Glucose-insulin Kinetics Research Articles

Oversupplying metabolizable protein during late gestation to beef cattle does not influence ante- or postpartum glucose-insulin kinetics but does affect prepartum insulin resistance indices and colostrum insulin content.

The objective of this study was to evaluate whether oversupplying metabolizable protein (MP) during late gestation influences glucose and insulin concentrations, and insulin resistance (IR) in late gestation and early lactation. Crossbred Hereford, first-lactation heifers were individually fed diets to supply 133% (HMP, n = 11) or 100% (CON, n = 10) of their predicted MP requirements for 55 ± 4 d (mean ± SD) prior to calving. All heifers received a common lactation ration formulated to meet postpartum requirements (103% MP and 126% ME). After feed was withheld for 12 h, cattle underwent an intravenous glucose tolerance test (IVGTT) on days -6.7 ± 0.9 and 14.3 ± 0.4 by infusing a 50% dextrose solution (1.36 g glucose/kg BW0.75) through a jugular catheter with plasma collected at -10, 0 (immediately after infusion), 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, and 120 min, respective to the infusion. Glucose and insulin concentrations were assessed. Insulin resistance indices (homeostasis model of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], revised quantitative insulin sensitivity check index [RQUICK], and RQUICKI incorporating serum beta-hydroxybutyrate concentrations [RQUICKIBHB]) were calculated from measurements of serum non-esterified fatty acids and beta-hydroxybutyrate and plasma glucose and insulin concentrations on days -34 ± 4, -15 ± 4, 7 ± 1, 28 ± 3, 70 ± 3, and 112 ± 3. Colostrum samples were collected within an hour of calving (prior to suckling) and analyzed for insulin concentration. Data were analyzed as a randomized block design using the PROC GLIMMIX of SAS, accounting for repeated measurements when necessary. Baseline (-10 min) plasma glucose and insulin concentrations were elevated (P ≤ 0.038) for HMP heifers during the antepartum IVGTT, but not (P ≥ 0.25) during the postpartum IVGTT. Plasma glucose and insulin concentrations throughout the antepartum or postpartum IVGTT did not differ (P ≥ 0.18) by prepartum treatment, nor did other glucose and insulin IVGTT parameters (i.e., max concentration and time to reach max concentration, nadir values, clearance rates and half-lives, area-under-the-curve, and insulin sensitivity index; P ≥ 0.20). Antepartum IVGTT IR indices indicated that HMP heifers were more (P ≤ 0.011) IR than their counterparts. Similarly, the prepartum HOMA-IR was greater (P = 0.033) for HMP heifers, suggesting increased IR. Postpartum IR indices did not (P ≥ 0.25) indicate that prepartum MP consumption impacted postpartum IR. Colostrum insulin concentration was increased (P = 0.004) by nearly 2-fold for HMP relative to CON heifers. These data demonstrate that prepartum MP overfeeding alters baseline glucose-insulin concentrations in late-pregnant beef heifers and increases colostrum insulin content without having carry-over effects on postpartum glucose-insulin concentrations and IR.

Effects of energy source in milk replacer on glucose metabolism of neonatal dairy calves

