Medication and supplement pharmacokinetic changes following bariatric surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.

Sex-Specific Cardiometabolic Determinants of Postoperative Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Cardiometabolic diseases increase the risk of postoperative atrial fibrillation (POAF), a complication leading to higher long-term risk of major cardiovascular events (MACE). It remains unknown whether the effect of these risk factors differs according to sex. We sought to evaluate the sex-specific predictors of POAF after coronary artery bypass grafting (CABG). METHODS: In a prospective registry of patients undergoing isolated CABG, we compared predictors of POAF between sexes with logistic regression models. Because of high prevalence of abdominal obesity in women, > 80% having a waist circumference (WC) ≥ 88 cm, median WC values were used to define abdominal obesity (men ≥ 102 cm, women ≥ 100 cm). RESULTS: This analysis included 6177 individuals (17% women). Mean age was 65.6 ± 8.9 years. POAF occurred in 32% of men and 28% of women (P < 0.05). Compared with men, women with POAF had similar WC; higher prevalence of hypertension and diabetes; lower high-density lipoprotein (HDL)-cholesterol; and higher glucose, triglyceride, low- density lipoprotein (LDL)-cholesterol, and C-reactive protein levels (all P < 0.05). After adjustment, age and abdominal obesity were associated with POAF in both sexes (P < 0.05). The interaction of WC with sex suggested a worse impact of WC on POAF risk among women (adjusted odds ratio [OR], 1.97; 95% confidence interval [CI], 1.48-2.62 vs in men 1.33; 95% CI, 1.17-1.50; P for interaction = 0.01). CONCLUSIONS: Abdominal obesity is a major predictor of POAF in both sexes, with higher risk in women. These results emphasize the need for enhanced strategies to manage abdominal obesity and its cardiometabolic consequences in the general population and the potential to develop sex-specific preventive interventions to reduce risk of POAF.

Preoperative predictors of type 2 diabetes remission after bilio-pancreatic diversion with duodenal switch.

BACKGROUND: Many patients achieve short-term type 2 diabetes (T2D) remission after bariatric surgery, but relapses are common. Diabetes outcomes after bariatric surgery vary across procedures and populations. T2D remission scores are simple clinical tools developed to predict remission after bariatric surgery. However, they have never been tested after Biliopancreatic diversion with duodenal switch (BPD-DS). OBJECTIVES: The aim of this study was to compare the predictive value of T2D remission scores and preoperative diabetes characteristics in predicting T2D remission after BPD-DS. SETTING: Quebec Heart and Lung Institute - Laval University. METHODS: We retrospectively identified 918 patients with preoperative T2D who had undergone BPD-DS. Retrospective chart review was performed and variables used to calculate predictive scores were captured. T2D status was assessed annually for up to 10 years postop. Predictive values for each score (DiarRem, Ad Diarem, and Diabetter) and single preoperative diabetes characteristics used to construct these algorithms were evaluated by area under receiver operating characteristic curves (AUC). RESULTS: Diabetter showed greater performance for prediction of durable diabetes remission than other algorithms with acceptable discriminative ability (AUC between .69 and .79), but was not superior to T2D duration as a single predictor (P = .24 and P = .18). At 10 years, T2D duration had a better discriminative ability for the prediction of T2D remission than all 3 predictive models (AUC = .85, P < .05). CONCLUSIONS: Better chances for T2D remission following BPD-DS are associated with a shorter duration or T2D before surgery. Duration of T2D alone offers an excellent predictive ability and is a convenient alternative to diabetes remission scores to estimate chances of long-term diabetes remission after BPD-DS.

Early benefits of bariatric surgery on subclinical cardiac function: Contribution of visceral fat mobilization.

