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      Preserved C-peptide secretion is associated with higher time in range (TIR) on intermittently scanned continuous glucose monitoring in Chinese adults with type 1 diabetes

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          Abstract

          Objective

          To explore the relationship between C-peptide secretion and time in range (TIR) in adult patients with type 1 diabetes.

          Methods

          From December 2018 to December 2020, 76 type 1 diabetes participants were enrolled from the Department of Endocrinology and Metabolism of Peking University People’s Hospital. All participants wore intermittently scanned continuous glucose monitoring (isCGM), and insulin dosage was adjusted according to standardized clinical procedures. Subjects were divided into low C-peptide group (<10 pmol/L) and preserved C-peptide group (10–200 pmol/L) based on fasting serum C-peptide levels. Differences of TIR, metrics related to glucose variability and hypoglycemic events were compared.

          Results

          A total of 94,846 isCGM values obtained from 39 male and 37 female participants were analyzed. Individuals with preserved C-peptide secretion had shorter diabetes duration (2.0 (0.5, 10.0) vs 10.0 (3.0, 18.3) years, P = 0.002). TIR was higher in the individuals with preserved C-peptide than those with decreased C-peptide (67.1% (54.2, 75.8) vs 45.5% (33.9, 56.1), P < 0.001), and time above range was significantly lower in those with preserved C-peptide (28.0% (15.6, 42.4) vs 49.4% (39.1, 64.2), P < 0.001). Preserved C-peptide was associated with lower glucose variability, as defined by s.d. (3.0 mmol/L (2.6, 3.4) vs 3.8 mmol/L (3.2, 4.3), P < 0.001) and interquartile range (4.3 mmol/L (3.1, 4.8) vs 5.3 mmol/L (4.5, 6.3), P < 0.001). Metrics related to hypoglycemia were not different between the two groups.

          Conclusion

          Preserved C-peptide secretion was associated with higher TIR and lower glucose variability in Chinese type 1 diabetes adults.

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          Most cited references21

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          The clinical utility of C-peptide measurement in the care of patients with diabetes

          C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C-peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C-peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C-peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C-peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C-peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C-peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients. Utility is greatest after 3–5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C-peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.
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            Residual Insulin Production and Pancreatic β-Cell Turnover After 50 Years of Diabetes: Joslin Medalist Study

            OBJECTIVE To evaluate the extent of pancreatic β-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS Characterization of clinical and biochemical parameters and β-cell function of 411 Medalists with correlation with postmortem morphologic findings of 9 Medalists. RESULTS The Medalist cohort, with a mean ± SD disease duration and age of 56.2 ± 5.8 and 67.2 ± 7.5 years, respectively, has a clinical phenotype similar to type 1 diabetes (type 1 diabetes): mean ± SD onset at 11.0 ± 6.4 years, BMI at 26.0 ± 5.1 kg/m2, insulin dose of 0.46 ± 0.2 u/kg, ∼94% positive for DR3 and/or DR4, and 29.5% positive for either IA2 or glutamic acid decarboxylase (GAD) autoantibodies. Random serum C-peptide levels showed that more than 67.4% of the participants had levels in the minimal (0.03–0.2 nmol/l) or sustained range (≥0.2 nmol/l). Parameters associated with higher random C-peptide were lower hemoglobin A1C, older age of onset, higher frequency of HLA DR3 genotype, and responsiveness to a mixed-meal tolerance test (MMTT). Over half of the Medalists with fasting C-peptide >0.17 nmol/l responded in MMTT by a twofold or greater rise over the course of the test compared to fasting. Postmortem examination of pancreases from nine Medalists showed that all had insulin+ β-cells with some positive for TUNEL staining, indicating apoptosis. CONCLUSIONS Demonstration of persistence and function of insulin-producing pancreatic cells suggests the possibility of a steady state of turnover in which stimuli to enhance endogenous β cells could be a viable therapeutic approach in a significant number of patients with type 1 diabetes, even for those with chronic duration.
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              Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial.

              In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining beta-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual beta-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: 40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia ( approximately 65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level >0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of approximately 30%. Therefore, even modest levels of beta-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                22 September 2022
                01 November 2022
                : 11
                : 11
                : e220244
                Affiliations
                [1 ]Department of Endocrinology and Metabolism , Peking University People’s Hospital, Beijing, People’s Republic of China
                [2 ]School of Automation , Beijing Institute of Technology, Beijing, People’s Republic of China
                Author notes
                Correspondence should be addressed to X Cai or L Ji: dr_junel@ 123456sina.com or jiln@ 123456bjmu.edu.cn

                *(W Liu and Y Ma contributed equally to this work)

                Author information
                http://orcid.org/0000-0001-8270-6274
                http://orcid.org/0000-0002-7881-0543
                http://orcid.org/0000-0002-3262-2168
                Article
                EC-22-0244
                10.1530/EC-22-0244
                9641764
                36136936
                d4e3cbde-57a9-421a-b89d-d34c916ac9fa
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 06 September 2022
                : 22 September 2022
                Categories
                Research

                intermittently scanned continuous glucose monitoring (iscgm),serum c-peptide,type 1 diabetes,time in range

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