Journal of the American College of Nutrition, Vol. 19, No. 2, 270-274 (2000)
Published by the American College of Nutrition
Body Composition and Energy Expenditure after Weight Loss Following Bariatric Surgery
Giuseppe Benedetti, MD,
Geltrude Mingrone, MD, PhD, FACN,
Stefania Marcoccia, MD,
Maria Benedetti, MD,
Annalisa Giancaterini, MD,
Aldo Virgilio Greco, VM,
Marco Castagneto, MD, FACS and
Giovanni Gasbarrini, MD
Cattedra di Medicina Interna II (G.B., G.M., S.M., M.B., A.G., A.V.G., G.G.), CNR Centro di Fisiopatologia dello Shock, Università Cattolica del Sacro Cuore, Rome, ITALY
e Cattedra di Chirurgia Sostitutiva e dei Trapianti d’Organo (M.C.), CNR Centro di Fisiopatologia dello Shock, Università Cattolica del Sacro Cuore, Rome, ITALY
Address reprint requests to: Giuseppe Benedetti, MD, Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Istituto di Medicina Interna & Geriatria, Largo Gemelli 8, 00168 Roma - ITALY
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ABSTRACT
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Objectives: To assess the effectiveness of biliopancreatic diversion (BPD) in the treatment of morbid obesity and to evaluate how the procedure affects body weight.
Subjects: Fourteen morbidly obese subjects studied before and 30 months after BPD and fifteen healthy volunteers matched for age, sex and height (controls).
Methods: Comparison of the following parameters were made in the study groups before surgery and 30 months after BPD and with those of the controls group: fat mass, fat-free mass, non-protein substrate oxidation, basal metabolic rate, plasma glucose, insulin and free fatty acid concentrations.
Results: Obese subjects lost 60.38±10.71 kg of weight during 18 months following surgery and then remained stable for another 12 months, when this study was performed. Weight loss was substantially due to a loss of fat mass (FM: 60.13±13.01 kg before and 19.02±8.61 kg after BPD; p<0.001). FM were not statistically different between post-obese subjects and controls; however, post-obese patients retained significantly more fat free mass (FFM) than controls. Subsequently, basal metabolic rates of post-obese subjects were higher than those of the control group (p<0.05). Fasting non-protein respiratory quotient (npRQ) was significantly lower before BPD than 30 months after the surgery (0.798±0.04 vs. 0.90±0.048, p<0.001), suggesting that, while obese, patients oxidized more lipids than carbohydrates. Moreover, fasting and two-hour plasma glucose and insulin concentrations decreased significantly after BPD to values comparable to those of the control group.
Conclusion: Weight loss in obese patients after BPD is mainly due to lipid malabsorption, but increased energy expenditure associated with retaining a high FFM in physically active post-obese subjects may also play a role, enabling them to maintain long-term reduced body weights.
Key words: weight loss, obesity, metabolism, energy expenditure, bariatric surgery
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INTRODUCTION
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Obesity, type 2 diabetes mellitus, hypertension and coronary heart disease (CHD) are frequent disorders in Western societies and seem to share a common pathogenic pathway [1–3]. It has been hypothesized that resistance to insulin-stimulated glucose uptake is involved in the etiology of type 2 diabetes, hypertension, dyslipidemia (increased plasma triglyceride concentration and decreased HDL-cholesterol levels) and CHD [4].
Obesity itself is associated with insulin resistance, and a decline of 30% to 40% in insulin sensitivity has been noted with an increase of 35% to 40% above the ideal body weight in non-diabetic subjects [5–8]. Insulin resistance is primarily located at the skeletal muscle level and involves both the oxidative [9–11] and nonoxidative pathways of glucose disposal [12]. Initially, resistance to insulin-stimulated glucose uptake is associated with an increased pancreatic insulin secretion. Whether insulin resistance represents the primary metabolic defect with subsequent increase in insulin secretion by the pancreatic-cells as a compensatory mechanism or hyperinsulinemia caused by high caloric intake is the primum movens is still controversial.
