Preoperative Plasma Aldosterone Predicts Complete Remission of Type 2 Diabetes after Bariatric Surgery.

INTRODUCTION: Bariatric surgery (BS) has beneficial effects on body weight and type 2 diabetes. However, 44-52%, 20-40%, and 19-25% of patients with type 2 diabetes who undergo sleeve gastrectomy, sleeve gastrectomy with duodenal-jejunal bypass, and Roux-en-Y gastric bypass, respectively, show insufficient improvement 1 year after BS. It is thus important to predict the improvement in type 2 diabetes before BS. Many hormones are related to hyperglycemia. However, the relationship between hormones and improvement in type 2 diabetes after BS has not been studied. We aimed to evaluate the relationship between the improvement in type 2 diabetes and hormones in patients with obesity and type 2 diabetes who underwent BS. METHODS: We retrospectively reviewed 79 patients with obesity and type 2 diabetes who underwent BS, with a follow-up period of 12 months. We analyzed the relationship between some clinical parameters and complete remission (CR) of type 2 diabetes after BS. Patients were divided into two groups (type 2 diabetes CR and non-CR). Multiple regression analysis was performed to determine the parameters associated with type 2 diabetes resolution after BS. RESULTS: BS significantly improved body weight and glucose metabolism. Preoperative liver function, glycated hemoglobin (HbA1c), insulin secretion (homeostatic model assessment [HOMA]2-%B), renin activity, plasma aldosterone level, and duration of type 2 diabetes were significantly different between the CR and non-CR groups. Multiple regression analysis showed that preoperative HbA1c, HOMA2-%B, aldosterone concentration, and duration of type 2 diabetes were predictors of CR of type 2 diabetes after BS. Plasma aldosterone was the strongest predictor. DISCUSSION/CONCLUSION: Preoperative plasma aldosterone levels were related to the CR of type 2 diabetes after BS. Measuring plasma aldosterone levels preoperatively is useful for predicting the CR of type 2 diabetes after BS.

Association of Plasma Xanthine Oxidoreductase with Arterial Stiffness in Type 2 Diabetes with Liver Dysfunction.

BACKGROUND: Type 2 diabetes is a risk factor for atherosclerosis. Oxidative stress, which is a causative factor in insulin resistance, leads to atherosclerosis in patients with diabetes. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is related to oxidative stress. We aimed to examine the influence of plasma XOR activity on arterial stiffness in patients with type 2 diabetes. METHODS: In total, 458 patients with type 2 diabetes not receiving antihyperuricemic agents were enrolled and their clinical parameters including plasma XOR activity and the cardio-ankle vascular index (CAVI) were measured. Patients were divided into the liver dysfunction and absence of liver dysfunction groups. Multiple regression analysis was performed. RESULTS: The median plasma XOR activity level was 64.3 pmol/h/mL (33.3-147.3 pmol/h/mL). Plasma XOR activity was correlated significantly and positively with aspartate transaminase and alanine transaminase (ρ > 0.5). The level of plasma XOR activity in the liver dysfunction group was eight-fold higher than that in the absence of liver dysfunction group. A significant positive correlation was observed between plasma XOR activity and the CAVI only in the liver dysfunction group (ρ = 0.3968, P < 0.0043). Multiple regression models demonstrated that plasma XOR activity was an independent predictor of the CAVI in the liver dysfunction group (P = 0.0055). CONCLUSIONS: Our results suggest that plasma XOR activity is associated with arterial stiffness and may have a role in atherosclerosis development in patients with type 2 diabetes and liver dysfunction.

The Relationship between Serum Insulin-Like Growth Factor-1 Levels and Body Composition Changes after Sleeve Gastrectomy.

INTRODUCTION: We previously reported that preoperative serum insulin-like growth factor-1 (IGF-1) is a predictor of total weight loss percentage (%TWL) after laparoscopic sleeve gastrectomy (LSG). IGF-1 may suppress muscle loss after surgery. IGF-1 almost accurately reflects the growth hormone (GH) secretion status, and GH has lipolytic effects. Therefore, IGF-1 may influence both the maintenance of skeletal muscle and the reduction of adipose tissue after LSG. The identification of the relationship between preoperative serum IGF-1 and body composition changes after LSG can help in understanding the pathophysiology of obesity. METHODS: We retrospectively reviewed 72 patients with obesity who underwent LSG and were followed up for 12 months. We analyzed the relationship between preoperative serum IGF-1 levels and body composition changes after LSG. A multiple regression model was used. RESULTS: LSG led to a significant reduction in body weight. Both body fat mass and skeletal muscle mass decreased after LSG. Preoperative serum IGF-1 levels significantly correlated with %TWL, changes in skeletal muscle mass, and body fat mass after LSG. The multiple regression model showed that preoperative serum IGF-1 levels were related to decreased body fat mass and maintaining skeletal muscle mass after LSG. DISCUSSION/CONCLUSION: Preoperative IGF-1 measurement helps predict not only successful weight loss but also decreases body fat mass and maintains skeletal muscle mass after LSG.

Determinants of type 2 diabetes remission after bariatric surgery in obese Japanese patients: a retrospective cohort study.

