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Andrea Caumo

Publications and source records attributed to Andrea Caumo.

At least 19 recordsLinked to original sources
PubMed2006

A new dynamic index of insulin sensitivity.

Insulin sensitivity is a crucial parameter of glucose metabolism. The standard measures of insulin sensitivity obtained by an euglycaemic hyperinsulinaemic clamp, Si(clamp), or by the minimal model (MM), SI, do not account for the dynamics of insulin action, i.e., how fast or slow insulin action reaches its plateau value. This is an important physiological information. In this paper we formally define a new insulin sensitivity index which also incorporates information on the dynamics of insulin action, SD(I), show its properties, and exemplify how it can be measured both with the clamp and the MM method. Then, by resorting to real and synthetic data, we show both in IVGTT MM and clamp studies why this new index SD(I) offers, in comparison with SI, a more comprehensive picture of the control of insulin on glucose.

Blood Glucose↗
PubMed2006

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis.

OBJECTIVE: Liver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome. Therefore, we investigated the dynamic changes in circulating total, free, and bioactive IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binary complex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis. METHODS: Seven Caucasian males with liver cirrhosis and seven healthy males matched for age (54.4+/-3.2 vs 54.6+/-4.4 years) and body mass index (25.3+/-1.2 vs 25.9+/-1.3 kg/m2) were studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binary complex, while bioactive IGF-I was measured at 0, 30, 60, 120, and 180 min. RESULTS: In comparison with healthy subjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower, while IGFBP-1 (268%) was higher (P<0.05), IGFBP-2 (172%) tended to be higher (P>0.05), and the binary complex unchanged (approximately 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchanged in both study groups during the OGTT. Bioactive IGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT (P<0.05). A similar tendency was observed in healthy controls (P=0.052). Concomitantly, IGFBP-1, binary complex, and IGFBP-1 saturation index decreased significantly in both groups. The disappearance of the binary complex was about twofold faster than that of IGFBP-1 (P < 0.05). CONCLUSION: Despite unchanged concentrations of total and free IGF-I, bioactive IGF-I declined significantly after an oral glucose load in patients with liver cirrhosis and the same tendency was observed in healthy subjects. We speculate that the reduction in bioactive IGF-I may be related to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I.

Blood Glucose↗
PubMed2005

Insulin sensitivity by oral glucose minimal models: validation against clamp.

Measuring insulin sensitivity in the presence of physiological changes in glucose and insulin concentrations, e.g., during a meal or OGTT, is important to better understand insulin resistance in a variety of metabolic conditions. Recently, two oral minimal models have been proposed to measure overall insulin sensitivity (S(I)) and its selective effect on glucose disposal (S(I)*) from oral tests. S(I) and S(I)* have been successfully validated against multiple tracer meal estimates, but validation against euglycemic hyperinsulinemic clamp estimates is lacking. Here, we do so in 21 subjects who underwent both a multiple-tracer OGTT and a labeled euglycemic hyperinsulinemic clamp. Correlation between minimal-model S(I), S(I) and corresponding clamp estimates S(I)(*clamp), S(I)(*clamp) was satisfactory, respectively r = 0.81, P < 0.001, and r = 0.71, P < 0.001. S(I) was significantly lower than S(I)(clamp) (8.08 +/- 0.89 vs. 13.66 +/- 1.69 10(-4) dl.kg(-1).min(-1) per microU/ml, P = 0.0002), whereas S(I) and S(I)(*clamp) were very similar (8.17 +/- 1.59 vs. 8.84 +/- 1.39 10(-4) dl.kg(-1).min(-1) per microU/ml, P = 0.52). These results add credibility to the oral minimal-model method as a simple and reliable physiological tool to estimate S(I) and S(I)*, also in large-scale clinical trials.

Adult↗
PubMed2005

Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model.

