Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis
Introduction The progression to insulin deficiency in type 1 diabetes is heterogenous. This study aimed to identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course.Research design and methods Stimulated C-peptide was assessed b...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-11-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/10/6/e002991.full |
| _version_ | 1798016950223241216 |
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| author | Johnny Ludvigsson Annika Grönberg Daniel Espes Per-Ola Carlsson |
| author_facet | Johnny Ludvigsson Annika Grönberg Daniel Espes Per-Ola Carlsson |
| author_sort | Johnny Ludvigsson |
| collection | DOAJ |
| description | Introduction The progression to insulin deficiency in type 1 diabetes is heterogenous. This study aimed to identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course.Research design and methods Stimulated C-peptide was assessed by mixed meal tolerance test in 50 children (<18 years) during 2004–2017, at regular intervals for 6 years from type 1 diabetes diagnosis. 40% of the children had a rapid decline of stimulated C-peptide defined as no measurable C-peptide (<0.03 nmol/L) 30 months after diagnosis.Results At diagnosis, higher frequencies of detectable glutamic acid decarboxylase antibodies (GADA) and IA-2A (p=0.027) were associated with rapid loss of beta-cell function. C-peptide was predicted positively by age at 18 months (p=0.017) and 30 months duration (p=0.038). BMI SD scores (BMISDS) at diagnosis predicted higher C-peptide at diagnosis (p=0.006), 3 months (p=0.002), 9 months (p=0.005), 30 months (p=0.022), 3 years (p=0.009), 4 years (p=0.016) and 6 years (p=0.026), whereas high HbA1c and blood glucose at diagnosis predicted a lower C-peptide at diagnosis (p=<0.001) for both comparisons. Both GADA and IA-2A were negative predictors of C-peptide at 9 months (p=0.011), 18 months (p=0.008) and 30 months (p<0.001). Ten children had 22 events of severe hypoglycemia, and they had lower mean C-peptide at 18 months (p=0.025), 30 months (p=0.008) and 6 years (p=0.018) compared with others. Seven of them had a rapid decline of C-peptide (p=0.030), and the odds to experience a severe hypoglycemia were nearly fivefold increased (OR=4.846, p=0.04).Conclusions Low age and presence of multiple autoantibodies at diagnosis predicts a rapid loss of beta-cell function in children with type 1 diabetes. Low C-peptide is associated with an increased risk of severe hypoglycemia and higher Hemoglobin A1C. A high BMISDS at diagnosis is predictive of remaining beta-cell function during the 6 years of follow-up. |
| first_indexed | 2024-04-11T15:59:04Z |
| format | Article |
| id | doaj.art-5a9bb5bc89a24d7692da353b2dc14b0e |
| institution | Directory Open Access Journal |
| issn | 2052-4897 |
| language | English |
| last_indexed | 2024-04-11T15:59:04Z |
| publishDate | 2022-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj.art-5a9bb5bc89a24d7692da353b2dc14b0e2022-12-22T04:15:05ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972022-11-0110610.1136/bmjdrc-2022-002991Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosisJohnny Ludvigsson0Annika Grönberg1Daniel Espes2Per-Ola Carlsson3Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenDepartment of Women`s and Children`s Health, Uppsala Universitet Institutionen for kvinnors och barns halsa, Uppsala, SwedenScience for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Uppsala, SwedenDepartment of Medical Sciences, Uppsala University, Uppsala, SwedenIntroduction The progression to insulin deficiency in type 1 diabetes is heterogenous. This study aimed to identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course.Research design and methods Stimulated C-peptide was assessed by mixed meal tolerance test in 50 children (<18 years) during 2004–2017, at regular intervals for 6 years from type 1 diabetes diagnosis. 40% of the children had a rapid decline of stimulated C-peptide defined as no measurable C-peptide (<0.03 nmol/L) 30 months after diagnosis.Results At diagnosis, higher frequencies of detectable glutamic acid decarboxylase antibodies (GADA) and IA-2A (p=0.027) were associated with rapid loss of beta-cell function. C-peptide was predicted positively by age at 18 months (p=0.017) and 30 months duration (p=0.038). BMI SD scores (BMISDS) at diagnosis predicted higher C-peptide at diagnosis (p=0.006), 3 months (p=0.002), 9 months (p=0.005), 30 months (p=0.022), 3 years (p=0.009), 4 years (p=0.016) and 6 years (p=0.026), whereas high HbA1c and blood glucose at diagnosis predicted a lower C-peptide at diagnosis (p=<0.001) for both comparisons. Both GADA and IA-2A were negative predictors of C-peptide at 9 months (p=0.011), 18 months (p=0.008) and 30 months (p<0.001). Ten children had 22 events of severe hypoglycemia, and they had lower mean C-peptide at 18 months (p=0.025), 30 months (p=0.008) and 6 years (p=0.018) compared with others. Seven of them had a rapid decline of C-peptide (p=0.030), and the odds to experience a severe hypoglycemia were nearly fivefold increased (OR=4.846, p=0.04).Conclusions Low age and presence of multiple autoantibodies at diagnosis predicts a rapid loss of beta-cell function in children with type 1 diabetes. Low C-peptide is associated with an increased risk of severe hypoglycemia and higher Hemoglobin A1C. A high BMISDS at diagnosis is predictive of remaining beta-cell function during the 6 years of follow-up.https://drc.bmj.com/content/10/6/e002991.full |
| spellingShingle | Johnny Ludvigsson Annika Grönberg Daniel Espes Per-Ola Carlsson Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis BMJ Open Diabetes Research & Care |
| title | Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis |
| title_full | Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis |
| title_fullStr | Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis |
| title_full_unstemmed | Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis |
| title_short | Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis |
| title_sort | higher risk of severe hypoglycemia in children and adolescents with a rapid loss of c peptide during the first 6 years after type 1 diabetes diagnosis |
| url | https://drc.bmj.com/content/10/6/e002991.full |
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