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      Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus

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          Abstract

          Purpose

          Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM.

          Patients and Methods

          Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L).

          Results

          The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = −3.71, p < 0.001).

          Conclusion

          Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment.

          Graphical Abstract

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          Most cited references26

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          2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023.

          The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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            Glucagon and regulation of glucose metabolism.

            As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Compared with healthy subjects, diabetic patients and animals have abnormal secretion of not only insulin but also glucagon. Hyperglucagonemia and altered insulin-to-glucagon ratios play important roles in initiating and maintaining pathological hyperglycemic states. Not surprisingly, glucagon and glucagon receptor have been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.
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              Studies of pancreatic alpha cell function in normal and diabetic subjects.

              The development of a glucagon radioimmunoassay with a relatively high degree of specificity for pancreatic glucagon made possible studies of alpha cell function in healthy nondiabetic subjects and in patients with diabetes mellitus. In the former group mean fasting plasma glucagon averaged 108 mumug/ml (SEM +/-10). In 12 juvenile-type diabetics fasting glucagon averaged 110 (+/-9) and in 33 adult-type diabetics the average was 114 (+/-8). The diabetic averages did not differ significantly from the nondiabetic subjects; however, when hyperglycemia was induced by glucose infusion in the nondiabetic subjects so as to simulate the fasting hyperglycemia of the diabetics, mean glucagon fell to 57 mumug (+/-8), which was significantly below the diabetic mean. In 28 healthy subjects the infusion of arginine elicited a rise in glucagon of at least 100 mumug/ml with a peak level averaging 331 mumug/ml (+/-22) at 40 min. This response to arginine was diminished but not abolished during hyperglycemia induced by simultaneous glucose infusion. In everyone of 45 diabetic subjects tested the infusion of arginine elicited a rise in glucagon of at least 140 mumug/ml to levels significantly greater than in nondiabetics. The peak glucagon level in juvenile-type diabetics averaged 458 mumug/ml (SEM +/-36) and in adult-type diabetics averaged 452 mumug/ml (SEM +/-38). The glucagon response to arginine was unrelated to duration of diabetes, to body weight, type of diabetic treatment, or to other known factors. Marked hyperresponsiveness of glucagon to arginine infusion was observed in two patients with advanced Kimmelsteil-Wilson disease. Glucagon levels were markedly elevated in certain patients with severe diabetic ketoacidosis before treatment with insulin. The findings suggest that alpha cell function is inappropriately increased in diabetes mellitus and could play a significant role in the diabetic syndrome.
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                Author and article information

                Journal
                Diabetes Metab Syndr Obes
                Diabetes Metab Syndr Obes
                dmso
                Diabetes, Metabolic Syndrome and Obesity
                Dove
                1178-7007
                17 April 2024
                2024
                : 17
                : 1769-1780
                Affiliations
                [1 ]Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital , Tianjin, People’s Republic of China
                Author notes
                Correspondence: Qing He; Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email heqing202301@tmu.edu.cn; mingliu@tmu.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-7982-4157
                http://orcid.org/0000-0003-2665-4072
                Article
                459392
                10.2147/DMSO.S459392
                11032662
                38645659
                035420a0-1c2f-4bbf-bfe0-0ea0b33529dc
                © 2024 Chang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 12 January 2024
                : 10 April 2024
                Page count
                Figures: 3, Tables: 6, References: 26, Pages: 12
                Funding
                Funded by: Tianjin Key Medical Discipline (Specialty) Construction Project;
                This work was supported by Tianjin Key Medical Discipline (Specialty) Construction Project (grant number TJYXZDXK-030A), Tianjin Major Science and Technology Projects (grant number 21ZXJBSY00060), Neuroendocrine Tumor Clinical Specialized Disease Research Center (Cultivation), Tianjin Health Science and Technology Key Project (TJWJ2021ZD001), Tianjin Medical University General Hospital Clinical Research Program (22ZYYLCZD02).
                Categories
                Original Research

                Endocrinology & Diabetes
                c-peptide,glucose control,glucagon,type 2 diabetes mellitus
                Endocrinology & Diabetes
                c-peptide, glucose control, glucagon, type 2 diabetes mellitus

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