Calorie restriction and Roux-en-Y gastric bypass have opposing effects on circulating FGF21 in morbidly obese subjects.

OBJECTIVE: To study the effect of different weight loss strategies on levels of the metabolic regulator FGF21 in morbidly obese females with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM). DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Weight reduction was achieved by Gastric Banding (GB, n = 11) or Roux-en-Y Gastric Bypass (RYGB, n = 16) in subjects with NGT, and by RYGB (n = 15) or a very-low-calorie diet (VLCD, n = 12) in type 2 diabetics. Fasted and/or postprandial levels of FGF21, FGF19 (an FGF21-related postprandial hormone) and bile salts (implicated in regulation of FGF21 and FGF19 expression) were measured before, and 3 and 12 weeks after intervention. RESULTS: Fasted FGF21 levels were elevated in T2DM subjects. Calorie restriction by either GB or VLCD lowered bile salt and FGF21 levels. In contrast, RYGB surgery was associated with elevated bile salt and FGF21 levels. CONCLUSIONS: Calorie restriction and RYGB have opposite effects on serum bile salt and FGF21 levels. Calorie restriction results in FGF21 approaching nonobese control levels, suggesting that this intervention is effective in reducing the "nutritional crisis" that appears to underly FGF21 elevation in obesity. FGF21 elevation after RYGB may contribute to the beneficial effect of this procedure.

Autonomic nervous system activity in diabetic and healthy obese female subjects and the effect of distinct weight loss strategies.

OBJECTIVE: Obesity and type 2 diabetes mellitus (T2DM) are reported to be associated with relative overactivity of the sympathetic nervous system (SNS), which is reversible by weight loss. However, direct effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass (RYGB) on SNS overactivity were not studied in parallel. This study compared the effects of RYGB vs restrictive weight loss in obese patients with normal glucose tolerance (NGT) and with T2DM on SNS function as measured by heart rate variability (HRV). DESIGN AND METHODS: Lean (n=12), obese NGT (n=27) and T2DM (n=27) subjects were included in this study. Weight reduction in NGT subjects was achieved by gastric banding (GB) or RYGB and in T2DM subjects by RYGB or high-protein very-low-calorie diet (VLCD). HRV analysis was performed and blood samples were taken at baseline, 3 weeks and 3 months after intervention. RESULTS: At baseline, T2DM subjects showed SNS overactivity and NGT subjects showed similar, but non-significant, findings when compared with lean controls. Weight loss after 3 weeks was comparable in all treatment groups, whereas after 3 months, weight loss was most in VLCD and RYGB subjects. RYGB and VLCD treatment reduced SNS activity within 3 weeks in T2DM patients. After 3 months, restoration to normal autonomic nervous system activity was evident for all groups, except for the NGT-GB group. CONCLUSION: We can conclude that SNS overactivity is more pronounced in obese T2DM subjects when compared with NGT subjects. Reduction of SNS overactivity coincides with weight loss with the time-course of reduction dependent on the type of intervention. Surgery or caloric restriction may transiently induce SNS overactivity but do not prevent a direct restoration of sympathovagal balance.

Endoscopic corticosteroid injections do not reduce dysphagia after endoscopic dilation therapy in patients with benign esophagogastric anastomotic strictures.

BACKGROUND & AIMS: Benign anastomotic strictures are often difficult to treat. We assessed the efficacy of adding corticosteroid injections to endoscopic dilation therapy with Savary bougienage. METHODS: In a multicenter, double-blind trial, 60 patients (mean age, 63 ± 9 years; 78% male) with an untreated cervical anastomotic stricture after esophagectomy with gastric tube reconstruction and dysphagia for at least solid food were randomly assigned to groups given 4 quadrant injections of 0.5 mL triamcinolone (40 mg/mL, n = 29) or saline (controls, n = 31) into the stricture, followed by Savary dilation to 16 mm. Dysphagia, complications, and quality of life were assessed after 1 and 2 weeks and 1, 3, and 6 months. The primary end point was a dysphagia-free period of 6 months. RESULTS: In the corticosteroid group, 45% of the patients remained dysphagia-free for 6 months, compared with 36% of controls (relative risk, 1.26; 95% confidence interval, 0.68-2.36; P = .46). Median time to repeat dilation was 108 days (range, 15-180 days) in the corticosteroid group vs 42 days (range, 17-180 days) for controls (P = .11). A median number of 2 dilations (range, 1-7) was performed in the corticosteroid group vs 3 dilations (range, 1-9) in controls (relative risk, 0.76; 95% confidence interval, 0.42-1.38; P = .36). Two major intervention-related complications occurred, 1 submucosal laceration in the corticosteroid group and 1 hemorrhage in the control group. Four patients in the corticosteroid group, but none of the controls, developed Candida esophagitis (P = .03). CONCLUSIONS: Corticosteroid injections do not provide a statistically significant decrease in frequency of repeat dilations or prolongation of the dysphagia-free period in patients with benign anastomotic esophagogastric strictures. Dutch Trial Registration Number 2236.