AIMS: We explored the early effects of bariatric surgery on subclinical myocardial function in individuals with severe obesity and preserved left ventricular (LV) ejection fraction. METHODS: Thirty-eight patients with severe obesity [body mass index (BMI) ≥35 kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) (Surgery group), 19 patients with severe obesity managed with usual care (Medical group), and 18 age and sex-matched non-obese controls (non-obese group) were included. Left ventricular global longitudinal strain (LV GLS) was evaluated with echocardiography speckle tracking imaging. Abnormal myocardial function was defined as LV GLS <18%. RESULTS: Age of the participants was 42 ±â€¯11 years with a BMI of 48 ±â€¯8 kg/m2 (mean ±â€¯standard deviation); 82% were female. The percentage of total weight loss at 6 months after bariatric surgery was 26.3 ±â€¯5.2%. Proportions of hypertension (61 vs. 30%, P = 0.0005), dyslipidemia (42 vs. 5%, P = 0.0001) and type 2 diabetes (40 vs. 13%, P = 0.002) were reduced postoperatively. Before surgery, patients with obesity displayed abnormal subclinical myocardial function vs. non-obese controls (LV GLS, 16.3 ±â€¯2.5 vs. 19.6 ±â€¯1.7%, P < 0.001). Six months after bariatric surgery, the subclinical myocardial function was comparable to non-obese (LV GLS, 18.2 ±â€¯1.9 vs. 19.6 ±â€¯1.7%, surgery vs. non-obese, P = NS). On the contrary, half of individuals with obesity managed medically worsened their myocardial function during the follow-up (P = 0.002). Improvement in subclinical myocardial function following bariatric surgery was associated with changes in abdominal visceral fat (r = 0.43, P < 0.05) and inflammatory markers (r = 0.45, P < 0.01), whereas no significant association was found with weight loss or change in insulin sensitivity (HOMA-IR) (P > 0.05). In a multivariate model, losing visceral fat mass was independently associated with improved subclinical myocardial function. CONCLUSIONS: Bariatric surgery was associated with significant improvement in the metabolic profile and in subclinical myocardial function. Early improvement in subclinical myocardial function following bariatric surgery was related to a greater mobilization of visceral fat depot, linked to global fat dysfunction and cardiometabolic morbidity.

Determinants of Cardiorespiratory Fitness After Bariatric Surgery: Insights From a Randomised Controlled Trial of a Supervised Training Program.

BACKGROUND: Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery-induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery. METHODS: Fifty-eight severely obese patients (46.1 ± 6.1 kg/m2, 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery. RESULTS: Weight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (V̇O2peak) increased significantly (P < 0.0001) in both groups but more importantly in the exercise group (exercise group: from 18.6 ± 4.2 to 23.2 ± 5.7 mL/kg/min; control group: from 17.4 ± 2.3 to 19.7 ± 2.4 mL/kg/min; P value, group × time = 0.01). In the exercise group, determinants of absolute V̇O2peak (L/min) were peak exercise ventilation, oxygen pulse, and heart rate reserve (r2 = 0.92; P < 0.0001), whereas determinants of V̇O2peak indexed to body mass (mL/kg/min) were peak exercise ventilation and early-to-late filling velocity ratio (r2 = 0.70; P < 0.0001). CONCLUSIONS: A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.

Effects of bariatric surgery on lipid-lipoprotein profile.

Most patients with severe obesity will present some lipid-lipoprotein abnormalities. The atherogenic dyslipidemia associated with severe obesity is characterized by elevated fasting and postprandial triglyceride levels, low high-density lipoprotein cholesterol concentrations, and increased proportion of small and dense low-density lipoproteins. Bariatric surgery has been proven safe and successful in terms of long-term weight loss and improvement in obesity co-existing metabolic conditions including lipid-lipoprotein abnormalities. Nevertheless, bariatric surgery procedures are not all equivalent. We conducted a comprehensive critical analysis of the literature related to severe obesity, bariatric surgery and lipid-lipoprotein metabolism/profile. In this review, we described the metabolic impacts of different bariatric surgery procedures on the lipid-lipoprotein profile, and the mechanisms linking bariatric surgery and dyslipidemia remission based on recent epidemiological, clinical and preclinical studies. Further mechanistic studies are essential to assess the potential of bariatric/metabolic surgery in the management of lipid-lipoprotein abnormalities associated with severe obesity. Understanding the beneficial effects of various bariatric surgery procedures on the lipid-lipoprotein metabolism and profile may result in a wider acceptance of this strategy as a long-term metabolic treatment of lipid-lipoprotein abnormalities in severe obesity and help clinician to develop an individualized and optimal approach in the management of dyslipidemia associated with severe obesity. BRIEF SUMMARY: Abnormal lipid-lipoprotein profile is frequent in patients with severe obesity. Significant improvements in lipid-lipoprotein profile following bariatric surgery occur early in the postoperative period, prior to weight loss, and persists throughout the follow-up. The mechanisms that facilitate the remission of dyslipidemia after bariatric surgery, may involve positive effects on adipose tissue distribution/function, insulin sensitivity, liver fat content/function and lipid-lipoprotein metabolism.

