Debljina je kronična endokrino-metabolička bolest karakterizirana prekomjernim nakupljanjem masti u organizmu i povećanjem tjelesne težine. To je bolest koja se treba liječiti jer ako se ne liječi napreduje i sa sobom nosi rizik nastanka različitih kliničkih komplikacija. U slučajevima ekstremne debljine u obzir dolazi liječenje intragastričnim balonom ili barijatrijskim kirurškim zahvatom. Liječenje intragastričnim balonom (BIB) provodi se u periodu od šest mjeseci. Barijatrijsko kirurško liječenje debljine je metoda za dugotrajnu kontrolu tjelesne mase kod ekstremno debelih ljudi. Cilj ovog istraživanja bilo je analizirati promjene u koncentracijama grelina, leptina, inzulina i hormona rasta, HOMA-IR i HOMA β nakon pojedinog barijatrijskog zahvata, te utvrditi povezanost koncentracije grelina, leptina i hormona rasta nakon pojedinog barijatrijskog zahvata s gubitkom tjelesne mase 12 mjeseci nakon zahvata, te pokušati pronaći prognostičke čimbenike uspjeha pojedine barijatrijske metode. U istraživanje je uključeno 102 ispitanika, od kojih je sedam odustalo iz osobnih razloga. Dob ispitanika kretala se od 18-60 godina, ITM > 35 kg/m2. Ispitivanje je trajalo 12 mjeseci i bilo je prospektivnog tipa. Kod 21 ispitanika laparoskopski je postavljen LAGB, kod 15 bolesnika učinjena je LSG, a kod 15 RYGB. Kod 44 ispitanika gastroskopski je postavljen BIB. Istraživanjem smo zaključili da su ispitanici u LSG skupini imali značajno veći ITM u odnosu na preostale skupine, a ITM se značajno smanjio u svim skupinama. Inzulin i HOMA-IR su se značajno smanjili, a HOMAβ značajno porastao LSG skupini. Iz navedenog se indirektno može zaključiti da je LSG metoda liječenja, kojom se postiže najpovoljniji učinak na funkciju beta-stanice i metabolizam glukoze. Značajan porast HR zabilježen je u svim skupinama, najveći u RYGB skupini. U ispitanika u BIB skupini, HOMAβ u prvom mjesecu negativno korelirala s EWL u šestom mjesecu, a HOMAβ u trećem negativno korelirala s uspjehom nakon 12 mjeseci. HOMAβ jest prognostički čimbenik uspjeha liječenja BIB-om uz osjetljivost 75,8% i specifičnost 100,0%. HR je pozitivno korelirao s EWL, a leptin negativno u BIB skupini. Porast HR ovisi o padu inzulinske rezistencije, a pad leptina o gubitku na tjelesnoj masi. NaĎena je snažna pozitivna korelacija grelina prije početka liječenja i EWL nakon 6 mjeseci i 12 mjeseci liječenja. Istraživanjem smo dokazali da su bazalne vrijednosti grelina neovisni prognostički čimbenik ishoda u ispitanika liječenih LSG metodom uz osjetljivost 81,8% i specifičnost 100,0%. Pacijenti s koncentracijom grelina većom od 664 pg/ml trebali bi se liječiti LSG metodom, pošto će većina tih pacijenata postići uspjeh. Nismo našli značajne povezanosti metaboličkih hormona i uspjeha liječenja u RYGB skupini.
|Abstract (english)|| |
Introduction: Obesity is a chronic metabolic disease that is characterized by an excessive accumulation of body fat and increased body weight. In the last decade, the worldwide prevalence of obesity has increased significantly; with 400 million obese adults worldwide. Obesity is a serious metabolic disease that has many clinical complications. It is associated with decreased life expectancy as well as a decreased quality of life. Multiple factors contribute to the development of obesity. In order to maintain optimal body weight, it is important to establish and maintain a balance between food intake and energy expenditure. Obesity is the result of complex interactions between genetic, hormonal and environmental factors. Obesity-related morbidity places a burden on healthcare systems. If left untreated, obesity is associated with the development of serious clinical complications such as type 2 diabetes, myocardial infarction, stroke, degenerative changes of the locomotor system, and hormone-dependent malignant tumors. If morbidly obese patients are unable to reduce their body weight by various measures (increasing physical activity, diet, and pharmacotherapeutic measures) then intragastric balloon procedures or bariatric surgery is taken into consideration. Treatment with the intragastric balloon is carried out over a period of six months, and if caloric reductions and life style changes are maintained, weight loss varies from 5 to 30%. Numerous studies have shown that in obese subjects, long-term weight control can be achieved with surgical methods. Bariatric surgery is a branch of abdominal surgery that is specialized in the treatment of obesity, and patients undergoing bariatric surgery experience a weight loss of approximately 35-40%. Improvements in obesity-related comorbidities are also seen. Bariatric procedures are divided into malabsorptive, restrictive and predominantly restrictive procedures. Malabsorptive procedures ("jejunoileal bypass", "biliopancreatic diversion with duodenal switch") shorten or bypass part of the small intestine, which reduces the amount of calories and nutrients the body absorbs. These procedures are used for the most severe forms of obesity (BMI ≥50 kg/m2). Restrictive operations ("sleeve resection", "horizontal gastroplasty", "silastic ring gastroplasty", "vertical banded gastroplasty," "gastric banding adjustable / non-adjustable") do not affect food digestion or absorption, but physically limit the amount of food the stomach can hold. In Roux-en Y gastric bypass, weight loss is attributed to limited food intake, as well as decreased absorption. Bariatric surgery has proved to be the most effective method for long-term weight loss in obese patients; however, not all patients experience the same degree of weight loss. For example, 15-20% of patients have insignificant weight loss and require repeated procedures. Weight loss after intragastric balloon procedures is even more variable. Satisfactory weight loss after 6 months is seen in only 50% of patients, and after balloon removal, only 25% continue to lose weight. Given the above, it would be useful to identify patients that will have unsuccessful weight loss following bariatric procedures, in order to provide these patients with additional weight loss methods such as diet, medical therapy, and psychotherapy. Furthermore, prognostic factors that could be used to determine which bariatric procedure the patient would most likely benefit from