in vivo 29: 757-762 (2015)

Abdominoplasty in Mildly Obese Patients (BMI 30-35 kg/m2): Metabolic, Biochemical and Complication Analysis at One Year

ROBERTO CUOMO, FRANCESCO RUSSO, ANDREA SISTI, GIUSEPPE NISI, LUCA GRIMALDI, CESARE BRANDI and CARLO D’ANIELLO

Unit of Plastic and Reconstructive Surgery, University of Siena, Siena, Italy

Abstract. Background/Aim: Dermolipectomy dramatically quality of life of previously obese patients from an aesthetic improves the quality of life of previously obese patients. functional view. A statistically significant increase of removal in patients undergoing and reduction adiponectin after the procedure was found. A low level of mammoplasty has positive effects, but no data regarding adiponectin after surgery indicates a higher probability of sequelae of abdominal dermolipectomy on metabolism have complications. been reported. Thus, the aim of the present study was to assess metabolic and biochemical modifications occurring The worldwide spread of documented by many after abdominoplasty. A correlation between the results and recent epidemiological studies showed a parallel increase in the rate of complications was also evaluated. Patients and such complications often referred to as 'metabolic syndrome' Methods: One hundred and twenty-eight patients with body (insulin resistance, hypertension, and dyslipidemia) (1). mass index (BMI) between 30 and 35 kg/m2 were enrolled. is a metabolically active tissue (2). Clinical assessment, anthropometric measurements, blood Nevertheless, fat cells have both a role in the regulation of biochemical analysis (fasting plasma glucose, total inflammatory system and a recognized endocrine action (3). cholesterol, free fatty acids, plasma insulin), plasma This last aspect is linked to the adipose secretion of several adipocytokines (leptin, adiponectin,resistin), levels of proteins, collectively regarded as 'adipokines' (4). Plasma inflammatory markers [tumor factor-alpha (TNFα), levels of tumor necrosis factor-alpha (TNFα) and interleukin- interleukin-6 (IL6), C-reactive protein (CRP)] and insulin 6 (IL6) have been shown to increase in human obesity (5), sensitivity by Homeostasis Model Assessment were performed resulting in hyperstimulation of the innate immune system three times. Results: The average age was 37.6 years. At with a subsequent chronic inflammatory state; on the other baseline, the mean (±SD) BMI of patients overall was 33.44 hand, adiponectin is present at lower levels in obese patients (±2.3) kg/m2 and the amount of fat surgically removed was (6), being one of the complex mechanisms involved in the 1,578.33 (±1,013.02) g. A significant decrease in BMI at 1 onset of insulin resistance (3). year was found. Adiponectin levels were found to have The role of the plastic surgeon in the improvement of significantly increased (p<0.05) in long-term evaluation. We functional aspects linked to massive weight loss (e.g. noted significant increases in the mean TNFα (p<0.05), IL6 functional sequelae, aesthetical problems or complaints of (p<0.01) and CRP (p<0.05), with a return to baseline values dermatitis) (7) is well-recognized. The evidence of the of all variables. The majority of patients were satisfied with endocrine role played by adipose tissue has raised great the surgical procedure after 12 months. We noted a lower rate debate on the efficacy of plastic surgical procedures of (10%) of complications in patients whose blood analysis subcutaneous fat removal as a means of improving insulin showed an increase of adiponectin. Conclusion: Abdominal sensitivity and altering levels of plasma adipokines (8). dermolipectomy is a safe surgical procedure that improves the Dermolipectomy/panniculectomy can be adopted as a first surgical approach for adequately selected obese people with a body mass index (BMI) between 30 and 35 kg/m2 who are not candidates for . Besides its role Correspondence to: Roberto Cuomo, Santa Maria Alle Scotte in body contouring at the end of lengthy bariatric Hospital, Unit of Plastic and Reconstructive Surgery, University of procedures, or after massive weight loss, can Siena, Mario Bracci Street, 53100 Siena (SI), Italy. Tel./Fax: +39 be incorporated into a multidisciplinary program of lifestyle 0577585158, e-mail: [email protected] changes, allowing these selected obese patients to obtain Key Words: Obesity, dermolipectomy, systemic inflammation, weight loss and to maintain the reduced weight in the long adipokines, adiponectin, complications. term (9).