Clinical Impact of Weight-Loss Pharmacotherapy in Patients with Atherosclerotic Cardiovascular Disease.

Obesity is associated with the development and progression of multiple cardiovascular risk factors, such as hypertension, dyslipidemia, and type 2 diabetes mellitus, and is an important contributor to the global burden of atherosclerotic cardiovascular disease (CVD). Guidelines suggest that clinicians provide lifestyle counseling and promote lifestyle modifications before considering weight-loss surgery. However, despite lifestyle modifications and increased physical activity, most patients with obesity will not lose significant weight or will experience weight regain. Weight-loss pharmacotherapy added to lifestyle modification has long been perceived as a bridge between lifestyle modifications alone and weight-loss surgery. However, since its inception, weight-loss pharmacotherapy has been plagued by variable efficacy and concern about cardiovascular safety. Following requirements from regulatory authorities, efficacy and cardiovascular safety trials have been conducted for the currently available weight-loss pharmacotherapeutic agents. Overall, these trials have shown that weight-loss pharmacotherapy is only modestly efficient for the inducement of weight loss. Recent trials have also demonstrated the cardiovascular safety of some of these agents. We review these trials with a focus on the clinical impact of these weight-loss pharmacotherapeutic agents in patients with atherosclerotic CVD.

Secondary prevention after CABG: do new agents change the paradigm?

PURPOSE OF REVIEW: Coronary artery bypass graft (CABG) surgery remains the gold-standard treatment for multivessel and left main coronary artery disease. Despite significant improvement in cardiovascular outcomes, patients undergoing CABG remain at risk for recurrent adverse ischemic events and other cardiovascular outcomes (coronary revascularisation, stroke, cardiac death, etc.). The purpose of this review is to summarize the most recent evidence in pharmacological preventive therapies addressing the residual cardiovascular risk in patients who have undergone CABG. RECENT FINDINGS: Novel cardiovascular pharmacological preventive strategies targeting inflammatory, metabolic and prothrombotic (antiplatelet and anticoagulation) pathways have been recently assessed, with promising results for secondary prevention after CABG. SUMMARY: Secondary prevention is an essential part of postoperative care after CABG. Novel lipid-lowering and glucose-controlling agents suggest a strong and consistent benefit on native coronary artery disease and overall cardiovascular outcomes. The role and the choice of enhanced antiplatelet/anticoagulation/lipid/glucose-modulating therapies following CABG should be better defined and deserves further investigation. Additional studies are required to identify new therapeutic target addressing the specific multifactorial nature of the graft CV disease and identifying the best preventive strategies for long-term graft patency.

Acute and Chronic Impact of Biliopancreatic Diversion with Duodenal Switch Surgery on Plasma Lipoprotein(a) Levels in Patients with Severe Obesity.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) level is an independent risk factor for cardiovascular diseases. Lifestyle intervention studies targeting weight loss revealed little to no significant changes in Lp(a) levels. The impact of interventions that induce substantial weight loss, such as bariatric surgery, on Lp(a) levels is currently unclear. OBJECTIVE: To determine the acute and long-term impact of bariatric surgery on Lp(a) levels in patients with severe obesity. METHODS: Sixty-nine patients with severe obesity underwent biliopancreatic diversion with duodenal switch (BPD-DS) surgery. The lipid profile was evaluated and Lp(a) levels were measured before surgery and at 6 and 12 months after BPD-DS surgery. RESULTS: Median Lp(a) levels at baseline were 11.1 (4.1-41.6) nmol/L. Six months and 12 months after the BDP-DS surgery, we observed an improvement of lipid profile. At 6 months, we observed a 13% decrease in Lp(a) levels (9.7 (2.9-25.6) nmol/L, p < 0.0001) but this decrease was not sustained at 12 months (11.1 (3.9-32.8) nmol/L, p = 0.8). When the patients were separated into tertiles according to Lp(a) levels at baseline, we observed that the Lp(a) reduction at 12 months after BPD-DS surgery remained significant but modest in patients of the top Lp(a) tertile. CONCLUSION: Our results suggest that BPD-DS surgery modestly reduces Lp(a) levels in the short term (6 months) in patients with severe obesity but this improvement is sustained over time only in patients with higher Lp(a) levels.

Obesity Phenotypes, Diabetes, and Cardiovascular Diseases.

