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Novel Insights from Clinical Practice

Horm Res Paediatr DOI: 10.1159/000354301

Hunger Hormone Profile Monitoring after Gastroplication in an Adolescent

Valeria Calcaterra   a, b Gloria Pelizzo   c Ghassan Nakib   c Daniela Larizza   a, b Maria Luisa Fonte   d Mara De Amici   a Hellas Cena   d  

a   Pediatric Unit, Department of the Mother and Child Health, IRCCS Policlinico San Matteo Foundation Pavia, b   Department of Internal Medicine, University of Pavia, c   Pediatric Surgery Unit, Department of the Mother and Child Health, IRCCS Policlinico San Matteo Foundation Pavia and University of Pavia, and d   Human Nutrition Section, Department of Public Health, Neurosciences, Experimental and Forensic Medicine, University of Pavia, Pavia , Italy

went gastroplication. Hunger hormone levels (leptin, ghrelin and insulin), weight loss and eating behavior were moni-tored at 3, 6 and 12 months after surgery. Results: Weight loss was obtained, progressively achieving a loss of 45.6 kg 1 year after surgery. A strong reduction in insulin concentra-tion and insulin resistance was documented. At 3 months after the operation, a surprising leptin level drop was ob-served. During the following months a progressive increase in leptin levels and leptin/kg of fat mass were documented. Fasting ghrelin levels increased in the first 3 months, then fell

Key Words

Gastroplication · Adolescent · Ghrelin · Leptin · Hunger

Abstract

Introduction: Gut and adipose tissue hormones play an im-portant role in energy balance control, particularly through the regulation at either short- or long-term food intake after bariatric surgery. Case: A 15-year-old obese female (BMI 42.2) who was unresponsive to medical treatment under-

Received: May 13, 2013 Accepted: July 8, 2013 Published online: August 31, 2013

HORMONERESEARCH IN PÆDIATRICS

Prof. Gloria Pelizzo Pediatric Surgery Unit, IRCCS Policlinico S. Matteo Foundation P. le Golgi n.2 IT–27100 Pavia (Italy) E-Mail g.pelizzo   @   smatteo.pv.it

© 2013 S. Karger AG, Basel1663–2818/13/0000–0000$38.00/0

www.karger.com/hrp

Established Facts

• Bariatric surgery remains the only approach able to achieve significant weight loss with long-term maintenance of results in the morbid obese even in adolescence.

• Postsurgical changes within the neurohormonal system may account for a proportion of postsurgical weight loss.

• No long-term data on hunger hormone profiles after gastroplication has been described to date.

Novel Insights

• We report a significant change in hunger hormones after gastroplication in pediatrics. • Hormone level changes seem to be involved in weight loss and eating behavior also in youths.

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over the next 6 months. Up to 6 months after gastroplication, we observed a less marked drop in plasma ghrelin after meal ingestion, while the values after 1 year showed a substantial fall in the postprandial period despite a further fasting ghre-lin increased level. Early achievement of satiety was found. Conclusion: Hunger hormones level changes seem to be in-volved in weight loss and eating behavior after gastroplica-tion in adolescents. Copyright © 2013 S. Karger AG, Basel

Introduction

The prevalence of obesity is increasing at an alarming rate around the globe [1] . Among current treatments, bariatric surgery remains the only approach able to achieve significant weight loss with long-term mainte-nance of results in the morbid obese [2] . The traditional belief that bariatric surgery acts only by limiting the space for food consumption or diminishing the absorption of nutrients seems to be enriched by new theories that strongly support the implication of a new balance be-tween the various hormones of hunger and satiety in weight loss [3, 4] . Regulation of food intake is a complex interplay of central and peripheral signals. Gut and adi-pose tissue hormones play an important role in control-ling the energy balance, particularly through the regula-tion of food intake in either the short or long term [5] . We report changes in hormones levels involved in hunger, food intake and satiety following robotic-assisted gastro-plication in a morbid obese adolescent.

Case Report

A 15-year-old obese female adolescent (BMI 42.2), who did not respond to medical treatment, underwent gastroplication. She re-ported snoring, fatigue, perception of a low quality of life and a history of being mocked. She was affected by hyperinsulinism, hy-perandrogenism, amenorrhea, signs of polycystic ovarian syn-drome on ultrasound and hypertension with left ventricular hy-pertrophy as comorbidities. A multidisciplinary intervention was programmed with specific nutritional and psychological sessions, as well as physical training, and performed before and after sur-gery. The psychological evaluation had the aim of excluding the presence of clinically significant binge-eating behavior. The an-thropometric and biochemical characteristics as well as body com-position assessed by bioelectrical parameters before surgery are reported in table 1 .