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Several previous investigations have focused on the impact Blood analysis. Fasting plasma glucose, total cholesterol, of liposuction (2, 8-13), (14) and triglycerides and free fatty acids (FFA) [according to Dole and dermolipectomy (8) on metabolic profile and body weight. Meinertz (17)] were determined by laboratory methods; in addition, serum levels of plasma insulin were obtained. The enzyme-linked Although physical improvement and aesthetic benefits of immunoassay (ELISA) quantified leptin, adiponectin, resistin, patients undergoing abdominal dermolipectomy are well- TNFα, IL6 and C-reactive protein (CRP) levels. recognized, no such data exist on its effects on metabolism. Our study aimed to determine the modifications of weight Insulin sensitivity determination. Besides the determination of and of levels of plasma adipokines in mildly obese patients fasting plasma insulin, HOMA score was adopted to assess insulin (BMI between 30 and 35 kg/m2) and the correlations resistance. This index expresses the relationship between the between these parameters and the rate of complications after pancreatic secretion of insulin with FPG. This mathematic model allows the estimation of both insulin resistance and the percentage surgical procedure. of secretion operated by β-pancreatic cells. A HOMA score greater than 2.4 indicates insulin resistance by the main cells (adipocytes Patients and Methods and muscle cells) depending on it for glucose uptake (18).

Patients. From January 2008 to January 2010, 128 women Dermolipectomy. The removal of excess skin and fat from the undergoing abdominal dermolipectomy with a main central body fat middle and lower abdomen was performed through a classic distribution were recruited at the Plastic Surgery Unit of the transverse abdominal dermolipectomy. This operation was carried University of Siena (Italy). These patients all suffered from obesity out through a long incision from hipbone to hipbone, just above the and had tried for years to lose weight with hypocaloric diet and pubic area, with umbilical transposition and an average cutaneous- physical exercise with no relevant results. adipose mass tissue removal of ~1600 g. 2 Participants were required to have a BMI between 30 and 35 kg/m . The patients were under total anaesthesia. Patients were Exclusion criteria were failure, cardiovascular disease, mobilized 24 hours following surgery and were discharged after 72 hypertension, type 2 diabetes, chronic obstructive bronchopneumopathy, hours with antibiotic therapy (amoxicillin and clavulanic acid, 2 × 1 connective tissue disease, chronic hepatitis, renal insufficiency and g tablets per day) for 5 days. cancer. All the patients (age range 32-48 years) volunteered for the study, Statistical analysis. For all statistical analyses, SPSS for Windows and none of them received drugs. Anthropometric data (height, version 13 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism v.5 weight, bioimpedence analysis, digital plicometry), clinical status were used. (GraphPad Software - San Diego, CA, USA). assessment, blood analysis [fasting plasma glucose (FPG), and For all considered variables, data are expressed as the mean and insulin, plasma cholesterol and triglycerides, plasma adipocytokines standard deviation (SD) or as absolute frequency and percentage and inflammatory marker levels] and Homeostasis Model (%). The normality of distributions and homogeneity of variances Assessment (HOMA) score (10) were obtained preoperatively were tested by Shapiro-Wilk and Levene tests, respectively. The (baseline) and then at 6 months (T1) and at 12 months (T2) after the comparisons between times (baseline, T1 and T2) were performed surgical procedure. by one-way analysis of variance (ANOVA) for repeated measures All measurements were performed during the follicular phase of and, when necessary, by Bonferroni post hoc test for multiple the menstrual cycle. To eliminate possible bias due to changes in comparisons. A p-value of less than 0.05 (two-tailed) was lifestyle none of the patients followed a particular diet after considered statistically significant. abdominoplasty(15, 16). At the end of the study 12 months after the surgical procedure, in order to analyse the effect of plastic surgery on quality of life, the satisfaction level was reported by all patients Results on a scale from 1 (dissatisfied) to 5 (completely satisfied). All the enrolled patients gave their informed written consent and A total of 64 women were included in the study and the study protocol followed the Principles of the Declaration of completed the follow-up. The mean amount of surgically Helsinki. removed fat was 1,578.33 (±1,013.02) g. The average BMI of these patients at baseline was 33.44 (±1.89) kg/m2 and Anthropometric determinations. Anthropometric parameters such as they ranged in age from 32 to 48 years (mean age 37.6-5.4 height and weight by using a standard beam balance and then BMI years). The mean waist circumference at baseline was 112.88 were first determined. A graduated plastic tape was used to measure waist and hip circumference in the standing position determining (±21.58) cm and was reduced to 107.63 (±21.68) cm at T2. waist hip ratio (WHR). Waist circumference was determined at the The metabolic parameters remained constant (p>0.05) level of the iliac crest and hip circumference was measured at the throughout the follow-up period; there were statistically trochanter level. Then, in order to determine fat mass and free fat significant differences in BMI, particular comparing the mass, bioimpedance analysis was performed. The procedure of baseline value with that at T2 (p<0.05) (Table I). bioimpedance was conducted in an automated manner with Wunder - Table II shows the adipocytokine levels at each time of Body composition analyzer TBF-300 model (Tanita Corporation, follow-up. Even if the observed leptin mean showed a low Rotherham, Yorkshire, United Kingdom). The machine records the BMI of the patient, the fat mass, lean mass and percentage of water decrease at T1, persisting at T2, it was not statistically and fat present in the body by metal plates on which the patient rests significant (p=0.151). There was a significant difference standing. (p<0.01) in the mean adiponectin level between all times of

