Is Dermolipectomy Effective in Improving Insulin Action and Lowering Inflammatory Markers in Obese Women?

M. R. Rizzo; G. Paolisso; R. Grella; M. Barbieri; E. Grella; E. Ragno; R. Grella; G. Nicoletti F. D'Andrea

Disclosures

Clin Endocrinol. 2005;63(3):252-258. 

In This Article

Materials and Methods

Twenty obese nonsmoking females (age range 25–40 years) volunteered for the study. All subjects had had a stable body weight (± 1 kg) for 2 months before the study. Exclusion criteria included heart failure, cardiovascular disease, hypertension, type 2 diabetes, pulmonary disease, connective tissue disease, thyroid dysfunction, acute and chronic hepatitis, renal insufficiency and cancer. No patients received any drugs and all measurements were made during the follicular phase of the menstrual cycle. All patients had glucose tolerance evaluated according to American Diabetes Association (ADA) criteria.[30]

All subjects, after being enrolled, underwent a 2-week standard diet (50% carbohydrate, 27% fat and 23% protein) with a daily caloric value of 1400 kcal. This diet therapy was maintained throughout the study. Weight stability (excluding the changes in fat mass due to dermolipectomy) was carefully maintained before and after dermolipectomy to eliminate confounding effects of changes in energy balance on the study end-points.

Anthropometric measurements, body composition and clinical status assessment and metabolic determinations (indirect calorimetry and hyperinsulinaemic glucose clamp) were made at baseline preoperatively and 40 days after dermolipectomy. The 40-day delay was intended to eliminate the confounding effects of postsurgical inflammation on the study end-points.

Subjects were asked to avoid strenuous exercise before the resting metabolic rate (RMR) and respiratory quotient (Rq) were measured. Subjects were also requested not to change their lifestyle in the 40 days following the dermolipectomy.

All subjects gave their written informed consent to participate in the study, which was approved by our ethics committee.

Weight and height were measured by using a standard beam balance. Body mass index (BMI) was calculated as body weight (kg) divided by height squared (m2). Waist circumference was measured at the midpoint between the lower rib margin and the iliac crest and hip circumference was measured at the trochanter level. Both circumferences were measured in the standing position to the nearest 0·5 cm with a plastic tape and the ratio between them provided the waist-hip ratio (WHR). Bioimpedance analysis allowed us to determine fat free mass (FFM) and fat mass (FM).

Glucose levels were measured by an enzymatic colorimetric assay using a modified glucose oxidaseperoxidase method (Roche Diagnostics, GmbH, Mannheim, Germany) and a Roche-Hitachi 917 analyser. Commercial enzymatic tests were also used to determine serum total cholesterol and triglyceride (Roche Diagnostics) levels. Plasma FFA concentrations were determined according to Dole and Meinertz.[31]

Several 0·5 ml aliquots of serum were collected and immediately stored at –80ºC, and subsequently used for assessment of hormones and cytokines. Plasma insulin (Sorin Biomedica, Milan Italy), leptin (Linco Research, St Louis, MO, USA), resistin (resistin human ELISA kit, VinciBiochem, Vinci-FI, Italy) and adiponectin (Linco Research) levels were determined by radioimmunoassay (RIA). TNF-α, sIL-6r, IL-6 and IL-10, were quantified by immunoassay kits (BioSource Cytoscreen, Camarillo). The minimum detectable concentrations were 0·10 ng/l for IL-6, 8·00 ng/l for sIL-6r, 0·09 ng/l for TNF-α and 0·01 ng/l for IL-10, and the interassay coefficient of variation was 7·0% for all the kits. All plasma samples for biochemical determinations, including metabolites, hormones and cytokines, were drawn after a 12-h overnight fast, and before and 40 days after dermolipectomy. A 24-h collection of urine urea nitrogen was obtained in all subjects and used for oxidative substrate calculation.

RMR was assessed by lightweight indirect calorimetry (Cosmed K4 b2, Cosmed, Italy). The instrument K4 measures the total volume of expired air (TV), oxygen volume (VO2) consumed in litres per minute, carbon dioxide volume (VCO2) expired in litres per minute, Rq, as the ratio of VCO2 to VO2, heart rate (HR) and respiratory frequency (RF). K4 consists of a face mask (with a photoelectric turbine that measures ventilation), a portable unit, an electrode to record heart rate and a battery pack. Each morning before the RMR measurements, K4 was calibrated by using a gas mixture with known composition (16% O2; 5% CO2).

The test was undertaken in a supine position at an environmental temperature of 22–23ºC. All measurements were taken in the morning (07 00#150;09 00 h) after a 12-h fast and a minimum of 8 h of sleep. Indirect calorimetry was started 60 min before and continued throughout a hyperinsulinaemic clamp. The last 30 min of steady state of each experiment was kept for measurement.

To test the precision and accuracy of measurements made by the K4 system, eight subjects in random order had respiratory parameters compared with those obtained by another device (Deltatrac II Monitor, Datex, Helsinki, Finland), which is an open-circuit ventilated-canopy measurement system. The degree of agreement between the measurements obtained with the two systems was estimated using the BlandAltman analysis.[32] A significant correlation (r = 0·89, P < 0·001) between the two systems of measurement was found.

The evening before the test, all patients received the standard diet. No further food or drink other than water was permitted until completion of the test.

Subjects were studied in the supine position with catheters inserted into an antecubital vein for infusion of glucose and insulin and into a dorsal hand vein, in retrograde fashion, for drawing blood samples. After drawing blood for baseline determination, the hyperinsulinaemic glucose clamp was initiated and all subjects underwent square wave infusion of insulin (1 mU/kg/min) for 120 min. Exogenous glucose infusion (as a 20% solution) allowed us to keep plasma glucose oscillations within a narrow range and close to fasting plasma glucose levels. Throughout the clamp study, blood samples were drawn at 10-min intervals to obtain plasma for glucose and insulin determinations. Plasma glucose values were determined using a bedside glucose analyser, and the glucose infusion rate was adjusted to maintain the target level of glycaemia.

Insulin sensitivity (IS) was calculated as the glucose infusion rate (mg/kg/min) over the past 60 min (M-value).

Classic transverse dermolipectomy is a major surgical procedure to remove excess skin and fat from the middle and lower abdomen.[16] The operation was performed with the patient under total anaesthesia and was made through a long incision from hipbone to hipbone, just above the pubic area, with umbilical transposition and cutaneous adipose mass tissue removal of 2·3 ± 0·2 kg (range 1·9–3 kg). Patients were mobilized 24 h following surgery and were discharged after 72 h with antibiotic therapy for 5 days.

Data were analysed by using the SPSS for Windows (Version 10, SPSS) statistical software package. All data not normally distributed (insulin range 43·0–107·6 pmol/l; triglyceride range 13·5–17·1 mmol/l) were log transformed for all calculations and than back- transformed for data presentation. An analysis of variance (anova) for comparing variables before and after dermolipectomy was used while an analysis of covariance (ancova) was used to test differences in inflammatory markers independently of covariates. Pearson's R investigated the association among variables while partial correlations were used to test the association independently of covariates. All data are presented as means ± SD.

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