Daniela Guarino

Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: Mechanisms of Diabetes Remission and Role of Gut Hormones

CONTEXT In obese patients with type 2 diabetes (T2DM), Roux-en-Y-gastric-bypass (RYGB) and sleeve gastrectomy (SLG) improve glycemic control. OBJECTIVE The objective of this study was to investigate the mechanisms of surgery-induced T2DM improvement and role of gastrointestinal hormones. PATIENTS, SETTING, AND INTERVENTION: In 35 patients with T2DM, we performed a mixed-meal test before and 15 days and 1 year after surgery (23 RYGB and 12 SLG). MAIN OUTCOME MEASURES Insulin sensitivity, β-cell function, and amylin, ghrelin, PYY, pancreatic polypeptide (PP), glucagon, and glucagon-like peptide-1 (GLP-1) responses to the meal were measured. RESULTS T2DM remission occurred in 13 patients undergoing RYGB and in 7 patients undergoing SLG. Similarly in the RYGB and SLG groups, β-cell glucose sensitivity improved both early and long term (P < .005), whereas insulin sensitivity improved long term only (P < .006), in proportion to body mass index changes (P < .001). Early after RYGB, glucagon and GLP-1 responses to the meal increased, whereas the PP response decreased. At 1 year, PYY was increased, and PP, amylin, ghrelin, and GLP-1 were reduced. After SLG, hormonal responses were similar to those with RYGB except that PP was increased, whereas amylin was unchanged. In remitters, fasting GLP-1 was higher (P = .04), but its meal response was flat compared with that of nonremitters; postsurgery, however, the GLP-1 response was higher. Other hormone responses were similar between the 2 groups. In logistic regression, presurgery β-cell glucose sensitivity (positive, P < .0001) and meal-stimulated GLP-1 response (negative, P = .004) were the only predictors of remission. CONCLUSIONS RYGB and SLG have a similar impact on diabetes remission, of which baseline β-cell glucose sensitivity and a restored GLP-1 response are the chief determinants. Other hormonal responses are the consequences of the altered gastrointestinal anatomy.

The Role of beta-Cell Function and Insulin Sensitivity in the Remission of Type 2 Diabetes after Gastric Bypass Surgery

CONTEXT Bariatric surgery can induce remission in a high proportion of severely obese patients with type 2 diabetes mellitus (T2DM). OBJECTIVE Our objective was to investigate predictors and mechanisms of surgery-induced diabetes remission. PATIENTS AND SETTING Forty-three morbidly obese subjects (body mass index = 45.6 ± 5.0 kg/m(2)), 32 with T2DM and 11 nondiabetic [normal glucose tolerance (NGT)], participated at a clinical research center. INTERVENTION Patients underwent Roux-en-Y gastric bypass. MAIN OUTCOME MEASURES Diabetes remission and β-cell function were evaluated. RESULTS Subjects were tested before and 45 d and 1 yr after surgery. Weight decreased similarly in T2DM and NGT (-39 kg at 1 yr, P < 0.0001). Insulin sensitivity improved in both groups in proportion to the changes in body mass index but remained lower in T2DM than NGT (386 ± 91 vs. 479 ± 89 ml/min · m(2), P < 0.01). Based on glycosylated hemoglobin and oral glucose testing, diabetes had remitted in nine patients at 45 d and in an additional 16 at 1 yr. In T2DM, β-cell glucose sensitivity increased early after surgery but was no further improved and still abnormal at 1 yr [median, 48 (coefficient interval, 53) pmol/min · m(2) · mm vs. median, 100 (coefficient interval, 68) of NGT, P < 0.001]. Baseline β-cell glucose sensitivity was progressively worse in early remitters, late remitters, and nonremitters (median, 54[coefficient interval, 50] vs. median, 22[coefficient interval, 26] vs. median, 4[coefficient interval, 10] pmol/min · m(2) · mm) and, by logistic regression, was the only predictor of failure [odds ratio for bottom tertile = 7.9 (95% confidence interval = 1.2-51.9); P = 0.03]. CONCLUSIONS In morbid obesity, Roux-en-Y gastric bypass causes rapid and profound metabolic adaptations; insulin sensitivity improves in proportion to the weight loss, and β-cell glucose sensitivity increases independently of weight loss. Over a period of 1 yr after surgery, diabetes remission depends on the starting degree of β-cell dysfunction.

