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Keywords:

  • leptin;
  • insulin;
  • weight reduction;
  • BMI;
  • vertical banded gastroplasty

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

Objective: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty.

Research Methods and Procedures: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls.

Results: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration.

Discussion: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti-obesity surgery.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

Leptin, the product of the obesity gene, is a hormone secreted mainly by the adipocytes (1). In rodents, leptin plays a major role in the homeostasis of body weight (1, 2, 3, 4). In humans, a strong positive correlation between serum leptin concentration and body fat content has been found (5, 6, 7, 8, 9). In obese subjects, plasma leptin concentration is elevated due to the increased production per unit of fat and the secretion from a larger total fat mass (10). Starvation and chronic caloric restriction is associated with lowered serum leptin concentration (11, 12, 13, 14). In obese people, plasma leptin concentration is reduced after reduction in body weight, as well as during both fasting (15) and long-term weight reduction with dietary-intervention programs (12, 13, 14). The fall in plasma leptin concentration associated with weight loss varies considerably among individuals of similar body composition (5, 12, 13). This suggests that in addition to the loss of body fat, other factors determine the change in plasma leptin concentration that occurs with weight reduction. Some data indicate that insulin has a significant influence on plasma leptin concentration changes in response to hypocaloric diet-induced weight loss (nonsurgical obesity treatments) (16, 17, 18). However, Toornvliet et al. (19) suggest that BMI is the main determinant of the plasma leptin concentration in obese humans, whereas changes in insulin concentration do not seem to influence plasma leptin concentration in obese humans.

Plasma leptin concentration changes have also been reported in surgically induced weight loss (after gastric bypass operation) (20, 21, 22, 23, 24). Guldstrand et al. (20) have suggested that the reduction in insulin concentration is a key factor responsible for serum leptin reduction after vertical banded gastroplasty (20). Essentially similar results have been reported after biliopancreatic diversion; plasma leptin concentration decreased rapidly without correlation with BMI (22). However, Geloneze et al. (23) have reported that after bariatric surgery and massive weight loss, serum leptin concentration is not dependent on serum insulin variation, but is strongly correlated with BMI. Carmichael et al. (21) have reported that after bariatric surgery, plasma leptin concentration is strongly correlated with both BMI and plasma insulin concentration.

The above data suggest that the associations between serum leptin concentration changes and BMI and between serum leptin and insulin concentrations after gastric bypass operation are still open questions.

To explore further the above-mentioned controversial points, we studied the effect of massive weight reduction after banded vertical gastroplasty on BMI, body fat mass, serum leptin, and insulin concentrations. Because obesity plays a central role in insulin resistance (25), the second goal was to assess the possible relationship between serum leptin concentration and insulin resistance after surgery.

Research Methods and Procedures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

This research was carried out in accordance with the Declaration of Helsinki of the World Medical Association and was approved by the Medical University of Gdansk Ethics Committee. All of the patients signed an informed consent for this investigation. Patients were admitted to the Department of Surgery (Medical University of Gdansk, Gdansk, Poland) to undergo surgery.

Patients

Eighteen morbidly obese women 39 ± 9 years old (range, 23 to 61 years old) and 8 morbidly obese men 43 ± 5.7 years old (range, 29 to 59 years old) underwent banded vertical gastroplasty. The patients had no clinical evidence of endocrine, cardiac, hepatic, or renal failure diseases. Among the women, 55% had hypertension (>150/90 mm Hg), 55% had familial obesity, 50% were cigarette smokers, and 89% were premenopausal. Among the men, 88% had hypertension, 25% had familial obesity, and 25% were cigarette smokers. None of our patients was taking drugs affecting glucose tolerance. Most of the patients displayed an impaired glucose tolerance. The diabetic patients were excluded from this study. Other characteristics of surgically treated patients determined before surgery are presented in Table 1. All of these subjects had anthropometric and laboratory parameters checked before surgery and at different times after surgery (usually 2 and 4 weeks after surgery and later once per 6 to 8 weeks for 50 weeks). After overnight fast, blood specimens were obtained for the serum glucose, cholesterol, triacylglycerol, leptin, and insulin assays.

Table 1. . Body weight, BMI, body fat, serum leptin levels, insulin levels, insulin resistance, triacylglycerol levels, and cholesterol levels in control and obese subjects before vertical banded gastroplasty
 FemalesMales
 Control (n = 10)Obese (n = 18)Control (n = 10)Obese (n = 8)
  • *

    p < 0.05 (vs. control).

  • p < 0.01 (vs. control).