This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.

Impact of a 12-Week Randomized Exercise Training Program on Lipid Profile in Severely Obese Patients Following Bariatric Surgery.

PURPOSE: The benefit of exercise training on lipid profile in bariatric surgery patients is scarce. We assess the effect of a supervised exercise-training program on lipid profile following bariatric surgery. MATERIALS AND METHODS: A total of 60 patients were prospectively recruited, of those 49 completed the study (age 41 ± 11 years; body mass index 45.9 ± 6.1 kg/m2, 75% women). The bariatric surgery procedures performed were sleeve gastrectomy (SG) (n = 24) and biliopancreatic diversion with duodenal switch (BPD-DS) (n = 25). Of the 49 patients who completed the study, 34 had been randomized to a 12-week supervised exercise training program (exercise group) between the 3rd and the 6th month following bariatric surgery (SG = 17 and BPD-DS = 17). Fasting blood samples and anthropometric measurements were performed preoperatively and at 3, 6, and 12 months after bariatric surgery. RESULTS: At 6 months and 12 months, percentage of weight loss was similar between groups (6 months: - 29.6 ± 5.5 vs. - 27.8 ± 7.7%; P = 0.371; 12 months: - 38.4 ± 10.4 vs. - 37.9 ± 9.5%; P = 0.876 exercise vs. control). Both groups had an increase in HDL values between the 3nd and the 6th month following bariatric surgery. There was a significantly greater increment in HDL values in the exercise group (0.18 ± 0.14 vs. 0.07 ± 0.12 mmol/L, P = 0.014; exercise vs. control). CONCLUSION: Our results showed a beneficial effect of a 12-week supervised exercise-training program in bariatric surgery patients showing similar weight loss on HDL-cholesterol levels without additional effect on LDL-cholesterol levels.

Changes in fat-free mass and muscle mass at 6 and 12 months after biliopancreatic diversion with duodenal switch surgery.

BACKGROUND: Bariatric surgery is associated with concomitant loss in both fat and muscle masses. Literature on muscle composition/quality after bariatric surgery is limited. OBJECTIVES: To measure and compare the changes in fat-free mass with the changes in muscle composition after biliopancreatic diversion with duodenal switch surgery (BPD/DS). SETTING: Bariatric surgery is associated with concomitant loss in both fat and muscle masses. Literature on muscle composition/quality after bariatric surgery is limited. METHODS: Forty patients underwent BPD/DS and 22 patients are considered as controls. Bioelectrical impedance analysis (body composition) and computed tomography scan at the midthigh and abdominal levels (muscle composition) were performed at baseline, 6, and 12 months. RESULTS: At 6 and 12 months, the BPD/DS group displayed significant reduction in weight (12 months: -46.6 ± 13.5 kg) and fat-free mass (12 months: -8.2 ± 4.4 kg; both P < .001). A significant reduction in abdominal (-15 ± 8%, P < .001) and midthigh muscle areas (-18 ± 7%, P < .001) was observed during the first postoperative 6 months, followed by a plateau after 6 months (abdominal: -1 ± 5%, midthigh: -1 ± 4%, both P > .05). At 6 months, both midthigh fat-infiltrated muscle (-22 ± 10%, P < .001) and normal-density muscle (-16 ± 9%, P < .001) areas decreased. Further reduction at 12 months was only observed in the fat-infiltrated muscle (-11 ± 8%, P < .001) in comparison with an increase in the normal-density muscle area (5 ± 8%, P = .001). There was no significant change for the control group. CONCLUSIONS: Reduction in muscle, assessed with computed tomography scans, occurs mostly during the first 6 months postoperatively after BPD/DS. Focus on muscle quantity as well as quality, using precise imaging methods, instead of quantifying total body lean mass, is likely to provide better assessment in body content modulation after BPD/DS.

Metabolic profiles among COPD and controls in the CanCOLD population-based cohort.