However, reversibility of insulin resistance has been recently demonstrated in morbidly obese subjects, who reached a near normal and stable body weight after biliopancreatic diversion surgery [13], suggesting that the procedure might have favorable effects on both body weight and metabolic status of a very difficult to treat group of patients. In a five-year follow-up study of 30 subjects who had undergone biliopancreatic bypass surgery, a significant weight loss has been achieved, without nutritional deficiencies [14].
This study investigated the changes in body composition and energy metabolism in subjects with morbid obesity (body mass index, BMI>40 kg/m2), who, after biliopancreatic diversion surgery (BPD) [15–17], attained a nearly normal weights which remained stable during the year before final measurements of the study.
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MATERIALS AND METHODS
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Subjects
Fourteen patients with morbid obesity (nine women and five men) who underwent biliopancreatic diversion were studied before and 30 months after surgery. Fifteen healthy volunteers (nine women and five men), matched for age, gender and height were also studied as a control group. The anthropometric characteristics are shown in Table 1. All obese patients had diabetes mellitus [18] prior to surgery. None of the women examined had menstrual flow, and they were studied in the follicular phase of menstrual cycle.
Surgical Procedure
The surgical technique used was that described by Scopinaro et al. [15–17]. It consists of a distal gastrectomy with a long Roux-en-Y reconstruction, the enteroenterostomy being placed 200 cm distal to the gastroenterostomy and 50 cm proximal to the ileocaecal valve. Three intestinal limbs are recognized: a) the alimentary loop from the gastroenterostomy to enteroenterostomy, b) the common loop from the enteroenterostomy to the ileocaecal valve and c) the pancreaticobiliary loop from the duodenum to the enteroenterostomy [17]. The role of gastrectomy is to allow a rapid emptying of gastric content in the ileum. After the first months, during which there is a symptomatology characterized by a sense of fullness accompanied by vomiting one to two hours after a meal, the gastric pouch gradually undergoes dilatation. Patients are allowed to ingest food ad libitum and the malabsorptive mechanism causes the weight loss. Bilio pancreatic bypass, as compared with the classic ileal bypass procedure, which has been largely abandoned because of long-term sequelae, has the following advantages: 1) a selective malabsorption of fat, 2) an intact enterohepatic bile salt circulation and 3) the absence of a long excluded intestinal loop. Side effects such as diarrhea, vomiting, flatulence and sideropenic anemia were noted in six of our patients, but no significant nutritional deficiencies requiring support therapy (other than iron) were observed at 30 months follow-up.
Experimental Protocol
The study protocol followed the guidelines of the Institutional Review Board, and all subjects gave their written informed consent.
The subjects were admitted to the metabolic unit at 7:00 a.m. one day prior to the study. All were assigned diets with energy contents similar to those computed from their alimentary diaries [18]. Such a diet tried to reproduce the usual alimentary behavior of each subject. The nutrient contents (carbohydrates, lipids and proteins) of all foodstuff items were derived from computerized tables. All experiments were performed at 8:00 a.m. after an overnight fast. After voiding, the subjects lay down on the bed, and a venous catheter was inserted into the antecubital vein for blood sampling. The line was kept patent with physiological saline.
To measure the basal metabolic rate (BMR), respiratory gas exchange measurements were performed over 60 minutes by continuous indirect calorimetry using a ventilated hood metabolic monitor (Delatrac, Datex Instrumentarium, Finland) [20]. To compare the BMR measured by indirect calorimetry with the estimated values for each subject, BMR (kcalories/24 hours) was also computed using the Harris-Benedict equations [21]:
Men: 66.473+13.751 (weight in kg)+5.03 (height in cm)-6.755 (age in years)
Women: 655.5095+9.463 (weight in kg)+1.8496 (height in cm)-4.675 (age in years).
Blood samples were drawn for plasma glucose, insulin, triglycerides and free fatty acids (FFA) determination. Plasma glucose and insulin levels were also assayed two hours after an oral glucose load of 75 g.
