Former gestational diabetes: Mathematical modeling of intravenous glucose tolerance test for the assessment of insulin clearance and its determinants

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

doi:10.3934/mbe.2020084

Mathematical Biosciences and Engineering

2020, Volume 17, Issue 2: 1604-1615. doi: 10.3934/mbe.2020084

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Former gestational diabetes: Mathematical modeling of intravenous glucose tolerance test for the assessment of insulin clearance and its determinants

1.
Department of Information Engineering, Università Politecnica delle Marche, Ancona 60131, Italy
2.
Division of Obstetrics and Feto-maternal Medicine, Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna A-1090, Austria
3.
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria
4.
Metabolic Unit, Institute of Neuroscience, National Research Council, Padova 35127, Italy

Received: 31 May 2019 Accepted: 14 November 2019 Published: 10 December 2019

Women with a previous history of gestational diabetes mellitus (GDM) have increased risk of developing GDM in future pregnancies (i.e. recurrent GDM) and also Type 2 Diabetes (T2D). Insulin clearance represents one of the processes regulating glucose tolerance but has been scarcely investigated for its possible impairment in high-risk subjects. The aim of this study was to identify possible determinants of insulin clearance in women with a previous history of GDM. A detailed model-based analysis of a regular 3-hour, insulin-modified intravenous glucose tolerance test (IM-IVGTT) has been performed in women with a previous history of GDM (pGDM, n = 115) and in women who had a healthy pregnancy (CNT, n = 41) to assess total, first-phase and second-phase insulin clearance (Cl_INS-TOT, Cl_INS-FP and Cl_INS-SP) and other metabolic parameters (insulin sensitivity S_I, glucose effectiveness S_G, beta-cell function and disposition index DI). CL_INS-SP was found increased in pGDM with respect to CNT and was found significantly inversely linearly correlated with S_G (r = -0.20, p = 0.03, slope: -16.2, 95% CI -30.9 to -1.4, intercept: 1.1, 95% CI 0.7–1.4) and also with DI (r = -0.22, p = 0.02, slope: -10.0, 95% CI -18.5 to -1.6, intercept: 0.9, 95% CI 0.7–1.3). Disposition index, accounting for the combined contribution of insulin sensitivity and beta-cell function, and glucose effectiveness were identified as possible determinants of insulin clearance in women with a previous history of GDM. This may be of relevance for more accurate estimation and prevention of the risk for recurrent GDM and T2D.
- mathematical model,
- deconvolution,
- pregnancy-induced diabetes,
- insulin extraction,
- type 2 diabetes risk,
- C-peptide,
- Liver metabolism
Citation: Micaela Morettini, Christian Göbl, Alexandra Kautzky-Willer, Giovanni Pacini, Andrea Tura, Laura Burattini. Former gestational diabetes: Mathematical modeling of intravenous glucose tolerance test for the assessment of insulin clearance and its determinants[J]. Mathematical Biosciences and Engineering, 2020, 17(2): 1604-1615. doi: 10.3934/mbe.2020084

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Abstract

Women with a previous history of gestational diabetes mellitus (GDM) have increased risk of developing GDM in future pregnancies (i.e. recurrent GDM) and also Type 2 Diabetes (T2D). Insulin clearance represents one of the processes regulating glucose tolerance but has been scarcely investigated for its possible impairment in high-risk subjects. The aim of this study was to identify possible determinants of insulin clearance in women with a previous history of GDM. A detailed model-based analysis of a regular 3-hour, insulin-modified intravenous glucose tolerance test (IM-IVGTT) has been performed in women with a previous history of GDM (pGDM, n = 115) and in women who had a healthy pregnancy (CNT, n = 41) to assess total, first-phase and second-phase insulin clearance (Cl_INS-TOT, Cl_INS-FP and Cl_INS-SP) and other metabolic parameters (insulin sensitivity S_I, glucose effectiveness S_G, beta-cell function and disposition index DI). CL_INS-SP was found increased in pGDM with respect to CNT and was found significantly inversely linearly correlated with S_G (r = -0.20, p = 0.03, slope: -16.2, 95% CI -30.9 to -1.4, intercept: 1.1, 95% CI 0.7–1.4) and also with DI (r = -0.22, p = 0.02, slope: -10.0, 95% CI -18.5 to -1.6, intercept: 0.9, 95% CI 0.7–1.3). Disposition index, accounting for the combined contribution of insulin sensitivity and beta-cell function, and glucose effectiveness were identified as possible determinants of insulin clearance in women with a previous history of GDM. This may be of relevance for more accurate estimation and prevention of the risk for recurrent GDM and T2D.

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