Body weight (kg)62.7 ± 8.9122 ± 15.672.1 ± 8.34143 ± 17
BMI (kg/m2)23.2 ± 2.445 ± 5.8323.2 ± 2.7146 ± 4
Body fat (kg)13.8 ± 2.362 ± 13.516.6 ± 563.4 ± 17.7
Leptin (ng/mL)5.53 ± 1.7727 ± 7.22.9 ± 2.514 ± 4.2
Insulin (mU/L)12.2 ± 2.2536.2 ± 1413.1 ± 3.132 ± 12.3
Insulin resistance index3.1 ± 0.59.4 ± 3.0*3.6 ± 0.78.28 ± 2.0
Triacylglycerol (mg/dL)103.4 ± 18.7191 ± 75*112 ± 23.1177.5 ± 54.3*
Cholesterol (mg/dL)138.3 ± 35.3216 ± 31.6154 ± 29.3240 ± 65.3

Table 1 also shows some characteristic of lean (control) patients. The reason for surgery of most lean patients was cholelithiasis, hernia, or cancer of the stomach or colon (at early stages).

After an overnight fast, patients were taken to the operating room for elective surgery. The preoperative medication for patients was dormicum or dolarganum plus relanium. General anesthesia was induced and maintained by a mixture of oxygen (35%), nitrous oxide (65%), and fentanil. No other medication was used before obtaining specimens.

Analysis

Serum glucose, triacylglycerol, and cholesterol concentrations were analyzed by standard enzymatic procedures (Boehringer Mannheim, Mannheim, Germany). Height and weight were determined with the subjects wearing light clothing without shoes. Fat mass was measured using the Bodystat 1500 unit (Bodystat Ltd., Douglas, Isle of Man, United Kingdom). Serum leptin and insulin concentrations were analyzed with a radioimmunoassay technique (Linco Research, St. Charles, MO). The homeostasis model insulin resistance index (HOMA-R)1 was used to assess insulin resistance in patients according to the following formula: HOMA-R = fasting glucose (millimolar) × fasting insulin (milliunits per liter)/22.5, as described previously (26).

With the use of Systat software (Systat Corp., Evanston, IL), the statistical significance of differences between lean and obese subjects were assessed by one-way ANOVA, followed by Student's t test. Correlations were determined by univariate regression analysis for repeated evaluation at each point. To identify the main determinants of the serum leptin changes after surgery, multivariate regression analyses for repeated evaluation in each patient were performed. All calculations were performed using the Statistica 6.0 program for Windows (StatSoft, Inc., Tulsa, OK).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

The mean whole body weight, body fat mass, BMI, serum leptin and insulin concentrations, insulin resistance index, and serum triacylglycerol and cholesterol concentrations in patients (both women and men) tested before vertical banded gastroplasty are shown in Table 1. Most of these parameters were essentially similar in control women and men. In the case of serum leptin concentrations, significant differences were observed, a finding that confirmed previously reported results (5, 6, 7, 8, 9). Table 1 shows that all the parameters mentioned were significantly higher in morbidly obese subjects. The changes in BMI, body fat mass, serum leptin, and insulin concentrations in patients (both women and men) tested for 50 weeks after vertical banded gastroplasty are shown in Figures 1, 2, 3. All of the parameters studied decreased constantly during the 50-week follow-up. A mean body fat mass was reduced by ∼50% in both men and women (Fig. 1B). As a consequence of these changes, a significant reduction in whole body weight (∼40 kg both in men and women) and BMI (Figure 1A) was observed. At the end of the 50 weeks, follow-up serum triacylglycerol concentrations decreased ∼60%, whereas serum cholesterol concentration did not change significantly (not shown). During the same period, serum leptin (Figure 2) and serum insulin (Figure 3) concentrations decreased by ∼70%. However, it should be noted that the course of serum leptin concentration over the study period showed a different pattern between men and women. In women, a continuous, albeit slower, decrease in serum leptin concentration was found. In men, during the first 10 weeks, a rapid decrease in serum leptin concentration was observed. The data presented in Fig. 4A indicate that the reduction of serum leptin concentration correlated with BMI after vertical banded gastroplasty both in men and in women. Essentially similar results were found if the correlation between serum leptin concentration and body fat mass was considered (Figure 4B). The reduction of serum leptin concentration also showed a close correlation with the reduction of circulating insulin concentration after vertical banded gastroplasty (Fig. 5). Fasting plasma glucose concentrations were significantly higher before operation in the most morbidly obese patients (7.1 ± 0.8 mM), then decreased constantly to control value after surgery (4.9 ± 0.5 mM) (p < 0.05). Insulin resistance, as calculated by HOMA-R, was significantly higher in the morbidly obese patients than in the lean patients (Table 1). The insulin resistance index was decreased constantly during the 50-week follow-up in women (Figure 6A). The changes in insulin resistance index did correlate well with serum leptin concentration after surgery in women (Figure 6B). Essentially similar changes in insulin resistance index and correlation with leptin in man were found (not shown). However, it should be noted that only eight men were tested. To elucidate further the relationship between serum leptin concentration and other variables (including BMI, serum triacylglycerol, cholesterol and insulin concentration, insulin resistance index, body weight, and body fat content) after surgery, multiple regression analysis was performed. The results presented in Table 2 indicate that only BMI changes after surgery were independently associated with the changes in serum leptin concentration in women. Due to the small number of men included in this study, we did not perform multiple regression analysis in this case.

