If the minimal model is too minimal, who suffers more: SG or SI?
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Blood Glucose↗
Biomedical subjects
A Caumo
Publications and source records attributed to A Caumo.
Effects of a change in the pattern of insulin delivery on carbohydrate tolerance in diabetic and nondiabetic humans in the presence of differing degrees of insulin resistance.
While it is well established that people with non-insulin dependent diabetes mellitus have defects in both insulin secretion and action, the relative contribution of each to glucose intolerance is not known. Therefore, nondiabetic (lean and obese) and non-insulin dependent diabetes mellitus subjects were studied on two occasions. On each occasion, insulin secretion was inhibited with somatostatin and glucose was infused in a pattern and amount that mimicked the systemic delivery rate normally observed after ingestion of 50 g of glucose. Insulin also was infused so as to mimic postprandial insulin profiles observed in separate groups of diabetic and nondiabetic subjects after food ingestion. Glucose turnover was measured using the isotope dilution method. A delayed pattern of insulin delivery (i.e., a "diabetic" insulin profile) led to higher (P < 0.05) glucose concentrations in all groups; however, the effects were transient, resulting in only a modest increase in the integrated glycemic responses. An isolated defect in insulin action had little effect on peak glucose concentration; however, it prolonged the duration of hyperglycemia, leading to a 2.5-4.2-fold increase (P < 0.05) in the integrated glycemic response. A combined defect in the pattern of insulin secretion and action was additive rather than synergistic. Both defects caused hyperglycemia by altering suppression of endogenous glucose release and stimulation of glucose disposal. Whereas obese diabetic and nondiabetic subjects had comparable defects in glucose clearance, non-insulin dependent diabetes mellitus subjects also had defects in hepatic insulin action. Thus, abnormalities in the pattern of insulin secretion and action alone or in combination impair glucose tolerance. An isolated defect in insulin action has a more pronounced and prolonged effect than does an isolated change in the pattern of insulin secretion. Hepatic and extrahepatic insulin resistance results in marked and sustained hyperglycemia.
Blood Glucose↗
Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects.
Despite extensive recent studies, understanding of the normal postprandial processes underlying immediate storage of substrate and maintenance of glucose homeostasis in humans after a mixed meal has been incomplete. The present study applied 13C nuclear magnetic resonance spectroscopy to measure sequential changes in hepatic glycogen concentration, a novel tracer approach to measure postprandial suppression of hepatic glucose output, and acetaminophen to trace the pathways of hepatic glycogen synthesis to elucidate the homeostatic adaptation to the fed state in healthy human subjects. After the liquid mixed meal, liver glycogen concentration rose from 207 +/- 22 to 316 +/- 19 mmol/liter at an average rate of 0.34 mmol/liter per min and peaked at 318 +/- 31 min, falling rapidly thereafter (0.26 mmol/liter per min). The mean increment at peak represented net glycogen synthesis of 28.3 +/- 3.7 g (approximately 19% of meal carbohydrate content). The contribution of the direct pathway to overall glycogen synthesis was 46 +/- 5 and 68 +/- 8% between 2 and 4 and 4 and 6 h, respectively. Hepatic glucose output was completely suppressed within 30 min of the meal. It increased steadily from 60 to 255 min from 0.31 +/- 32 to 0.49 +/- 18 mg/kg per min then rapidly returned towards basal levels (1.90 +/- 0.04 mg/kg per min). This pattern of change mirrored precisely the plasma glucagon/insulin ratio. These data provide for the first time a comprehensive picture of normal carbohydrate metabolism in humans after ingestion of a mixed meal.
Adult↗
Is the minimal model too minimal?
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Blood Glucose↗
The hot but not the cold minimal model allows precise assessment of insulin sensitivity in NIDDM subjects.