The oral glucose minimal model (OMM) measures insulin sensitivity (S(I)) and the glucose rate of appearance (R(a)) of ingested glucose in the presence of physiological changes of insulin and glucose concentrations. However, S(I) of OMM measures the overall effect of insulin on glucose utilization and glucose production. In this study we show that, by adding a tracer to the oral dose, e.g., of a meal, and by using the labeled version of OMM, OMM* to interpret the data, one can measure the selective effect of insulin on glucose disposal, S(I)*. Eighty-eight individuals underwent both a triple-tracer meal with the tracer-to-tracee clamp technique, providing a model-independent reference of the R(a) of ingested glucose (R(a meal)(ref)) and an insulin-modified labeled intravenous glucose tolerance test (IVGTT*). We show that OMM* provides not only a reliable means of tracing the R(a) of ingested glucose (R(a meal)) but also accurately measures S(I)*. We do so by comparing OMM* R(a meal) with the model-independent R(a meal)(ref) provided by the tracer-to-tracee clamp technique, while OMM* S(I)* is compared with both S(I)(* ref), obtained by using as known input R(a meal)(ref), and with S(I)* measured during IVGTT*.

Adult↗
PubMed2005

Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis: assessment during physiological glucose and insulin concentrations.

It is well established that subjects with liver cirrhosis are insulin resistant, but the contribution of defects in insulin secretion and/or action to glucose intolerance remains unresolved. Healthy individuals and subjects with liver cirrhosis were studied on two occasions: 1) an oral glucose tolerance test was performed, and 2) insulin secretion was inhibited and glucose was infused in a pattern and amount mimicking the systemic delivery rate of glucose after a carbohydrate meal. Insulin was concurrently infused to mimic a healthy postprandial insulin profile. Postabsorptive glucose concentrations were equal (5.36 +/- 0.12 vs. 5.40 +/- 0.25 mmol/l, P = 0.89), despite higher insulin (P < 0.01), C-peptide (P < 0.01), and free fatty acid (P = 0.05) concentrations in cirrhotic than in control subjects. Endogenous glucose release (EGR; 11.50 +/- 0.50 vs. 11.73 +/- 1.00 mumol.kg(-1).min(-1), P = 0.84) and the contribution of gluconeogenesis to EGR (6.60 +/- 0.47 vs. 6.28 +/- 0.64 mumol.kg(-1).min(-1), P = 0.70) were unaltered by cirrhosis. A minimal model recently developed for the oral glucose tolerance test demonstrated an impaired insulin sensitivity index (P < 0.05), whereas the beta-cell response to glucose was unaltered (P = 0.72). During prandial glucose and insulin infusions, the integrated glycemic response was greater in cirrhotic than in control subjects (P < 0.05). EGR decreased promptly and comparably in both groups, but glucose disappearance was insufficient at the prevailing glucose concentration (P < 0.05). Moreover, identical rates of [3-(3)H]glucose infusion produced higher tracer concentrations in cirrhotic than in control subjects (P < 0.05), implying a defect in glucose uptake. In conclusion, carbohydrate intolerance in liver cirrhosis is determined by insulin resistance and the ability of glucose to stimulate insulin secretion. During prandial glucose and insulin concentrations, EGR suppression was unaltered, but glucose uptake was impaired, which demonstrates that intolerance can be ascribed to a defect in glucose uptake, rather than abnormalities in glucose production or beta-cell function. Although insulin secretion ameliorates glucose intolerance, impaired glucose uptake during physiological glucose and insulin concentrations produces marked and sustained hyperglycemia, despite concurrent abnormalities in glucose production or insulin secretion.

Carbohydrate Metabolism↗
PubMed2005

Effect of repaglinide and gliclazide on postprandial control of endogenous glucose production.

The effect of repaglinide and gliclazide on postmeal suppression of endogenous glucose production (EGP) has been studied using a variable-rate tracer methodology. Groups of age-, sex-, and weight-matched type 2 diabetic subjects randomized to gliclazide or repaglinide were studied after ingesting a standard mixed meal (550 kcal; 67% carbohydrate, 19% fat, 14% protein). Plasma glucose profiles were similar in each group and markedly different from that of a nondiabetic control group. Endogenous glucose production was similar basally (3.01 +/- 0.30 vs 3.06 +/- 0.19 mg/kg per minute, gliclazide and repaglinide, respectively). After glucose ingestion, EGP declined rapidly in both the groups until 30 minutes and the greatest suppression was reached earlier in the repaglinide group [0.88 mg/kg per minute at 120 minutes vs 0.77 mg/kg per minute at 210 minutes in gliclazide group (P < .05); median time, 85 vs 195 minutes, respectively (P < .05)]. The area under the curve (30-150) for EGP was significantly greater in the gliclazide group than in the nondiabetic control group (109 +/- 11 vs 198 +/- 22 mg/kg per min 2 ; P > .02) but not significantly different in the repaglinide group (153 +/- 25 mg/kg per min 2 ; P = .17). Repaglinide has minimal physiological advantage over gliclazide, but both therapies for type 2 diabetes fall far short of correcting the endocrine and metabolic abnormalities.

