Diabetes & Metabolism Journal

Original Articles

Metabolic Risk/Epidemiology
Glucose Effectiveness from Short Insulin-Modified IVGTT and Its Application to the Study of Women with Previous Gestational Diabetes Mellitus: Micaela Morettini, Carlo Castriota, Christian Göbl, Alexandra Kautzky-Willer, Giovanni Pacini, Laura Burattini, Andrea Tura; Diabetes Metab J. 2020;44(2):286-294. Published online January 13, 2020; DOI: https://doi.org/10.4093/dmj.2019.0016

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Background

This study aimed to design a simple surrogate marker (i.e., predictor) of the minimal model glucose effectiveness (S_G), namely calculated S_G (CS_G), from a short insulin-modified intravenous glucose tolerance test (IM-IVGTT), and then to apply it to study women with previous gestational diabetes mellitus (pGDM).

Methods

CS_G was designed using the stepwise model selection approach on a population of subjects (n=181) ranging from normal tolerance to type 2 diabetes mellitus (T2DM). CS_G was then tested on a population of women with pGDM (n=57). Each subject underwent a 3-hour IM-IVGTT; women with pGDM were observed early postpartum and after a follow-up period of up to 7 years and classified as progressors (PROG) or non-progressors (NONPROG) to T2DM. The minimal model analysis provided a reference S_G.

Results

CS_G was described as CS_G=1.06×10⁻²+5.71×10⁻²×K_G/G_peak, K_G being the mean slope (absolute value) of loge glucose in 10–25- and 25–50-minute intervals, and G_peak being the maximum of the glucose curve. Good agreement between CS_G and S_G in the general population and in the pGDM group, both at baseline and follow-up (even in PROG and NONPROG subgroups), was shown by the Bland-Altman plots (<5% observations outside limits of agreement), and by the test for equivalence (equivalence margin not higher than one standard deviation). At baseline, the PROG subgroup showed significantly lower S_G and CS_G values compared to the NONPROG subgroup (P<0.03).

Conclusion

CS_G is a valid S_G predictor. In the pGDM group, glucose effectiveness appeared to be impaired in women progressing to T2DM.

Citations

Citations to this article as recorded by

Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
Unraveling the Factors Determining Development of Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus Through Machine-Learning Techniques
Ludovica Ilari, Agnese Piersanti, Christian Göbl, Laura Burattini, Alexandra Kautzky-Willer, Andrea Tura, Micaela Morettini
Frontiers in Physiology.2022;[Epub] CrossRef
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2021; 36(3): 628. CrossRef

Clinical Diabetes & Therapeutics
Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction?: Veronica Falcone, Grammata Kotzaeridi, Melanie Hanne Breil, Ingo Rosicky, Tina Stopp, Gülen Yerlikaya-Schatten, Michael Feichtinger, Wolfgang Eppel, Peter Husslein, Andrea Tura, Christian S. Göbl; Diabetes Metab J. 2019;43(6):785-793. Published online March 12, 2019; DOI: https://doi.org/10.4093/dmj.2018.0218

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Abstract PDF PubReader

Background

An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.

Methods

A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15⁺⁶ weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.

Results

Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).

Conclusion

Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.

Citations

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Future clinical prospects of C-peptide testing in the early diagnosis of gestational diabetes
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First-trimester fasting plasma glucose as a predictor of subsequent gestational diabetes mellitus and adverse fetomaternal outcomes: A systematic review and meta-analysis
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Gestationsdiabetes (GDM) (Update 2023)
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欢欢赵
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Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
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Impact Of Prepregnancy Overweight And Obesity On Treatment Modality And Pregnancy Outcome In Women With Gestational Diabetes Mellitus
Tina Linder, Anna Eder, Cécile Monod, Ingo Rosicky, Daniel Eppel, Katharina Redling, Franziska Geissler, Evelyn A. Huhn, Irene Hösli, Christian S. Göbl
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Association between early-pregnancy serum C-peptide and risk of gestational diabetes mellitus: a nested case–control study among Chinese women
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Endocrine Practice.2021; 27(6): 579. CrossRef
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Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2021; 36(3): 628. CrossRef
Early Gestational Diabetes Mellitus: Diagnostic Strategies and Clinical Implications
Saptarshi Bhattacharya, Lakshmi Nagendra, Aishwarya Krishnamurthy, Om J. Lakhani, Nitin Kapoor, Bharti Kalra, Sanjay Kalra
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Early markers of gestational diabetes mellitus
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Response: Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction? (Diabetes Metab J 2019;43:785–93)
Christian S. Göbl, Andrea Tura
Diabetes & Metabolism Journal.2020; 44(1): 209. CrossRef
First-trimester fasting glycemia as a predictor of gestational diabetes (GDM) and adverse pregnancy outcomes
G. Sesmilo, P. Prats, S. Garcia, I. Rodríguez, A. Rodríguez-Melcón, I. Berges, B. Serra
Acta Diabetologica.2020; 57(6): 697. CrossRef
Letter: Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction? (Diabetes Metab J 2019;43:785–93)
Ye Seul Yang, Hye Seung Jung
Diabetes & Metabolism Journal.2020; 44(1): 199. CrossRef
Auch schon im 1. Trimenon ist Nüchternglukose Prädiktor für Gestationsdiabetes
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Comparison of Machine Learning Methods and Conventional Logistic Regressions for Predicting Gestational Diabetes Using Routine Clinical Data: A Retrospective Cohort Study
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Journal of Diabetes Research.2020; 2020: 1. CrossRef
Predictive Power of Unconjugated Estriol in Diagnosis of Gestational Diabetes: A Cohort Study
Azam Amirian, Nourossadat Kariman, Mehdi Hedayati, Nasrin Borumandnia, Zohre Sheikhan
Iranian Red Crescent Medical Journal.2019;[Epub] CrossRef

