*Agnieszka Swidnicka-Siergiejko1, Eugeniusz Wroblewski1, Hady Razak Hady2, Dagmara Bogdanowska-Charkiewicz1, Andrzej Dabrowski1
Beneficial effects of intragastric balloon therapy associated with hormonal changes on weight loss and serum metabolic, inflammatory and liver parameters**
Korzyści leczenia balonem dożołądkowym związane ze zmianami hormonalnymi na masę ciała oraz metaboliczne, zapalne i wątrobowe parametry krwi
1Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Poland
21st Clinical Department of General and Endocrine Surgery, Medical University of Bialystok, Poland
Wstęp. Korzyści leczenia balonem dożołądkowym (ang. intragastric balloon – IGB) wywierane na masę ciała oraz choroby związane z otyłością są wciąż przedmiotem dyskusji i mogą być zależne od zmian hormonalnych.
Cel pracy. Celem badania była ocena bezpieczeństwa oraz korzyści leczenia IGB związanych ze zmianami hormonalnymi we krwi obwodowej.
Materiał i metody. Prospektywne, obserwacyjne badanie 25 otyłych pacjentów z oceną bezpieczeństwa IGB oraz wpływu na redukcję masy ciała, chorobę refluksową przełyku (endoskopia, objawy), badania laboratoryjne oraz zmiany stężenia leptyny i omentyny w surowicy. Uzyskano zgodę komisji bioetycznej Uniwersytetu Medycznego w Białymstoku oraz pisemne zgody pacjentów. Badanie przeprowadzono w ramach grantu NCN nr N N402 456839.
Wyniki. Zaobserwowano duży spadek BMI po 6 miesiącach terapii IGB. %TBWL (ang. total body weight loss) wyniósł 15,55 ± 8,9 i nie zmienił się znacząco po 12 miesiącach. %EWL (ang. excess weight loss) wynoszący co najmniej 25% uzyskano u 53% chorych po 6 miesiącach i 56% chorych po 12 miesiącach leczenia. Po leczeniu zaobserwowano znacząco niższe stężenia triglicerydów, aminotransferaz, glukozy, HbA1c i HOMA-IR. Zauważalnie wyższe stężenia leptyny i omentyny w surowicy wykazano u pacjentów z %EWL < 25 niż u pacjentów z %EWL > 25%. Stężenia leptyny korelowały z HOMA-IR, stężeniem insuliny i aktywnością aminotransferazy alaninowej. Stężenia omentyny korelowały pozytywnie ze stężeniem cholesterolu HDL i negatywnie z aktywnością aminotransferazy alaninowej. Refluksowe zapalenie przełyku stwierdzono u 5 i 3 chorych odpowiednio przed leczeniem i po nim. Nie wykazano różnicy w częstości zgłaszanych objawów refluksowych przed terapią i po jej zakończeniu. Nie zaobserwowano poważnych powikłań z wyjątkiem przypadku częściowej deflacji balonu stwierdzonego w trakcie planowego usuwania balonu. Satysfakcję z leczenia podało 80% chorych.
Wnioski. Leczenie balonem dożołądkowym jest bezpieczną i skuteczną metodą redukcji masy ciała. Korzystny wpływ na masę ciała oraz metaboliczne i wątrobowe parametry laboratoryjne związane są ze zmianami hormonalnymi w surowicy krwi.
Introduction. Beneficial effect of intragastric balloon (IGB) on weight loss and obesity-related complications is still questionable and may be related to serum hormonal changes.
Aim. The aim of the study was to assess the safety and benefits of IGB therapy associated with hormonal changes in peripheral blood.
Material and methods. This was a prospective, observational study of 25 obese patients treated with an IGB with assessment of safety, weight loss, gastroesophageal reflux, serum laboratory tests, and circulating leptin and omentin. The consent of bioethical committee of Medical University of Bialystok, as well as written consent from all subjects were obtained. The study was supported by the Polish National Science Center grant No. N N402 456839.
Results. A six-month IGB therapy resulted in a significant BMI decrease. The mean % total body weight loss at 6 months was 15.55 ± 8.96 and did not significantly change at 12 months. A 25% excess weight loss was achieved by 52 and 56% patients at 6 and 12 months, respectively. The therapy decreased mean levels of aminotransferases, glucose, C-reactive protein, hemoglobin A1c, and insulin resistance (HOMA-IR). Patients with % excess weight loss less than < 25 had significantly higher levels of leptin and lower levels of omentin. Leptin levels correlated with HOMA-IR, insulin, and alanine aminotransferase levels. Omentin levels correlated positively with HDL-cholesterol and negatively with alanine aminotransferase. Reflux esophagitis was found in 5 and 3 patients before and after therapy, respectively. The frequency of typical reflux symptoms did not differ significantly before and after therapy. There were no serious adverse events except one partial balloon deflation found on the day of its planned removal. Up to 80% patients were satisfied with therapy.
