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C Cobelli

Publications and source records attributed to C Cobelli.

At least 19 recordsLinked to original sources
PubMed2006

A markerless motion capture system to study musculoskeletal biomechanics: visual hull and simulated annealing approach.

Human motion capture is frequently used to study musculoskeletal biomechanics and clinical problems, as well as to provide realistic animation for the entertainment industry. The most popular technique for human motion capture uses markers placed on the skin, despite some important drawbacks including the impediment to the motion by the presence of skin markers and relative movement between the skin where the markers are placed and the underlying bone. The latter makes it difficult to estimate the motion of the underlying bone, which is the variable of interest for biomechanical and clinical applications. A model-based markerless motion capture system is presented in this study, which does not require the placement of any markers on the subject's body. The described method is based on visual hull reconstruction and an a priori model of the subject. A custom version of adapted fast simulated annealing has been developed to match the model to the visual hull. The tracking capability and a quantitative validation of the method were evaluated in a virtual environment for a complete gait cycle. The obtained mean errors, for an entire gait cycle, for knee and hip flexion are respectively 1.5 degrees (+/-3.9 degrees ) and 2.0 degrees (+/-3.0 degrees ), while for knee and hip adduction they are respectively 2.0 degrees (+/-2.3 degrees ) and 1.1 degrees (+/-1.7 degrees ). Results for the ankle and shoulder joints are also presented. Experimental results captured in a gait laboratory with a real subject are also shown to demonstrate the effectiveness and potential of the presented method in a clinical environment.

Biomechanical Phenomena↗
PubMed2005

Ovarian cancer identification based on dimensionality reduction for high-throughput mass spectrometry data.

MOTIVATION: High-throughput and high-resolution mass spectrometry instruments are increasingly used for disease classification and therapeutic guidance. However, the analysis of immense amount of data poses considerable challenges. We have therefore developed a novel method for dimensionality reduction and tested on a published ovarian high-resolution SELDI-TOF dataset. RESULTS: We have developed a four-step strategy for data preprocessing based on: (1) binning, (2) Kolmogorov-Smirnov test, (3) restriction of coefficient of variation and (4) wavelet analysis. Subsequently, support vector machines were used for classification. The developed method achieves an average sensitivity of 97.38% (sd = 0.0125) and an average specificity of 93.30% (sd = 0.0174) in 1000 independent k-fold cross-validations, where k = 2, ..., 10. AVAILABILITY: The software is available for academic and non-commercial institutions.

Algorithms↗
PubMed2002

Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance.

AIMS/HYPOTHESIS: We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT). METHODS: Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f(b), f(d), f(s), T(up), T(down) ), and insulin sensitivity (Si). RESULTS: ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f(b)) and stimulated (f(d), f(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T(up)) and -down (T(down)) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5.)min(-2) x l) was lower in Obese-IGT compared to Controls, both during step-up (919 +/- 851 vs 3192 +/- 1185, p < 0.05) and step-down (1455 +/- 1203 vs 3625 +/- 691, p < 0.05) phases. Consistently, the product f(s) x Si (10(-14.)min(-2). pmol(-1) x l) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05). CONCLUSION/INTERPRETATION: Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.

Adult↗
PubMed2002

A telemedicine support for diabetes management: the T-IDDM project.

In the context of the EU funded Telematic Management of Insulin-Dependent Diabetes Mellitus (T-IDDM) project, we have designed, developed and evaluated a telemedicine system for insulin dependent diabetic patients management. The system relies on the integration of two modules, a Patient Unit (PU) and a Medical Unit (MU), able to communicate over the Internet and the Public Switched Telephone Network. Using the PU, patients are allowed to automatically download their monitoring data from the blood glucose monitoring device, and to send them to the hospital data-base; moreover, they are supported in their every day self monitoring activity. The MU provides physicians with a set of tools for data visualization, data analysis and decision support, and allows them to send messages and/or therapeutic advice to the patients. The T-IDDM service has been evaluated through the application of a formal methodology, and has been used by European patients and physicians for about 18 months. The results obtained during the project demonstration, even if obtained on a pilot study of 12 subjects, show the feasibility of the T-IDDM telemedicine service, and seem to substantiate the hypothesis that the use of the system could present an advantage in the management of insulin dependent diabetic patients, by improving communications and, potentially, clinical outcomes.