OBJECTIVE: Bariatric surgery (BS) improves glycemic control in type 2 diabetes; however, some patients show insufficient improvement. Understanding the pathophysiology of type 2 diabetes in obese patients can facilitate appropriate treatment for type 2 diabetes after BS. The homeostatic model assessment (HOMA) 2 enables the calculation of the values from C-peptide data and evaluation of insulin users. We aimed to evaluate the pathophysiology of type 2 diabetes using pre- and postoperative parameters and HOMA2 in obese patients who underwent BS. METHODS: We retrospectively reviewed data from 45 obese patients with type 2 diabetes who underwent BS. They were followed-up for 12 months. The relationship between the HOMA2 score and complete remission (CR) of type 2 diabetes after BS was analyzed. Patients with and without CR were assigned to the CR and non-CR groups, respectively. Multiple regression analysis was used to identify factors associated with improvement in type 2 diabetes after BS. RESULTS: BS significantly improved body weight and glucose metabolism. The preoperative glycosylated hemoglobin A1c level and insulin secretion (HOMA2-%B) significantly differed between the CR and non-CR groups. Postoperative weight reduction and improved insulin sensitivity correlated significantly with CR; multiple regression showed that the preoperative HOMA 2-%B independently predicted CR of type 2 diabetes after BS. CONCLUSION: Preoperative insulin secretion, improvement in insulin sensitivity, and weight reduction after BS are related to CR of type 2 diabetes after BS. The results better reveal the pathophysiology of and treatment for type 2 diabetes in obese patients who undergo BS.

Fatty acid desaturase 2 is up-regulated by the treatment with statin through geranylgeranyl pyrophosphate-dependent Rho kinase pathway in HepG2 cells.

Statins have been reported to increase the plasma concentration of arachidonic acid (AA), an omega-6 long chain polyunsaturated fatty acid (LCPUFA) in several clinical studies indicating that statins affect the endogenous synthesis of LCUFAs. In the present study, we investigated the roles of the intrinsic mevalonate cascade and Rho-dependent pathway in LCPUFA synthesis, especially focusing on fatty acid desaturases (Fads) 2, using the human hepatocellular carcinoma cell line HepG2. Cell number and the activity of caspase-3 and 7 (caspase-3/7) was measured using a commercial kit. Gene expression was analyzed by quantitative real-time PCR. Protein expression was detected by Western blot analysis. Atorvastatin decreased cell viability and increased caspase-3/7 activity in a dose-dependent manner. At lower concentrations, atorvastatin stimulated both mRNA and protein expression of Fads2, and increased mRNA expression of FADS1 and ELVOL5. Both mevalonate and geranylgeranyl-pyrophosphate (GGPP), but not cholesterol, fully reversed atorvastatin-induced upregulation of Fads2, and mevalonate-effected reversal was inhibited by treatment with the Rho-associated protein kinase inhibitor Y-27632. These data clearly demonstrated that in human HepG2 cells, statins affect the endogenous synthesis of LCPUFAs by regulation of not only Fads2, but also Fads1 and Elovl5, through the GGPP-dependent Rho kinase pathway.

Laparoscopic Sleeve Gastrectomy Significantly Increases Serum Lipoprotein Lipase Level in Obese Patients.

OBJECTIVES: Obesity is one of the causes of metabolic disorders. Laparoscopic sleeve gastrectomy (LSG) confers beneficial effects not only on body weight (BW) but also on metabolic disorders. The lipoprotein lipase (LPL) level in preheparin serum is associated with visceral adipose tissue and reflects insulin resistance. However, the change in serum preheparin LPL levels after LSG remains unclear. This study aimed to examine the effect of LSG on preheparin LPL level in obese patients compared with nonsurgical treatment. METHODS: We retrospectively reviewed a total of 100 obese patients who were treated for obesity and had preheparin LPL levels measured before and 12 months after LSG or after 12 months of nonsurgical treatment. Fifty-six patients received LSG (LSG group), and 44 patients had no surgical treatment (nonsurgical group). We compared clinical parameters such as body mass index (BMI), hemoglobin A1c (HbA1c), and preheparin LPL level before and 12 months after treatment. RESULTS: BMI and HbA1c decreased significantly in both groups, but decreases in both parameters were greater in the LSG group than in the nonsurgical group. Estimated glomerular filtration was significantly improved only in the LSG group. Preheparin LPL level increased significantly only in the LSG group (from 45.8 ± 21.6 to 75.0 ± 34.9 ng/mL, p < 0.001). Multiple regression identified LSG and decreased BMI as independent predictors of preheparin LPL level increase. CONCLUSIONS: These results suggest that LSG independently increases pre-heparin LPL level beyond BW reduction in obese patients.

Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells.

Numerous clinical studies have reported that statins increase the plasma concentration of arachidonic acid, which is an ω-6 long-chain polyunsaturated fatty acid (LCPUFA), and decrease the concentrations of eicosapentaenoic acid and docosahexaenoic acid, which are ω­3 LCPUFAs. These findings indicate that statins may affect the endogenous synthesis of LCPUFAs, which is regulated by fatty acid desaturases (FADSs) and elongation of very long­chain fatty acids proteins (ELOVLs). The present study aimed to investigate the roles of the intrinsic mevalonate cascade and Rho­dependent pathway in statin­induced regulation of these desaturases and elongases, as well as cell viability using mouse 3T3­L1 cells. mRNA expression was analyzed by quantitative polymerase chain reaction. Treatment with atorvastatin decreased cell viability and increased the mRNA expression levels of Fads1, Fads2 and ELOVL fatty acid elongase 5 (Elovl5) in a dose­dependent manner. Mevalonate and geranylgeranyl pyrophosphate (GGPP), but not cholesterol, fully reversed the atorvastatin­induced downregulation of cell viability and upregulation of gene expression; however, mevalonate itself did not affect cell viability and gene expression. The Rho­associated protein kinase inhibitor Y­27632 inhibited the mevalonate­ and GGPP­mediated reversal of atorvastatin­induced upregulation of Fads1, Fads2 and Elovl5. These findings indicated that statins may affect the endogenous synthesis of LCPUFAs by regulating Fads1, Fads2 and Elovl5 gene expression via the GGPP­dependent Rho kinase pathway in mouse 3T3-L1 cells.