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Le evidenze scientifiche attribuiscono agli ormoni dell’asse entero-insulare (GLP-1 e GIP), molteplici azioni che vanno dalla regolazione dell’omeostasi glicemica e lipidica al controllo del senso di fame, dell’assunzione di cibo e, quindi, dell’introito energetico. Molte funzioni svolte dagli ormoni dell’asse entero-insulare si sono evidenziate solo dopo gli interventi di chirurgia bariatrica attuati per la terapia dell’obesità morbigena. Durante il triennio del corso di dottorato in “Scienza dell’Alimentazione e della Nutrizione” la mia attività di ricerca ha riguardato lo studio dell’asse entero-insulare dopo diversi interventi nutrizionali e dopo interventi di chirurgia bariatrica effettuati con differenti tecniche chirurgiche. A tal fine sono stati condotti tre studi: Studio 1. Obiettivo: valutare gli effetti di acidi grassi n-3 e/o polifenoli sulla risposta lipidica ed entero-ormonale in soggetti ad alto rischio cardio-metabolico. Materiali e metodi: 78 soggetti, di età compresa tra i 35 e i 70 anni, sovrappeso/obesi, con circonferenza vita elevata ed almeno una delle componenti della sindrome metabolica, sono stati randomizzati a seguire per 8 settimane una tra le seguenti diete: (A) controllo, povera in polifenoli e acidi grassi n-3, (B) ricca in acidi grassi n-3, (C) ricca in polifenoli, (D) ricca in acidi grassi n-3 e polifenoli. Le diete erano isocaloriche e simili per contenuto in acidi grassi saturi, monoinsaturi, colesterolo, carboidrati, fibre, proteine e vitamine. Prima e dopo le 8 settimane d’intervento, sono state determinate le concentrazioni di GLP-1, dei lipidi e dell’apo-lipoproteina B48 (apo-B48) nel plasma e nelle subfrazioni lipoproteiche ricche in trigliceridi (chilomicroni e VLDL grandi), sia a digiuno che dopo somministrazione di un pasto ricco in grassi che rifletteva la stessa composizione delle diete assegnate. Risultati: In fase acuta, la concentrazione postprandiale dei trigliceridi e del colesterolo dei chilomicroni dopo pasto test ricco in n-3 era significativamente maggiore rispetto al pasto controllo (p

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 postmeal 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.

Summary Objective To explore the possible mechanisms behind the lower glycemic response observed when extra-virgin olive oil (EVOO) is added to a high-glycemic index meal in patients with type 1 diabetes (T1D). Research design and methods According to a randomized cross-over design, eleven T1D patients (6 women, 5 men) on insulin pump consumed in the metabolic ward, one week apart, three high-glycemic index meals differing only for amount and quality of fat: high-monounsaturated fat (EVOO), high-saturated fat (Butter), and low-fat (LF). Before and after the meals, blood glucose (continuous glucose monitoring), gastric emptying rate (ultrasound technique), and plasma concentrations of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide GIP (ELISA), glucagon (RIA), and lipids (colorimetric assays) were evaluated. Results Blood glucose iAUC (mmol/lx360 min) was lower after the EVOO (690 ± 431) than after the Butter (1320 ± 600) and LF meals (1007 ± 990) (M ± SD, p = 0.041 by repeated measures ANOVA). Gastric antrum volume was significantly larger in the early (60–90 min) postprandial phase (106 ± 21 vs. 90 ± 16 ml, p = 0.048) and significantly smaller in the late phase (330–360 min) (46 ± 10 vs. 57 ± 22 ml, p = 0.045) after the EVOO than after Butter meal. EVOO significantly increased postprandial GLP-1 iAUC (261 ± 311) compared to Butter (189 ± 349) (pmol/Lx180 min, p = 0.009). Postprandial GIP and glucagon responses were not significantly different between EVOO and Butter. Postprandial triglyceride iAUC was significantly higher after EVOO (100 ± 53) than after Butter (65 ± 60) (mmol/l × 360 min, p = 0.048). Conclusions Changes in gastric emptying and GLP-1 secretion and reduced glucose absorption through glucose-lipid competition may contribute to lower glycemia after a high-glycemic index meal with EVOO in T1D patients. Clinical trials number NCT02330939.