Adult↗
PubMed2004

Minimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method.

Measuring insulin sensitivity during the physiological milieu of oral glucose perturbation, e.g., a meal or an oral glucose tolerance test, would be extremely valuable but difficult since the rate of appearance of absorbed glucose is unknown. The reference method is a tracer two-step one: first, the rate of appearance of glucose (R(a meal)(ref)) is reconstructed by employing the tracer-to-tracee ratio clamp technique with two tracers and a model of non-steady-state glucose kinetics; next, this R(a meal)(ref) is used as the known input of a model describing insulin action on glucose kinetics to estimate insulin sensitivity (SI(ref)). Recently, a nontracer method based on the oral minimal model (OMM) has been proposed to estimate simultaneously the above quantities, denoted R(a meal) and SI, respectively, from plasma glucose and insulin concentrations measured after an oral glucose perturbation. This last method has obvious advantages over the tracer method, but its domain of validity has never been assessed against a reference method. It is thus important to establish whether or not the "nontracer" R(a meal) and SI compare well with the "tracer" R(a meal)(ref) and SI(ref). We do this comparison on a database of 88 subjects, and it is very satisfactory: R(a meal) profiles agree well with the R(a meal)(ref) and correlation of SI(ref) with SI is r = 0.86 (P < 0.0001). We conclude that OMM candidates as a reliable tool to measure both the rate of glucose absorption and insulin sensitivity from oral glucose tests without employing tracers.

Absorption↗
PubMed2004

First-phase insulin secretion: does it exist in real life? Considerations on shape and function.

To fulfill its preeminent function of regulating glucose metabolism, insulin secretion must not only be quantitatively appropriate but also have qualitative, dynamic properties that optimize insulin action on target tissues. This review focuses on the importance of the first-phase insulin secretion to glucose metabolism and attempts to illustrate the relationships between the first-phase insulin response to an intravenous glucose challenge and the early insulin response following glucose ingestion. A clear-cut first phase occurs only when the beta-cell is exposed to a rapidly changing glucose stimulus, like the one induced by a brisk intravenous glucose administration. In contrast, peripheral insulin concentration following glucose ingestion does not bear any clear sign of biphasic shape. Coupling data from the literature with the results of a beta-cell model simulation, a close relationship between the first-phase insulin response to intravenous glucose and the early insulin response to glucose ingestion emerges. It appears that the same ability of the beta-cell to produce a pronounced first phase in response to an intravenous glucose challenge can generate a rapidly increasing early phase in response to the blood glucose profile following glucose ingestion. This early insulin response to glucose is enhanced by the concomitant action of incretins and neural responses to nutrient ingestion. Thus, under physiological circumstances, the key feature of the early insulin response seems to be the ability to generate a rapidly increasing insulin profile. This notion is corroborated by recent experimental evidence that the early insulin response, when assessed at the portal level with a frequent sampling, displays a pulsatile nature. Thus, even though the classical first phase does not exist under physiological conditions, the oscillatory behavior identified at the portal level does serve the purpose of rapidly exposing the liver to elevated insulin levels that, also in virtue of their up-and-down pattern, are particularly effective in restraining hepatic glucose production.

Animals↗
PubMed2004

Approximate entropy of respiratory patterns in panic disorder.