Milk replacers (MR) formulated to contain more lactose than whole milk could potentially reduce insulin sensitivity in dairy calves. This study evaluated how partially replacing lactose in MR with fat on a weight/weight basis affects glucose-insulin kinetics in neonatal dairy calves fed high quantities of MR. Thirty-four Holstein bull calves were blocked by dam parity (1.6 ± 0.3) and randomly assigned to 1 of 2 treatments (n = 17): a high-lactose MR (HL; 46.1% lactose, 18.0% crude fat, and 23.9% crude protein on a dry matter basis) or a high fat MR (HF; 39.9% lactose, 24.6% crude fat, and 24.0% crude protein on a dry matter basis). Calves were individually housed and fed pooled colostrum at 1.5 h and 12 h postnatal at 18 and 9% of metabolic body weight (BW0.75), respectively. From 24 h postnatal until the end of the study (d 7), calves were transitioned to MR (prepared at 150 g/L) at 18% of BW0.75 twice daily at 0700 and 1900 h. On d 4, an insulin-modified intravenous glucose tolerance test was conducted 8 h after the morning meal by intravenous infusion of glucose (0.54 g/kg of BW0.75, min 0) and insulin (3.9 µg/kg of BW0.75, min 20). During postprandial sampling on d 6, abomasal emptying was assessed by dosing acetaminophen (0.13 g/kg of BW0.75) with MR and measuring its appearance within plasma. Sequential blood samples were collected and analyzed for plasma glucose, insulin, and acetaminophen concentrations. Calves were killed on d 7 and liver and pancreatic tissues were collected for histomorphological analysis. Partially replacing lactose in MR with fat increased body weight gain (679.6 vs. 462.0 ± 69.68 g/d) and gain:metabolizable energy intake (186.6 vs. 120.5 ± 20.21 g of body weight/Mcal) compared with feeding HL MR. Furthermore, abomasal emptying rate was reduced in calves fed HF MR. Calculated variables based on postprandial glucose and insulin concentrations, such as maximum concentration or area under the curve, were or tended to be lower in HF than in HL calves. Postprandial insulin sensitivity tended to be reduced in HL compared with HF, although insulin sensitivity estimated from the insulin-modified intravenous glucose tolerance test was not different. Calves fed HF MR showed enhanced glucose-stimulated insulin secretion. In conclusion, partially replacing lactose in MR with fat resulted in smaller fluctuations in postprandial glucose and insulin concentrations and tended to increase postprandial but not fasting insulin sensitivity in neonatal dairy calves.

Lexicographic derivatives of nonsmooth glucose-insulin kinetics under normal and artificial pancreatic responses

Parametric sensitivities of nonsmooth glucose-insulin kinetics models are investigated in this article. In particular, we study several variations on a model of the so-called Intravenous Glucose Tolerance Test (IVGTT), which measures a subject’s insulin response to glucose over time and yields data useful for characterizing and diagnosing diabetes. Nonsmoothness refers here to continuous behavior that is punctuated by “switches” (physiological events) arising due to biochemical and control thresholds being crossed. Insulin secretion from a typical pancreatic response and insulin infusion from an external device (for diabetic patients) are both considered here. The presence of nonsmoothness means that classical sensitivity theory and associated numerical methods are ill-equipped to handle these models. Motivated by this, lexicographic directional differentiation and lexicographic “sensitivity functions” are used, which are recently developed tools in nonsmooth analysis. Using this new approach, we derive nonsmooth sensitivity systems associated with the considered glucose kinetics models, whose unique solutions provide local sensitivity information analogous to classical forward parametric sensitivity functions. Moreover, the theory is practically implementable and the resulting sensitivity functions are computationally relevant, as they can be supplied to dedicated nonsmooth numerical methods (e.g., optimization). The nonsmooth sensitivity systems are solved numerically, giving new insights into the model, and thus into the dynamics of glucose kinetics under the simulated conditions. It is hoped that the results here may be used to improve the design of assessments for diabetes (e.g., the IVGTT) and its treatment.

393 Beef cow antepartum glucose-insulin kinetics are altered by overfeeding metabolizable protein during late gestation and influenced by test-day relative to calving