A high prevalence of intermediate cardiometabolic risk factors and obesity in chronic obstructive pulmonary disease (COPD) has suggested the existence of pathophysiological links between hypertriglyceridemia, insulin resistance, visceral adiposity, and hypoxia or impaired pulmonary function. However, whether COPD contributes independently to the development of these cardiometabolic risk factors remains unclear. Our objective was to compare ectopic fat and metabolic profiles among representative individuals with COPD and control subjects and to evaluate whether the presence of COPD alters the metabolic risk profile. Study participants were randomly selected from the general population and prospectively classified as non-COPD controls and COPD, according to the Global Initiative for Chronic Obstructive Lung Disease classification. The metabolic phenotype, which consisted of visceral adipose tissue area, metabolic markers including homeostasis model assessment of insulin resistance (HOMA-IR), and blood lipid profile, was obtained in 144 subjects with COPD and 119 non-COPD controls. The metabolic phenotype was similar in COPD and controls. The odds ratios for having pathologic values for HOMA-IR, lipids and visceral adipose tissue area were similar in individuals with COPD and control subjects in multivariate analyses that took into account age, sex, body mass index, tobacco status and current medications. In a population-based cohort, no difference was found in the metabolic phenotype, including visceral adipose tissue accumulation, between COPD and controls. Discrepancies between the present and previous studies as to whether or not COPD is a risk factor for metabolic abnormalities could be related to differences in COPD phenotype or disease severity of the study populations.

Acute and chronic effect of bariatric surgery on circulating autotaxin levels.

Autotaxin (ATX), an adipose tissue-derived lysophospholipase, has been involved in the pathophysiology of cardiometabolic diseases. The impact of bariatric surgery on circulating ATX levels is unknown. We examined the short- (24 h, 5 days) and longer-term (6 and 12 months) impact of bariatric surgery; as well as the short-term effect of caloric restriction (CR) on plasma ATX levels in patients with severe obesity. We measured ATX levels in 69 men and women (mean age: 41 ± 11 years, body mass index: 49.8 ± 7.1 kg/m2 ), before and after biliopancreatic diversion with duodenal switch surgery (BPD-DS) as well as in a control group (patients with severe obesity without surgery; n = 34). We also measured ATX levels in seven patients with severe obesity and type 2 diabetes who underwent a 3-day CR protocol before their BPD-DS. At baseline, ATX levels were positively associated with body mass index, fat mass, insulin resistance (HOMA-IR) as well as insulin and leptin levels and negatively with fat-free mass. ATX concentrations decreased 26.2% at 24 h after BPD-DS (342.9 ± 152.3 pg/mL to 253.2 ± 68.9 pg/mL, P < 0.0001) and by 16.4% at 12 months after BPD-DS (342.9 ± 152.3 pg/mL to 286.8 ± 182.6 pg/mL, P = 0.04). ATX concentrations were unchanged during follow-up in the control group (P = 0.4), and not influenced by short-term CR. In patients with severe obesity, bariatric surgery induced a rapid and sustained decrease in plasma ATX levels. Acute changes in ATX may not be explained by bariatric surgery-induced CR.

Benefits of 1-Year Lifestyle Modification Program on Exercise Capacity and Diastolic Function Among Coronary Artery Disease Men With and Without Type 2 Diabetes.

BACKGROUND: To assess the benefits of a 1-year lifestyle modification program on exercise capacity and diastolic function in men with left ventricular (LV) diastolic dysfunction (LVDD) and coronary artery disease (CAD), according to glucose tolerance status. METHODS: Fifty-three men (62 ± 8 years; BMI: 27.3 ± 3.5 kg/m2) with LVDD and CAD were enrolled in a 1-year lifestyle modification program based on dietary management and increased physical activity. Patients were classified by using a 75 grams oral glucose tolerance test as having normal glucose tolerance (n = 16), prediabetes (n = 23), or type 2 diabetes mellitus (T2DM) (n = 14). Cardiac morphology and function, visceral fat, and cardiac fat depots were measured using magnetic resonance imaging, whereas exercise capacity [cardiorespiratory fitness (CRF)] (VO2peak) was assessed with a maximal treadmill test. RESULTS: The 1-year lifestyle modification program was associated with reductions in body weight, and visceral and cardiac fat levels (all P < 0.05). CRF increased by 13% (24.9 ± 4.1 vs. 28.2 ± 4.8 mL O2/kg/min, P < 0.0001). Moreover, half of patients (53%) improved LV diastolic function in response to the lifestyle intervention. Multiple regression analyses revealed that age (partial R2 = 26.9, P < 0.0001) and presence of T2DM (partial R2 = 5.9, P = 0.04) were the stronger predictors of change in diastolic function, while favorable change in LV remodeling index was the best predictor of improvement in LV diastolic function after the lifestyle intervention (R2 = 21.9, P = 0.002). CONCLUSIONS: Irrespective of glucose tolerance status, a 1-year lifestyle modification program in men with LVDD and CAD is associated with significant improvements in exercise capacity and LV diastolic function in more than half of patients.

