Mechanisms of action of the intragastric balloon in obesity: Effects on hunger and satiety

Appetite, 1990, 15, 3-l 1

Mechanisms of Action of the lntragastric Balloon in Obesity: Effects on Hunger and Satiety RENATO PASQUALI, LOREl-l-A BESTEGHI, FRANCESCO CASIMIRRI, NAZARIO MELCHIONDA, GIULIO DI FEBO, GIUSEPPE ZOCCOLI and LUIGI BARBARA lnsrirure of Clinical Medicine and Gasrroenrerology, University Alma Marer Studiorum of Bologna, &a/y

UMBERTO TASSONI Institute of Radiology,

S. Orsola Hospital, Bologna,

Italy.

We evaluated the effect of a SOO-ml intragastric balloon (Ballobes@) on some aspects of eating-related behaviour and weight loss on nine massively obese patients. An 800-kcal mixed meal test was performed some days before, 2-3 days and 2 months after the implant of the balloon. A hypocaloric program was started after the second meal test. At hourly intervals, before and after the meal, patients were asked to rate the desire to eat, hunger, satiety and prospective consumption of food. After 2 months, weight loss was 12.02 5.1 kg. A significant decrease in the balloon diameters was observed, but none completely deflated. During the meal test performed 2-3 days after the implant, subjects rated themselves as significantly less hungry, fuller and desiring to eat less food. These patterns, however,

returned to the baseline levels at the meal test performed after 2 months. No relationship was found between weight loss and reduction in the balloon diameters, nor between the latter and the changes in temporal profiles of eating ratings. The effect of a 500-ml balloon on meal-related hunger and satiety therefore seems to disappear with time.

INTRODUCTION

The treatment of patients with morbid obesity is often difficult and may require different therapeutic approaches. Conventional or severe dietary restriction, increased physical activity and drug therapy may be helpful in the short run, but the long term results are frequently discouraging (Garrow, 1988). Different types of surgical procedures have been devised, aimed at reducing energy intake and/or producing malabsorption (Kral, 1983), but their long-term safety is unknown and requires continual revision. In recent years, there has been some interest in the use of intragastric balloons as a complementary method of achieving weight loss in obese patients and various types of balloons have been developed, with different shapes and volumes (Nieben & Harboe, 1982; Garren et al., 1984; Percival, 1984; Durrans & Taylor, 1986; Shapiro et al., 1987). Despite their widespread use over the last 4-5 years, problems relative to We thank SIM Italia Srl, Bologna, Italy, for supplying us with some of the balloons used in this study, and MS Susan West who supervised and typed this manuscript. Address reprint requests to: Dr Renato Pasquali, Istituto di Clinica Medica e Gastroenterologia. Osp, S. Orsola, via Massarenti 9,40138 Bologna, Italy.

0 19%6663/90/040003 + 09 SO3.00/0

8 1990 Academic Press Limited

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the efficacy of these devices are still unsolved. Recent controlled studies have provided adequate evidence that a balloon, developed by M. Garren et al. (1984), and widely used and publicized in the U.S.A., was no more effective than a sham procedure in favouring weight loss in obese patients (Hogan et al., 1987; Lindor et al., 1987; Levine et al., 1987; Stoltemberg et al., 1987; Benjamin et al., 1988; Meshkinpour et al., 1988). On the other hand, preliminary data relative to a study carried out in Europe on the efficacy of a device called Ballobes @, first developed by Nieben & Harboe (1982) in Denmark and which differs from the former in its oval shape and its volume which may be two or three times greater (400-600 ml), seem to indicate that it may favour a greater weight loss than the sham procedure in obese patients over 30% above their ideal body weight (Ramhamadany & Baird, 1988). Mechanisms of action of intragastric balloons are still not clear. Several studies have reported that patients reveal a decrease in hunger and increased early satiety when the device is inserted (Kaufmann, 1987) but no controlled studies have been performed and no information is available on the duration of these effects. We therefore studied a group of patients with morbid obesity to investigate the chronic effects of the intragastric balloon on mealstimulated eating behaviour and to analyze the relationship between eating pattern profiles and the rate of weight loss. MATERIALSAND