OBJECTIVE: Considerable evidence suggests a connection between panic disorder and respiration, but the nature of the respiratory abnormalities in panic disorder remains unclear. The authors investigated the breath-by-breath complexity of respiration dynamics in panic disorder. METHOD: Respiratory physiology was assessed in 40 patients with panic disorder and 31 healthy comparison subjects by using a breath-by-breath stationary system for testing cardiorespiratory function. Irregularity in the breathing pattern was determined by applying the approximate entropy index, which is an indicator of the irregularity and the "disorder" of the measure. RESULTS: The patients with panic disorder showed significantly higher approximate entropy indexes than the healthy subjects for the measured respiratory parameters. Sighs contributed to the irregularity of breathing patterns but did not account for all the differences in approximate entropy between the patients with panic disorder and the comparison subjects. Anxiety state, severity of illness, and somatic and individual variables such as participation in sports and cigarette smoking did not seem to influence the results. CONCLUSIONS: Patients with panic disorder showed greater entropy in baseline respiratory patterns, indicating higher levels of irregularity and complexity in their respiratory function. Greater respiratory entropy could be a factor in vulnerability to panic attacks.

Adult↗
PubMed2003

Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting.

BACKGROUND: Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting. METHODS AND RESULTS: Both patients with CHD undergoing coronary stenting (120 patients) and control subjects (58 patients) were submitted to an oral glucose tolerance test (OGTT). Fasting leptin levels and fasting and postglucose load insulin sensitivity were assessed. Endothelial function was measured by nitrite and nitrate release (NOx) during OGTT. More than 50% of patients treated with stent implantation presented impaired glucose tolerance or type 2 diabetes, which was previously undiagnosed. These patients also had higher glucose, insulin, and leptin levels than control subjects. Among the stented patients, insulin and leptin levels were higher in patients with restenosis than in patients without restenosis. A significant increase in NOx levels was found during OGTT both in patients without restenosis and in control subjects. On the contrary, NOx profiles were blunted in patients with restenosis. At multiple regression analysis, only DeltaAUC-NOx areas and insulin sensitivity index showed an independent correlation with the minimal lumen diameter at follow-up. CONCLUSIONS: We demonstrated that insulin resistance and endothelial dysfunction are independent predictors of early restenosis after coronary stenting.

Area Under Curve↗
PubMed2003

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects.

Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P < 0.05), hypercortisolemia resulted in higher glucose (P < 0.05) and free fatty acid concentrations (P < 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P < 0.01), indicating the presence of steroid-induced insulin resistance. Postabsorptive glucose production (P = 0.64) and the fractional contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P < 0.05), implying a decrease in net glucose effectiveness (4.42 +/- 0.52 vs. 6.65 +/- 0.83 ml.kg-1.min-1; P < 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P < 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P < 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3H]glucose during hydrocortisone than during saline infusion (P < 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess impairs glucose tolerance by decreasing both insulin action and glucose effectiveness.

Adult↗
PubMed2003

Assessment of insulin sensitivity based on a fasting blood sample in men with liver cirrhosis before and after liver transplantation.

BACKGROUND: Insulin resistance is a key factor in the pathogenesis of hepatogenous diabetes and influences the prognosis of chronic liver diseases. In vivo assessment of insulin resistance in humans is expensive; therefore, surrogate indices based on a fasting plasma glucose and insulin concentrations (HOMA-IS, QUICKI) were proposed. This study aimed to test whether these simple indices are reliable measures of insulin sensitivity in patients with liver cirrhosis before and after liver transplantation (LTx). METHODS: HOMA-IS and QUICKI were compared with insulin sensitivity as assessed with the gold standard technique (insulin clamp) in 20 patients with liver cirrhosis, in 36 patients after LTx, and in 25 matched healthy subjects (predominantly men). To test whether these indices may be applied also in prospective studies, 10 patients with liver cirrhosis were studied longitudinally before and 2 years after LTx. RESULTS: Both HOMA-IS and QUICKI were associated with insulin sensitivity in patients with liver cirrhosis (r=0.63, P=0.005 and r=0.60, P=0.009) and in LTx patients (r=0.41, P=0.02 and r=0.46, P=0.05). Both were able to detect the improvement of insulin sensitivity after LTx in the patients studied prospectively. CONCLUSIONS: HOMA-IS and QUICKI are simple reliable tools to assess insulin sensitivity in clinical and epidemiologic investigations of chronic liver disease before and after LTx.

Adult↗
PubMed2003

Nonhepatic glucose production in humans.