image

Figure 1. (A) BMI changes in surgically treated women (○) (trend curve − intermittent line) and men (•) (trend curve − continuous line). Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times), and 30 determinations are presented for men (8 men were included in the study, each examined 3 to 4 times). (B) Body fat mass changes in surgically treated women (○) (trend curve − intermittent line) and men (•) (trend curve − continuous line). Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times), and 30 determinations are presented for men (8 men were included in the study, each examined 3 to 4 times).

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image

Figure 2. Serum leptin concentration changes in surgically treated women (○) (trend curve − intermittent line) and men (•) (trend curve − continuous line). Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times), and 30 determinations are presented for men (8 men were included in the study, each examined 3 to 4 times).

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image

Figure 3. Serum insulin concentration changes in surgically treated women (○) (trend curve − intermittent line) and men (•) (trend curve − continuous line). Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times), and 30 determinations are presented for men (8 men were included in the study, each examined 3 to 4 times).

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image

Figure 4. (A) Correlation between BMI and serum leptin concentration in surgically treated women (○) (trend curve − intermittent line) and men (•) (trend curve − continuous line). Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times), and 30 determinations are presented for men (8 men were included in the study, each examined 3 to 4 times). (B) Correlation between fat mass and serum leptin concentration in surgically treated women (○) (trend curve − intermittent line) and men (•) (trend curve − continuous line). Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times), and 30 determinations are presented for men (8 men were included in the study, each examined 3 to 4 times).

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image

Figure 6. (A) Insulin resistance index changes in surgically treated women. Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times). (B) Correlation between serum leptin concentration and insulin resistance index in surgically treated women. Seventy-five determinations are presented for women (18 women were included in the study, each examined 4 to 5 times).

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Table 2. . Univariate and multivariate regression analysis of the correlation between the changes in serum leptin concentration and independent variables examined in women after vertical banded gastroplasty
 Univariate regressionMultivariate regression
Independent variablerprp
  1. Seventy-five determinations were included in the statistical analysis (18 women, each examined 3–5 times).

BMI (kg/m2)0.87<0.0010.72<0.001
Body weight (kg)0.7<0.0010.17NS
Body fat (kg)0.74<0.001−0.03NS
Insulin (mU/L)0.65<0.001−0.28NS
Insulin resistance index0.6<0.0010.42NS
Triacylglycerol (mg/dL)0.7<0.01−0.08NS
Cholesterol (mg/dL)0.005NS0.11NS

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

To investigate the controversial points regarding relationship between serum leptin concentration and body weight and between serum leptin and insulin concentration in patients after anti-obesity surgery, we conducted a study in patients who showed massive weight loss after the ventricle banded gastroplasty. Our results demonstrate that vertical banded gastroplasty is an effective therapeutic approach for the treatment of morbidly obese patients because it reduces not only body weight but also body fat mass, BMI, and serum leptin, insulin, and triacylglycerol concentrations. Our results also confirmed the decrease of serum glucose concentration and insulin resistance after successful banded vertical gastroplasty. The observations presented in this report further extend information on the effect of anti-obesity surgery on the above-mentioned parameters. In some respects, our results are in accordance with earlier findings (20, 21, 22, 23, 24). It is interesting to note that serum glucose concentration and insulin resistance in banded vertical gastroplasty patients reached the values observed in lean patients. This suggests that some of the risk factors for diabetes are reversed after successful anti-obesity surgery. However, the other parameters studied, including serum leptin and insulin concentrations and body and fat mass, remained higher in obese patients after the successful anti-obesity surgery than in normal lean controls. Interestingly, serum cholesterol concentration did not change in our patients after the anti-obesity operation. This is in contrast to the results reported by Geloneze et al. (27), who observed significant reduction of total cholesterol concentration after bariatric surgery. In contrast to cholesterol, a significant decrease in serum triacylglycerol concentration in our patients after surgery was found. It is likely that the decrease in serum triacylglycerol concentration was associated with the decrease of insulin resistance after surgery and/or with the decrease of food intake. Obese patients usually consume more lipids than lean subjects (28). After surgical treatment, most of our patients were placed on 800 to 1000 kcal/d. Thus, the decrease of food intake could partly explain the decrease in serum triacylglycerol concentration after surgery. The decrease in food intake also might explain the decrease in serum glucose concentration after surgery. However, changes in gastrointestinal hormones may also influence the serum glucose concentration after surgery (29).