Reviews

Pyruvate Dehydrogenase Kinases: Therapeutic Targets for Diabetes and Cancers: Nam Ho Jeoung; Diabetes Metab J. 2015;39(3):188-197. Published online June 15, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.188

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Impaired glucose homeostasis is one of the risk factors for causing metabolic diseases including obesity, type 2 diabetes, and cancers. In glucose metabolism, pyruvate dehydrogenase complex (PDC) mediates a major regulatory step, an irreversible reaction of oxidative decarboxylation of pyruvate to acetyl-CoA. Tight control of PDC is critical because it plays a key role in glucose disposal. PDC activity is tightly regulated using phosphorylation by pyruvate dehydrogenase kinases (PDK1 to 4) and pyruvate dehydrogenase phosphatases (PDP1 and 2). PDKs and PDPs exhibit unique tissue expression patterns, kinetic properties, and sensitivities to regulatory molecules. During the last decades, the up-regulation of PDKs has been observed in the tissues of patients and mammals with metabolic diseases, which suggests that the inhibition of these kinases may have beneficial effects for treating metabolic diseases. This review summarizes the recent advances in the role of specific PDK isoenzymes on the induction of metabolic diseases and describes the effects of PDK inhibition on the prevention of metabolic diseases using pharmacological inhibitors. Based on these reports, PDK isoenzymes are strong therapeutic targets for preventing and treating metabolic diseases.

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Obstructive Sleep Apnea and Abnormal Glucose Metabolism: Nan Hee Kim; Diabetes Metab J. 2012;36(4):268-272. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.268

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Obstructive sleep apnea (OSA) is a chronic disorder that is prevalent, especially in subjects with obesity or diabetes. OSA is related to several metabolic abnormalities, including diabetes, insulin resistance, hypertension, and cardiovascular diseases. Although Koreans are less obese than Caucasians, the prevalence of OSA is comparable in both groups. Thus, the impact of OSA on metabolism may be similar. Many epidemiologic and experimental studies have demonstrated that OSA is associated with glucose intolerance and insulin resistance via intermittent hypoxia, sleep fragmentation, and sleep deprivation. The effect of continuous positive airway pressure treatment on glucose metabolism is still controversial. Randomized controlled trials are needed to evaluate the ability of OSA treatment to reduce the risk of diabetes and insulin resistance in subjects without diabetes and to ameliorate glucose control in patients with diabetes.

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Leptin in Relation to the Lipodystrophy-Associated Metabolic Syndrome: Christos S. Mantzoros; Diabetes Metab J. 2012;36(3):181-189. Published online June 14, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.3.181

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Leptin, an adipocyte-secreted hormone, regulates energy homeostasis as well as reproductive, neuroendocrine, immune and metabolic functions. Subjects with decreased amounts of fat in their adipose tissue, i.e., lipoatrophy, have low leptin levels. In the context of open-label, uncontrolled studies leptin administration, in physiological replacement doses, has been shown to have metabolically salutary effects in the rare patients with the syndrome of congenital lipodystrophy accompanied by leptin deficiency. Much more patients with lipodystrophy suffer from lipodystrophy and the metabolic syndrome associated with the use of highly active antiretroviral therapy. In this so called highly active antiretroviral therapy (HAART)-associated lipodystrophy and metabolic syndrome, patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Leptin administration has been shown to decrease central fat mass and to improve fasting insulin/glucose levels and insulin sensitivity in human immunodeficiency virus-infected hypoleptinemic patients with HAART induced lipodystrophy and the metabolic syndrome. By contrast, the results of leptin treatment in leptin replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. In this review, we present the emerging clinical applications and potential therapeutic uses of leptin in humans with lipodystrophy and the metabolic syndrome.

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