758 Cuomo et al: Abdominoplasty in Mildly Obese Patients

Table I. Metabolic and anthropometric determinations.

Variable (mean value) Baseline T1 T2 p-Value

BMI (kg/m2) 33.44 (±1.89) 32.93 (±1.41) 31.58 (±1.45) 0.019 HOMA index 3.60 (±2.28) 2.87 (±1.23) 3.42 (±1.68) 0.657 FPG (mg/dl) 82.84 (±3.51) 85.00 (±11.98) 91.25 (±7.46) 0.123 Plasma triglycerides (mg/dl) 132.60 (±38.18) 123.80 (±3.15) 110.00 (±12.07) 0.189 Plasma total cholesterol (mg/dl) 180.60 (±30.60) 157.30 (±24.88) 167.8 (±38.13) 0.167 Plasma insulin (mU/l) 16.77 (±12.36) 13.25±(3.81) 15.11 (±7.12) 0.480

BMI: Body mass index; HOMA: Homeostasis Model Assessment; FPG: fasting plasma glucose. T1: 6 months after dermolipectomy; T2: 12 months after dermolipectomy; p<0.05: baseline versus T2. Data expressed as means.

Table II. Adipocytokine levels in the follow-up period.

Variable Baseline T1 T2 p-Value

Leptin (mg/ml) 31.96 (±18.46) 27.81 (±16.91) 28.56 (±19.61) 0.214 Adiponectin (μg/ml) 8.11 (±4.43) 9.09 (±5.34) 9.31 (±5.00) 0.457 Resistin (ng/ml) 4.54 (±5.24) 7.51 (±12.35) 4.83 (±4.03) 0.498

T1: 6 Months after dermolipectomy; T2: 12 months after dermolipectomy. p<0.05: baseline versus T2. Data are expressed as means±SD.