Bioelectrical impedance analysis is an easy and applicable method for estimating body composition before, during and after weight loss since decrease in fat mass (FM) is one of the aims of pediatric obesity treatment. Bioelectrical impedance analysis was

measured using a single-frequency tetrapolar technique with an electrical current of 800 A at 50 kHz (STA-BIA; Akern, Florence, Italy). The electrodes were placed on the back of the hand and the feet: the signal electrodes were place on the phalanges and the sen-sor electrodes just beneath a line between the prominent bones of the wrist and the ankle on the right side of the body. Gastroplica-tion was done with robotic surgery using ‘Da Vinci’ system assis-tance [6] .

Immediately following surgery, the patient was placed on a very-low-calorie liquid diet (VLCD) with a high-protein content (about 40% of the energy intake). This was followed by a semiliq-uid then semisolid soft high-protein very-low-calorie liquid diet supplemented with symbiotic, multivitamin and essential amino acids. Thereafter, a moderately hypocaloric soft diet equivalent to the resting energy expenditure measured by indirect calorimetry was adopted.

Nutritional status was assessed weekly, providing her and her family psychological support. No vomiting episodes or dumping symptoms were documented. Diet compliance was evaluated by a registered dietician who performed a 24-hour recall at each medi-cal control. Anthropometric, bioelectrical and biochemical char-acteristics at the postsurgical evaluations are described in table 1 .

During the first 6 months, diet compliance was high and the patient did not report any difficulties in following the prescrip-tions. She reported no hunger but early satiation with some diffi-culties in completing the meals. After 6 months she reported in-creased hunger before meals, but with an early achievement of sa-tiety that prevented overeating episodes.

Table 1. Anthropometric, bioelectrical and biochemical character-istics before surgery, as well as at 3, 6 and 12 months after surgery

Parameters Before surgery

3 monthsafter surgery

6 monthsafter surgery

12 monthsafter surgery

Weight, kg 126.2 95.8 84.8 80.6Height, cm 173 173 173 173BMI, kg/m2 42.2 32 28.3 27BMI excess, % 75.8 33 16.6 12.5Waist circumference, cm 122 102.5 101 96.5Waist-to-height ratio, cm 0.70 0.59 0.58 0.55FM, % 42.8 32 34.8 31.1FM, kg 52 30.7 29.5 25.9Total body water, % 36.7 45.2 44.5 47Total body water, l 44.6 43.3 37.7 39.1Phase angle, φ 5.5 4.6 4.6 4.7Respiratory quotient 0.79 0.79 0.81 0.85Fasting blood glucose, mg/dlFasting insulin, μIU/ml

9066

819

824.9

7713

HOMA-IR 14.7 1.8 1 2.4Ghrelin, pg/ml

FastingPostprandial

38.228.3

75.568.9

34.928.4

127.762.0

Leptin, pg/mlFastingPostprandial

8,121.210,508

2,1912,537

13,26520,850

26,32133,264

Leptin, pg/ml/kg FM 156 71.3 449 1,016

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Hunger Hormone Profile after Gastroplication

Horm Res PaediatrDOI: 10.1159/000354301

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At her 3-month postsurgical evaluation, the patient had a strong reduction in her insulin concentration and a decrease in her homeostasis model assessment index of insulin resistance (HOMA-IR). Weight loss was 30.4 kg. The girl regained normal menstrual cycles 5 months after surgery. At that time, the resolution of hor-monal and ultrasonographic features of polycystic ovarian syn-drome was observed. Six months after the surgery, she had lost 41 kg and her BMI dropped from a severe obesity condition to a state of overweight. She reported a better quality of life perception and her body image perception improved with a significant im-provement of the overall psychometric score [7] . At the end of the first postsurgical year her BMI was 27.

We observed a fast leptin level drop after 3 months, during this period the patient lost about 40% of the presurgical FM. These data were confirmed by indirect calorimetry. During the ensuing months, we observed a progressive increase of leptin and leptin/kg of FM values.