Context Diabetes mellitus is associated with gastrointestinal (GI) motility dysfunction, ranging from delayed to accelerated gastric emptying (GE). Objective To evaluate GE in patients with type 1 diabetes mellitus (T1DM) without chronic complications and to investigate its relation with postprandial glucose and GI hormone responses. Design Cross-sectional study. Setting/Participants Forty-two patients with T1DM free of chronic complications referred to Federico II University and 31 healthy controls similar for age, sex, and body mass index. Interventions/Main Outcome Measures GE was assessed by using the 13C-octanoate breath test with a standardized solid meal. During the meal, plasma glucose, ghrelin, and glucagon-like peptide 1 (GLP-1) responses were assessed, and GI symptoms were evaluated by a specific questionnaire. Results Patients with T1DM showed a significantly slower GE half-emptying time (GE t1/2) (113 ± 34 minutes) than did controls (89 ± 17 minutes; P < 0.001). Thirty-six percent of T1DM showed a delayed GE (t1/2 > 120 minutes), whereas all controls showed a normal GE. When patients with T1DM were stratified according to GE t1/2, postmeal glucose response was significantly different between those with delayed and those with normal GE (P = 0.013). In particular, patients with T1DM and delayed GE showed a significantly longer mean time to peak glucose than did patients with normal GE (P = 0.004). In addition, GE t1/2 was an independent predictor of the time to peak glucose (β = 0.329; P = 0.025). GLP-1 and ghrelin responses to the test meal, as well as the prevalence of GI symptoms, were similar between patients with T1DM and controls and between patients with T1DM with normal GE and those with delayed GE. Conclusions Delayed GE time is associated with a longer time to peak glucose. GE evaluation could be useful for individualizing the timing of preprandial insulin bolus in patients with T1DM.

Dietary fiber and whole grain foods may contribute to the regulation of appetite; however, evidence has produced inconclusive findings. The objective was to evaluate the effects of an experimental wholemeal pasta on appetite ratings, plasma concentrations of gastrointestinal hormones involved in appetite control, and postprandial glucose/insulin responses in healthy adults. Fourteen healthy adults (7M/7F), mean age 30±2 yrs (mean±SEM), participated in a randomized, controlled, crossover trial. Participants consumed on two different days, at one week interval, 117g of wholemeal pasta or 100g of refined wheat pasta (control pasta), similar in energy and macronutrient composition except for fiber amount, which was higher in wholemeal pasta (11 vs 3 g). Appetite ratings, glucose/insulin/lipid and gastrointestinal hormone responses were measured at fasting and for 4-h after the ingestion of the pasta tests, after which self-reported energy intake for 8-h was evaluated. After the wholemeal pasta, the desire to eat and the sensation of hunger were lower (-16%, p=0.04 and -23%, p=0.004, respectively) and satiety was higher (+13%; p=0.08) compared with the control pasta; no effect on self-reported energy intake at subsequent meal was observed. After wholemeal pasta, glucose, triglyceride increased and GLP-1 responses were not different compared to control pasta but insulin response at 30 min (p

Idiopathic reactive hypoglycemia (IRH) is characterized by recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after meals. The underlying mechanisms remain obscure.This study aimed to investigate the response of the glucoregulatory and gastrointestinal hormones to an oral glucose load (OGTT) in individuals with documented IRH.This was a cross-sectional study composed of outpatients referred to "Federico II" University of Naples.We enrolled subjects with IRH documented by a mixed meal under ordinary life conditions and healthy subjects as controls.We measured plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), GIP, and glucagon response to a 75-g OGTT in cases and controls.Ten IRH and eight control subjects were enrolled. During the OGTT, mean plasma glucose tended to be lower in IRH than in control subjects, reaching a statistically significant difference at 240 minutes (T240) (43 ± 1.6 vs 72 ± 0.3 mg/dL; P = .001). Accordingly, the insulin response was higher in IRH than in control subjects (P.019) with a statistically significant difference (46%) at T90 (P = .045) and was associated with significantly lower glucagon levels in the late phase of the OGTT: at T120 (P = .031) and T180 (P = .048) in IRH than in control subjects. A greater GLP-1 response was found among IRH compared with control subjects (P = .005); GLP-1 peak was 2-fold higher in IRH individuals (9.77 ± 2.52 pmol/L) than in the control group (4.19 ± 0.53 pmol/L; P = .041). In the IRH group, GLP-1 peak inversely correlated with the nadir of plasma glucose (r = -0.66; P = .039). A multivariate analysis confirmed that GLP-1 peak independently predicted the plasma glucose nadir (β = -0.593; P = .026).GLP-1 may play a significant role in the pathogenesis of idiopathic IRH.

Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3) are associated with lower cardiovascular risk. This may relate to their influence on glucose metabolism and diabetes risk. We evaluated the effects of diets naturally rich in polyphenols and/or LCn3 of marine origin on glucose metabolism in people at high cardiometabolic risk. According to a 2 × 2 factorial design, individuals with high waist circumference and at least one more component of the metabolic syndrome were recruited at the obesity outpatient clinic. Eighty-six participants were randomly assigned by MINIM software to an isoenergetic diet: (1) control, low in LCn3 and polyphenol (analysed n = 20); (2) rich in LCn3 (n = 19); (3) rich in polyphenols (n = 19); or (4) rich in LCn3 and polyphenols (n = 19). The assigned diets were known for the participants and blinded for people doing measurements. Before and after the 8 week intervention, participants underwent a 3 h OGTT and a test meal with a similar composition as the assigned diet for the evaluation of plasma glucose, insulin and glucagon-like peptide 1 (GLP-1) concentrations, and indices of insulin sensitivity and beta cell function. During OGTT, polyphenols significantly reduced plasma glucose total AUC (p = 0.038) and increased early insulin secretion (p = 0.048), while LCn3 significantly reduced beta cell function (p = 0.031) (two-factor ANOVA). Moreover, polyphenols improved post-challenge oral glucose insulin sensitivity (OGIS; p = 0.05 vs control diet by post hoc ANOVA). At test meal, LCn3 significantly reduced GLP-1 total postprandial AUC (p

The amylose-amylopectin ratio influences starch properties. A higher amylose content is associated with slower starch digestion thus reducing the postprandial plasma glucose response and improving the overall postprandial metabolism. So far, limited evidence is available on the metabolic effect of wheat-based foods rich in amylose. This randomised controlled study investigated the acute metabolic effects of amylose-rich wheat-based rusks in overweight subjects focusing on potential mechanisms. Ten overweight subjects consumed in random order two test meals differing only in the carbohydrate source: rusks prepared with amylose-rich wheat flour (ARR) or conventional wheat flour (control). Blood samples were taken at fasting and over 4 h after the meal. Satiety and intestinal fermentation were evaluated by VAS and H2-breath test, respectively. ARR reduced plasma glucose response during the first two hours after the meal and the desire to eat, and increased breath hydrogen concentration at 4 h (p

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. 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. Age was 47 ± 8 years (mean ± SD) in bariatric surgery and 56 ± 9 years in medical treatment group (p

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.

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 β-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 β-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 (β = -0.352 p = 0.001), postprandial GLP-1 (β = -0.344; p = 0.001), HDL-cholesterol (β = -0.323; p = 0.002) and IFN-γ (β = 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.

C-reactive protein (CRP) is a marker of subclinical inflammation increased by Western diets and reduced by healthy dietary patterns, such as the Mediterranean diet. The role of dietary components is more controversial. Saturated and trans fatty acids may increase, whereas n-3 polyunsaturated fatty acids, either of plant and marine origin, may decrease CRP levels. Controversy in intervention studies may relate to differences in study design, including subjects' characteristics, dietary sources of fats, often-underpowered sample size, and type of comparator. Genetic factors influencing responses to dietary fats could contribute to interindividual heterogeneity. Available evidence does not allow envisaging in patients with diabetes different behaviors or mechanisms for dietary fats effects on inflammation than in nondiabetic populations. Although “ad hoc studies” are needed to clarify the role of confounding factors, the observed changes in CRP are in line with current recommended consumption of dietary fats.

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. 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. 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

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. 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. After BS, there was a significant reduction in body weight (p