Abstract The objective of this study was to determine whether antepartum glucose-insulin kinetics were affected when primiparous Hereford-cross heifers were fed diets containing 100 (CON; n = 10) or 133% (HMP; n = 11) of their metabolizable protein requirements from d -55.3 ± 3.7 until parturition. Intravenous glucose tolerance tests (IVGTT) were performed on d -5.4 and -7.1 ± 1.3 (CON and HMP, respectively; P = 0.34) by collecting baseline (-10 min) plasma, infusing 1.36 g glucose/kg BW0.75 via a jugular catheter, and subsequently sampling plasma for analysis of glucose and insulin. Data were analyzed with PROC GLIMMIX as a randomized block design with the fixed effects of diet, time (minute), and diet × time, considering cow (block) as a random effect. Pearson correlations were performed for IVGTT variables and test-day relative to parturition. Differences and trends were declared at P < 0.05 and 0.05 ≤ P < 0.10, respectively. Basal glucose was 13.5% greater (P = 0.048) and basal insulin tended to be 28.8% greater (P = 0.068) for HMP than CON heifers. Plasma glucose (-10 to 120 min) was greater (P = 0.047) for HMP than CON, whereas insulin was not (P = 0.54). Glucose and insulin were respectively elevated (time: P < 0.001) at 0 and 5 and 5 to 20 min and both equilibrated to baseline by 90- and 120-min. Diet × time tended to affect (P = 0.061) the glucose:insulin ratio. Test-day was correlated with time-to-max insulin (ρ = 0.60, P = 0.006), insulin clearance rate (ρ = 0.48, P = 0.027), and glucose area-under-the-curve (ρ = -0.47, P = 0.031). Time relative to calving can influence antepartum glucose-insulin kinetics. Oversupplying metabolizable protein increased baseline glucose and insulin and glucose throughout the IVGTT. Antepartum beef cattle may have altered energy partitioning that is responsive to protein consumption.

Effect of replacing lactose with fat in milk replacer on abomasal emptying and glucose–insulin kinetics in male dairy calves

ABSTRACT Objective Altering energy supply and the relative proportions of energy source in the first weeks of life of dairy calves may influence glycemic and insulinemic responses. The objective of this study was to assess the metabolic responses to high-lactose or high-fat milk replacer. Materials and Methods Forty male calves were fed 7 L of milk replacer per day in 2 meals given 10 h apart, considered either high lactose (44% lactose, HL) or high fat (37% lactose, HF), from the first week of life to 30 d of age. Postprandial blood plasma glucose, insulin, and acetaminophen (an abomasal emptying marker) concentrations were measured up to 420 min and used to fit a mathematical model of abomasal emptying and glucose–insulin dynamics. Additionally, an i.v. glucose tolerance test was used to assess glucose tolerance and insulin sensitivity. Results and Discussion Insulin sensitivity remained unchanged; however, glucose maximal concentration and change from baseline tended to be greater for HL in response to an i.v. glucose challenge. Postprandial glucose was elevated at 30 min for HL and HF at 60 and 90 min. Model parameterization showed no difference in abomasal emptying; however, intestinal glucose absorption tended to be faster with HL. Potentiation of insulin action was greater with HL, and pancreatic responsiveness tended to be greater with HF. Implications and Applications These results suggest HL increased early-phase postprandial glucose appearance, which may influence insulin action. In this study, modifying milk replacer composition to more closely resemble cow’s milk did not negatively affect glucose metabolism.

Grain source and chromium supplementation: Effects on health, metabolic status, and glucose-insulin kinetics in Holstein heifer calves

Carbohydrate-rich diets may increase urinary excretion of chromium (Cr) and the need to supplement the diet with Cr to meet animal requirements. The present study was performed to examine the effect of the type of grain (corn vs. barley) and Cr-methionine supplementation on health-related variables, blood levels of metabolites and hormones related to energy metabolism, and insulin sensitivity in Holstein calves. Forty-eight newborn heifers (3 d of age) were assigned randomly to 4 diets in a 2 × 2 factorial arrangement. Experimental diets were either corn-based (CBD) or barley-based (BBD) diets supplemented with 0 or 0.05 mg/kg of metabolic body weight. Chromium was provided in milk before weaning (d 3-73 of age) and in prewarmed water after weaning (d 74-94 of age). There was no interaction between the type of grain and Cr on the health-related variables and blood metabolites and hormones. Type of grain did not affect fecal score, respiration rate, and rectal temperature; however, there were tendencies for higher diarrhea occurrence (odds ratio = 1.69) and lower chance of having pneumonia (odds ratio = 0.49) in calves fed BBD versus CBD despite longer duration of diarrhea (0.54 d) and shorter days with pneumonia (0.63 d) in calves fed BBD. Calves supplemented with Cr had lower fecal score during the preweaning and overall periods and respiration rate throughout the study. Supplemental Cr decreased the duration (0.63 d) and chance of having pneumonia (odds ratio = 2.01). Calves fed BBD had lower blood levels of urea N during the postweaning period, with no changes in other blood variables between CBD and BBD. Tendencies were detected for lower blood levels of β-hydroxybutyric acid during the preweaning and overall periods and higher cortisol in Cr-supplemented calves. Chromium supplementation increased insulin clearance rate and decreased the time to half-maximal concentration and the area under the curve in BBD but not CBD calves. The calves were generally healthy, and the type of grain did not affect the health and blood variables related to energy metabolism. However, Cr supplementation increased fecal consistency, decreased respiration rate and days with pneumonia, and increased insulin sensitivity when added to BBD.