Assessment of insulin sensitivity in subjects with non-insulin-dependent diabetes mellitus (NIDDM) is of paramount importance but intrinsically difficult. The standard (hereafter cold) minimal model, in conjunction with an insulin-modified protocol, has been recently proposed, but the estimates of insulin sensitivity showed poor precision (Saad et al. Diabetes 43: 1114-1121, 1994). We propose the tracer (hereafter hot) minimal model as a highly reliable method to estimate insulin sensitivity (SI*) and fractional glucose clearance (SG*), reflecting glucose disposal only, in NIDDM subjects. A [6,6- 2H2] glucose-labeled insulin-modified intravenous glucose tolerance test was performed in seven NIDDM subjects. In particular, SI* was 1.07 +/- 0.34 x10(-4)min(-1).microU-1.ml estimated with an average precision (mean coefficient of variation of 12%, range 4-22%), whereas the cold minimal model SI was 0.96 +/- 0.26 x 10(-4) min-1. microU-1.ml (mean coefficient of variation of 105%, range 3-353%). Another advantage of the hot indexes with respect to the cold indexes is their ability to reflect glucose and insulin effect on glucose disposal only, and not also on hepatic glucose production. Finally, we also studied by simulation the effect of glucose urinary loss on cold and hot minimal model indexes; only cold glucose effectiveness (SG) was significantly affected, resulting in a mean approximately 40% lower. The hot minimal model appears therefore more reliable than the cold model for assessing glucose tolerance in NIDDM subjects. In particular its ability to dissect disposal from production processes, coupled with the very good precision of the estimated metabolic indexes, supports the clinical use of this method in NIDDM subjects.
Blood Glucose↗
Insulin regulation of glucose turnover and lipid levels in obese children with fasting normoinsulinaemia.
To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion. Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels. During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.
3-Hydroxybutyric Acid↗
Cephalic-phase insulin and glucagon release in normal subjects and in patients receiving pancreas transplantation.
The aim of the study was to evaluate whether the cephalic phase of insulin release is still present in patients submitted to simultaneous kidney and pancreas transplantation. Subjects were five kidney-pancreas-transplanted patients (group P) and five control (group C). The experimental protocol lasted 30 minutes, and blood samples were collected at 1-minute intervals. After a 20-minute period of steady-state fasting (premeal period), subjects received a palatable standard meal (pizza). Samples were collected over the subsequent 10 minutes (meal period). No evidence of an increase in serum free insulin, serum C-peptide, and plasma glucagon during food ingestion was observed in group P whereas the test was effective in eliciting cephalic-phase insulin and glucagon release in group C. Gastric inhibitory polypeptide and somatostatin did not show any variation during the test in both groups. In conclusion, the absence of cephalic-phase insulin and glucagon release in group P could be explained by denervation of the grafted pancreas. This early alteration could contribute to the impairment in glucose tolerance frequently observed in successfully pancreas-transplanted patients.
Adult↗
Glucose turnover in presence of changing glucose concentrations: error analysis for glucose disappearance.
The present studies were undertaken to determine whether 1) the cold- and hot-GINF techniques used with Steele's model provide equivalent estimates of the rates of glucose appearance (R(a)) and disappearance (R(d)) in the presence of physiological changes in glucose and insulin concentrations, 2) the conditions for the best estimation of R(a) are the same as those for R(d), 3) the magnitude of error (if present) differs in diabetic and nondiabetic subjects, and 4) situations exist in which the knowledge of R(d) allows inferences to be made on whole body glucose uptake. To do so we performed experiments in non-insulin-dependent diabetes mellitus and nondiabetic subjects using simultaneous infusions of [6-3H]glucose and [6-14C]glucose; glucose and insulin were infused to mimic normal postprandial glucose and insulin profiles; the infused glucose contained [6-14C]glucose but not [6-3H]glucose. Compared with the hot-GINF method, the traditional cold-GINF method underestimated (P < 0.05) R(a) and R(d) by 10-15% and hepatic glucose release by 25-50% during the 1st h of the study, with the magnitude of error being the same in both diabetic and nondiabetic subjects. Error analysis demonstrated that errors in R(a) and R(d) have different analytic expressions containing common structural but different volume errors. Both R(a) and R(d) can be accurately measured in diabetic and nondiabetic subjects if glucose specific activity is kept constant and the volume of the accessible pool is used to calculate glucose disappearance. The relationship between R(d) and whole body glucose uptake was also derived. Although R(d) can be determined by relying on measurements in the accessible pool only, the assessment of whole body glucose uptake requires a model of the nonaccessible portion of the glucose system. However, knowledge of R(d) can provide useful insights into the behavior of whole body glucose uptake.
Adult↗
The continuous low dose insulin and glucose infusion test: a simplified and accurate method for the evaluation of insulin sensitivity and insulin secretion in population studies.