Conclusions. IGB therapy is a safe and effective weight loss procedure and its beneficial effects on weight loss and several serum metabolic and liver function parameters are associated with hormonal changes.
Obesity has become a major public health problem as it is a chronic inflammatory disease associated with an increased risk of several diseases, higher medical costs, and decreased quality of life and productivity. Effective weight loss can significantly improve obesity-related complications such as hypertension and diabetes (1-3). Conservative treatments that include diets, physical activity, and pharmacology have limited efficacy. The most effective method of weight loss is bariatric surgery. However, it is not available for all obese patients, e.g. those with a higher surgical risk. In addition, younger patients commonly desire to lose weight using non-surgical methods and there are those who need to lose weight before non-bariatric procedures. Therefore, endoscopic therapy such as an intragastric balloon (IGB) fills the gap between conservative methods and bariatric surgery and has been added by the American Society for Metabolic and Bariatric Surgery (ASMBS) to the list of approved procedures for obesity treatment. IGB therapy potentially has fewer serious adverse events and costs less than bariatric surgery (4-6).
IGB therapy has been shown to be effective in weight loss and can improve obesity-related comorbidities such as hypertension, hyperlipidemia, and diabetes (4-9). However, the achieved weight loss is smaller and may be temporary without multidisciplinary management including lifestyle modification and consultations with dieticians (4, 5). The weight loss afforded by IGB is mostly due to increased satiety and delayed gastric emptying. However, the mechanism of weight loss seems to be more complex. Is it known that in the pathogenesis of obesity and obesity-related complications several mechanisms are involved such as, gastrointestinal hormones, cytokines, and growth factors, inflammatory and immune responses, gut microbiota, the gut-brain axis, or adipokines released by adipose tissue (1-3). Previously, we found that obese patients when compared to non-obese patients had higher leptin levels and lower levels of adiponectin, ghrelin, and omentin and that bariatric therapies had an impact on their blood levels (10). We found that the percentage of total body weight loss positively correlated with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had significantly lower leptin levels than patients who failed to respond to treatment (10).
The efficacy of IGB therapy, including weight loss and improvement of several conditions associated with obesity, may be related to changes in blood levels of adipokines as well as gastrointestinal hormones. This paper presents the results of a prospective, observational study of 25 obese patients treated with IGB that assessed: i) 6- and 12-month weight loss; ii) adverse events and quality of life; iii) changes in laboratory blood tests (lipids, liver enzymes, glucose, C-reactive protein, hemoglobin A1c) and insulin resistance; and iv) levels of ghrelin, leptin, and omentin before and after therapy as well as in relation to laboratory tests and weight loss.
The aim of the study was to assess the safety and benefits of IGB therapy associated with hormonal changes in peripheral blood.
MATERIAL AND METHODS
This was a prospective, observational study of 25 consecutive patients (17M/8F) with a mean age of 44.2 ± 12.2 yrs treated with a 6-month IGB therapy in the Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Poland. The consent of bioethical committee of Medical University of Bialystok, as well as written consent from all subjects were obtained. The study was supported by the Polish National Science Center grant No. N N402 456839.
We included adult patients with a body mass index (BMI) of 40 or 35 kg/m2 with at least one obesity concomitant disease who failed to lose weight through diet and exercise alone. The exclusion criteria were as follows: prior gastric or bariatric surgery, large hiatal hernia (≥ 5 cm), esophageal motility disorders, esophageal strictures, potential upper gastrointestinal bleeding conditions, malignancies, liver failure, concurrent use of anticoagulation or aspirin therapy, coagulopathy, alcoholism or drug addiction, and a lack of patient cooperation. All patients provided written informed consent and the study protocol was approved by the local ethics committee and conducted according to the 1975 Declaration of Helsinki guidelines.
The intragastric balloon (Orbera, Allergan, Irvine, CA) was endoscopically placed in the stomach and filled with 500-550 ml of normal saline dyed with methylene blue. At the day of balloon placement all patients received intravenous hydration, proton pump inhibitor therapy, and an antiemetic (if necessary). All patients received lifestyle modification instructions including diet and exercise recommendations. Patients were asked to consume only clear liquids for the first 2 days after balloon placement and a full liquid diet on days 3 to 14. Soft food (1200-1500 kcal/d) was introduced from day 15 and normal textured food after 3 weeks. The balloon was removed after 6 months. Patients were instructed to consume a liquid only diet for 2-3 days before balloon removal. All procedures were performed under conscious sedation. All procedure and patient-related adverse events were noted.
