Study design and setting
In this cross-sectional study, adult patients referred to two obesity centers providing bariatric surgery in South-Eastern Norway were invited to participate. Oslo University Hospital Aker (OUH-A) recruited patients living in an urban area and Innlandet Hospital Trust Gjøvik (IHT-G) recruited patients living in rural areas and small towns. The medical history, current medications and anthropometric evaluations including BMI were registered on the day of inclusion. A routine clinical examination was performed and blood samples were retrieved. Demographics and comorbidity were reported by the patients in a paper-based case report form. All patients filled in questionnaires for the classification of functional bowel disorders. Additional diagnostic procedures including endoscopic examinations were done at the discretion of the attending physician. Patients at OUH-A and IHT-G were recruited from February 2014 through April 2015, and from December 2012 through September 2014, respectively.
Participants
The inclusion criteria were age 18–65 years and morbid obesity, defined as BMI > 40 kg/m2 or BMI >35 kg/m2 with obesity-related comorbidity at the time of referral [20]. Exclusion criteria were major psychiatric disorders (schizophrenia, major depression or bipolar disorder), alcohol and drug addiction, organic gastrointestinal disorders, former obesity surgery and other major abdominal surgery. The case report form was printed in Norwegian, and patients not able to understand Norwegian were excluded. At IHT-G, patients were included only 3 days per week when the study nurse was present.
Variables
Demographics
Seven demographic variables were registered: Age (years), sex (male/female), ethnicity (% Caucasian), BMI (kg/m2), smoking habits (smoking/not smoking), work status (full-time/part-time/not working) and cohabitant status (living with partner/not living with partner).
Comorbidity and use of medication
Six present or previous comorbidities were reported by the patient on the case report form: Diabetes mellitus, hypothyroidism, hypertension, fibromyalgia, gallstones and self-reported psychiatric disorders. At OUH-A, the subjects were asked if they had been diagnosed with anxiety or depression (present/absent), and at IHT-G if they had sought professional help for psychiatric disorders (present/absent). At both centres, subjects with a diagnosis of major psychiatric disorders (schizophrenia, major depression or bipolar disorder) were excluded. When in doubt, the subjects were referred for a psychiatric evaluation. Regular use of medication was reported by the patients. All information concerning comorbidity and medication were reviewed by a clinician with full access to the patient’s medical record.
Abdominal complaints
Functional bowel disorders were diagnosed with a validated Norwegian translation of the Rome III questionnaire [2]. IBS and subtypes of IBS, functional constipation, functional diarrhea and functional bloating were coded as present/absent.
Blood tests
Thirty-tree variables were analyzed from the blood samples. The reference values for the 15 variables reported in the results were as follows: hemoglobin g/dl: women 11.7–15.3, men 13.4–17.0; white-cell count 109/l: 3.5–10.0; platelet count 109/l: 145–390; c-reactive protein (CRP) mg/l: <5; cholesterol mmol/l: age 18–29 2.9–6.1, age 30–49 3.3–6.9, age > 50 3.9–7.8; high-density lipoprotein mmol/l: women 1.0–2.7, men 0.8–2.1; low-density lipoprotein (LDL) mmol/l: age 18–29 1.3–4.3, age 30–49 1.5–4.8, age > 50 2.0–5.4; thyroid stimulating hormone (TSH) mIE/l: 0.27–4.20; free thyroxin (T4) pmol/l: 8.0–22.0; vitamin B1 nmol/l: 95–200; vitamin B6 nmol/l: 15–160; vitamin B12 pmol/l: 140–650; folic acid nmol/l: 7–40; HbA1C %: 4.0–6.0; total bilirubin μmol/l: 5–25. The other 18 variables were mean corpuscular volume, mean corpuscular hemoglobin, iron, transferrin, transferrin saturation, ferritin, transferrin iron binding capacity, sodium, potassium, magnesium, phosphate, glucose, creatinine, uric acid, alanine aminotransferase, total protein, albumin, and triglycerides.
Dietary registration
At IHT-G, the intake of micro- and macronutrients was estimated with a semi-quantitative food frequency questionnaire designed and validated for the Norwegian population [21].
Statistical analysis
Data are presented as mean (standard deviation), median (range) and proportion (percentage) according to the distribution of data. Student’s t-test, Mann-Whitney U test, Pearson chi-squared test, or Fisher’s exact test was used for the comparisons between the groups depending on the type of data and normality. Correlations were assessed with the Pearson or Spearman correlation coefficients. Because the prevalence of IBS differed between the centers, the predictors of IBS were analyzed one-by-one with logistic regression adjusted for the center after testing for statistical interaction. The effect of TSH differed strongly from linear. Therefore, fractional polynomials were used to transform this variable. Predictors that were significant in these analyses were included as independent variables in a multivariable logistic regression analysis with IBS as the dependent variable. The results are presented as odds ratios with 95% confidence intervals (CI). The presented predictors of IBS include all predictors that were significant in the analysis corrected for center only and a selection of other relevant variables. In the posthoc analysis, we examined the differences between the groups of patients with and without IBS separately at the two centers. Two-sided p-values <0.05 were judged to indicate statistical significance. Data analysis was performed with IBM SPSS Statistics for Windows, Version 21.0 (Armonk, NY: IBM Corp) and Stata Statistical Software, Release 13 (College Station, TX: StataCorp LP).
Power calculation
The prevalence of IBS was 8.4% in the general population from the same area [14] and was expected to be 18% in patients with morbid obesity [9]. A study including 350 participants with morbid obesity was calculated to have a power of 98% to detect a difference between the general population and the patients with morbid obesity, with α = 0.01.
Ethics
The study was approved by the Regional Committee for Medical and Health Research Ethics South East Norway, references 2012/966 and 2013/1264, and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all individual participants included in the study.