Effects of Bariatric Surgery on Sarcopenic Obesity Outcomes: A One-Year Prospective Study in Middle-Aged Women.

INTRODUCTION: Sarcopenic obesity (SO) is characterised by the confluence of muscle deterioration and high adiposity. When non-surgical interventions prove insufficient, bariatric surgery (BS) becomes the primary approach. This study aimed to address BS effects on SO outcomes 1 year post-surgery among middle-aged women, also considering physical exercise's impact. METHODS: Prospective single-centre study of 140 patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between November 2019 and December 2022. Participants were categorised into tertiles according to SO's diagnosis and severity (group 1-patients with the most severe SO; group 2-intermediate; group 3-the least severe or without SO), calculated considering the consensus issued by ESPEN and EASO in 2022. Evaluations of clinical and biochemical parameters were conducted before and 12 months after BS, and the variation was used for comparative purposes. Body composition was assessed using bone density scans. Linear regression analysis accounted for both surgery type and baseline body mass index (BMI). RESULTS: Before BS, SO prevalence in the overall sample was 89.3%, decreasing to 2.9% after BS. Group 1 had more body fat mass (56.9 vs 54.8 vs 50.7 kg, p < 0.001), total, trunk and leg fat at baseline and a significantly lower total skeletal muscle mass (47.2 vs 49.4 vs 51.8 kg, p < 0.001). One year post-BS, group 1 presented more weight loss (- 39.8 ± 11.4 kg, p = 0.031), BMI reduction (- 15.9 ± 4.6 kg/m2, p = 0.005) and lost more fat mass (- 32.6 vs - 30.5 vs - 27.9 kg, p = 0.005), but not total skeletal muscle mass (- 5.8 vs - 5.9 vs - 6.8 kg, p = 0.130). Remission rates for comorbidities were substantial among all groups, but more marked among patients within group 1 (type 2 diabetes mellitus 75%, hypertension 47.1% and dyslipidemia 52.8%). Engagement in physical exercise of any kind has increased post-BS (33.1% vs 79.1%). CONCLUSION: Despite concerns about malabsorptive mechanisms potentially worsening muscle loss, patients with the most severe SO undergoing BS lost more fat mass while experiencing the smallest reduction in total skeletal muscle mass. Remission rates for comorbidities following BS were notable among all groups.

Myocardial stretch-induced compliance is abrogated under ischemic conditions and restored by cGMP/PKG-related pathways.

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI. Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure-volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats. Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading. Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia.

Statin Therapy Among Bariatric Patients: The Impact on Metabolic Outcomes and Diabetes Status.

INTRODUCTION: Statin therapy is associated with an increased risk of developing diabetes. Among bariatric patients, the influence of this therapy on various metabolic outcomes, such as diabetes status and its remission, is largely unknown. METHODS: This was a retrospective study of 1710 patients who underwent bariatric surgery at our hospital between January/2010 and June/2017. We compared patients with and without statin therapy at baseline, 12 and 24 months after surgery regarding statin use and its impact on several clinical and analytical parameters. Multiple linear regression was performed, adjusting differences for age, sex, surgery type, antidiabetic drugs at baseline, hypertension at baseline, LDL cholesterol ˃ 130 mg/dL, weight variation one year after surgery, and age of obesity onset. RESULTS: The overall prevalence of statin use was 20.2% before, 13.6% 12 months after surgery, and 15.0% 24 months after surgery. There was a larger reduction in fasting glucose and HbA1c at 12 and 24 months after surgery among statin-treated patients, with the opposite trend for weight reduction and BMI. Statin-treated patients with diabetes had lower diabetes remission rates (45.3 vs 68.5%) 12 months after surgery, with the highest reduction in HbA1c (1.3±1.3 vs -1.1±1.2%; p=0.042), fasting glucose (-40.8±48.8 vs -30.9±41.6 mg/dL; p=0.028), and insulin (-21.7±28.2 vs -13.4±14.2 mIU/L; p=0.039). The proportion of new-onset cases of diabetes was equal between statin-treated vs non-treated individuals at 12 months (1.9%) and 24 months (1.0%) after surgery. CONCLUSION: Bariatric surgery seems to lead to diabetes remission more frequently in patients not treated with statins. A larger reduction was observed in fasting glucose and HbA1c among statin-treated patients. Statin did not contribute to an increased proportion of new-onset diabetes after surgery.

Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.

INTRODUCTION: Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. METHODS: Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS. RESULTS: The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB. CONCLUSION: The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.

Stretch-induced compliance: a novel adaptive biological mechanism following acute cardiac load.