As for ghrelin levels, we observed increased fasting values after 3 months. Six months after the surgical procedure, the ghrelin values were low. Up to 6 months after surgery, we observed a less marked drop in plasma ghrelin after meal ingestion, while the values after 1 year showed a substantial fall in the postprandial period despite a further increase of the fasting ghrelin concentration. In figure 1 , the pre- and postoperative leptin and ghrelin profiles can be seen.

Discussion

Bariatric surgery has become the preferred option for the treatment of morbid obesity. Relative to behavioral interventions, surgical treatment produces greater weight loss in both the short and long term [2] . An increasing number of studies suggest that postsurgical changes in appetite-related hormone levels can play a role in weight loss [3, 4, 8] . Whether the hormonal changes after surgery

are secondary to weight loss or due to the nature of the surgery is still under investigation.

In our patient who received gastroplication, we re-port a significant change in hunger hormones. Signifi-cant weight loss as well as a substantial change in insu-lin-resistance index, insulin, and leptin and ghrelin concentrations 1 month after surgical treatment has al-ready been reported [6] . The favorable change in leptin levels 3 months after surgery is linked to the loss of FM. A progressive increase of leptin values during the sub-sequent months and decreased hunger with early achievement of satiety confirmed the anorectic effect of this hormone.

Weight gain and obesity are associated with insulin resistance, raising the fundamental question of whether adaptations of energy homeostasis are linked to insulin resistance [8] . Parallel to leptin, insulin acts as the second powerful mediator of adiposity-related negative feedback signaling. Like leptin, insulin infusion directly into the brain decreases appetite and food intake, leading to weight loss. However, artificial disruption of receptor sig-naling for insulin in key brain areas increases hepatic glu-cose production, appetite and food intake, leading to weight gain. These findings were the first evidence sug-gesting a role for ‘brain insulin signaling’ in the control of food intake and energy homeostasis. Insulin may there-fore have an anorectic action in addition to its hypogly-cemic effect [9] . In addition, as an adiposity signal, insulin is believed to have a similar lipostatic role as leptin, al-though its central effects on food intake and energy ho-meostasis are less efficient [5, 9–12] . In our girl, a reduc-

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Fig. 1. Changes in leptin ( a ) and ghrelin ( b ) levels before surgery and at 3, 6 and 12 months after surgery.

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tion in circulating insulin levels was observed, with im-proved insulin sensitivity as measured by HOMA-IR. Improvement in insulin resistance has been reported as early as 3 months after surgery, before any major weight loss occurs. Probably, caloric restriction and the changes in adipocytokine and gut hormone profiles after surgery act simultaneously to variable intents to improve insulin sensitivity.

The mechanism of plasma ghrelin changes after bar-iatric surgery is not completely understood. In humans, ghrelin increases before the meals and is suppressed rap-idly by food intake, thus suggesting a possible role in meal initiation [5, 9–11] . Negative correlations between circu-lating ghrelin levels and BMI have been found. The lower fasting levels in obesity are suggestive of ghrelin down-regulation in response to overeating or excess body weight [13] .

Cummings et al. [14] showed that weight loss by ca-loric restriction paradoxically results in increasing plas-ma levels of ghrelin, both in the fasting and postpran-dial state. Different types of surgery appear to have op-posite effects on fasting and postprandial ghrelin: gastric bypass operations tend to reduce ghrelin, while restrictive ones increase or do not change ghrelin [13, 15] .

A less marked drop in plasma ghrelin after meal inges-tion, typical in obese subjects, was noted up to 6 months

after gastroplication, while a more efficient response after 1 year was noted with a substantial fall in the values dur-ing the postprandial period. If ghrelin levels are decreased after the intervention, it is possible that this could have contributed to the weight loss, but low ghrelin levels are not a consistent outcome in bariatric surgery. Therefore, we agree with Ionut and Bergman [15] that ghrelin chang-es after bariatric surgery may be an epiphenomenon and that other factors are involved in both the changes in hor-mones and weight loss. For our patient, gastroplication appears to have been successful, but she will continue to be monitored for long-term effects and complications.

Although durable weight loss after bariatric surgery is probably due to a new gastrointestinal hormone equilib-rium, more findings are needed to provide evidence on the role of bariatric procedures on weight loss and weight maintenance in this fast-moving area of research [15] . A multidisciplinary approach and continuous care through motivation reinforcement, nutritional education and an increase in energy expenditure play an important role in weight loss after bariatric surgery and long-term weight maintenance.

Disclosure Statement

None declared.

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