follow-up: in particular, statistical increase of this parameter Surgical management of obesity in plastic surgery mainly was found between baseline and T2 (p<0.05). A low increase consists of large superficial fat aspirations or excisions in resistin levels was observed, notwithstanding it not being through liposuction (2, 8-13) or dermolipectomies (8, 14). significant (p=0.273). These techniques are likely not only to result in an Concerning inflammatory marker levels (Figure 1), there improvement of anthropometric parameters but they could was a significant increase (p<0.01) in mean TNFα between also induce a favourable change of such metabolic factors. baseline and T1 (p<0.05), with no statistical difference This last aspect seems to be directly correlated to the between baseline and T2. Mean IL6 values showed the same percentage of body fat mass that is surgically removed (8). trend as those for TNFα since a significant increase was Available evidence provided by recent studies (3-6) detected between baseline and T1 (p<0.01), although no asserted that many metabolic parameters are under the statistical difference between baseline and T2 persisted. A influence of a complex network led by what is today called significant increase of CRP was noted between baseline and subcutaneous adipose tissue (SAT) (26, 27), whose removal T1 (p<0.05) that lost statistical difference at T2. is likely to induce biochemical changes (2, 8, 10-14, 18) with The administered questionnaire revealed a good patient unknown underlying molecular mechanisms. It is also satisfaction after reconstructive surgery: 82.25% of patients important to underline the key role visceral adipose tissue were completely satisfied, 14.62% were satisfied and only (VAT) (2, 3, 28) plays in the complex biochemical one patient (3.13%) was dissatisfied. homeostasis underlying cytokine expression and metabolic Correlations between patients whose blood analysis regulation of fatty acids. revealed an increase of adiponectin and those with no Results obtained in our study highlighted a statistically significant increase showed a higher percentage of significant long-term decrease in BMI that should likely be complications (blood transfusion, hospital stay, seroma) in correlated with a minor incidence of all the obesity-linked patients with lower levels of adiponectin (90%) metabolic disorders (diabetes and cardiovascular diseases) (29). A significant increase of adiponectin was shown one Discussion year from the surgical procedure of panniculectomy; higher blood levels of this cytokine have been correlated with an Nowadays, obesity represents one of the most relevant improvement of obesity-linked chronic inflammatory state problems worldwide, as the latest public health investigations and with a minor incidence of metabolic disorders by have shown (6). Fat excess is correlated with numerous previous investigations (4-6). We also noted a modification comorbidities (19-25). of TNFα, whose hyperexpression is regarded as a marker of

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consequence of adipose tissue hypertrophy and 'dystrophy' (3, 6, 8, 9). A similar trend was observed for the change of IL6, whose production depends on many cell types (fibroblasts, endothelial cells, monocytes); this cytokine is overproduced in obesity and represents an important link between obesity, inflammation and insulin resistance (3, 30, 31). A significant increase of adiponectin was also found: this molecule seems to counteract the metabolic actions of TNFα and IL6 (4, 8, 32, 33). Nevertheless, adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties, negatively correlated with obesity (6, 32). On the other hand, high plasma levels of TNFα and IL6 are found in obese patients and have effects both on the reduction of adiponectin mRNA expression and on the insulin signalling pathway (26). Most studies have shown that fat removal produces beneficial effects on insulin resistance, evidenced in the subclinical inflammatory condition linked to obesity (8, 9). Obviously, further studies would be necessary to better- understand the biological function of adipokines and it would be important to increase the size of the population studied. However, in our investigation, the analysis of molecules previously cited allowed us to appreciate the changes of the cross-talk between fat and metabolic tissues after SAT excision.

Conclusion

Our study demonstrates that dermolipectomy performed in obese patients with BMI between 30 and 35 kg/m2 results in a change of plasma adipokines probably linked to an improvement of insulin sensitivity without supportive programs such as diet or exercise. Further long-term studies in larger populations are still necessary to determine if this surgical procedure is directly correlated with a reduced incidence of type 2 diabetes and cardiovascular disease.

Conflicts of Interest

None. The Authors declare that they have no conflict of interest.

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