Aims: The heart is constantly challenged with acute bouts of stretching or overload. Systolic adaptations to these challenges are known but adaptations in diastolic stiffness remain unknown. We evaluated adaptations in myocardial stiffness due to acute stretching and characterized the underlying mechanisms. Methods and results: Left ventricles (LVs) of intact rat hearts, rabbit papillary muscles and myocardial strips from cardiac surgery patients were stretched. After stretching, there was a sustained >40% decrease in end-diastolic pressure (EDP) or passive tension (PT) for 15 min in all species and experimental preparations. Stretching by volume loading in volunteers and cardiac surgery patients resulted in E/E' and EDP decreases, respectively, after sustained stretching. Stretched samples had increased myocardial cGMP levels, increased phosphorylated vasodilator-stimulated phosphoprotein phosphorylation, as well as, increased titin phosphorylation, which was reduced by prior protein kinase G (PKG) inhibition (PKGi). Skinned cardiomyocytes from stretched and non-stretched myocardia were studied. Skinned cardiomyocytes from stretched hearts showed decreased PT, which was abrogated by protein phosphatase incubation; whereas those from non-stretched hearts decreased PT after PKG incubation. Pharmacological studies assessed the role of nitric oxide (NO) and natriuretic peptides (NPs). PT decay after stretching was significantly reduced by combined NP antagonism, NO synthase inhibition and NO scavenging, or by PKGi. Response to stretching was remarkably reduced in a rat model of LV hypertrophy, which also failed to increase titin phosphorylation. Conclusions: We describe and translate to human physiology a novel adaptive mechanism, partly mediated by titin phosphorylation through cGMP-PKG signalling, whereby myocardial compliance increases in response to acute stretching. This mechanism may not function in the hypertrophic heart.

Pregnancy after bariatric surgery: Maternal and fetal outcomes of 39 pregnancies and a literature review.

AIM: We aimed to evaluate the impact of bariatric surgery (BS) on maternal and fetal outcomes. METHODS: A retrospective, descriptive, observational study of 39 pregnant women who underwent BS in our institution between 2010 and 2014 was carried out. A sample of women who became pregnant after BS was evaluated, based on data concerning pregnancy, childbirth, and newborns. RESULTS: Of the 1182 patients who underwent BS at our institution during the study period, 1016 (85.9%) were women. Thirty-nine of these women (with an average age of 31 ± 4.8 years) became pregnant (one twin pregnancy) and 29 of the 39 had undergone a gastric bypass. The mean time interval between BS and pregnancy was 16.6 ± 4.8 months; however, 16 (41%) women became pregnant less than a year after BS. The pre-BS body mass index (BMI) of the 39 women was 44.5 ± 6.2 kg/m2 . The women had a mean BMI of 30.2 ± 3.8 kg/m2 when they got pregnant and they gained 13.2 ± 7.3 kg during pregnancy. Iron deficiency was observed in 18 (46.1%) women, 16 (45.7%) had vitamin B12 deficiency, 12 (66.8%) had zinc deficiency, and 20 (60.6%) had vitamin D deficiency. Three women developed gestational diabetes mellitus. Premature rupture of membranes occurred in two pregnancies, preterm delivery in five, and there was one spontaneous abortion. Cesarean section was performed in seven cases. The average newborn weight was 3002 ± 587 g, five were small for gestational age, and one had macrosomia. Three infants had to be admitted to an intensive care unit. CONCLUSION: Although pregnancy after BS is safe and well tolerated, close monitoring by a multidisciplinary team is required to evaluate complications resulting from BS, especially a deficit of micronutrients.

Acute Myocardial Response to Stretch: What We (don't) Know.

Myocardial stretch, as result of acute hemodynamic overload, is one of the most frequent challenges to the heart and the ability of the heart to intrinsically adapt to it is essential to prevent circulatory congestion. In this review, we highlight the historical background, the currently known mechanisms, as well as the gaps in the understanding of this physiological response. The systolic adaptation to stretch is well-known for over 100 years, being dependent on an immediate increase in contractility-known as the Frank-Starling mechanism-and a further progressive increase-the slow force response. On the other hand, its diastolic counterpart remains largely unstudied. Mechanosensors are structures capable of perceiving mechanical signals and activating pathways that allow their transduction into biochemical responses. Although the connection between these structures and stretch activated pathways remains elusive, we emphasize those most likely responsible for the initiation of the acute response. Calcium-dependent pathways, including angiotensin- and endothelin-related pathways; and cGMP-dependent pathways, comprising the effects of nitric oxide and cardiac natriuretic hormones, embody downstream signaling. The ischemic setting, a paradigmatic situation of acute hemodynamic overload, is also touched upon. Despite the relevant knowledge accumulated, there is much that we still do not know. The quest for further understanding the myocardial response to acute stretch may provide new insights, not only in its physiological importance, but also in the prevention and treatment of cardiovascular diseases.