Diabetes remission after bariatric surgery is characterized by high glycemic variability and high oxidative stress.

BACKGROUND AND AIM: To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS). METHODS AND RESULTS: Twenty-two patients (M/F10/12, age 50 ± 9 years, BMI 31 ± 6 kg/m2) who were in remission of T2DM (T2DM remitters) after BS since at least 1 year and 22 age-, sex- and BMI-matched control subjects were studied. Of the BS group, eleven subjects had undergone Roux-en-Y gastric bypass (RYGB) and eleven subjects sleeve gastrectomy (SG). Oral glucose tolerance test (OGTT), 7 days-continuous glucose monitoring, 24-h urinary excretion of 8-isoprostaglandin F2α (8-isoPGF2α) and dietary intake evaluation were performed. According to general linear model for repeated measures, glucose and insulin response during OGTT were significantly different in T2DM remitter than in control subjects (p < 0.001, for both). All measures of GV (standard deviation, coefficient of variation and mean amplitude of glucose excursions) were significantly higher in T2DM remitters than in controls, (p < 0.001 for all). These indexes were higher among RYGB than SG patients (p < 0.05). The time spent out of the 60-160 mg/dl range was significantly longer in T2DM remitters undergoing RYGB than in controls (p < 0.02). Mean 24-h urinary 8-isoPGF2α excretion was significantly higher in T2DM remitters than that of control subjects (p = 0.04). All GV indexes were directly correlated with blood glucose levels at 30 and 60 min during OGTT (p < 0.05-0.001). CONCLUSION: Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.

Comparative Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Glucose Homeostasis and Incretin Hormones in Obese Type 2 Diabetic Patients: A One-Year Prospective Study.

The aim of the work was to compare the hormonal and the metabolic mechanisms involved in weight loss and remission of T2DM one year after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in morbidly obese type 2 diabetic (T2DM) patients. Insulin sensitivity, insulin secretion, and the gastrointestinal (GI) hormone response to a mixed meal test (MMT) were evaluated before and one year after BS (14 RYGB and 19 VSG). RYGB and VSG groups had similar characteristics at baseline. Weight loss at one year was similar in the 2 groups (ΔBMI%: - 32±10 and - 30±7%, p=0.546). Insulin sensitivity and insulin secretion improved similarly after either procedures with a similar rate in T2DM remission (86% in RYGB and 76% in VSG). Meal-stimulated GLP-1 levels increased after both procedures reaching significantly higher levels after RYGB (p=0.0001). GIP response to MMT decreased to a similar extent after the 2 interventions (p=0.977). Both fasting and post-meal ghrelin concentrations were markedly suppressed after VSG and significantly lower than RYGB (p=0.013 to p=0.035). The improvement of insulin sensitivity and beta-cell function was significantly associated with weight loss (p=0.014 to p=0.035), while no relation was found with the changes in GI hormones. In conclusion, in morbidly obese T2DM patients, RYGB and VSG result in similar improvements of the glucose status in the face of different GI hormonal pattern. Weight loss is the key determinant of diabetes remission one year after surgery.

Insulin resistance, postprandial GLP-1 and adaptive immunity are the main predictors of NAFLD in a homogeneous population at high cardiovascular risk.

BACKGROUND AND AIMS: The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk. METHODS AND RESULTS: In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and ß-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers. H/R correlated positively with fasting and OGTT plasma glucose and insulin concentrations, HOMA-IR and ß-cell function, and IL-4, IL-17, IFN-γ, TNF-α, FGF and GCSF plasma concentrations (p < 0.05 for all), and negatively with insulin sensitivity (OGIS), dietary, polyphenols and fiber (p < 0.05 for all). By multiple stepwise regression analysis, the best predictors of H/R were OGIS (ß = -0.352 p = 0.001), postprandial GLP-1 (ß = -0.344; p = 0.001), HDL-cholesterol (ß = -0.323; p = 0.002) and IFN-γ (ß = 0.205; p = 0.036). CONCLUSION: A comprehensive evaluation of factors associated with liver fat, in a homogeneous population at high cardio-metabolic risk, indicated a pathogenic combination of the same pathways underlying the atherosclerotic process, namely whole body insulin sensitivity and inflammation. The higher predictive value of postprandial variables suggests that liver fat is essentially a postprandial phenomenon, with a relevant role possibly played by GLP-1. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT01154478.