In this study we investigated a simple nonlabor-intensive method to evaluate insulin sensitivity and beta-cell function which is suitable for application in population studies. The method is a refinement of the modified Harano test and consists of a continuous low dose insulin (25 mU/kg.h) and glucose (4 mg/kg.min) infusion test (LDIGIT) lasting 150 min. Insulin sensitivity was evaluated as the MCR of glucose divided by the steady state serum insulin level achieved at the end of the test. Insulin secretion was expressed as the incremental area for C-peptide concentration during the first 15 min of the test. We compared the indices of insulin sensitivity and insulin secretion yielded by LDIGIT with those derived from the euglycemic clamp and the hyperglycemic clamp, respectively. Fifty-four subjects underwent a LDIGIT (33 with normal glucose tolerance and 21 with impaired glucose tolerance); of the 54, 19 were submitted to a euglycemic clamp, 18 to a hyperglycemic clamp, and 10 to a modified Harano test (insulin infusion, 50 mU/kg.h; glucose infusion, 6 mg/kg.min). LDIGIT overcame the drawbacks associated with the modified Harano test because it resulted in more stable final glucose levels and prevented the occurrence of hypoglycemic episodes. No significant differences were found between the insulin sensitivity index (ISI) of the LDIGIT and that of the euglycemic clamp for each group of subjects. Moreover, there was a strong correlation between the ISI determined by LDIGIT and the ISI determined by clamp (r = 0.90; P < 0.0001), and the best regression line was not different from the identity line, suggesting that the two indices are equivalent. The index of insulin secretion provided by LDIGIT correlated well with that of the hyperglycemic clamp (r = 0.82; P < 0.001) and was significantly higher in overweight subjects than in normal weight subjects. In conclusion, LDIGIT is a simple and accurate method to assess insulin sensitivity and secretion. It can be useful in population studies and in situations when more complex techniques are not feasible.
Adult↗
Assessment of growth hormone (GH) plasma clearance rate, half-life, and volume of distribution in acromegalic patients: the combined GH-octreotide infusion.
In acromegaly, high GH levels are primarily attributable to GH hypersecretion, but the contribution of GH clearance is still under debate and is difficult to assess. In the present study, GH plasma clearance rate (PCR), half-life (t1/2), and volume of distribution (VD) were assessed in seven acromegalic patients and seven normal lean subjects, after suppression of endogenous GH release by octreotide, with use of a constant GH infusion. An octreotide sc infusion was started the night before the day of the test (2100 h) and maintained throughout the study. On the day of the test, exogenous GH was constantly infused iv for 6 h (0900-1500 h) in order to achieve a new steady state of GH levels. After the cessation of GH infusion, the decay curve of serum GH levels was monitored for 1 h. In both groups, GH PCR was calculated from the steady state serum GH levels, and GH t1/2 was estimated from the monoexponential analysis of the GH disappearance curve. Estimates of VD were derived from PCR and t1/2. In acromegalic patients, GH PCR was 2.5 +/- 0.2 mL/kg.min-1, and GH t1/2 and VD were 15.7 +/- 1.0 min and 54.9 +/- 5.5 mL/kg, respectively. GH PCR and GH t1/2 of acromegalic patients were higher and lower, respectively, than those of normal subjects (PCR, 1.7 +/- 0.2 mL/kg.min-1, P < 0.02; t1/2, 18.4 +/- 0.6 min, P < 0.05). VD was not significantly different in the two groups. In summary, in acromegalic patients GH kinetic parameters can be reliably assessed by using a constant GH infusion after suppression of endogenous GH release by octreotide. Our results also indicate that the increased circulating GH levels observed in acromegaly are attributable only to GH overproduction and do not depend on an alteration in the processes of GH distribution or disappearance.
Acromegaly↗
Acute pharmacologic blockade of lipolysis normalizes nocturnal growth hormone levels and pulsatility in obese subjects.
Obesity is associated with blunted growth hormone (GH) levels and pulsatility and elevated plasma free fatty acids (FFA) levels. To evaluate whether the two phenomena are correlated, in the present study we investigated the effects of an acute pharmacologic blockade of lipolysis on nocturnal GH levels and pulsatility in 10 obese and 10 control subjects. At 9 PM on two different nights with a 1-night interval in between, all subjects received either a single oral tablet of placebo or acipimox slow release (ACX-SR, 500 mg) in randomized order. Blood samples were drawn from 10 PM to 6 AM for evaluation of FFA, glycerol, GH, immunoreactive insulin (IRI), glucose, and insulin-like growth factor-I (IGF-I) levels. After placebo, FFA and glycerol levels were higher (P < .02) and GH levels, areas, peak amplitude, and peak increment (assessed by the Cluster algorithm) were lower in obese than in control subjects (P < .01). After ACX-SR, FFA and glycerol levels were reduced in both groups (P < .02 v placebo), and in obese subjects they became similar to those observed in control subjects after placebo. ACX-SR had no effect on GH levels and pulsatility in control subjects. GH levels, areas, peak, amplitude, peak increment, and interpeak valley levels were all increased after ACX-SR in obese subjects (P < .05 or less v placebo) and became similar to those observed in normal subjects after placebo, but no correlation was found between the reduction in FFA levels and the increase in GH levels and pulsatility.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
The dual tracer time-varying volume method for measuring hepatic glucose release in nonsteady state: theoretical and simulation results.