Extrahepatic glucose release was evaluated during the anhepatic phase of liver transplantation in 14 recipients for localized hepatocarcinoma with mild or absent cirrhosis, who received a bolus of [6,6-2H2]glucose and l-[3-13C]alanine or l-[1,2-13C2]glutamine to measure glucose kinetics and to prove whether gluconeogenesis occurred from alanine and glutamine. Twelve were studied again 7 mo thereafter along with seven healthy subjects. At the beginning of the anhepatic phase, plasma glucose was increased and then declined by 15%/h. The right kidney released glucose, with an arteriovenous gradient of -3.7 mg/dl. Arterial and portal glucose concentrations were similar. The glucose clearance was 25% reduced, but glucose uptake was similar to that of the control groups. Glucose production was 9.5 +/- 0.9 micromol.kg-1. min-1, 30% less than in controls. Glucose became enriched with 13C from alanine and especially glutamine, proving the extrahepatic gluconeogenesis. The gluconeogenic precursors alanine, glutamine, lactate, pyruvate, and glycerol, insulin, and the counterregulatory hormones epinephrine, cortisol, growth hormone, and glucagon were increased severalfold. Extrahepatic organs synthesize glucose at a rate similar to that of postabsorptive healthy subjects when hepatic production is absent, and gluconeogenic precursors and counterregulatory hormones are markedly increased. The kidney is the main, but possibly not the unique, source of extrahepatic glucose production.

Adult↗
PubMed2003

Bayesian two-compartment and classic single-compartment minimal models: comparison on insulin modified IVGTT and effect of experiment reduction.

Models describing plasma glucose and insulin concentration of an intravenous glucose tolerance test (IVGTT) allow a noninvasive cost-effective approach to estimate important indexes characterizing the efficiency of glucose-insulin control system, i.e., glucose effectiveness (S(G)) and insulin sensitivity (S(I)). To overcome some limitations of the classic single compartment minimal model (1CMM) of glucose kinetics , a two-compartment Bayesian minimal model (2CBMM) has been recently proposed for the standard IVGTT. This study aims to assess 2CBMM ability to describe the insulin-modified IVGTT (IM-IVGTT) which is the protocol of choice since it allows to study insulinopenic states. Both a full-length IM-IVGTT (240 min) as well as a reduced version (90 min) of it are studied. Results of the maximum a posteriori identification of IM-IVGTT (240 min) in 13 normals agree with those of standard IVGTT, i.e., a 42% decrease (P < 0.002) of S(G) and a 13% increase (P < 0.006) of S(I) with respect to ICMM. When identified from IM-IVGTT (90 min), 2CBMM not only provides S(G) and S(I) estimates 46% lower (P < 0.002) and 41% higher (P < 0.002) than 1CMM ones respectively, but also seems to overcome some limitations of the 240 min-based identification that probably arise because the minimal model is unable to properly account for the hyperglycemic hormonal response taking place in the second half of IM-IVGTT.

Bayes Theorem↗
PubMed2003

Contribution of abnormal insulin secretion and insulin resistance to the pathogenesis of type 2 diabetes in myotonic dystrophy.

OBJECTIVE: Myotonic dystrophy (MyD), the most common adult form of muscular dystrophy, is often complicated by diabetes. MyD is dominantly inherited and is due to heterozygosity for a trinucleotide repeat expansion mutation in a protein kinase gene able to induce derangement of RNA metabolism responsible of an aberrant insulin receptor expression. RESEARCH DESIGN AND METHODS: To assess insulin sensitivity and secretion before the onset of diabetes, we studied 10 MyD patients, 10 offspring of type 2 diabetes (OFF), and 10 healthy subjects with no family history of diabetes (control subjects) with dual X-ray energy absorption, euglycemic-hyperinsulinemic clamp (40 mU/[m(2). min]) combined with infusion of [6,6-D(2)]-glucose and oral glucose tolerance test (OGTT). RESULTS: MyD had reduced lean body mass, but peripheral insulin sensitivity was not different to that of control subjects in contrast to OFF, which showed insulin resistance. Insulin secretion, obtained by deconvolution of OGTT data, was also shown to be comparable with that of OFF and control subjects (index of beta-cell function = Phi; P = 0.91) even if increased parameters of insulin secretion were found during the first 30 min (Phi(30); P = 0.05) of the oral glucose challenge. Fasting plasma proinsulin concentrations (P = 0.01) and the ratio to insulin (P = 0.01) were increased in MyD patients. The proinsulin levels also failed to be suppressed during the clamp and showed exaggerated response after the OGTT. Increased proinsulin levels were shown to be peculiar of MyD patients when compared with OFF. CONCLUSIONS: In nondiabetic, young MyD patients, insulin sensitivity was preserved, and an increased early secretory response to oral glucose was detected. Abnormal plasma proinsulin levels in the fasting state, during the clamp, and during the OGTT were shown to be secretory dysfunctions peculiar of MyD patients and may be more important than insulin resistance in determining the high risk to develop diabetes in these patients.