METHODS

Patients This study examined nine massively obese patients (six women and three men) with mean&SD age 43.65 10.7 years (range 25-54), weight 132*9* 16.7 kg (range 105.3-l 54.2) and body mass index (BMI: weight in kg+ height in m’) 49.3 + 5.7 (range 39-6-57.5). There was no history of cardiovascular diseases, renal failure, chronic liver diseases or important gastrointestinal disease. Lesions of the upper digestive tract were ruled out by endoscopy and in the lower tract by X-ray examination. One patient suffered from non-insulin-dependent diabetes and another from mild hypertension. No patient was taking any drugs or following a hypocaloric dietary program. Spontaneous energy intake was assessed by means of the diet history and the 3-day record technique (Burke, 1947; Pekkarinen, 1970). The (9,053 f 2,019 kJ; range estimated energy intake was 2,173 f 483 kcal/day 7,102-12,770 kJ) containing 88 f 20 g of protein, 97 + 29 g of lipids and 247 + 69 g of carbohydrates per day. Informed written consent was obtained from all the patients participating in the study. Study Protocol Baseline evaluation included careful examination of the clinical history, complete X-ray examination of the digestive tract and chest, esophagus-gastricduodenoscopy, ECG and routine biochemical tests. All patients were also evaluated by a clinical psychologist to assess their suitability for treatment and any contraindications. The therapeutic program included a hypocaloric diet with either a lowor a very-low-calorie diet, depending on personal choice. The balloons (Ballobes@) were inserted using the procedure advised by the manufacturer (Ballobes@ intragastric balloon-Manual 1988, DOT, Islevdalvej 142, DK 2610 Rsdovre, Denmark). Patients had avoided food ingestion since the previous evening. After administration of xylocaine spray, a topical anesthetic agent, to the patient’s throat,

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the balloon system was inserted using the same technique as with a gastroscope. The air pump was then connected to the inflation tube and the balloons were inflated with 500 ml of air (5.5 pump strokes), except in one patient where the balloon was inflated with only 400ml of air (four pump strokes). The inflation tube was then removed from the valve with a quick pull, leaving the balloon lying free in the stomach. Dietary treatment began 334 days after balloon implanting. Seven patients followed a verylow-calorie diet of 514 kcal/day (2,148 kJ) containing daily protein 63g, lipids log and carbohydrates 40g for 3 weeks. The diet consisted of 200g/day of steamed or grilled meat (e.g. turkey, veal, horse-meat or chicken breast) and a liquid formula product (Precision N@, Wander Ltd., Switzerland, which provides protein from milk albumin). After this diet all but one of these patients were invited to follow a conventional low-calorie diet consisting of 800-1,000 kcal/day (3,3445,016 kJ) for the remaining period of the study. The other two patients were treated with a similar low-calorie diet for the entire period of the study. The correct position and inflation of the balloon was evaluated immediately after implant, and then checked each month, by X-ray films taken from front to back and from left side to side with the patient in an upright position. The longitudinal and transversal diameters were measured but the vertical diameter was not measured due to the impossibility of obtaining an accurate measurement; the balloon volume was not therefore measured. Starting from the day after the implant and throughout the entire period the patients were treated with ranitidine, 150mg per evening, since treatment with histamine HZ-receptor antagonists was said to increase the durability of the implanted balloon (White & Bakersfield, 1984). Evaluation of Eating Patterns: The Mixed Meal Test