Subcutaneous adipose tissue blood flow and vasomotion in morbidly obese patients: Long term effect of gastric bypass surgery

Since recent findings suggest a relationship between reduction in adipose tissue blood flow (ATBF) and metabolic or vascular complications in obese patients (Ob-pts), increase in ATBF may be considered as a further goal in the treatment of obesity, besides fat mass reduction. Therefore, this preliminary study aimed at assess subcutaneous ATBF and vasomotion in morbidly obese patients and whether sustained weight loss induced by Roux-en-Y gastric bypass (RYGB) affects the same parameters. Using laser-Doppler flowmetry (LDF) and spectral Fourier analysis, subcutaneous ATBF was measured and subcutaneous ATBF oscillations (ATBF-O) were analyzed - within three frequency intervals related to vasomotion - in 16 Ob-pts, before and about one year after RYGB, and in 10 lean, healthy control subjects (CS). Before RYGB, Ob-Pts showed an important reduction in subcutaneous ATBF compared to CS (4.8 ± 2.7 PU vs 79.9 ± 34.5 PU, respectively; p < 0.0001), as well as higher normalized power spectral density (N-PSD) values of subcutaneous ATBF-O, - related to vasomotion. One year after RYGB, sustained weight loss in Ob-pts was associated with a slight but significant increase in subcutaneous ATBF (10.0 ± 6.6 PU, p < 0.05) and with almost complete normalization in N-PSD values of ATBF-O, related to vasomotion, compared to before RYGB. The slight subcutaneous ATBF increase, we observed in Ob-pts after sustained weight loss, moves toward a desirable goal. This finding suggests verifying whether an even more sustained weight loss in Ob-pts could determine a greater increase in subcutaneous ATBF and/or, more importantly, it could also determine a significant increase in visceral ATBF.

The Role of the Autonomic Nervous System in the Pathophysiology of Obesity

Obesity is reaching epidemic proportions globally and represents a major cause of comorbidities, mostly related to cardiovascular disease. The autonomic nervous system (ANS) dysfunction has a two-way relationship with obesity. Indeed, alterations of the ANS might be involved in the pathogenesis of obesity, acting on different pathways. On the other hand, the excess weight induces ANS dysfunction, which may be involved in the haemodynamic and metabolic alterations that increase the cardiovascular risk of obese individuals, i.e., hypertension, insulin resistance and dyslipidemia. This article will review current evidence about the role of the ANS in short-term and long-term regulation of energy homeostasis. Furthermore, an increased sympathetic activity has been demonstrated in obese patients, particularly in the muscle vasculature and in the kidneys, possibily contributing to increased cardiovascular risk. Selective leptin resistance, obstructive sleep apnea syndrome, hyperinsulinemia and low ghrelin levels are possible mechanisms underlying sympathetic activation in obesity. Weight loss is able to reverse metabolic and autonomic alterations associated with obesity. Given the crucial role of autonomic dysfunction in the pathophysiology of obesity and its cardiovascular complications, vagal nerve modulation and sympathetic inhibition may serve as therapeutic targets in this condition.

IDENTIFICATION OF RADIAL VASCULAR WALL ABNORMALITIES BY VERY-HIGH FREQUENCY ULTRASOUND IN FIBROMUSCULAR DYSPLASIA AND SPONTANEOUS CORONARY ARTERY DISSECTION: THE FUCHSIA STUDY

Objective: Fibromuscular dysplasia (FMD) is an idiopathic disease of small-and medium-sized arteries. Subclinical alterations have been found also in non-affected segments, suggesting that FMD is a systemic disease. Spontaneous coronary dissection (SCAD) may represent a manifestation of FMD too. This case-control study is aimed at identifying vascular wall abnormalities in the radial arteries in patients with FMD and SCAD by means of a novel ultrasound technique. Figure. No caption available. Design and method: Two 5′-clips from the left radial artery were obtained by Vevo MD (70 MHz probe, FUJIFILM, VisualSonics). Radial wall showed two echogenic interfaces: the 1st (lumen-media) and the 2nd (media-adventitia). Intima-media (IMT), adventitia (AT), and global thickness (IMAT) and wall cross-sectional area (WCSA) Measured. Vascular wall disarray was assessed calculating the root mean square error (RMSE) between 20 gray-level profiles crossing the two interfaces and the profile obtained averaging them, normalized for the maximum value of the corresponding mean profile (RMSE/mean). Results: 12 SCAD patients, 21 FMD patients and 12 healthy controls (C), matched for age (51 ± 12, 47 ± 7, 43 ± 12, p = 0.12) and sex (2 M, 1 M, 2 M), were enrolled. IMT (0.182 ± 0.056, 0.170 ± 0.033, 0.133 ± 0.020 mm, p = 0.01), AT (0.108 ± 0.027, 0.116 ± 0.029, 0.076 ± 0.014 mm, p = 0.001) and IMAT (0.290 ± 0.076, 0.286 ± 0.045, 0.209 ± 0.029 mm, p = 0.001), were significantly higher in SCAD and FMD compared to C. WCSA, but not M/L, was increased too in SCAD and FMD. RMSE/mean was significantly increased in SCAD and FMD compared to controls either in the 1st (1.48 ± 0.84, 1.28 ± 0.52, 0.74 ± 0.26, p = 0.01) or in the 2nd interface (2.44 ± 1.38, 1.56 ± 0.58, 1.19 ± 0.93 p = 0.01). Conclusions: The radial artery walls of FMD and SCAD patients present similar subclinical abnormalities, namely increased thickness and and inhomogeneity, in comparison to controls.