Measurement of hepatic glucose release in nonsteady state is difficult and experimental approaches have been developed in order to circumvent Steele's model inadequacy. Recently, a resurgence of interest in the time-varying volume method developed by Issekutz has taken place. Issekutz's approach assumes that the volume of Steele's model is not constant but time-varying and that its time course can be measured by infusing two tracers with different patterns. The time-varying volume is then substituted into Steele's equation and hepatic glucose release is estimated. The aim of this study was to analyze some basic aspects of Issekutz's method and to determine the accuracy of its estimate of hepatic glucose release. A theoretical analysis showed that the time-varying volume measured by Issekutz's approach is not unique but depends on the format of administration of the two tracers. In addition, such a volume allows an accurate estimate of hepatic glucose release if one of the two tracers is infused in such a way that its specific activity is maintained perfectly constant during the experiment. Since it is impossible to achieve a perfect clamp of specific activity, we also evaluated the performance of Issekutz's approach in more realistic experimental conditions which were reproduced by resorting to computer simulation. We simulated a euglycaemic clamp with insulin rising from basal to a plateau of approximately 40 microU/ml and then returning to basal. Nonsteady-state glucose kinetics were described by a previously validated two-compartment model while the time course of hepatic glucose release was derived from the literature. Both noise-free and noisy experimental conditions were simulated. We showed that the degree of accuracy of Issekutz's approach is very good and better than the one associated with the hot-ginf method. On the other hand, the major problem with Issekutz's approach is the sensitivity of the volume estimate to the measurement noise, which may limit its applicability in practice. In conclusion, we elucidated the theoretical grounds of Issekutz's approach and assessed its performance during nonsteady state in a realistic scenario using computer simulation.
Body Fluid Compartments↗
Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans.
Insulin concentrations in humans continuously change and typically increase only when glucose also increases such as with eating. In this setting, it is not known whether the severity of hepatic and extrahepatic insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dependent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were clamped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hyperglycemia). Insulin was infused so as to simulate a "nondiabetic" postprandial profile. During euglycemia, insulin increased glucose disposal in nondiabetic but not diabetic subjects indicating marked extrahepatic resistance. In contrast, insulin-induced suppression of glucose release was only minimally less (P < 0.05) in diabetic than nondiabetic subjects (-1.06 +/- 0.09 vs. -1.47 +/- 0.21 nmol.kg-1 per 4 h). Hyperglycemia substantially enhanced disposal in both groups. Glucose effectiveness measured as the magnitude of enhancement of disposal (0.59 +/- 0.18 vs. 0.62 +/- 0.17 nmollkg-1 per 4 h) and suppression of release (-0.36 +/- 0.12 vs. -0.14 +/- 0.12 nmol.kg-1 per 4 h) did not differ in the diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM demonstrate: (a) profound extrahepatic insulin resistance, (b) modest hepatic insulin resistance, and (c) normal ability of glucose to stimulate its own uptake and suppress its own release.
Blood Glucose↗
Assessment of insulin action in NIDDM in the presence of dynamic changes in insulin and glucose concentration.
Both glucose and insulin are important regulators of glucose uptake and hepatic glucose release. Because insulin concentrations rarely if ever increase under daily living conditions, unless glucose concentrations also increase, we sought to determine whether hepatic and extrahepatic responses to changes in insulin and glucose concentration are impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). To address this question, glucose metabolism was measured in diabetic and nondiabetic subjects. A computer-driven infusion system was used to produce a nondiabetic postprandial insulin profile in both groups while sufficient exogenous glucose was infused to mimic nondiabetic postprandial glucose concentrations. Although NIDDM was associated with greater (P < 0.05) hepatic glucose release both before and during the prandial insulin infusion, suppression did not differ in the diabetic and nondiabetic subjects (-1.06 +/- 0.20 vs. -0.86 +/- 0.15 mmol/kg every 4 h). In contrast, stimulation of both glucose disappearance (0.77 +/- 0.27 vs. 1.68 +/- 0.27 mmol/kg every 4 h) and forearm glucose uptake (187 +/- 81 vs. 550 +/- 149 mumol/dl every 4 h) was lower (P < 0.05) in diabetic than in nondiabetic subjects. Thus, despite increased basal rates of glucose production, obese individuals with NIDDM had decreased stimulation of glucose disappearance but normal suppression of hepatic glucose release in response to nondiabetic prandial glucose and insulin concentrations. These data indicate that the increase in glucose that occurs with carbohydrate ingestion is likely to compensate for hepatic but not extrahepatic insulin resistance.
