Abstract
Extensive evidence supports the efficacy of bariatric surgery in reducing body weight and obesity-related comorbidities in severely obese patients. The present project was designed to assess the impact of bariatric surgery on clinically-relevant outcomes and to highlight the pros and cons of this therapeutic tool on specific metabolic, cardiovascular and nutritional aspects. In our studies, we found a significant improvement of glucose and lipid homeostasis in obese T2DM patients 1-2 years after bariatric surgery. The rate of diabetes remission at 1 year was 76% after SG and 86% after RYGB and the two major determinants of glucose homeostasis, i.e. beta cell function and insulin sensitivity, improved to a similar extent after either procedures. These results were achieved in the face of a different pattern of GI hormone profile, suggesting that weight loss and the consequent improvement of insulin sensitivity are the main determinants of diabetes remission, at least several months after surgery. Interestingly, while plasma triglycerides decreased to a similar extent with the two procedures, total and LDL-cholesterol decreased more consistently after RYGB than SG; furthermore, the decrease in LDL-cholesterol was inversely related to meal-induced GLP-1 response suggesting that GLP-1 restoration is crucial for the improvement of cholesterol metabolism, possibly through an increase in circulating bile acids. The overall metabolic improvement induced by bariatric surgery translates into clear benefits in terms of cardiovascular risk. Indeed, we have documented a reduction in carotid intima-media thickness and an increase in endothelial function after bariatric procedures. These changes in markers of subclinical atherosclerosis are in line with the reduction in cardiovascular morbidity and mortality, consistently shown by large population studies. Thus, the cardioprotective effects of bariatric surgery range from improvement in early signs of subclinical atherosclerosis to prevention of major fatal and non-fatal cardiovascular and cerebrovascular events. Further extending this finding, we have documented that bariatric surgery is able to improve the obesity-related hypercoagulable state characterized by increased levels of clotting factors and impaired fibrinolysis. However, it is important to note that at 2-month post-operative follow-up, we observed a significant decrease in natural anticoagulants, probably due to reduction of vitamin K absorption. This decrease could potentially lead to increased thrombotic risk. Since our data have been obtained in the early post-operative phase, no definite conclusion on the long-term effect of bariatric surgery on coagulant/anticoagulant balance can be drawn. Despite the proven efficacy of bariatric surgery in improving overall metabolic control and reducing total and cardiovascular mortality, some concerns can be raised regarding two main points: 1) increased glucose variability and 2) alterations of nutritional status. With regard to the former, we have found that some patients classified as diabetes remitters according to currently validated criteria, suffer from high glycemic variability, i.e., they present ample glucose excursions throughout the day, often reaching frank hypoglycemic threshold. This alteration is likely to be underdiagnosed since it can be detected only by continuous glucose monitoring. Even more interesting is the observation that high GV is associated with increased oxidative stress, indicating an increased risk of vascular damage. Based on these findings, we propose that GV be included among criteria for the definition of diabetes remission in order to have a comprehensive picture of the impact of bariatric surgery on glucose homeostasis. Furthermore, since high GV is likely involved in the pathogenesis of vascular complications and mortality risk, at least in diabetic patiens, ad hoc studies should be performed to identify and to manage appropriately glycemic variability. Of great interest is the possibility to reduce GV by proper nutritional measures, such as low-glycemic index food. The latter issue is one that involves nutrient deficiencies. Several studies have consistently documented a high prevalence of vitamin and mineral deficiencies after bariatric procedures. Poor postoperative nutrient intake, recurrent vomiting, inadequate supplementation are important risk factors. In addition, reviewing the available literature, we have documented that a considerable number of obese patients present vitamin and/or micronutrient deficiencies already before surgery, vitamin D deficit being the most frequent abnormality (about 60%). The high prevalence of pre-operative nutritional deficiency underlines the need of a careful nutritional screening in all patients scheduled for bariatric surgery in order to detect and correct any possible deficiency before intervention. Likewise, effective strategies should be implemented to improve long-term patients’ adherence to lifestyle and nutritional recommendations in order to maximize the benefits of bariatric surgery and reducing the risk of the above discussed complications.
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