Long-term risk of anaemia after bariatric surgery: results from the Swedish Obese Subjects study.

BACKGROUND: Nutritional deficiencies, such as iron and vitamin B12 deficiencies, are potential adverse consequences of bariatric surgery. Long-term data on anaemia after bariatric surgery are largely lacking. We aimed to investigate the risk of anaemia, iron and vitamin B12 deficiency anaemia, and vitamin B12 deficiency over 20 years in individuals who had bariatric surgery or received usual obesity care. METHODS: The prospective, controlled Swedish Obese Subjects study recruited people with obesity via recruitment campaigns in the mass media and at primary health-care centres, and was done at 480 primary health-care centres and in 25 surgical departments in Sweden. Eligible participants were aged 37-60 years and had a BMI of either 34 kg/m2 or more (for men) or 38 kg/m2 or more (for women). Participants were excluded if they had undergone previous bariatric surgery or had contraindicating conditions. Two main groups were formed: those who chose bariatric surgery, the type of which was determined by the operating surgeon, and a contemporaneously matched control group, created by use of 18 matching variables, who received usual non-surgical obesity care that ranged from lifestyle advice to no treatment. Haemoglobin concentration was measured during examination visits at baseline and at 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years of follow-up. Anaemia was defined as a haemoglobin concentration of less than 120 g/L for women and 130 g/L for men. The primary, non-specified outcome was the incidence of anaemia, and was assessed in the as-treated population, which comprised only patients who received the actual treatment. The associations between treatment type and anaemia are expressed as unadjusted hazard ratios (HRs) and HRs adjusted for age, sex, BMI, menopausal status, education, diabetes, and hypertension, with 95% CIs. This study is registered in ClinicalTrials.gov, NCT01479452, and is closed to new participants, with follow-up ongoing. FINDINGS: Between Sept 1, 1987, and Jan 31, 2001, 6905 individuals were assessed for eligibility, of whom 5335 were eligible. Of these, we included 2007 patients who chose bariatric surgery (266 in the gastric bypass group, 1365 in the vertical-banded gastroplasty group, and 376 in the gastric banding group) and 2040 matched controls who received usual obesity care. During a maximum of 20 years and a median of 10 years (IQR 3-20) of follow-up, there were 133 anaemia events in the gastric bypass group, 359 in the vertical-banded gastroplasty group, 101 in the gastric banding group, and 261 in the control group. Compared with the control group (13 cases per 1000 person-years, 95% CI 11-14), the incidence of anaemia was higher in the gastric bypass group (64 cases per 1000 person-years, 53-74; HR 5·05, 95% CI 3·94-6·48; p<0·0001), the vertical-banded gastroplasty group (23 cases per 1000 person-years, 21-26; 2·67, 2·25-3·18; p<0·0001), and the gastric banding group (26 per 1000 person-years, 21-31; 2·76, 2·15-3·52; p<0·0001). These associations remained after adjustment. INTERPRETATION: Our findings highlight the increased risk of anaemia after bariatric surgery and the importance of long-term compliance to nutritional supplementation and monitoring to enable prevention and early detection of serious nutritional deficiencies after bariatric surgery. FUNDING: Swedish Research Council, the Swedish state under the agreement between the Swedish Government and the county councils, the Swedish Diabetes Foundation, the Swedish Heart-Lung Foundation, and the Novo Nordisk Foundation.

Iodine Status After Bariatric Surgery-a Prospective 10-Year Report from the Swedish Obese Subjects (SOS) Study.

CONTEXT: Bariatric surgery can lead to nutrient deficiencies. Gastric by-pass (GBP) entails restriction and malabsorption, whereas, vertical banded gastroplasty (VBG) is only restrictive. OBJECTIVE: The objective of this study is to study whether GBP-patients develop iodine deficiency from malabsorption, and if GBP- and VBG-patients develop lower 24-h urinary iodine excretion (24-UIE) than obese non-operated controls (OB-controls) due to lower iodine intake. DESIGN: The Swedish Obese Subjects (SOS) study is a prospective, non-randomized study of 4047 obese patients included 1987-2001, who chose bariatric surgery or non-surgical treatment. SOS-groups were compared at baseline, after 2 and 10 years and with population-based subsamples (MONICA-controls). PATIENTS: One hundred eighty-eight GBP-patients were matched with 188 VBG-patients and 188 OB-controls and with three subgroups from 412 MONICA-controls. MAIN OUTCOME MEASUREMENTS: Primary outcome was 24-UIE. Secondary outcomes were iodine intake, iodine supplementation, TSH, FT4, and thyroid morbidity. RESULTS: At baseline, median 24-UIE was higher in GBP-patients, VBG-patients and OB-controls than in MONICA-controls (214, 201, 203 and 137 µg/day, p < 0.001). At 10 years, 24-UIE in GBP-patients (161 µg/day) and VBG-patients (149 µg/day) was lower compared with baseline (p < 0.01) and OB-controls (189 µg/day, p < 0.01), but similar to 24-UIE in MONICA-controls (137 µg/day). The 10-year-dietary iodine intake was similar in GPB-patients and OB-controls, but higher in VBG-patients. Iodine supplementation was taken by 0-9% in SOS-groups. CONCLUSION: After surgery, GBP- and VBG-patients did not suffer from iodine deficiency, but both groups had lower iodine status than OB-controls. Dietary supplements recommended after bariatric surgery do not need to include iodine, in iodine sufficient countries. TRIAL REGISTRATION: clinicaltrials.gov : NCT01479452.