Effect of chromium supplementation on growth performance, meal pattern, metabolic and antioxidant status and insulin sensitivity of summer-exposed weaned dairy calves

Stressful situations may result in serum chromium (Cr) depletion with increased urinary excretion of the mineral and increased Cr requirements. The objective of this study was to investigate the effects of Cr supplementation on growth performance, feeding behavior, blood metabolites and hormones, indicators of oxidative stress and glucose-insulin kinetics of summer-exposed weaned dairy calves. In total, 48 Holstein female calves (63 days of age; 77.0±1.45 kg of BW) were assigned randomly to one of two treatments: (1) a control group with no supplemental Cr (Cr−), and (2) a supplemental Cr group (Cr+) to supply 0.05 mg Cr as Cr-methionine/kg of BW0.75. Chromium was provided in the starter feed and adjusted weekly based on BW over the experimental period. All calves were on experiment for 4 weeks after weaning. The average maximum temperature–humidity index was 76.1 units during the study period, indicating a mild degree of environmental heat load. Results indicated that in summer-exposed dairy calves, increased dietary Cr provision tended to decrease fecal score, tended to change rumination pattern, increased antioxidant capacity by increasing serum concentration of catalase, but had no effects on growth performance, metabolic status or peripheral glucose and insulin metabolism.

Linear feedback-based control of blood glucose in a modified model for glucose–insulin kinetics: A theoretical study

In this paper, we present a modified minimal model for glucose and insulin kinetics model. The model proposed here is a smooth approximation of the original non-smooth minimal model. The dynamical properties like dissipativity, existence of equilibrium and stability of the system at the equilibrium points are investigated. A linear feedback-based control strategy is studied to control the blood glucose level in the situation where the physical system fails to regulate the blood glucose level automatically. A critical control parameter value [Formula: see text] is determined in terms of the system parameters. Extensive numerical simulation is performed with different parameter sets. Assuming different values for the feedback gain parameter, ranges of physiological parameter [Formula: see text] are determined where the feedback gain is sufficient to stabilize the control system.

1825 INTRAVENOUS GLUCOSE TOLERANCE TEST ASSESSMENT OF GLUCOSE-INSULIN KINETICS FOLLOWING TREATMENT OF THE KIDNEY WITH A SUPRA-MAXIMAL DOSE OF SHOCK WAVES IN A PORCINE MODEL OF METABOLIC SYNDROME