Diet
All subjects were allowed a nonrestricted diet. During the week prior to study they were asked to compile their own food diaries. The nutrient content of food was derived from computerized tables. The metabolizable energy content of the diet was computed as the difference between gross energy intake and energy lost in urine and feces.
Energy Loss
Nitrogen was measured in the 24-hour urine sample by BUN Analyzer II (Beckman Instruments, Fullerton, CA, USA).
Fat, starch and nitrogen were measured in a sample of the stools, collected over 24 hours, by near infrared reflectance analysis (NIRA). The method is based on the analysis of radiation in the infrared spectrum close to the visible spectrum reflected by the surface of the material under study [22].
Body Composition
Body weight was measured to the nearest 0.1 kg using a beam scale. Body composition was estimated from total body water (TBW) measurements assayed by isotopic dilution after giving 80 Ci of tritiated water (100 mCi/mL) in 5 mL of saline solution as an intravenous bolus injection on the day preceding the indirect calorimetric evaluation. The dpm were counted with a Beta-scintillation counter Canberra-Packard, Model 1600TR (Canberra, CT, USA) in duplicate on 0.5 mL of plasma, taken two hours after the bolus injection when the steady state of the plasma labelled molecule concentration was reached. To calculate the fat free mass (FFM), TBW values were divided by 0.73 [23].
Respiratory Exchange Measurements
Energy expenditure, non-protein respiratory quotient (npRQ) and substrate oxidation rates were calculated from oxygen consumption, carbon dioxide production and nitrogen urinary excretion [24].
Physical Activity Assessment
Physical activity (PA) was assessed with two-week diary activity records on work-related and leisure activities (walking, training exercises, etc.) in all subjects [25].
Analytical Methods
Serum glucose was measured by the glucose oxidase method using a Beckman Glucose Analyzer II (Beckman Instruments, Fullerton, California, USA). Plasma insulin was measured by microparticle enzyme immunoassay (Abbott Imx, Pasadena, California, USA). FFA were assayed by an enzymatic colorimetric method.
Statistical Analysis
All results are expressed as mean±SD. A Bonferroni-adjusted Wilcoxon paired test was used to assess pre-surgery versus post-surgery differences in obese vs. post-obese patients. Mann-Whitney U test was used to assess differences in control subjects vs. obese, and in control vs. post-obese subjects. A p-value of 0.05 or less was considered statistically significant.
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RESULTS
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Obese subjects attained a maximal mean weight loss of 60.38±10.71 kg at 18 months following the biliopancreatic bypass and remained stable (2 kg) for at least another 12 months, until present evaluation took place (30 months after surgery). Weight loss was due largely to a loss of fat mass (FM), from 60.13±13.01 kg prior to surgery to 19.02±8.61 kg after BPD (p<0.001), but included a decrease in FFM (72.50±12.42 vs. 53.22±9.07 kg, p<0.001). This was expected since it is well known that obese subjects have an increased FFM, in addition to a higher FM, compared to normal weight people (Table 1). However, when compared with the control group, post-obese patients still had a higher FFM (46.47±7.09 vs. 53.22±9.07 kg, p<0.05), although their FM was not statistically different (Table 1). Caloric intake of the obese was significantly (p<0.001) greater than in normals and increased further (p<0.05) after surgery (Table 2). Physical activity energy expenditure was significantly lower in obese patients than in normal subjects (p<0.001), but increased after BPD to levels that were even higher than in controls (p<0.02, Table 2). Fig. 1 shows the composition of 24-hour fecal sample (in %) of post-obese patients (30 months after BPD), where 75% of nutrient lost were lipids. BMR (measured and estimated) was higher in obese subjects before surgery and decreased significantly after BPD (p<0.001 for each). However, BMR measured by indirect calorimetry was higher in post-obese subjects following BPD than in controls (1640.2±254.5 vs. 1478.1±164.2 kcal/24 h, Table 2). Fasting npRQ increased significantly in post-obese patients compared with values measured before BPD (0.90±0.048 vs. 0.798±0.04, p<0.001), suggesting a shift in substrate oxidation from lipids to carbohydrates.