Blood Glucose Self-Monitoring↗
PubMed2002

A morphometric model of lung mechanics for time-domain analysis of alveolar pressures during mechanical ventilation.

In this study we propose, and implement in the time domain, an anatomically consistent model of the respiratory system in critical care conditions that allows us to evaluate the impact of different ventilator strategies as well as of constrictive pathologies on the time course of acinar pressures and flows. We discuss the simplifications of the original Horsfield structure (Horsfield, K., et al. Models of the human bronchial tree. J. Appl. Physiol. 31:207-217, 1971), which were needed to enable the model implementation. The model has a binary tree structure including large airways represented as a combination of wall compliance and laminar resistance, small airways that have the same arrangement but can be heterogeneously constricted, and alveolar compartments that are viscoelastic second-order models to represent the stress adaptation behavior of lung tissue. We have described patient-ventilator interactions modeling the ventilator and the endotracheal tube. In conclusion this model makes it possible to investigate realistically the effect of homogeneous versus heterogeneous constrictive pathologies and the impact of different ventilatory patterns on pressure and flow distribution at the acinar level in the mechanically ventilated patient.

Bronchi↗
PubMed2001

Impact of cyclosporine and low-dose steroid therapy on insulin sensitivity and beta-cell function in patients with long-term liver grafts.

To examine whether factors controlling glucose tolerance, i.e., insulin sensitivity (SI) and first-(phi1) and second-phase insulin secretion (phi2), are impaired in after orthotopic liver transplantation (OLT), they were assesssed in patients that had undergone OLT for cirrhosis (n = 10) with cyclosporin A and low-dose steroid therapy (5 mg prednisone per day) and were compared with those of healthy matched control subjects (n = 10). These factors were determined by means of computer-based analysis of frequently sampled intravenous glucose tolerance tests (FSIGTT). Glucose and insulin profiles (posthepatic insulin) did not differ between both groups, whereas C-peptide levels (prehepatic insulin) were elevated in the transplant group after the FSIGTT, indicating an increased hepatic insulin degradation. SI and (phi1 did not differ between both groups. phi2, however, was significantly enhanced (23.94 +/- 2.63 vs 13.88 +/- 1.25 min(-1), P < 0.05). These results indicate that cyclosporine and low-dose steroid therapy do not impair SI and phi1. However, enhanced phi2 compensates the increased hepatic insulin clearance.

Adult↗
PubMed2001

Assessing skeletal muscle glucose metabolism with positron emission tomography.

Insulin has a marked effect to stimulate the transport and metabolism of glucose in skeletal muscle in healthy individuals, whereas an impaired response, termed insulin resistance, is a major risk factor for diabetes mellitus and other metabolic diseases. Studies of the molecular physiology of insulin action in skeletal muscle indicate that a principal loci of control resides within the proximal steps of glucose transport and phosphorylation. Deoxyglucose, the metabolism of which is limited to these proximal steps, is widely used for in vitro studies of insulin action on glucose transport. The technologies of PET imaging provide a unique opportunity to carry out similar studies in vivo in human skeletal muscle. In this instance, a short-lived positron labeled tracer, [18F] FDG, can be given at sufficiently high specific activity to image not only glucose uptake, but by dynamic PET imaging, by monitoring the time course of [18F] FDG tissue activity, data can be generated to examine the kinetics of glucose transport and phosphorylation. The experimental procedures of this approach, including an overview of the mathematical modeling, are described in this review, along with some of the key findings of the initial applications of PET for the study of glucose metabolism in human skeletal muscle.

Biological Transport↗
PubMed2001

Global identifiability of nonlinear models of biological systems.

A prerequisite for well-posedness of parameter estimation of biological and physiological systems is a priori global identifiability, a property which concerns uniqueness of the solution for the unknown model parameters. Assessing a priori global identifiability is particularly difficult for nonlinear dynamic models. Various approaches have been proposed in the literature but no solution exists in the general case. In this paper, we present a new algorithm for testing global identifiability of nonlinear dynamic models, based on differential algebra. The characteristic set associated to the dynamic equations is calculated in an efficient way and computer algebra techniques are used to solve the resulting set of nonlinear algebraic equations. The algorithm is capable of handling many features arising in biological system models, including zero initial conditions and time-varying parameters. Examples of usage of the algorithm for analyzing a priori global identifiability of nonlinear models of biological and physiological systems are presented.