The imprinted gene neuronatin is regulated by metabolic status and associated with obesity.

Using restriction fragment differential display (RFDD) technology, we have identified the imprinted gene neuronatin (Nnat) as a hypothalamic target under the influence of leptin. Nnat mRNA expression is decreased in several key appetite regulatory hypothalamic nuclei in rodents with impaired leptin signaling and during fasting conditions. Furthermore, peripheral administration of leptin to ob/ob mice normalizes hypothalamic Nnat expression. Comparative immunohistochemical analysis of human and rat hypothalami demonstrates that NNAT protein is present in anatomically equivalent nuclei, suggesting human physiological relevance of the gene product(s). A putative role of Nnat in human energy homeostasis is further emphasized by a consistent association between single nucleotide polymorphisms (SNPs) in the human Nnat gene and severe childhood and adult obesity.

DNA microarray analysis of transforming growth factor-beta and related transcripts in nasal biopsies from patients with allergic rhinitis.

Decreased activity of anti-inflammatory cytokines like transforming growth factor (TGF)-beta may contribute to allergic inflammation. In vivo effects of TGF-beta-effects are difficult to infer from local concentrations, since TGF-beta-effects depend on a complex system of regulatory proteins and receptors. Instead the effects of TGF-beta might be inferred by examining TGF-beta-inducible transcripts. In this study DNA microarrays were used to examine local expression of TGF-beta, TGF-beta-regulatory and -inducible transcripts in nasal biopsies from patients with symptomatic allergic rhinitis and healthy controls. In addition, nasal fluids were analysed with cytological and immunological methods. Nasal fluid eosinophils, albumin, eosinophil granulae proteins and IgE, but not TGF-beta, were higher in patients than in controls. DNA microarray analysis of nasal mucosa showed expression of transcripts encoding TGF-beta, TGF-beta-regulatory proteins and -receptors at variable levels in patients and controls. By comparison, analysis of 28 TGF-beta-inducible transcripts indicated that 23 of these had lower measurement values in patients than in controls, while one was higher, and the remaining four were absent in both patients and controls. In summary, TGF-beta and a complex system of regulatory genes and receptors are expressed in the nasal mucosa. Low expression of TGF-beta-inducible transcripts may indicate decreased TGF-beta activity in allergic rhinitis. DNA microarray analysis may be a way to study cytokine effects in vivo.

Increased expression of Vascular Endothelial Growth Factor-A in seasonal allergic rhinitis.

Increased vascular dilatation and permeability characterize allergic rhinitis. In this study oligonucleotide microarrays (Affymetrix HuGe95A) were used to identify differentially expressed vasoactive genes in nasal biopsies from 23 patients with symptomatic seasonal allergic rhinitis (SAR) and 12 healthy controls. RNA was extracted from the biopsies and pooled in three patient and three control pools. Out of 12,626 analysed transcripts, 39 were higher and 81 lower in the patients. Of these transcripts two have vasoactive effects: Vascular Endothelial Growth Factor-A (VEGF-A) and the Beta-1-Adrenergic Receptor. Both were higher in patients than in controls. The mean +/- SEM expression levels in arbitrary units of VEGF-A were 130 +/- 123 in the patients and 59 +/- 53 in the controls. The fold ratio in expression levels between patients/controls was 2.2. The corresponding values for the beta-1-adrenergic receptor were 129 +/- 123 in the patients and 40 +/- 31 in the controls. The fold ratio between patient/controls was 3.2. The role of VEGF-A was assessed by determining VEGF-A concentrations in nasal fluids from another 30 patients with SAR before and after allergen provocation. VEGF-A increased from 124.3 +/- 30.2 to 163.2 +/- 37.8 pg/ml after challenge, P < 0.05. In summary, oligonucleotide microarray analysis of nasal biopsies and protein analyses of nasal fluids indicate that VEGF-A may be an important mediator in SAR.