INTRODUCTION AND OBJECTIVES: In our continuing efforts to determine whether shock wave lithotripsy (SWL) is a risk factor for the development of diabetes mellitus, we treated the kidney of metabolic syndrome (MetS) pigs with a supra-maximal dose of shock waves (SWs) and assessed the SWL effect on the glucose-insulin kinetic response to an intravenous glucose tolerance test (IVGTT). METHODS: Adult female Ossabaw pigs (9-month-old) were fed an excess calorie atherogenic diet to induce MetS. At 15 months of age, the MetS pigs underwent SWL treatment (4000 SWs, 24 kV at 120 SWs/min using the HM-3 lithotripter; n 7). SWs were targeted to the upper pole calyx of the left kidney because of its close association with the tail of the pancreas?a segment rich in insulin containing -cells. IVGTTs were performed on conscious, fasting MetS pigs before SWL and at 1-month and 2-months post-SWL with frequent blood samples taken for glucose and insulin measurement. RESULTS: Pigs fed an excess calorie atherogenic diet developed features of MetS: obesity, dyslipidemia, insulin resistance and glucose intolerance. Fasting levels of plasma glucose and insulin, as well as their response profile to IVGTTs, were similar before and after SWL. Estimates of insulin resistance, glucose tolerance and pancreatic beta cell function derived from the glucose-insulin kinetics calculated from IVGTTs were not significantly altered following SWL. CONCLUSIONS: The pig?s MetS status was unchanged following overtreatment of the kidney with 4000 high-energy SWs. These findings do not support a single session of SWL in MetS patients as a risk factor for the onset of diabetes mellitus?at least in the short-term.

Structural identifiability and indistinguishability analyses of the Minimal Model and a Euglycemic Hyperinsulinemic Clamp model for glucose–insulin dynamics

Many mathematical models have been developed to describe glucose–insulin kinetics as a means of analysing the effective control of diabetes. This paper concentrates on the structural identifiability analysis of certain well-established mathematical models that have been developed to characterise glucose–insulin kinetics under different experimental scenarios. Such analysis is a pre-requisite to experiment design and parameter estimation and is applied for the first time to these models with the specific structures considered. The analysis is applied to a basic (original) form of the Minimal Model (MM) using the Taylor Series approach and a now well-accepted extended form of the MM by application of the Taylor Series approach and a form of the Similarity Transformation approach. Due to the established inappropriate nature of the MM with regard to glucose clamping experiments an alternative model describing the glucose–insulin dynamics during a Euglycemic Hyperinsulinemic Clamp (EIC) experiment was considered. Structural identifiability analysis of the EIC model is also performed using the Taylor Series approach and shows that, with glucose infusion as input alone, the model is structurally globally identifiable. Additional analysis demonstrates that the two different model forms are structurally distinguishable for observation of both glucose and insulin.

Population analysis of ethnicity and first-phase insulin release

Objective A mechanistic, physiologically-based pharmacokinetic (PK/PD) model was developed to describe the biphasic insulin release and evaluate the racial effects on the glucose–insulin kinetics in response to intravenous glucose. Methods Fifteen African-American and 18 Caucasian children and adolescents between 8 and 18 years of age were enrolled in the study. Intravenous bolus of glucose (250 mg/kg) was administered and blood samples collected at frequent intervals for three hours following the glucose injection. A nonlinear mixed-effect population kinetic analysis with covariate structure was performed using Monolix. Results A significantly higher initial insulin secretion from a readily releasable pool, which is responsible for the first-phase insulin secretion, was detected in African-Americans compared to Caucasians ( p < 0.05). Conclusions The proposed kinetic model is able to describe the glucose-stimulated insulin response, account for the first-phase insulin release and identify a racially-based pharmacokinetic difference in insulin's biphasic secretion behavior. It is hypothesized that the first-phase insulin component may play an important role in the development of type 2 diabetes. The proposed mechanistic model provides a quantitative analysis of the biphasic insulin release that may be useful in the early detection of diabetes.

Analysis of PK/PD risk factors for development of type 2 diabetes in high risk population using Bayesian analysis of glucose–insulin kinetics