Algorithms↗
PubMed2001

Reconstructing insulin secretion rate after a glucose stimulus by an improved stochastic deconvolution method.

Reconstructing insulin secretion rate (ISR) after a glucose stimulus by deconvolution is difficult because of its biphasic pattern, i.e., a rapid secretion peak is followed by a slower release. Here, we refine a recently proposed stochastic deconvolution method by modeling ISR as the multiple integration of a white noise process with time-varying statistics. The unknown parameters are estimated from the data by employing a maximum likelihood criterion. A fast computational scheme implementing the method is presented. Monte Carlo simulation results are developed which numerically show a more reliable ISR profile reconstructed by the new method.

Biomedical Engineering↗
PubMed2001

Insulin secretion rate during glucose stimuli: alternative analyses of C-peptide data.

The ability to evaluate the pancreatic insulin secretion rate (ISR) is essential for a quantitative understanding of the glucose regulation system in man. Various approaches have been developed for evaluation of the ISR in vivo. The aim of this study was to compare input/output and compartmental models of C-peptide to reconstruct the ISR in response to both physiological and nonphysiological glucose stimuli in healthy humans. In particular we applied the nonparametric stochastic deconvolution and the C-peptide minimal model approaches to the graded up&down glucose infusion protocol, where glucose was infused at progressively increasing and then decreasing rates, and to the intravenous glucose tolerance test (IVGTT), where an impulse dose of glucose was administered. Our results show that the two models give virtually identical results when glucose and C-peptide (and thus ISR) profiles are smooth and regular, but when vigorous nonstationarities are present, like during the first 4 min of the IVGTT, the two ISR profiles are different (but not their areas under the curve). The C-peptide minimal model, albeit requiring, at variance with deconvolution, the knowledge of glucose data, has the advantage of providing quantitative indices of the beta-cell function, which is important in the parametric definition of different physiopathological states.

Adult↗
PubMed2001

The iterative two-stage population approach to IVGTT minimal modeling: improved precision with reduced sampling. Intravenous glucose tolerance test.

The minimal model method is widely used to estimate glucose effectiveness (S(G)) and insulin sensitivity (S(I)) from intravenous glucose tolerance test (IVGTT) data. In the standard protocol (sIVGTT, 0.33 g/kg glucose bolus given at time 0), which allows the simultaneous assessment of beta-cell function, the precision of the individualized estimates often degrades and particularly so in the presence of reduced sampling schedules. Here, we investigated the use of a population approach, the iterative two-stage (ITS) approach, to analyze 16 sIVGTTs in healthy subjects and to obtain refined estimates of S(G) and S(I) in the population and in the individual subjects. The ITS is based on calculation of the population mean and standard deviation of the parameters at each iteration and then use of them as prior information for the individual analyses. Theoretically, the use of a prior in the ITS should improve the precision of the individual estimates. The customary approach (standard two stage, STS), where modeling is performed separately for each individual subject, does not take the population knowledge into account. We used both frequent (FSS, 30 samples) and (quasi-optimally) reduced (RSS, 14 samples) sampling schedules. For the FSS, STS gave estimates (mean +/- SD) for S(G) = 2.66 +/- 1.09 x 10(-2). min(-1) and S(I) = 6.46 +/- 6.99 10(-4). min(-1). microU(-1). ml, with an average precision of 51 (range 5-176) and 33% (3-91), respectively. RSS radically worsened the precision of both S(G) and S(I). However, RSS and ITS gave S(G) = 2.59 +/- 0.73 and S(I) = 6.06 +/- 7.28, with an average precision of 23 (12-42) and 27% (), respectively. In conclusion, population minimal modeling of sIVGTT data improves the precision of individual estimates of glucose effectiveness and insulin sensitivity, as the theory predicts, and, even with reduced sampling, the improvement is substantial.

Adult↗
PubMed2001

Quantitative indexes of beta-cell function during graded up&down glucose infusion from C-peptide minimal models.

