Nicholas J. Swerdlow

Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.

Aneurysmal disease can affect any segment of the aorta, from the aortic root to the aortic bifurcation. The treatment of aortic aneurysms has evolved dramatically in the past 3 decades, with the introduction of endovascular aneurysm repair using stent grafts causing a major paradigm shift in the field of aortic aneurysm surgery. While the technical details of the management of aortic aneurysms vary greatly depending on the location of an aneurysm, the principles remain the same. Successful aortic aneurysm treatment depends on either open replacement or endovascular exclusion of the aneurysmal segment with healthy artery proximal and distal to the repair. Major aortic branches of the arch and visceral segment add additional technical complexity to aneurysms involving these regions. Even as endovascular repair becomes the primary treatment modality for most aortic aneurysms, open repair remains an essential treatment modality in many circumstances. Additionally, long-term results of endovascular repair suggest that younger patients with long life expectancy and low-perioperative risk may benefit more from open repair. Therefore, technical expertise in both endovascular and open treatment is necessary for a comprehensive aortic aneurysm surgery practice.

CONTEXT: The mechanisms by which Roux-en-Y gastric bypass surgery (GBP) results in sustained weight loss and remission of type 2 diabetes are not fully understood. OBJECTIVE: We hypothesized that the anorexic hormone oxyntomodulin (OXM) might contribute to the marked weight reduction and the rapid improvement in glucose metabolism observed in morbidly obese diabetic patients after GBP. METHODS: Twenty obese women with type 2 diabetes were studied before and 1 month after GBP (n=10) or after a diet-induced equivalent weight loss (n=10). Patients from both groups were matched for age, body weight, body mass index, and diabetes duration and control. OXM concentrations were measured during a 50-g oral glucose challenge before and after weight loss. RESULTS: At baseline, OXM levels (fasting and stimulated values) were indistinguishable between the GBP and the diet group. However, OXM levels rose remarkably in response to an oral glucose load more than 2-fold (peak, 5.25+/-1.31 to13.8+/-16.2 pmol/liter; P=0.025) after GBP but not after diet. The peak of OXM after glucose was significantly correlated with glucagon-like peptide-1 and peptide YY3-36. CONCLUSIONS: Our data suggest that the observed changes in OXM primarily occur in response to GBP and not as a consequence of weight loss. These changes were observed early after surgery and occurred in parallel with previously reported increases in incretins and peptide YY. We speculate that the combination of gut hormone changes is essential for the improved glucose homeostasis and may partially explain the success of this surgery on diabetes resolution and weight loss.