Diurnal variations of adiponectin levels have been studied in normal-weight men and in diabetic and nondiabetic obese subjects, but no data have been reported in obese subjects after weight loss. We collected blood samples at 1-h intervals over 24 h from seven severely obese subjects before and after massive weight loss consequent to surgical operation (bilio-pancreatic diversion [BPD]) to measure adiponectin, insulin, glucose, and cortisol levels. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp (M value). Studies of diurnal variations and pulsatility of adiponectin, insulin, and cortisol were performed. The pulsatility index (PI) of adiponectin increased after BPD from 0.04 to 0.11 g/min (P ‫؍‬ 0.01). Insulin PI significantly increased after the operation (1.50 vs. 1.08 pmol ⅐ l -1 ⅐ min -1 , P ‫؍‬ 0.01), while cortisol PI did not significantly change. The adiponectin clearance rate changed from 0.001 ؎ 10 ؊4 ⅐ min ؊1 before BPD to 0.004 ؎ 8 ⅐ 10 ؊4 ⅐ min ؊1 after BPD (P ‫؍‬ 0.03). Insulin clearance increased from 0.006 ؎ 6 ⅐ 10 ؊4 ⅐ min ؊1 before BPD to 0.009 ؎ 4 ⅐ 10 ؊4 ⅐ min ؊1 after BPD (P ‫؍‬ 0.02). The M value doubled after surgery (27.08 ؎ 8.5 vs. 53.34 ؎ 9.3 mol ⅐ kg FFM ؊1 ⅐ min ؊1 ; P < 0.001) becoming similar to the values currently reported for normal-weight subjects. In conclusion, in formerly severely obese subjects, weight loss paired with the reversibility of insulin resistance restores homeostatic control of the adiponectin secretion, contributing to the reduction of cardiovascular risk already described in these patients. Diabetes 53:939 -947, 2004 R ecent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ but also a secretory organ, producing a variety of bioactive substances, including leptin, tumor necrosis factor (TNF)-␣, resistin, and adiponectin, thus acting as an endocrine organ. These adipocyte-specific proteins, termed adipokines, present a variety of local, peripheral, and central effects. It has been shown that the adipose tissue secretes metabolites such as nonesterified fatty acids (NEFAs), glycerol, and hormones (1) in a pulsatile fashion, similar to leptin. The regulation of this pulsatility seems to be mediated by hormonal (2) or neural (2,3) mechanisms. Insulin plays a critical role in the regulation of both the hormonal and metabolic activity of the adipocytes.Higher absolute leptin levels coupled with blunted relative diurnal excursions and dampened pulsatility have been found in obese subjects (4). Similarly, insulin pulse amplitudes are restored (5). Weight loss restores leptin pulsatility (4) and reverses insulin resistance (6).Recently, diurnal variations in circulating levels of adiponectin in diabetic and nondiabetic obese subjects (7) and in healthy normal-weight male human subjects have been investigated (3). Hotta et al. (7) did not observe any daily changes in circulating levels of adiponectin in obesity. In normal-weight subjects, Gavrila et al. (3) found an ultradian pulsatility as well as a diu...

A respiratory chamber is used for monitoring O(2) consumption (Vo(2)), CO(2) production (Vco(2)), and respiratory quotient (RQ) in humans, enabling long term (24-h) observation under free-living conditions. Computation of Vo(2) and Vco(2) is currently done by inversion of a mass balance equation, with no consideration of measurement errors and other uncertainties. To improve the accuracy of the results, a new mathematical model is suggested in the present study explicitly accounting for the presence of such uncertainties and error sources and enabling the use of optimal filtering methods. Experiments have been realized, injecting known gas quantities and estimating them using the proposed mathematical model and the Kalman-Bucy (KB) estimation method. The estimates obtained reproduce the known production rates much better than standard methods; in particular, the mean error when fitting the known production rates is 15.6 +/- 0.9 vs. 186 +/- 36 ml/min obtained using a conventional method. Experiments with 11 humans were carried out as well, where Vo(2) and Vco(2) were estimated. The variance of the estimation errors, produced by the KB method, appears relatively small and rapidly convergent. Spectral analysis is performed to assess the residual noise content in the estimates, revealing large improvement: 2.9 +/- 0.8 vs. 3,440 +/- 824 (ml/min)(2) and 1.8 +/- 0.5 vs. 2,057 +/- 532 (ml/min)(2), respectively, for Vo(2) and Vco(2) estimates. Consequently, the accuracy of the computed RQ is also highly improved (0.3 x 10(-4) vs. 800 x 10(-4)). The presented study demonstrates the validity of the proposed model and the improvement in the results when using a KB estimation method to resolve it.