A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome.

BACKGROUND AND AIM: Until recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome. METHODS AND RESULTS: Sixty-one men and women age range 40-65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated. CONCLUSIONS: A twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease.

Effects of Sleeve Gastrectomy and Gastric Bypass on Postprandial Lipid Profile in Obese Type 2 Diabetic Patients: a 2-Year Follow-up.

BACKGROUND: Bariatric surgery (BS) is known to favorably impact fasting lipid profile. Fasting and postprandial lipids were evaluated before and 2 years after BS in obese type 2 diabetic (T2DM) patients. METHODS: A prospective study was conducted in 19 obese T2DM patients: ten undergoing sleeve gastrectomy (SG) and nine undergoing Roux-en-Y gastric bypass (RYGB). Before and 2 years after BS, clinical parameters and the response of lipid and incretin hormones to a mixed meal (MM) were assessed. RESULTS: The two groups had similar characteristics at baseline. After BS, weight loss was similar in the two groups (p ≤ 0.01). Fasting glucose, insulin, and triglycerides decreased while HDL cholesterol increased in a similar way (p < 0.05); in contrast, fasting LDL cholesterol decreased only after RYGB (p < 0.05). Post-meal glucose concentrations decreased while early insulin response significantly improved after both procedures (p < 0.001 for both). Postprandial triglycerides decreased after both procedures (p < 0.05) while postprandial LDL cholesterol decreased only after RYGB (p < 0.05). Meal-GLP-1 increased postoperatively in both groups although to a greater extent after RYGB (p < 0.001 vs. SG). GIP decreased after both procedures, especially after RYGB (p = 0.003). At multivariate analysis, GLP-1 peak was the best predictor of LDL reduction (ß = -0.552, p = 0.039) while the improvement of HOMA-IR (ß = 0.574, p = 0.014) and weight loss (ß = 0.418, p = 0.036) predicted triglycerides reduction. CONCLUSIONS: Both surgical procedures markedly reduce fasting and postprandial triglycerides and increase HDL cholesterol levels. LDL cholesterol decreases only after RYGB through a mechanism likely mediated by the restoration of GLP-1.

Clinical efficacy of bariatric surgery versus liraglutide in patients with type 2 diabetes and severe obesity: a 12-month retrospective evaluation.

AIMS: To evaluate the clinical efficacy of bariatric surgery vs medical therapy with liraglutide on weight loss, glycemic control and cardiovascular risk profile in patients with type 2 diabetes and severe obesity. METHODS: A retrospective evaluation was conducted in 31 patients with type 2 diabetes and severe obesity who had undergone bariatric surgery and in 31 patients with type 2 diabetes and comparable body weight who had added liraglutide to their background medical treatment in the period 2009-2013. Anthropometric parameters, glycemic control, treatment of diabetes and other comorbidities, safety and side effects before and 12 months after treatment were assessed. RESULTS: Age was 47 ± 8 years (mean ± SD) in bariatric surgery and 56 ± 9 years in medical treatment group (p < 0.001); body mass index before treatment was 44 ± 7 and 40 ± 4 kg/m(2) in bariatric surgery and medical treatment, respectively (p = 0.03). Twelve months after treatment, average weight loss was 38 ± 15 kg among bariatric surgery patients, and 5 ± 8 kg in medical treatment group (p < 0.001). Glycemic control improved in both groups with greater improvement in bariatric surgery patients. The UKPDS risk score decreased in both groups, although it remained higher in medical treatment than in bariatric surgery patients (p < 0.001). Of note, almost 60 % of patients on liraglutide met the target of glycated hemoglobin <7 % (53 mmol/mol) and lost ≥5 % of body weight. CONCLUSIONS: In severely obese type 2 diabetic patients, bariatric surgery reduced body weight and improved overall metabolic control to a greater extent than medical treatment. Randomized clinical studies are necessary.