Mixed meal tests were performed during the week before implanting and 2-3 days and 2 months afterwards. Patients were invited not to change their eating pattern and daily energy intake until after the second meal test. The test meal consisted of 796 kcal (3,327 kJ) containing protein 36 g, lipids 32 g and carbohydrates 91 g, administered as bread, cheese and an apple. This was consumed in 20 min. At regular intervals before and up to 5 h after the meal, the patients were asked to fill in a questionnaire (A) consisting of visual analogue ratings of subjective states regarding eating patterns. This temporal tracking (Hill et al., 1984; Hill & Blundell, 1986) of hunger and satiety was made on lOO-mm visual analogue scales (word anchored at either end) in the following order: (a) “How strong is your desire to eat?” (very strong-very weak); (b) “How hungry do you feel?” (as hungry as I have ever felt-not at all hungry); (c) “How full do you feel?” (very full-not at all full), and (d) “How much food do you think you could eat?” (a large amount-nothing at all). This last rating is called prospective consumption. The questionnaire was filled in by the patient himself in the presence of one of the authors (B.L.) and he was not able to see the replies given at the previous times. Statistics

The results were analyzed using the Wilcoxon rank sum test and regression analysis. Areas under the curves during the meal test were calculated by means of the trapezoidal method, taking values at 0 times as basal values. The results presented are the mean + SD unless otherwise indicated. p < 0.05 was considered significant.

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RESULTS

Weight Loss Body weight was recorded before and 2-3 days after the intragastric balloon implant on the same day as the mixed meal tests were made. Despite the instructions not to alter total energy intake, the weight measured 2-3 days after balloon implant was slightly but significantly lower than that measured before (129. I + 18.1 vs. 13 1.5 f 16.9 kg; ~~0.05). After 2 months, however, it was 119.8f 19.9 (p
Meal Test and Eating Patterns

The eating patterns during the mixed meals before, 2-3 days after and 2 months are shown in Figure 1. Desire to eat, hunger and after Ballobes@ implantation prospective consumption decreased significantly 2 h after meal ingestion, whilst fullness increased. However, different profiles were obtained during the three meals. In fact, 2-3 days after balloon implant, premeal values of scores related to desire to eat and hunger were significantly lower and the score related to fullness was significantly higher when compared to pretreatment values. Moreover, the subjects rated themselves as significantly less hungry, fuller and desiring or wanting to eat less food after meal ingestion. These patterns, however, seemed to disappear after 2 months, so that the pre- and postmeal profiles of ratings were not significantly different from those observed at basal conditions. Figure 2 represents the integrated total areas of each profile: these provide data which confirm those obtained from the analysis of the profiles at each single time. The figure also reports the areas recorded at the various early phase times (O-120min) as compared to the late phase (180-300 min) after meal consumption. Only marginal differences were detected as compared to the results of the total areas examined: in particular, the reduction in rated desire to eat and hunger during the meal 2-3 days after implant was significantly more evident during the late phase than during the early phase. Interrelationships

Between

Weight Loss, Eating Pattern Projiles and Balloon Size

No correlation was found between the reduction in body weight measured after 2 months, the reduction in the size of the balloons and eating rating profile modifications at 2 months.

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FIGURE 1. Eating pattern profiles (mean + SEM) during a 795kcal (3327-U) mixed meal test (from -60 to + 300 min) performed before (0-O) and 2-3 days (0 ---- 0) and 2 months (*-. -. - *) after the implant of the intragastric balloon (Ballobes@). After the second meal test (2-3 days after the implant), patients also followed a hypocarloric diet. Statistics: a, b = significant difference vs. before (p < 0.05 and 0.0 I, respectively), c, d = significant difference vs. 223 days values (p < 0.05 and 0.01, respectively).

DISCUSSION In this study we have shown that patients presented significantly different mealrelated eating behaviour after the implant of an intragastric balloon, i.e. reduced ratings of hunger and desire to eat and increased satiety, thus confirming what was previously suggested in several clinical reports, based on the subjective impressions reported by the patients (Nieben & Harboe, 1982; Garren et al., 1984; Durrans & Taylor, 1986; Kaufmann, 1987; Benjamin et al., 1988). On the other hand, we found that these effects were transitory since they had, for the most part, disappeared 2 months after balloon implant. Before deciding whether the results were observed were truly attributable to the balloons or not, a series of considerations must be taken into account. Diet prescription began just after the second meal test and it is therefore possible that, by 2 months, compliance with the diet could have led to an increase in hunger. It seems improbable, however, that it could have induced the difference in fullness ratings observed between the third meal test and that performed 2-3 days after the implant. Moreover, several patients experienced mild but transitory side effects which could