Availability of quantitative indexes of insulin secretion is important for definition of the alterations in beta-cell responsivity to glucose associated with different physiopathological states. This is presently possible by using the intravenous glucose tolerance test (IVGTT) in conjunction with the C-peptide minimal model. However, the secretory response to a more physiological slowly increasing/decreasing glucose stimulus may uncover novel features of beta-cell function. Therefore, plasma C-peptide and glucose data from a graded glucose infusion protocol (seven 40-min periods of 0, 4, 8, 16, 8, 4, and 0 mg. kg(-1). min(-1)) in eight normal subjects were analyzed by use of a new model of insulin secretion and kinetics. The model assumes a two-compartment description of C-peptide kinetics and describes the stimulatory effect on insulin secretion of both glucose concentration and the rate at which glucose increases. It provides in each individual the insulin secretion profile and three indexes of pancreatic sensitivity to glucose: Phi(s), Phi(d), and Phi(b), related, respectively, to the control of insulin secretion by the glucose level (static control), the rate at which glucose increases (dynamic control), and basal glucose. Indexes (means +/- SE) were Phi(s) = 18.8 +/- 1.8 (10(9) min(-1)), Phi(d) = 222 +/- 30 (10(9)), and Phi(b) = 5.2 +/- 0.4 (10(9) min(-1)). The model also allows one to quantify the beta-cell times of response to increasing and decreasing glucose stimulus, equal to 5.7 +/- 2.2 (min) and 17.8 +/- 2.0 (min), respectively. In conclusion, the graded glucose infusion protocol, interpreted with a minimal model of C-peptide secretion and kinetics, provides a quantitative assessment of pancreatic function in an individual. Its application to various physiopathological states should provide novel insights into the role of insulin secretion in the development of glucose intolerance.

Adult↗
PubMed2001

Kinetic modeling of [(18)F]FDG in skeletal muscle by PET: a four-compartment five-rate-constant model.

Various modeling strategies have been developed to convert regional [(18)F]fluorodeoxyglucose ([(18)F]FDG) concentration measured by positron emission tomography (PET) to a measurement of physiological parameters. However, all the proposed models have been developed and tested mostly for brain studies. The purpose of the present study is to select the most accurate model for describing [(18)F]FDG kinetics in human skeletal muscle. The database consists of basal and hyperinsulinemic-euglycemic studies performed in normal subjects. PET data were first analyzed by an input-output modeling technique (often called spectral analysis). These results provided guidelines for developing a compartmental model. A new model with four compartments and five rate constants (5K model) emerged as the best. By accounting for plasma and extracellular and intracellular kinetics, this model allows, for the first time, PET assessment of the individual steps of [(18)F]FDG kinetics in human skeletal muscle, from plasma to extracellular space to transmembrane transport into the cell to intracellular phosphorylation. Insulin is shown to affect transport and phosphorylation but not extracellular kinetics, with the transport step becoming the main site of control. The 5K model also allows definition of the domain of validity of the classic three-compartment three- or four-rate-constant models. These models are candidates for an investigative tool to quantitatively assess insulin control on individual metabolic steps in human muscle in normal and physiopathological states.

Adult↗
PubMed2001

Glucose production, gluconeogenesis, and insulin sensitivity in children and adolescents: an evaluation of their reproducibility.

The prevalence of overweight and obese children has doubled, and the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold during the past several decades. As a result we can anticipate an increased number of metabolic studies in children. There are few data on measures of glucose metabolism in normal children, and virtually none relating to their reproducibility. The aims of this study were 1) to provide new data on energy expenditure and glucose, lipid, and protein metabolism in nonobese, healthy children and adolescents; 2) to evaluate their reproducibility; and 3) on the basis of these data, to perform power calculations for metabolic studies. Eight nonobese subjects (8-16 y) were studied on two occasions, preceded by 7 d of a diet with identical energy content and macronutrient distribution. Gluconeogenesis, measured by deuterium oxide, accounted for 50% of glucose production. Insulin sensitivity, measured by the labeled minimal model, averaged 4.9 x 10(-4) mL(mU x min)(-1). Glucose appearance rate was significantly higher (p < 0.01) in the children than in the adolescents. Furthermore, we demonstrated that for energy intake and expenditure, plasma concentrations of glucose and C-peptide, and rates of appearance of glucose and leucine, a 10% difference can be detected in fewer than five subjects with a power of 80% and a type I error of 5%. Insulin concentration, gluconeogenesis, insulin secretory indices, insulin sensitivity, and glucose effectiveness were more variable, but with the above power a difference of 25% could be detected in 7-11 subjects using a paired study design.