This study was designed to investigate the pharmacokinetics/pharmacodynamics (PK/PD) risk factors preceding the onset of type 2 diabetes using a population-based Bayesian nonlinear hierarchical model to describe the glucose-insulin kinetics. One hundred fifty-two healthy subjects with a family history of type 2 diabetes were recruited. Each subject received an intravenous glucose tolerance test (IVGTT) and the data of glucose and insulin was collected when entering the study. After the test, subjects were followed up to 25 years and further divided into the diabetic outcome group and non-diabetic outcome group according to the follow-up results. A glucose-insulin kinetic model was developed to account for the physiology and molecular biology of the insulin biphasic secretion and glucose-insulin interactions with a minimal structure. The population PK/PD parameters of the two groups were estimated from the proposed glucose-insulin kinetic model. The relationships between the population PK/PD parameters and the diabetic follow-up results were evaluated. A high insulin baseline concentration, a lower maximum insulin-dependent glucose removal and a lower insulin removal rate constant were found associated with the development of type 2 diabetes in the high risk population. The study shows that the very early pre-diabetic pharmacokinetic differences exist and can be helpful for prediction of development of type 2 diabetes.

Practical Approach to Design and Implementation of a Control Algorithm in an Artificial Pancreatic Beta Cell

The rate limiting bottleneck in the development of an artificial pancreatic beta cell is currently the control algorithm used to make insulin dosing decisions. In this paper, a solution for the rapid development of a personalized control algorithm was proposed and the methodology was tested on the pilot scale using a physiological model of glucose—insulin kinetics and a hardware-in-the-loop (HIL) implementation of an artificial pancreatic beta cell. A model-based controller was developed from the identification tests and was augmented with advanced control strategies. The resulting controller improved glycemia from the open-loop case with no hypoglycemic events and a reduction in time spent hyperglycemic. Robustness issues were addressed with a 50% mismatch in insulin sensitivity from model to plant. The HIL platform provided insight into the effects of sensor drift and practicalities of continuous insulin delivery based on glucose sensor feedback.

Structural Identifiability of the Minimal Model and a Euglycemic Hyperinsulinemic Clamp Model for glucose-insulin dynamics

Many mathematical models have been developed to describe glucose and insulin kinetics as a means of analysing the effective control of diabetes. Of these probably the most widely accepted is the so-called “Minimal Model”. This paper concentrates on structural identifiability analyses of two well-established mathematical models that have been developed to characterise glucose-insulin kinetics under different experimental scenarios. Such analysis is a pre-requisite to experiment design and parameter estimation and is applied for the first time to these models with the structures considered. The analysis is initially applied to a basic form of the Minimal Model using the Taylor Series approach, demonstrating global identifiability contrary to previously published results. A now well-accepted extended form of the Minimal model is then considered where the model is provided in an augmented form in order to apply the Similarity Transformation approach. This augmentation was necessary to cater for the particular structure for the Minimal Model that includes a time term. Once more the system, proved to be globally identifiable when both glucose and insulin are observed. Due to the inappropriate nature of the Minimal Model with regard to glucose clamping an alternative model describing the glucose-insulin dynamics during Euglycemic Hyperinsulinemic Clamp was considered. The structural identifiability analysis of the Euglycemic Hyperinsulinemic Clamp model is also performed using the Taylor Series Approach and results show that, with glucose infusion as input alone, the model is structurally globally identifiable.

Glucose-Insulin Kinetics of the Extravascular Bioartificial Pancreas A Study Using Microencapsulated Rat Islets

The success of the extravascular bioartificial pancreas (BAP) is contingent on the rapid transfer of the glycemic signal across both an extravascular compartment and a semipermeable membrane and of insulin from the BAP to the recipient. To examine the possibility of microencapsulated islets such as the BAP to achieve satisfactory in vivo glucose-insulin kinetics, islets were isolated from Lewis rats, encapsulated in poly-L-lysine-alginate membranes, and isogenically transplanted into the peritoneal cavity of 14 streptozotocin induced diabetic rats. Fasting blood glucose (BG) was measured and intravenous glucose tolerance was tested at 8-10 weeks and compared with three control groups: 1) normal Lewis rats (n = 6); 2) untreated diabetic rats (n = 5); and 3) diabetic rats that received intraperitoneal implants of empty capsules (n = 4). Ten animals that received microencapsulated islets (5,271 +/- 431) promptly became normoglycemic, with a mean BG of 128 +/- 17 ng/dl 3 days after transplantation and maintained this level > 100 days. Intravenous glucose tolerance K-value for the group was 3.84 +/- 0.32 compared with 3.96 +/- 0.39 (p = 0.83) for the normal control group, and 0.60 +/- 0.12 (p < 0.01) and 0.40 +/- 0.15 (p < 0.01) for the diabetic control groups with and without empty capsules. The authors conclude from these results that, given sufficient beta-cell mass, a BAP without any vascular access can respond appropriately to an increase in blood glucose concentration, without overshoot hypoglycemia and within a lag lapse compatible with normal physiologic insulin delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Difference equations and an artificial pancreatic beta‐cell