Adult↗
PubMed2002

The oral glucose minimal model: estimation of insulin sensitivity from a meal test.

Recently, a new approach has been proposed to estimate insulin sensitivity (S(I)) from an oral glucose tolerance test or a meal using an "integral equation". Here, we improve on the "integral equation" by resorting to a "differential equation" approach. The classic glucose kinetics minimal model was used with the addition of a parametric model for the rate of appearance into plasma of oral glucose (Ra). Three behavioral models of Ra were proposed: piecewise-linear (P), spline (S) and dynamic (D). All three models performed satisfactorily allowing a precise estimation of S(I) and a plausible reconstruction of Ra. Mean S(I) estimates were virtually identical: S(I)P = 6.81 +/- 0.87 (SE); S(I)S = 6.53 +/- 0.80; and S(I)D = 6.62 +/- 0.79. S(I) strongly correlated with the integral-equation index (I) S(I)I: r = 0.99, p < 0.01 for models D and S, and r 0.97, p < 0.01 for P. Also, SI compared well with insulin sensitivity estimated from intravenous glucose tolerance test in the same subjects (r = 0.75, p < 0.01; r = 0.71, p < 0.01; r = 0.73, p < 0.01, respectively, for P, S, and D models versus s(I)IVGTT). Finally, the novel approach allows estimation of SI from a shorter test (120 min): model P yielded S(I)R = 7.16 +/- 1.0 (R for reduced) which correlated very well with S(I)P and S(I)I (respectively, r = 0.94, p < 0.01; r = 0.95, p < 0.01) and still satisfactorily with S(I)IVGTT (r = 0.77, p < 0.01).

Blood Glucose↗
PubMed2002

Regulation of endogenous glucose production after a mixed meal in type 2 diabetes.

The extent and time course of suppression of endogenous glucose production (EGP) in type 2 diabetes after a mixed meal have been determined using a new tracer methodology. Groups of age-, sex-, and weight-matched normal controls (n = 8) and diet-controlled type 2 diabetic subjects (n = 8) were studied after ingesting a standard mixed meal (550 kcal; 67% carbohydrate, 19% fat, 14% protein). There was an early insulin increment in both groups such that, by 20 min, plasma insulin levels were 266 +/- 54 and 190 +/- 53 pmol/l, respectively. EGP was similar basally [2.55 +/- 0.12 mg x kg(-1) x min(-1) in control subjects vs. 2.92 +/- 0.16 mg x kg(-1) x min(-1) in the patients (P = 0.09)]. After glucose ingestion, EGP declined rapidly in both groups to approximately 50% of basal within 30 min of the meal. Despite the initial rapid decrease, the EGP was significantly greater in the diabetic group at 60 min (1.75 +/- 0.12 vs. 1.05 +/- 0.14 mg x kg(-1) x min(-1); P < 0.01) and did not reach nadir until 210 min (0.96 +/- 0.17 mg x kg(-1) x min(-1)). Between 60 and 240 min, EGP was 47% higher in the diabetic group (0.89 +/- 0.09 vs. 1.31 +/- 0.13 mg x kg(-1) x min(-1), P < 0.02). These data quantitate the initial rapid suppression of EGP after a mixed meal in type 2 diabetes and the contribution of continuing excess glucose production to subsequent hyperglycemia.

Blood Glucose↗