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.

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity.

Increased cortical porosity has been suggested as a possible factor increasing fracture propensity in patients with type 2 diabetes mellitus (T2DM). This is a paradox because cortical porosity is generally associated with high bone turnover, while bone turnover is reduced in patients with T2DM. We therefore wanted to test the hypothesis that women with T2DM have lower bone turnover markers (BTM) and lower cortical porosity than those without diabetes, and that higher serum glucose and body mass index (BMI) are associated with lower BTM, and with lower cortical porosity. This cross-sectional study is based on a prior nested case-control study including 443 postmenopausal women aged 54-94years from the Tromsø Study, 211 with non-vertebral fracture and 232 fracture-free controls. Of those 443 participants, 22 women exhibited T2DM and 421 women did not have diabetes. All had fasting blood samples assayed for procollagen type I N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX) and glucose, and femoral subtrochanteric architecture was quantified using low-resolution clinical CT and StrAx1.0 software. Women with T2DM had higher serum glucose (7.2 vs. 5.3mmol/L), BMI (29.0 vs. 26.4kg/m2), and higher femoral subtrochanteric total volumetric bone mineral density (vBMD) (783 vs. 715mgHA/cm3), but lower cortical porosity (40.9 vs. 42.8%) than nondiabetic women (all p<0.05). Each standard deviation (SD) increment in glucose was associated with 0.10-0.12 SD lower PINP and CTX, and 0.13 SD lower cortical porosity (all p<0.05). Each SD increment in BMI was associated with 0.10-0.18 SD lower serum PINP and CTX, and 0.19 SD thicker cortices (all p<0.05). Increasing glucose and BMI were associated with lower bone turnover suggesting that reduced intracortical and endocortical remodeling leads to reduced porosity and thicker cortices. Using low-resolution clinical CT, cortical porosity was lower in women with T2DM compared to women without diabetes. This indicates that other changes in bone qualities, not increased cortical porosity, are likely to explain the increased fracture propensity in patients with T2DM.

Chronic Abdominal Pain and Symptoms 5 Years After Gastric Bypass for Morbid Obesity.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is widely performed as treatment of morbid obesity. Long-term weight loss, effects on co-morbidities, and quality of life after RYGB have been well addressed. Other long-term outcomes are less elucidated. The aim of this study was to evaluate the prevalence, symptom characteristics, and possible predictors of chronic abdominal pain and gastrointestinal symptoms during consultations 5 years after RYGB. METHODS: A 5-year follow-up study of patients operated with RYGB 2008-2009 was performed. The patients completed questionnaires regarding chronic abdominal pain, the Gastrointestinal Symptom Rating Scale (GSRS), the ROME III questionnaire, the Hospital Anxiety and Depression Scale, Pain Catastrophing Scale (PCS), the Brief Pain Inventory, and SF-36. Uni- and multivariable logistic regression analyses of characteristics associated with chronic abdominal pain were performed. RESULTS: A total of 165/234 (71%) patients met to the follow-up, 160 of these accepted study inclusion. The mean follow-up was 64 (SD 4.2) months. The mean age was 42.5 (SD 8.7) years and 59% were females. The mean total weight loss was 23.9% (SD 11.2). Chronic abdominal pain was reported by 33.8%. Female gender, average strength of bodily pain, and the PCS sum score were associated with chronic abdominal pain. Symptoms of indigestion and irritable bowel syndrome were reported by 48.8% and 29.1%, respectively. Chronic abdominal pain was associated with reduced health related quality of life. CONCLUSION: A substantial proportion of patients experienced chronic abdominal pain and symptoms 5 years after RYGB. Abdominal pain should be addressed at follow-up consultations after RYGB.