Some difference equations are developed to model glucose—insulin kinetics. The resulting algorithm permits continuous subcutaneous insulin infusion for hospitalized insulin‐dependent diabetics. Three venal catheters infuse glucose and insulin and sample the plasma glucose levels to constitute an artificial pancreatic beta‐cell. This application of a discrete segments approach to modelling illustrates the need for a balanced approach to the undergraduate mathematics curriculum.

Mathematical analysis of a novel bioartificial pancreas design for the control of type I diabetes

A novel spiral wound membrane sandwich (SWMS) design for an implantable bioartificial pancreas is presented and is numerically evaluated using a comprehensive model of the glucose-insulin kinetics within the device. The spiral blood flow pattern in this design induces a convective flow of blood ultrafiltrate directly through the islet chamber. Use of ultrafiltration in addition to diffusion allows rapid transmission of blood glucose changes to the islet chamber and efficient transport of insulin from the islet chamber back to the blood stream. Simulation results suggest that the implantable bioartificial pancreas design presented in this paper may offer a means of improving the control of blood glucose levels in type I diabetics.

Numerical investigation of a novel spiral wound membrane sandwich design for an implantable bioartificial pancreas

A novel spiral wound membrane sandwich (SWMS) design for an implantable bioartificial pancreas is presented and is numerically evaluated using a comprehensive model of the glucose-insulin kinetics within the device. The spiral blood flow pattern in this design induces a convective flow of blood ultrafiltrate directly through the islet chamber. Use of ultrafiltration in addition to diffusion allows rapid transmission of blood glucose changes to the islet chamber and efficient transport of insulin from the islet chamber back to the blood stream. Simulation results suggest that the implantable bioartificial pancreas design presented in this paper may offer a means of improving the control of blood glucose levels in type I diabetics.

Alternative method for minimal model analysis of intravenous glucose tolerance data.

The minimal models of glucose-insulin kinetics were used to analyze sets of data obtained from human subjects and dogs during frequently sampled intravenous glucose tolerance tests (FSIGTs). Analysis of some data sets from both species resulted in poor identification of parameters. To improve the parameter resolution, the information base on which the parameters are estimated was enlarged. This was accomplished by incorporating into the analysis 1) glucose data obtained between 0 and 8 min of the FSIGT and some of the insulin data obtained prior to the insulin peak and 2) a second set of FSIGT data for each individual obtained during a physiological perturbation. As a result, data analysis was considerably enhanced, with parameter fractional standard deviation being routinely reduced to less than 0.5. Analysis of stimulated data with noise levels for glucose and insulin set between 0.05 and 0.15 confirmed the improvement in parameter estimates. This modified approach to analysis of FSIGTs therefore consistently leads to well-defined kinetic descriptions of experimental data in various situations and supports the usefulness of the minimal model in examining the complex interplay between the parameters that influence overall glucose tolerance.

An electrical equivalent circuit model of glucose-insulin kinetics during intravenous glucose tolerance tests in dogs and in man

A new quantitative method was developed for separation of three interactive physiological factors (hepatic glucose balance, peripheral tissue's insulin resistivity and insulin secretion rate) influencing glucose intolerance in diabetic mellitus using an equivalent circuit model and the intravenous glucose tolerance test (IVGTT) in six dogs and 20 humans. The results show that the estimated model parameters of the above three factors are useful for evaluating different glucose-insulin kinetics in normal and diabetic subjects.