could be of great clinical significance. Studies examining prognostic factors for successful long-term weight loss have found that age, preoperative weight loss, initial body mass index, dietary habits, presence of depression, the desire for a change of diet and intensified physical activity are all correlated with treatment outcome. The primary aim of this research was to determine the correlation of HOMAβ (activity of beta cells) and HOMA IRv (sensitivity to insulin) values, before and after bariatric surgery, with successful weight loss on the 12th postoperative month. Secondary aims included determining changes in the concentrations of ghrelin, leptin, insulin and growth hormone (GH) after bariatric surgical procedures and to examine their correlation with successful weight loss after 12 months. In addition, to determine the association of ghrelin, leptin and GH before and after the first postoperative month with HOMAβ and HOMA IR values. Another aim was to determine if HOMAβ and HOMA IR measured on the 1st postoperative month, as well as concentrations of ghrelin, leptin, insulin and GH, could be used as prognostic factors for successful weight loss following bariatric procedures. The hypothesis: HOMA IR and leptin concentrations before and after the first postoperative month will be negatively correlated with weight loss 12 months after bariatric surgery, while HOMAβ, ghrelin and growth hormone will be positively correlated with weight loss. Patients and Methods: This prospective study was conducted at the University hospital centre ‘Sestre Milosrdnice’ and lasted 12 months. The study included 102 patients, seven of which left the study, due to personal reasons. The study was approved by the hospital ethics committee. All patients signed informed consent. Patient age ranged from 18 to 60 years, and all patients had a BMI> 35 kg/m2. In the group of patients treated with surgery, 21 patients were treated with laparoscopic adjustable gastric band (LAGB), 15 patients underwent gastric "sleeve resection" (LSG), and 15 patients underwent Roux-en bypass (RYGB) procedures.
All patients underwent routine hematological and biochemical laboratory evaluation. The following was measured in all patients: serum glucose (GUP) insulin, c-peptide, growth hormone (GH) and regulatory peptide ghrelin and leptin. All the patients had venous blood samples taken between 7:00 and 09:00 am, after a 12 h fast. All patients underwent abdominal ultrasound with emphasis on the sequelae of obesity. In addition, all patients underwent esophagogastroduodenoscopy to identify possible endoscopic contraindications for the various bariatric procedures. All patients were examined by and anesthesiologist and were approved for surgery. Psychological testing was done in all patients. Blood samples were taken for analysis and anthropometric measurements were recorded. BMI before treatment, and one, three, six and 12 months after treatment were recorded. Percent of expected weight loss (% EWL) was determined. Intragastric balloon procedures were performed by an experienced gastroenterologist. All bariatric surgical procedures were performed by the same experienced abdominal surgeon. Results: The treatment of obesity is extremely complex and requires an interdisciplinary approach. We assessed the role of insulin, leptin, ghrelin and growth hormone on weight loss following bariatric procedures. Based on these parameters, optimal bariatric procedures could be planned for obese patients. These parameters could also help predict which patients are at an increased risk of treatment failure, so that additional interventions could be performed. This is the first research that has examined the role of hormones, regulatory peptides and metabolic parameters for prediction of successful weight loss following bariatric treatment. We found the following results: Patients with successful weight loss in the LSG group had a significantly higher BMI compared to other groups, and BMI was significantly decreased in all groups. Overall, insulin and HOMA-IR were significantly reduced, and HOMAβ significantly increased in patients. HOMA-IR was significantly decreased only in the BIB group and LSG group and HOMAβ increased significantly only in the LSG group. Based on the above findings, we can conclude that the LSG provides the most favorable effect on beta cell function and glucose metabolism. Therefore, LSG is the method of choice in obese patients that require treatment of metabolic complications. A significant increase in HR was observed in all groups, but the largest increase was seen in the RYGB group with successful weight loss. In the BIB group HOMAβ in the 1st month was negatively correlated with the EWL in 6th month, and HOMAβ in the 3rd month was negatively correlated with success after 12 months. HOMAβ was a prognostic factor for successful weight loss in the BIB group with sensitivity of 75,8% and specificity of 100,0%. GH was positively correlated with the EWL, and leptin was negatively correlated with EWL in BIB group. No correlation with GH was seen after adjustment for HOMAβ, and the correlation with leptin was lost after correcting for EWL in the first and 3rd month. From the following we can conclude that the increase in GH depends on a decrease in insulin resistance, and a decrease in leptin depends on weight loss. In LAGB group, ghrelin in the first month was positively correlated with the EWL at 12 months, but this association disappeared after adjustment of EWL in the 1st month. This means that ghrelin is not an independent prognostic factor, but depends on weight loss in the 1st month. We also found a strong positive correlation between ghrelin before treatment and EWL after 6 and 12 months. The above correlation remained statistically significant even after adjusting for initial BMI. Baseline ghrelin was an independent prognostic factor for outcome in patients treated with LSG, with a sensitivity 81,8% and specificity of 100,0%. Conclusion: We can conclude that patients with ghrelin concentration greater than 664 pg / ml should be treated LSG, since the majority of these patients achieve success. However we did not find significant association between metabolic hormones and the success of treatment in the RYGB group.