during clinical training. However, most medical curricula do not teach self-care skills. The COVID-19 pandemic has disrupted medical education causing increased distress among students. AIM: To report the implementation and impact of an eight-week multifaceted mindfulness-based self-care program on medical students' distress and well-being during the COVID-19 pandemic. MATERIAL AND METHODS: One hundred twenty-three fourth-year medical students attended the program as part of a mandatory course from April to May 2020, during the rising phase of COVID-19 in Chile. They were evaluated using validated tests before and immediately after the program. The measures included burnout, dispositional mindfulness, perceived stress, traumatic stress reactions, general well-being, resilience, and stress coping strategies. RESULTS: Burnout prevalence decreased from 48% to 24%, whereas students with high dispositional mindfulness increased from 25% to 44%. Burnout reduction was mostly due to decreased emotional exhaustion. Additionally, students reported lower levels of stress, self-blaming, and traumatic stress reactions alongside an increased use of active coping strategies and resilience levels after the program. CONCLUSIONS: A formal educational intervention, teaching self-awareness and self-regulation skills can help reduce medical students' distress and promote their well-being even amidst a pandemic.