Insulin clearance is altered in women with a history of gestational diabetes progressing to type 2 diabetes

Tura, Andrea; Göbl, Christian; Morettini, Micaela; Burattini, Laura; Kautzky‐Willer, Alexandra; Pacini, Giovanni

doi:10.1016/j.numecd.2020.04.004

Cited by 8 publications

(8 citation statements)

References 38 publications

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“…Insulin resistance was estimated at fasting by the homeostasis model assessment index, HOMA-IR (10), and insulin sensitivity from the OGTT by PREDIM (11), a surrogate of the clamp M-value. Insulin clearance, CL ins , was obtained as ratio between the area-underthe-curve of total insulin secretion and that of plasma insulin (12).…”

Section: Parameters Of Glucose Metabolismmentioning

confidence: 99%

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study

et al. 2021

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Section: Parameters Of Glucose Metabolismmentioning

confidence: 99%

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study

et al. 2021

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“…In the study of glucose metabolism, established methodologies exist for the assessment of metabolic aspects of major relevance, such as insulin sensitivity, insulin secretion and possible incretin-based enhancement, and insulin clearance, as assessed for instance in some of our previous OGTT-based studies ( 45 – 47 ). The model of glucagon kinetics presented in this study will have the potential to complement the information derived from an OGTT, provided from the indicated established methodologies.…”

Section: Discussionmentioning

confidence: 99%

Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test

et al. 2021

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Glucagon is secreted from the pancreatic alpha cells and plays an important role in the maintenance of glucose homeostasis, by interacting with insulin. The plasma glucose levels determine whether glucagon secretion or insulin secretion is activated or inhibited. Despite its relevance, some aspects of glucagon secretion and kinetics remain unclear. To gain insight into this, we aimed to develop a mathematical model of the glucagon kinetics during an oral glucose tolerance test, which is sufficiently simple to be used in the clinical practice. The proposed model included two first-order differential equations -one describing glucagon and the other describing C-peptide in a compartment remote from plasma - and yielded a parameter of possible clinical relevance (i.e., SGLUCA(t), glucagon-inhibition sensitivity to glucose-induced insulin secretion). Model was validated on mean glucagon data derived from the scientific literature, yielding values for SGLUCA(t) ranging from -15.03 to 2.75 (ng of glucagon·nmol of C-peptide-1). A further validation on a total of 100 virtual subjects provided reliable results (mean residuals between -1.5 and 1.5 ng·L-1) and a negative significant linear correlation (r = -0.74, p < 0.0001, 95% CI: -0.82 – -0.64) between SGLUCA(t) and the ratio between the areas under the curve of suprabasal remote C-peptide and glucagon. Model reliability was also proven by the ability to capture different patterns in glucagon kinetics. In conclusion, the proposed model reliably reproduces glucagon kinetics and is characterized by sufficient simplicity to be possibly used in the clinical practice, for the estimation in the single individual of some glucagon-related parameters.

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“…Thus, data derived by tests with slower dynamics, such as oral glucose tolerance tests, may not be adequate to be analyzed with the modeling approach proposed in this study for separate assessment of the hepatic and extrahepatic insulin clearance components, as the model parameters may be estimated with insufficient accuracy. In addition, it should be observed that, in humans (women with a history of gestational diabetes), insulin clearance derived by an insulin-modified intravenous glucose tolerance test was found to be more relevant than that derived by an oral glucose tolerance test for the assessment of type 2 diabetes risk [35]. On the other hand, it has to be noted that, in [35], only total clearance was analyzed, without dissection into its hepatic and extrahepatic components.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it should be observed that, in humans (women with a history of gestational diabetes), insulin clearance derived by an insulin-modified intravenous glucose tolerance test was found to be more relevant than that derived by an oral glucose tolerance test for the assessment of type 2 diabetes risk [35]. On the other hand, it has to be noted that, in [35], only total clearance was analyzed, without dissection into its hepatic and extrahepatic components.…”

Section: Discussionmentioning

confidence: 99%

Hepatic and Extrahepatic Insulin Clearance in Mice with Double Deletion of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Receptors

et al. 2021

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The aim of this study was to investigate whether incretins, at physiological levels, affect hepatic and/or extrahepatic insulin clearance. Hepatic and extrahepatic insulin clearance was studied in 31 double incretin receptor knockout (DIRKO) and 45 wild-type (WT) mice, which underwent an Intravenous Glucose Tolerance Test (IVGTT). A novel methodology based on mathematical modeling was designed to provide two sets of values (FEL-P1, CLP-P1; FEL-P2, CLP-P2) accounting for hepatic and extrahepatic clearance in the IVGTT first and second phases, respectively, plus the respective total clearances, CLT-P1 and CLT-P2. A statistically significant difference between DIRKO and WT was found in CLT-P1 (0.61 [0.48–0.82] vs. 0.51 [0.46–0.65] (median [interquartile range]); p = 0.02), which was reflected in the peripheral component, CLP-P1 (0.18 [0.13–0.27] vs. 0.15 [0.11–0.22]; p = 0.04), but not in the hepatic component, FEL-P1 (29.7 [26.7–34.9] vs. 28.9 [25.7–32.0]; p = 0.18). No difference was detected between DIRKO and WT in CLT-P2 (1.38 [1.13–1.75] vs. 1.69 [1.48–1.87]; p = 0.10), neither in CLP-P2 (0.72 [0.64–0.81] vs. 0.79 [0.69–0.87]; p = 0.27) nor in FEL-P2 (37.8 [35.1–43.1] vs. 39.8 [35.8–44.2]; p = 0.46). In conclusion, our findings suggest that the higher insulin clearance observed in DIRKO compared with WT during the IVGTT first phase may be due to its extrahepatic component.

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Insulin clearance is altered in women with a history of gestational diabetes progressing to type 2 diabetes

Cited by 8 publications

References 38 publications

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study

Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: An IMI DIRECT Study

Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test

Hepatic and Extrahepatic Insulin Clearance in Mice with Double Deletion of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Receptors

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