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.

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.

Contrast-enhanced ultrasound evaluation of peripheral microcirculation in diabetic patients: effects of cigarette smoking.

PURPOSE: Cigarette smoking and diabetes mellitus predisposes to vascular disease. Our study aimed to evaluate the chronic effects of cigarette smoking on peripheral microcirculation assessed with contrast-enhanced ultrasound (CEUS) in diabetic patients. MATERIALS AND METHODS: The study population comprised ten smoker (7/3 M/W, age 42-76 years) and 16 nonsmoker (8/8 men/women, age 47-80 years) diabetic patients. The ankle-brachial index (ABI) was determined, and colour Doppler ultrasound (CDUS) of the lower legs was performed to determine the presence of peripheral arteriopathy disease (PAD). Microvascular blood flow in the gastrocnemius muscle was evaluated with CEUS. RESULTS: No differences were observed in ABI and CDUS examination between smokers and nonsmokers. Smoking had a significant effect on microcirculatory function. Timeto-peak (TTP), arrival time in tissue (ATt) and artery/ tissue transit time (A/Ttt) were significantly prolonged in smokers (TTP 43.76 ± 9.38 s vs. 34.12 ± 6.8 s, p=0.011, ATt 28.9 ± 7.5s vs. 22.4 ± 6.4 s, p=0.017 and A/Ttt 6.81 ± 4.52 s vs. 3.25 ± 3.27 s, p=0.02), with no significant differences between patients with and without PAD. CONCLUSIONS: The long-term exposure to cigarette smoke affects microcirculatory function. Contrast imaging is a noninvasive technique that can document these effects.

Impact of sleeve gastrectomy on weight loss, glucose homeostasis, and comorbidities in severely obese type 2 diabetic subjects.

This study was undertaken to assess medium-term effects of laparoscopic sleeve gastrectomy (LSG) on body weight and glucose homeostasis in severely obese type 2 diabetic (T2DM) subjects. Twenty-five obese T2DM subjects (10 M/15 F, age 45 ± 9 years, BMI 48 ± 8 kg/m(2), M ± SD) underwent evaluation of anthropometric/clinical parameters and glucose homeostasis before, 3 and 9-15 months after LSG. Mean BMI decreased from 48 ± 8 kg/m(2) to 40 ± 9 kg/m(2) (P < .001) at 3 months and 34 ± 6 kg/m(2) (P < .001) at 9-15 months after surgery. Remission of T2DM (fasting plasma glucose < 126 mg/dL and HbA1c < 6.5% in the absence of hypoglycemic treatment) occurred in all patients but one. There was a remarkable reduction in the percentage of patients requiring antihypertensive and hypolipidemic drugs. Our study shows that LSG is effective in producing a significant and sustained weight loss and improving glucose homeostasis in severely obese T2DM patients.

Diabetes, vascular complications and antiplatelet therapy: open problems.

Diabetes mellitus is commonly associated with both microvascular and macrovascular complications (coronary artery disease, cerebrovascular events, severe peripheral vascular disease, nephropathy and retinopathy). There is wide evidence demonstrating that platelet degranulation and synthesis of TxA2 are increased in diabetic patients. For this reason, many studies on anti-platelet therapy have been made to reduce thrombotic complication of diabetes mellitus. Some diabetic patients, although treated with ASA, have a high prevalence of recurrent thrombotic events, which may presumably be due to an "ASA resistance". Nevertheless, this drug remains the one with the greatest benefit. To optimize its function, we should try to understand the causes of "aspirin resistance", try to find the most suitable dosage, recommending patients to comply constantly with the prescription given and to avoid interactions with other drugs. "Clopidogrel resistance" is a term not clearly defined. The clinical implications of "clopidogrel resistance" are unknown. An important consideration affecting the use of aspirin in diabetic patients is its interaction with ACE-inhibitors. Another question is antiplatelet therapy in nephropathic diabetic patients. Although these patients are at high thrombotic and haemorrhagic risk, they should nevertheless be considered eligible to undergo antithrombotic therapy, taking into account the individual's haemorrhagic risk.

Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women.

UNLABELLED: In humans, dehydroepiandrosterone (DHEAS) has been postulated to have anabolic and lipolytic properties that could potentially counteract the catabolic effect of cortisol. DHEAS secretion is reduced in morbid obesity, likely due to hyperinsulinemia, and laparoscopic adjustable gastric banding (LASGB), by inducing considerable and rapid weight loss, reduces insulin levels. To investigate the role of decreased insulin levels after LASGB-induced weight loss on DHEAS levels and on body composition changes, we studied 30 pre-menopausal morbidly obese women (BMI ranging 37-62 kg/m2) before, 6, 12 and 24 months after LASGB. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis; tissue hydration was also assessed by impedance vector analysis. At study ending, the subjects had a total weight loss of 28% of baseline body weight (15% after 6 months). After LASGB, weight loss was mainly due to decreased FM, and TBW, FFM, and body hydration were not significantly reduced. Weight loss was associated with an 82% rise in serum DHEAS already after 6 months while cortisol, cortisol/DHEAS molar ratio, and insulin levels fell by 5.5, 62 and 50%, respectively, after 6, 12 and 24 months (p<0.05). CONCLUSIONS: LASGB associated with a well balanced low-calorie diet permits a satisfactory 2-yr weight loss, sparing FFM and without body fluid alterations. As the result of a stable weight reduction program weight loss is associated to decrease in cortisol, cortisol/DHEAS molar ratio, and insulin plasma levels with marked rise in DHEAS. Higher cortisol/DHEAS molar ratio values at baseline are also associated to lower weight loss after LASGB, with lower decrease in FM and higher reduction in FFM and body cell mass, in spite of no differences in dietary regimes. Cortisol/DHEAS molar ratio is likely to represent a reliable marker of favourable modifications in body composition.

Non-alcoholic fatty liver disease in young adult severely obese non-diabetic patients in South Italy.

BACKGROUND/AIMS: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II-III obesity in a metropolitan area of South Italy. METHODS: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18-50 years (mean 31.9 +/- 8.8), body mass index (BMI) > or =30 (mean 47.5 +/- 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0-39.9, and (2) BMI> or =40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. RESULTS: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesity, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotransferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI> or =40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (gammaGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and gammaGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. CONCLUSION: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.

Long term metabolic effects of two dietary methods of treating hyperlipidaemia.

OBJECTIVES: To compare the long term metabolic effects of two diets for treating hyperlipidaemia. DESIGN: Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. SETTING: Lipid clinic of tertiary referral centre in Naples. SUBJECTS: 63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. INTERVENTIONS: Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. MAIN OUTCOME MEASURES: Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. RESULTS: In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. CONCLUSIONS: Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.

Effects of bezafibrate on insulin secretion and peripheral insulin sensitivity in hyperlipidemic patients with and without diabetes.

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.