All patients were followed up to one year and had ambulatory control visits with clinical and physical examinations and (if necessary) consultations with a dietician and psychologist. We assessed BMI (kg/m2), the percentage of total body weight loss (%TBWL), and the percentage of excess weight loss (%EWL) after 6 and 12 months. A threshold of a minimum 25% EWL was used to distinguish between success and failure of weight loss (11). Patients with insufficient weight loss were next referred for bariatric surgery. In addition, the 36-item Short Form survey 36 (SF-36) (12, 13), typical reflux symptoms (heartburn, regurgitation), GerdQ self-assessment questionnaire score (14), and the results of an endoscopy were analyzed before and after therapy.
The homeostatic model assessment insulin resistance (HOMA-IR) as well as several laboratory tests were analyzed before and after 6 months of IGB therapy. Laboratory tests included leukocytes, hemoglobin, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, hemoglobin A1c (HbA1c), C-reactive protein (CRP), d-dimer, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and electrolytes. In addition, we assessed the concentration of leptin, ghrelin, and omentin-1 levels in peripheral venous blood also before and after 6 months of IGB therapy. All measurements of leptin (Human Leptin Elisa, Biovendor), ghrelin (Human Ghrelin Total, RIA, Millipore), and omentin-1 (Human Omentin-1 Elisa, Biovendor) were performed according to manufacturers’ instructions.
The STATISTICA 10.0 package was used for all analyses. Patients’ characteristics were described using relative (%) frequency. Results were described as mean and SD. Comparisons of variables before and after treatment were performed with the Wilcoxon matched-pairs signed-ranks test or the paired sample t-test. Comparisons between tested groups were analyzed with the Mann-Whitney U-test. Correlations were performed by means of Spearman’s coefficient. A p value less than 0.05 was considered as significant.
Baseline patient characterization
We included 25 patients with a mean BMI of 47.36 ± 8.89 kg/m2. There were 15 (60%) patients with hypertension, 3 (12%) patients with cardiac failure, 2 (8%) patients with obstructive sleep apnea, 4 (16%) patients with asthma, and 3 (12%) patients with hyperuricemia. Eight patients (32%) had a diagnosis of diabetes and received antidiabetic drugs. Hepatic steatosis was found in 7 (28%) patients.
All patients had an endoscopy before the IGB therapy. The study was normal in 18 (72%) patients. Reflux esophagitis was found in 5 (20%) patients and hiatal hernia in 2 (8%) patients. Typical reflux symptoms such as heartburn and regurgitation were reported by 7 (29.0%) and 17 (68%) patients, respectively. The mean baseline GERDQ questionnaire score was 6.36 ± 1.82.
The mean BMI significantly decreased compared to its baseline value after 6 months of IGB therapy (tab. 1). The mean %TBWL was 15.55 ± 8.96%. In addition, the 25% EWL was achieved by 13 (52%) patients, and a 10% EWL was achieved by 23 (92%) patients.
Tab. 1. The impact of intragastric balloon therapy on body mass index, blood pressure, and serum hormones
|Parameter, mean (SD)||Before therapy||After therapy||p|
|Body mass index (kg/m2)||47.36 ± 8.89||40.16 ± 9.57||< 0.0001|
|Body mass (kg)||142.68 ± 33.55||122.44 ± 32.87||< 0.0001|
|Systolic blood pressure (mmHg)||127.60 ± 14.87||121.33 ± 8.27||0.1024|
|Diastolic blood pressure (mmHg)||82.00 ± 12.91||80.93 ± 6.45||0.8241|
|Serum hormones levels|
|Leptin (ng/mL)||41.56 ± 24.12||24.12 ± 17.17||0.0021|
|Omentin (ng/mL)||496.88 ± 231.49||503.52 ± 201.00||0.9317|
|Ghrelin (pg/mL)||632.85 ± 209.06||617.95 ± 221.38||0.3967|
Weight loss was maintained by all patients after 12 months of IGB therapy except for one patient who had weight gain after removal of the IGB removal. However, there were no significant differences in the median BMI between 6 and 12 months (40.16 ± 9.57 vs 41.68 ± 10.72, kg/m2, p = 0.4229) and %TBWL (15.55 ± 8.96 vs 15.83 ± 10.26, %, p = 0.9702). The 25% EWL was noted in 14 (56%) patients at 12 months.
Laboratory tests before and after 6 months of IGB therapy
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