Adolescent↗
PubMed2001

Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity.

The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies-the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT300-22) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (phis [10(9) min(-1)] and phid [10(9)]) and the insulin sensitivity index (SI) (10(5) dl/kg per min per pmol/l) were estimated by using the minimal model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the minimal model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT300-11) is the test of choice because the indexes it provides (phis = 36 +/- 3 [means +/- SE]; phid = 710 +/- 111; SI = 10.2 +/- 2.4) show excellent correlation and are not statistically different from those of FSOGTT300-22 (phis = 33 +/- 3; phid = 715 +/- 120; SI = 10.1 +/- 2.3). In conclusion, OGTT300-11, interpreted with C-peptide and glucose minimal models, provides a quantitative description of beta-cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT.

Adult↗
PubMed2000

Regulation of glucose tolerance in patients after liver transplantation: impact of cyclosporin versus tacrolimus therapy.

BACKGROUND: We investigated the factors regulating glucose homeostasis in 10 healthy (control) subjects, as well as in stable, long-term, liver-grafted patients receiving monotherapy in the form of either cyclosporin A (n=10) or tacrolimus (n=10). METHODS: We measured insulin sensitivity, first- and second-phase insulin secretion, with a minimal modeling technique based on the analysis of glucose, insulin, and C-peptide profiles during frequently sampled intravenous glucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT. RESULTS: Glucose and insulin concentrations before and after glucose loading did not differ in liver transplant patients and in control subjects. Fasting C-peptide levels in both liver-grafted groups were higher than in healthy subjects and remained elevated during FSIGTT (P<0.05). Intravenous glucose tolerance [(K(G)), i.e. the slope of the regression of logarithm of the blood glucose concentrations vs. time], insulin sensitivity, and first-phase insulin secretion did not differ in liver-grafted groups and healthy subjects. Second-phase insulin secretion was about 56% higher in liver-grafted patients than in controls (P<0.05). Body mass index was the overall determinant of insulin sensitivity in all groups. CONCLUSIONS: Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitivity (posthepatic insulin effect) and enhanced second-phase insulin secretion (prehepatic insulin) point to an accelerated hepatic insulin clearance rate in liver transplant patients. Increased hepatic insulin clearance is compensated by enhanced insulin secretion, indicating that insulin clearance is the major determinant of pancreatic function in liver-grafted patients.

Adult↗
PubMed2000

Muscle blood flow and flow heterogeneity during exercise studied with positron emission tomography in humans.

Blood flow is the main regulator of skeletal muscle's oxygen supply, and several studies have shown heterogeneous blood flow among and within muscles. However, it remains unclear whether exercise changes the heterogeneity of flow in exercising human skeletal muscle. Muscle blood flow and spatial flow heterogeneity were measured simultaneously in exercising and in the contralateral resting quadriceps femoris (QF) muscle in eight healthy men using H2(15)O and positron emission tomography. The relative dispersion (standard deviation/mean) of blood flow was calculated as an index of spatial flow heterogeneity. Average muscle blood flow in QF was 29 (10) ml x (kg muscle)(-1) x min(-1) at rest and 146 (54) ml x (kg muscle)(-1) x min(-1) during exercise (P = 0.008 for the difference). Blood flow was significantly (P < 0.001) higher in the vastus medialis and the vastus intermedius than in the vastus lateralis and the rectus femoris, both in the resting and the exercising legs. Flow was more homogeneous in the exercising vastus medialis and more heterogeneous (P < 0.001) in the exercising vastus lateralis (P = 0.01) than in the resting contralateral muscle. Flow was more homogeneous (P < 0.001) in those exercising muscles in which flow was highest (vastus intermedius and vastus medialis) as compared to muscles with the lowest flow (vastus lateralis and the rectus femoris). These data demonstrate that muscle blood flow varies among different muscles in humans both at rest and during exercise. Muscle perfusion is spatially heterogeneous at rest and during exercise, but responses to exercise are different depending on the muscle.

Exercise↗