Pain sensitivity after Roux-en-Y gastric bypass - associations with chronic abdominal pain and psychosocial aspects.

OBJECTIVES: The aims of this study were to investigate modifications in pain sensitivity after RYGB and to explore associations between pain sensitivity and weight loss, chronic abdominal pain, total body pain, anxiety, depression, and pain catastrophizing. METHODS: In total, 163 patients with obesity were examined with a cold pressor test for pain sensitivity before and two years after RYGB. Two aspects of pain sensitivity were registered: Pain intensity (numeric rating scale, range 0-10) and pain tolerance (seconds). Associations between pain sensitivity and the explanatory variables were assessed with linear regression. RESULTS: Two years after RYGB the pain intensity increased (mean ± SD 0.64 ± 1.9 score units, p<0.001). Pain tolerance decreased (7.2 ± 32.4 s, p=0.005). A larger reduction in body mass index was associated with increased pain intensity, ß=-0.090 (95 % CI -0.15 to -0.031, p=0.003), and decreased pain tolerance ß=1.1 (95 % CI 0.95 to 2.2, p=0.03). Before surgery, participants with chronic abdominal pain reported 1.2 ± 0.5 higher pain intensity (p=0.02) and had 19.2 ± 9.3 s lower pain tolerance (p=0.04) than those without abdominal pain. No differences in pain sensitivity were observed between participants who did or did not develop chronic abdominal pain after RYGB. Pain sensitivity was associated with symptoms of anxiety but not with pain catastrophizing, depression or bodily pain. CONCLUSIONS: The pain sensitivity increased after RYGB and was associated with larger weight loss and anxiety symptoms. Changes in pain sensitivity were not associated with development of chronic abdominal pain after RYGB in our study.

Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans.

CONTEXT: Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown. OBJECTIVE: This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity. METHODS: We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization. RESULTS: In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (ß [95% CI] -0.19 [-0.21 to -0.17]), body fat (-0.12 [-0.14 to -0.10), and fasting C-peptide (-2.04 [-2.46 to -1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58], and -0.20 [-0.36 to -0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R. CONCLUSION: BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling.

Bone Turnover Markers After Standard and Distal Roux-en-Y Gastric Bypass: Results from a Randomized Controlled Trial.

BACKGROUND: Roux-en-Y gastric bypass is associated with increased risk of bone fractures. Malabsorptive procedures may be associated with secondary hyperparathyroidism and detrimental effects on bone health. We aimed to compare the effects of standard and distal gastric bypass on bone turnover markers 2 years after surgery. METHODS: Patients with body mass index (BMI) 50-60 kg/m2 (n = 113) were randomized to standard or distal gastric bypass, 105 patients (95%) completed 2-year follow-up. Serum C-terminal telopeptide of type I collagen (CTX-1), procollagen type I N-propeptide (PINP), and bone-derived alkaline phosphatase (BALP) was measured at baseline and up to 2 years after surgery. ANCOVA and linear mixed models were used to compare groups. RESULTS: The levels of bone turnover markers increased significantly in both groups, with no statistically significant difference between groups. Two years after standard and distal gastric bypass mean (SD) CTX-1 were 0.81 (0.32) and 0.83 (0.31) µg/L (p = 0.38), mean PINP was 77.6 (23.2) and 77.7 (29.3) µg/L (p = 0.42), and BALP 47.9 (21.9) vs. 50.7 (19.6) µg/L (p = 0.38), respectively. Multiple linear regression analyses showed that PINP and BALP correlated positively (p = 0.01 and p < 0.001) with PTH, but only BALP was significantly higher in patients with secondary hyperparathyroidism (p = 0.001). Type of surgery, vitamin D serum concentrations, and 2-year BMI were all independently associated with PTH levels. CONCLUSION: A comparable increase in bone turnover markers 2 years after standard and distal gastric bypass was observed. There was a higher prevalence of secondary hyperparathyroidism after distal gastric bypass, but this did not impact bone turnover markers. TRIAL REGISTRATION: Clinical Trials.gov number NCT00821197.

Diagnosis and treatment of chronic abdominal pain 5 years after Roux-en-Y gastric bypass.

BACKGROUND: Knowledge of optimal diagnostic workup, etiology, and response to treatment of chronic abdominal pain after Roux-en-Y gastric bypass (RYGB) is limited. OBJECTIVE: To define the etiology of chronic abdominal pain presenting at the 5-year follow-up after RYGB and to evaluate response to treatment. SETTING: Oslo University Hospital (tertiary referral center for obesity surgery). METHODS: Of 234 patients operated during a randomly selected 12-month period, 165 (71%) returned for 5-year follow-up, and 160 responded to study questionnaires. Of these, 54 (34%) reported chronic abdominal pain and were invited to participate in a structured diagnostic and treatment algorithm. These patients were contacted for the evaluation of their response to treatment. RESULTS: Fifty-one of 54 patients (94%) reporting chronic abdominal pain at the 5-year follow-up were included in the study. Of the 45 patients with onset of symptoms post-RYGB, 28 (62%) underwent one or more radiologic evaluations, 10 (22%) underwent endoscopy, and 13 (29%) underwent laparoscopy. Diagnosis and treatment were established for 34 patients (76%), whereas 11 (24%) had abdominal pain of unknown cause. The most common etiology was internal herniation (n = 6), dumping (n = 6), food intolerance (n = 6), gallstones (n = 5), and irritable bowel syndrome (n = 4). After a median follow-up of 13.0 months (standard deviation, 11.5), 37 (82%) patients reported remission or improvement of symptoms, 6 had unchanged symptoms, and 2 patients were lost to follow-up. CONCLUSIONS: The etiology of long-term chronic abdominal pain post-RYGB is diverse. A multidisciplinary team can help most patients with dedicated follow-up, but a subset of patients has symptoms of unknown etiology.