Plasma leptin and growth hormone (GH) profile and pulsatility have been studied in morbidly obese subjects before and 14 months after bilio-pancreatic diversion (BPD), a bariatric technique producing massive lipid malabsorption. The maximum leptin diurnal variation (acrophase) decreased (10.27+/-1.70 vs. 22.60+/-2.79 ng x ml(-1); P=0.001), while its pulsatility index (PI) increased (1.084+/-0.005 vs. 1.050+/-0.004 ng x ml(-1) x min(-1); P=0.02) after BPD. Plasma GH acrophase increased (P=0.0001) from 0.91+/-0.20 to 4.58+/-0.80 microg x l(-1) x min(-1) after BPD as well as GH PI (1.70+/-0.13 vs. 1.20+/-0.04 microg x l(-1) x min(-1); P=0.024). Whole-body glucose uptake (M), assessed by euglycemic-hyperinsulinemic clamp, almost doubled after BPD (from 0.274+/-0.022 to 0.573+/-0.027 mmol x kgFFM(-1) x min(-1); P<0.0001), while 24 h lipid oxidation was significantly (P<0.0001) reduced (131.94+/-35.58 vs. 44.56+/-15.10 g). However, the average lipid oxidation was 97.2+/-3.1% (P<0.01) of the metabolizable lipid intake after the bariatric operation, while it was 69.2+/-8.5% before. After the operation, skeletal muscle ACC2 mRNA decreased (P<0.0001) from 452.82+/-76.35 to 182.45+/-40.69% of cyclophilin mRNA as did the malonyl-CoA (from 0.28+/-0.02 to 0.16+/-0.01 nmol x g(-1); P<0.0001). Leptin changes negatively correlated with M changes (R2=0.69, P<0.001). In a stepwise regression (R2=0.87, P=0.0055), only changes in 24 h free fatty acids (B=0.105+/-0.018, P=0.002) and glucose/insulin ratio (B=0.247+/-0.081, P=0.029) were the best predictors of leptin variations. In conclusion, the reversion of insulin resistance after BPD might allow reversal of leptin resistance, restoration of leptin pulsatility, and consequent inhibition of ACC2 mRNA expression, translating to a reduced synthesis of malonyl-CoA, which, in turn, results in increased fatty acid oxidation. Finally, since leptin inhibits GH secretion, a reduction of circulating leptin levels might have produced an increase in GH secretion, as observed in our series.

Weight loss induced by malabsorptive bariatric surgery is associated with greater ghrelin concentrations, which, however, remain consistently lower than those in control subjects, whereas ghrelin pulsatility is subverted. Higher ghrelin concentrations may contribute to the high calorie intakes observed in post-BPD subjects. The lack of normal pulsatility may explain the new impulse of these subjects to eat very frequently.

Monitoring of respiratory gas exchange in humans is an important task in order to establish the physical condition of the patient and to control important physiological indices. In a previous work, we proposed an approximated linear dynamical model of gas exchange within a controlled volume, to be used as a basis for Kalman filtering technique in order to improve the accuracy of the estimates. In this paper, we propose an alternative nonlinear dynamical model of the same phenomenon and suggest the use of a nonlinear estimation technique. A simulation study demonstrates that operative conditions exist where the latter results are more accurate than the estimates based on the linear model. A set of controlled experiments are also designed in order to create situations in which the above difference is significant. In the paper it is evidenced that, in different operative conditions, the analysis both of simulated and experimental data, give systematically the same indications about the choice of the filtering method. The conclusive result of this paper is that a nonlinear model, and the corresponding nonlinear estimation technique, turn out to be convenient when the operative volume and the accuracy of the instrumentation of the experimental set up are both low (operative volumes of about ten liters and flows measurements errors with variances not less than 1 [liter/min]2). It should be also remarked that the proposed model-based estimation techniques, both linear and nonlinear, are highly superior to conventional methods used in medical practice. The present study provides insights and guidelines that can also be useful when dealing with similar gas exchange estimation problems in many other different application areas.