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Fig. 1. 24 hour fecal losses (%) of lipids, starch and carbohydrates (CHO) and proteins in post-obese patients.
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Fasting and two-hour plasma glucose and insulin concentration in obese patients were higher than in controls. In fact, all patients had type 2 diabetes and hyperinsulinemia prior to surgery. After weight loss, both fasting and two-hour glucose and insulin, as well as fasting FFA concentrations, decreased significantly (p<0.001 vs. obese, for each variable), and they were even lower than in controls (p<0.001, for each, Table 2).
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DISCUSSION
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Since ileal bypass, as a surgical treatment for morbid obesity, has been largely abandoned because of long-term complications, gastric restrictive procedures have became the surgical choice in the Eighties. Favorable effects on weight loss were, however, less important, compared with long-term side-effects associated with this procedures. Moreover, the weight reached was difficult to maintain over time [26]. Gastric stapling combined with biliopancreatic diversion seems to lead to a degree of malabsorption, less intense than with the ileal bypass (and, therefore, without causing nutritional deficiencies), but high enough to induce a significant weight loss [14,17,27,28]. In our series, obese patients who repeatedly failed to obtain a stable weight reduction with low-calorie diets reached a near-normal weight after BPD. Furthermore, the weight achieved was maintained over a 30 month follow-up period, in spite of a considerably higher caloric intake, with respect to healthy individuals (Table 2). This probably reflects the effect of lipid malabsorption following BPD (Fig. 1). The (recommended) high caloric and high protein intake, as well as the increased physical activity, aided in the retention of FFM after weight loss, which was higher than in controls. This is, probably, the explanation of higher measured BMR in post-obese patients compared with matched controls (Table 2). Another important finding was the reversibility of insulin resistance in post-obese subjects following BPD, supported by the significant decrease in plasma glucose and insulin levels to concentrations within normal range, even lower than in the control group. This finding may also be ascribed to lipid malabsorption following BPD, with reduced levels of plasma FFA and interruption of the Randle’s cycle. It is well known that stored triglycerides are hydrolyzed to fatty acids and glycerol by the hormone sensitive lipase, whose action is inhibited by insulin [29]. Increased lipolysis, a characteristic of obesity, leads to an increase in circulating FFA [30], which are transported and oxidized in skeletal muscle [31]. The increased FFA oxidation subsequently leads to inhibition of glucose oxidation. In fact, obese subjects tend to oxidize more lipids than carbohydrates, compared with lean individuals [32], as we have also shown in our series. Reduced levels of FFA following BPD is, probably, the explanation of higher npRQ observed in post-obese patients, after weight loss (Table 2). Furthermore, according to our previous report [27], after an oral glucose load, the RQ rose to values higher than one, suggesting a de novo synthesis of free fatty acids, which are impoverished due to a massive lipid malabsorption, from glucose. This represents a wasting process which causes a loss of energy in the form of ATP which, in turn, contributes to the patients’ weight loss. In the present series, the post-obese patients who underwent bilio-pancreatic diversion for morbid obesity showed a high RQ in the fasting state as a possible consequence of the activation of neoglucogenesis pathway or of an increased glycogen mobilization, as happens in patients treated with low-calorie diet [33]. The reduced FFA levels in post-obese subjects support previous findings regarding reversibility of insulin resistance in obese patients after biliopancreatic bypass [13,27,28]. In addition, our study demonstrates the efficiency of this procedure in reaching a normal body weight and maintaining it for more than two years. Weight loss is primarily due to a selective lipid malabsorption, while weight maintenance probably reflects the increased energy expenditure in physically active post-obese subjects. Finally, no important long-term side-effects have been noted with this procedure in our group.
Received July 1, 1997.
Accepted March 1, 1999.
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ABSTRACT
INTRODUCTION