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FIGURE 2. Areas of eating pattern profiles (mean+SD) obtained during a 796-kcal (3,327-kJ) mixed meal test performed before (W), 2-3 days (0) and 2 months after ( q) the implant of the intragastric balloon (Ballobes@). Total, early (O-120 min) and later (180-300 min) areas are represented separately. Statistics: *p < 0.05; **p < 0.01. have affected rating patterns during the second meal test, despite the fact that the energy content of meals was similar. However, in a recent study performed to evaluate the effects of acute gastric distension on energy intake, Geliebter et al. (1988) observed that discomfort after balloon insertion was probably not a factor in inducing satiety, in obese as well as normal-weight subjects. Finally, it is improbable that ranitidine influenced the difference in eating ratings behaviour, since patients were under treatment on both days on which the second and third meal tests were carried out. There are, however, no studies which have shown ranitidine to have any effects on eating behaviour in either the short or the long term. The putative mechanisms of action of the intragastric balloon are not at all clear. Morley (1987) suggested that vagal and humoral signals may play an important role in the effects of gastric distension on meal-related eating behaviour. Stomach

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distension, whether achieved by a balloon or by calorically inert food, can effectively regulate food intake in dogs (Janowitz & Grossmann, 1949). In growing rats, it has been found that a gastric balloon inflated to occupy approximately one-third of their estimated stomach capacity reduced food intake by 30% and led to lower weight gain after 2 months as compared to control rats or rats with deflated balloons. When balloons were deflated, however, rats rapidly increased their food intake and regained lost body weight (Geliebter et al., 1983). Similar findings were observed by Yang et al. (1987) in experiments performed on pigs. More recently, Geliebter et al. (1988) showed that acute distension of the stomach with a balloon reduced spontaneous food intake in proportion to the volume of the balloon inserted. It seems, therefore, that the effects of intragastric balloons on eating behaviour could be due to their volume. If a sufficiently large volume of the balloon is an important factor in regulating food intake, this would explain the negative results obtained in the controlled studies using the Garren device (Hogan et al., 1987; Levine et uf., 1987; Lindor et al., 1987; Stoltemberg et al., 1987; Benjamin et al., 1988; Meshkinpour et al., 1988). If we take the Geliebter study as the only database referring to man (Geliebter ef al., 1988), it is evident that a volume of at least 400-600 ml is necessary to obtain an acute reduction of at least 30% in food intake, whereas with an inflated volume of 200 ml (equal to the Garren balloon) the reduction is only 10%. On the other hand, it is also necessary to consider the possibility of the intervention of adaptive gastric mechanisms since, as we have seen, the effects of the balloon appeared to be transitory. In fact, dilation of the stomach and hypertrophy of the stomach walls (Geliebter et al., 1983, 1986) have been demonstrated in experimental animals after they had received an inflatable device for a long period of time. Although it has not been confirmed, it is probable that this adaptive phenomenon also occurs in man, which could explain why, after 2 months of treatment, the subjects no longer report a reduction in hunger or desire to eat or even an increase in satiety when eating a meal, and why no relationship could be observed between the reduction in the volume of the balloon (although this was only slight) and changes in the subjective eating patterns during the meal test. This study, however, did not fully investigate the possibility of intermeal or premeal ratings being influenced by the balloon. Our tests included the evaluation of eating ratings only 1 h before meal administration, and mean values of each rating after 2 months did not significantly differ from those observed in the preballoon test. Therefore, our data do not seem to indicate (but a priori they cannot exclude) that the balloon was helping the patients by keeping motivation a little lower during the phase of hypocaloric diet. To summarize, we evaluated the effects of a 500-ml inflated intragastric balloon on some aspects of eating-related behaviour in a small group of massively obese patients who were also following a hypocaloric regimen. The balloon proved to reduce hunger and desire to eat and increase postmeal satiety, but these effects appeared to wear off with time. REFERENCES

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16 May 1989, revision 21 July 1989