Blood Glucose↗
Hyperinsulinemia decreases second-phase but not first-phase arginine-induced insulin release in humans.
The aim of this study was to investigate the effect of hyperinsulinemia on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 min): a control study using saline infusion and two euglycemic clamps using a low-dose (0.33 mU.kg-1.min-1) and a high-dose (1.20 mU.kg-1.min-1) insulin infusion. After a 3-h equilibration period, arginine (25 g) was infused for 30 min, and insulin and C-peptide responses to arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels were (means +/- SE) 60.0 +/- 2.4, 165.6 +/- 1.8, and 455.4 +/- 7.8 pmol/l during saline, low-dose, and high-dose insulin infusions, respectively. The time course of insulin release during the arginine test was calculated from C-peptide concentrations by using C-peptide kinetic modeling and deconvolution. In particular, first-phase and second-phase insulin response was obtained by integrating the time course of the insulin release during either the first 5 min or the following 40 min of the arginine test, respectively. Whereas first-phase insulin release was independent of any effect induced by either insulin infusion, second-phase insulin release was reduced in a similar degree by both insulin infusion doses. First phase was 75.5 +/- 10.1, 73.7 +/- 12.8, and 73.4 +/- 10.3 pmol/kg, whereas second phase was 266.1 +/- 46.0, 143.1 +/- 33.5, and 133.0 +/- 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Methods for assessment of the rate of onset and offset of insulin action during nonsteady state in humans.
Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52:215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU.kg-1 x min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187:15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within approximately 40 min (P < 0.01 vs. other methods). The hot-GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot-GINF and variable-pV methods avoid non-steady-state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.
Adult↗
Hepatic and extrahepatic insulin action in humans: measurement in the absence of non-steady-state error.
The isotope dilution technique has been extensively used to assess insulin action in humans. To determine if nonsteady state (NSS) has led to erroneous estimates of hepatic and extrahepatic insulin sensitivity, we measured glucose turnover in healthy subjects during infusion of insulin at rates of 0.25, 0.6, and 2.0 mU.kg-1.min-1. Turnover was calculated using Steele's traditional NSS equations [fixed-effective volume (pV) method] as well as with methods [radioactive infused glucose (hot-GINF) or variable pV] designed to minimize NSS error. In contrast to the fixed-pV method, both the hot-GINF and variable-pV methods indicated that several hours were required for suppression of hepatic glucose release at all insulin concentrations and that small increases in plasma insulin (approximately 100 pmol/l) had comparable effects on glucose disappearance and hepatic glucose release. Nevertheless, despite these differences, when turnover during the final hour of the insulin infusions was plotted vs. the prevailing insulin concentration, all three methods yielded similar insulin dose-response curves for suppression of hepatic glucose release. Thus despite previous errors in measurement of glucose turnover, the widely accepted belief that the human liver is exquisitely sensitive to small changes in insulin is correct.
Adult↗
Hepatic glucose production during the labeled IVGTT: estimation by deconvolution with a new minimal model.
A method for the estimation of hepatic glucose production during a labeled intravenous glucose tolerance test (IVGTT) is proposed. Stable-label IVGTT data in normal subjects have been considered. The method is based on deconvolution and uses a new two-compartment minimal model of glucose kinetics to describe the time-varying impulse response of the glucose system. A new model of glucose kinetics was needed because the available single-compartment minimal model, specifically developed to interpret labeled IVGTT data, provided a nonphysiological pattern of hepatic glucose production. The new minimal model has two novel features: glucose kinetics are described by a two-compartment structure, and insulin exerts its action on the irreversible loss of the slowly exchanging glucose pool. The deconvolution scheme used to reconstruct hepatic glucose production is described in detail both in terms of computational aspects and reliability. Confidence limits of the reconstructed hepatic glucose production in each individual are derived by taking into account both the measurement error of the data and the uncertainty associated with the description of the impulse response. Physiological plausibility of the time course of hepatic glucose production provided by this new method is discussed. The ability of the new model to reconstruct hepatic glucose production considerably enriches the kinetic portrait of glucose metabolism that can be obtained from the minimal-model analysis of labeled IVGTT data.
Blood Glucose↗