As mentioned above, the objective of the present study was to assess the main determinant of serum leptin concentration changes in morbidly obese patients after the massive weight reduction induced by the vertical banded gastroplasty. Univariate analysis showed that the serum leptin concentration changes were well correlated with BMI, fat mass, serum insulin concentration, and insulin resistance index (Table 2). One could conclude that serum leptin concentration after vertical banded gastroplasty is determined by an interaction between adipose tissue mass and serum insulin concentration. This conclusion agrees with the suggestion by Schwartz et al. (18), who showed that plasma leptin and insulin concentrations are associated with body adiposity through different mechanisms. However, multivariate analysis clearly indicated a strong link only between BMI and serum leptin concentration after surgery (Table 2). These results suggest that changes in BMI are the main determinant of the decrease in serum leptin concentration in our patients after vertical banded gastroplasty. Thus, our results agree with the observation reported by Geloneze et al. (23), who found a strong link between changes in serum leptin concentration and BMI associated with massive weight reduction induced by bariatric surgery. Our findings also agree with the observation of Toornvliet et al. (19), who found that BMI is the main determinant of the plasma leptin concentration in patients losing weight in response to hypocaloric diet. However, our results are in contrast to those reported by De Marinis et al. (22), Guldstrand et al. (20), and Adami et al. (24). These investigators did not observe a correlation between the changes in serum leptin concentration and BMI after weight loss induced by surgery. The discrepancy could be explained by the fact that the number of patients studied by De Marinis et al. (22) and by Guldstrand et al. (20) was small. However, other factors cannot be excluded because Adami et al. (24) studied a large number of patients and did not show a correlation between the serum leptin concentration and BMI. Because the controversial results have been published concerning the relationship between serum leptin and insulin concentration changes after the massive weight loss induced by a hypocaloric diet (16, 17, 18, 19) or surgery (20, 21, 22, 23), we studied the pattern of changes in serum insulin and leptin concentration in our patients. Univariate analysis presented in this paper indicates that serum leptin concentration changes were well correlated with serum insulin concentration and with insulin resistance index. However, multivariate analysis displayed no correlation between serum insulin concentration and serum leptin concentration, nor between insulin resistance index and serum leptin concentration. Therefore, in our patients treated by vertical banded gastroplasty, the changes in serum leptin concentration did not seem to be associated with changes in serum insulin concentration. This finding agrees with those reported by Geloneze et al. (23) and Toornvliet et al. (19).

The studies on the effect of anti-obesity surgery on body and fat mass and serum leptin and insulin concentrations reported to date have been performed on obese women (20) and on both women and men (21, 22), but in the latter case, the results were not examined separately for women and men. Because Nicklas et al. (30) reported gender differences in the response of plasma leptin concentration to the weight loss in obese individuals, in this study, changes in fat mass and plasma leptin and insulin concentrations were analyzed separately for men and women after successful banded vertical gastroplasty. Both in control lean subjects and morbidly obese patients, serum leptin concentration was ∼2-fold higher in women than in men. Moreover, the course of serum leptin concentration changes showed a different pattern in men and women after surgery. This suggests that there are some gender differences in the response of plasma leptin concentration to weight loss after the vertical banded gastroplasty. Thus, in this respect, our data confirm earlier studies reported by other groups (20, 21, 22). Other parameters studied before the operation were essentially similar in men and women. No significant differences were found between men and women, with regard to body and fat mass and serum insulin concentrations changes after the anti-obesity surgery.

Finally, it should be noted that one obvious limitation of the present study was the number of patients studied (only 18 women and 8 men). However, each patient was evaluated three to five times. A small number of analyzed patients may have influenced the results that were obtained, as well as the interpretations of these results. Moreover, because our patients displayed an impaired glucose tolerance, our findings may be applicable only to subjects with the impaired glucose tolerance.

In conclusion, this study has confirmed a strong correlation between BMI and serum leptin concentration changes in morbidly obese patients after massive weight loss induced by vertical banded gastroplasty. This indicates that BMI is the main determinant of the decrease of serum leptin concentration after surgery. Our results also indicate that some of the risk factors for diabetes and coronary heart disease are reversed partly after the successful vertical banded gastroplasty.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

We thank Professor Mariusz M. Zydowo for critique and discussion of the manuscript. The work was supported by a grant from the Committee for Scientific Research (KBN) within Projects ST-41 and W-721.

Footnotes
  • 1

    Nonstandard abbreviation: HOMA-R, homeostasis model insulin resistance index.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References
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