Early improvement of postprandial lipemia after bariatric surgery in obese type 2 diabetic patients.

BACKGROUND: Bariatric surgery (BS) is able to positively influence fasting lipid profile in obese type 2 diabetic patients (T2DM), but no data is available on the impact of BS on postprandial lipid metabolism neither on its relation with incretin hormones. We evaluated the short-term (2 weeks) effects of BS on fasting and postprandial lipid metabolism in obese T2DM patients and the contribution of changes in active GLP-1. METHODS: We studied 25 obese T2DM patients (age = 46 ± 8 years, BMI = 44 ± 7 kg/m2), of which 15 underwent sleeve gastrectomy and 10 underwent gastric bypass. Lipid and incretin hormone concentrations were evaluated for 3 h after ingestion of a liquid meal before and 2 weeks after BS. RESULTS: After BS, there was a significant reduction in body weight (p < 0.001), fasting plasma glucose (p < 0.001), fasting plasma insulin (p < 0.05), HOMA-IR (p < 0.001), and fasting plasma lipids (p < 0.05). The meal response of plasma triglycerides, total cholesterol, and HDL cholesterol was significantly lower compared to pre-intervention (p < 0.05, p < 0.001). In particular, the incremental area under the curve (IAUC) of plasma triglycerides decreased by 60% (p < 0.005). The meal-stimulated response of active GLP-1 increased, reaching a statistical significance (p < 0.001). CONCLUSIONS: BS leads to an early improvement of fasting and postprandial lipemia. The fall in fasting triglycerides is associated with an improvement of insulin resistance, while the reduction of postprandial lipemia is likely related to reduced intestinal lipid absorption consequent to bariatric surgery.

Test meals rich in marine long-chain n-3 polyunsaturated fatty acids increase postprandial chylomicron response.

Postprandial lipid abnormalities are considered an independent cardiovascular risk factor. Hence, it is important to find nutritional strategies that are able to positively influence these abnormalities. Since the effect of n-3 polyunsaturated fatty acids (PUFA) and polyphenols on postprandial lipids in humans is still under debate, we evaluated the acute response of triglyceride-rich lipoproteins to test meals that are naturally rich in polyphenols and/or marine long-chain (LC) n-3 PUFAs. We hypothesized that LC n-3 PUFA would have a different effect on chylomicron and very low density lipoproteins when compared with polyphenols or their combination. We randomly assigned 78 individuals who were at high cardiometabolic risk to 4 isoenergetic diets. These diets only differed in amount of LC n-3 PUFA and/or polyphenols. Prior to starting the intervention, each subject underwent a test meal similar to the type of diet assigned: low in LC n-3 PUFA and polyphenols (control), rich in LC n-3 PUFA and low in polyphenols, rich in polyphenols and low in LC n-3 PUFA, or rich in both. Blood samples were taken before and up to 6 hours after the test meal in order to evaluate cholesterol and triglycerides (plasma and triglyceride-rich lipoprotein), apolipoprotein B-48 (large very low density lipoprotein), glucagon-like peptide-1, and free fatty acid plasma levels. The levels of chylomicron cholesterol and triglyceride in response to the test meal rich in LC n-3 PUFA were significantly higher than after the control meal (P = .037 and P = .018); there was no difference in the other variables. In conclusion, this study indicates that acute administration of marine LC n-3 PUFA increases postprandial chylomicron response in contrast with their lowering chronic effects. These differences underline the importance of understanding the acute and chronic effects of nutritional, as well as of other types of, interventions.