Obesity, ectopic fat and cardiac metabolism.

INTRODUCTION: Obesity is recognized as a risk factor for cardiovascular disease, expending independent adverse effects on the cardiovascular system. This relationship is complex due to several associations with cardiovascular disease risk factors/markers such as hypertension, dyslipidemia, insulin resistance/dysglycemia, or type 2 diabetes mellitus. Obesity induces a variety of cardiovascular system structural adaptations, from subclinical myocardial dysfunction to severe left ventricular systolic heart failure. Abnormalities in cardiac metabolism and subsequent cardiac energy, have been proposed as major contributors to obesity-related cardiovascular disease. Ectopic fat depots play an important role in several of the hypotheses postulated to explain the association between obesity, cardiac metabolism and cardiac dysfunction. AREAS COVERED: In this review, we addressed with contemporary studies how obesity-associated metabolic conditions and ectopic cardiac fat accumulation, translate into cardiac energy metabolism disturbances that may lead to adverse effects on the cardiovascular system. EXPERT COMMENTARY: Obesity and ectopic fat accumulation has long been related to metabolic diseases and adverse cardiovascular outcomes. Recent imaging advances have just started to address the complex interplays between obesity, ectopic fat depots, cardiac metabolism and the risk of obesity-related cardiovascular disease. A better comprehension of these obesity-associated metabolic disturbances will lead to earlier detection of patients at increased risk of cardiovascular disease and to the development of novel therapeutic metabolic targets to treat a wide variety of cardiovascular diseases.

Safety of Blood Glucose Response Following Exercise Training After Bariatric Surgery.

INTRODUCTION: Safety of exercise training in relationship with the risk of hypoglycemia post-bariatric surgery is unknown. OBJECTIVE: To evaluate the safety and magnitude of changes in blood glucose levels during exercise training following bariatric surgery. MATERIAL AND METHODS: Twenty-nine severely obese patients undergoing either sleeve gastrectomy (SG) (n = 16) or biliopancreatic diversion with duodenal switch (BPD-DS) (n = 13) were prospectively enrolled. Three months after surgery, patients participated in a 12-week supervised exercise training program, (35-min aerobic training with a 25-min resistance exercises) three times a week. Capillary blood glucose (CBG) levels were measured immediately before and after each exercise session. RESULTS: Seven patients (24%) had type 2 diabetes before surgery (mean duration: 10 years); four patients still have type 2 diabetes 3 months post-bariatric surgery. A total of 577 exercise training sessions with CBG monitoring were recorded. Only seven sessions (1.2%) were associated with an episode of asymptomatic hypoglycemia (CBG ≤ 3.9 mmol/L). Patients with type 2 diabetes at baseline showed a larger decrease in CBG with pre-exercise CBG being between 6.1 and 8.0 mmol/L (- 1.6 ± 1.2 vs. - 1.1 ± 0.9 mmol/L, p = 0.02). BPD-DS patients with CBG ≥ 6.1 mmol/L showed higher reduction in CBG following exercise vs. SG patients (- 1.7 ± 1.0 vs. - 1.1 ± 1.1 mmol/L; p < 0.001 and - 4.3 ± 1.0 vs. - 2.2 ± 1.4 mmol/L, p < 0.001, respectively). CONCLUSION: Three months after bariatric surgery, exercise training program in patients without and with type 2 diabetes is safe, and is associated with a desirable glycemic profile, with few episodes of asymptomatic hypoglycemia.

Overview of Epidemiology and Contribution of Obesity and Body Fat Distribution to Cardiovascular Disease: An Update.

Obesity is recognized as a heterogeneous condition in which individuals with similar body mass index may have distinct metabolic and cardiovascular risk profiles. Susceptibility to obesity-related cardiometabolic complications is not solely mediated by overall body fat mass, but is largely dependent upon individual differences in regional body fat distribution and ability of subcutaneous adipose tissue to expand. The present review will discuss to what extent the individual variation in body fat distribution is one of the clinical key variables explaining the metabolic heterogeneity of obesity and its related cardiovascular risk. We will present the evidence for the complex nature of the relationship between obesity and cardiovascular disease, outline our current understanding of the mechanisms involved, and identify future direction of research pertinent to this interaction.