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Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index

Year 2022, , 32 - 38, 30.04.2022
https://doi.org/10.25048/tudod.1059061

Abstract

Aim: The contemporaneous increase in type 1 diabetes (T1D) and obesity prevalence in children has led to conflicting reports regarding
the effects of weight excess on beta-cell function and clinical manifestation of T1D. We aimed to analyze the association between body
mass index (BMI) and beta-cell function in a large cohort of new-onset T1D youth.
Material and Methods: This study included 204 consecutive children with T1D aged 1-18 years. We retrospectively reviewed the
medical data. The preservation of C-peptide was defined as a C-peptide level ≥0.6 ng/mL. Comparisons of variables between groups
were made using appropriate statistical procedures.
Results: Eighteen percent of children were overweight or obese. Overweight/obesity was associated with significantly higher C-peptide
levels at onset [0.57 (0.05-2.99) vs 0.41 (0.05-2.58) ng/ml, p=0.01]. Preservation of C-peptide levels was observed in 67% of patients.
Patients with preserved C-peptide levels were older at onset [10.4 (1.9-16.5) vs 7.5 (1.1-17.3) yr, p<0.001], more likely to be pubertal
(61.2% vs 22.6%, p<0.001) and had a higher BMI SDS (0.03±1.37 vs -0.67±1.47, p=0.001). The proportion of individuals with preserved
C-peptide levels increased with increasing BMI, but the difference did not reach statistical significance (29.9% to 45.9%, p=0.06). While
there was a positive correlation between BMI SDS and C-peptide levels (rs=0.24, p=0.001), HbA1c levels negatively correlated with BMI
SDS (r=-0.16, p=0.025).
Conclusion: Overweight/obesity was present in a significant proportion of the study population. Obese and overweight children had
a greater residual beta-cell function at the onset of T1D. It could be speculated that they were diagnosed at an earlier phase of beta-cell
damage.

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References

  • 1. Ludvigsson J, Carlsson A, Forsander G, Ivarsson S, Kockum I, Lernmark A, Lindblad B, Marcus C, Samuelsson U. C-peptide in the classification of diabetes in children and adolescents. Pediatr Diabetes. 2012 Feb;13(1):45-50.
  • 2. Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26:832-6.
  • 3. Panero F, Novelli G, Zucco C, Fornengo P, Perotto M, Segre O, Grassi G, Cavallo-Perin P, Bruno G. Fasting plasma C-peptide and micro- and macrovascular complications in a large clinic-based cohort of type 1 diabetic patients. Diabetes Care. 2009 Feb;32(2):301-5.
  • 4. Lachin JM, McGee P, Palmer JP; DCCT/EDIC Research Group. Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes 2014;63:739–748.
  • 5. Besser RE. Determination of C-peptide in children: when is it useful? Pediatr Endocrinol Rev 2013;10:494-502.
  • 6. Li X, Cheng J, Huang G, Luo S, Zhou Z. Tapering decay of β-cell function in Chinese patients with autoimmune type 1 diabetes: A four-year prospective study. J Diabetes. 2019 Oct;11(10):802-808.
  • 7. Pinhas-Hamiel O, Levek-Motola N, Kaidar K, Boyko V, Tisch E, Mazor-Aronovitch K, Graf-Barel C, Landau Z, Lerner-Geva L, Frumkin Ben-David R. Prevalence of overweight, obesity and metabolic syndrome components in children, adolescents and young adults with type 1 diabetes mellitus. Diabetes Metab Res Rev. 2015 Jan;31(1):76-84.
  • 8. Sosenko JM, Geyer S, Skyler JS, Rafkin LE, Ismail HM, Libman IM, Liu YF, DiMeglio LA, Evans-Molina C, Palmer JP. The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1. Pediatr Diabetes. 2018 May;19(3):403-409.
  • 9. Lauria A, Barker A, Schloot N, Hosszufalusi N, Ludvigsson J, Mathieu C, Mauricio D, Nordwall M, Van der Schueren B, Mandrup-Poulsen T, Scherbaum WA, Weets I, Gorus FK, Wareham N, Leslie RD, Pozzilli P. BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children. Eur J Endocrinol. 2015 Feb;172(2):107-13.
  • 10. Demir K, Özen S, Konakçı E, Aydın M, Darendeliler F. A comprehensive online calculator for pediatric endocrinologists: ÇEDD Çözüm/TPEDS metrics. J Clin Res Pediatr Endocrinol 2017;9:182–4.
  • 11. Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2018 Oct;19 Suppl 27(Suppl 27):7-19.
  • 12. Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, Sperling MA, Codner E. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19(Suppl 27):155- 177.
  • 13. The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med. 1998;128:517-523.
  • 14. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care. 2014;37(Suppl. 1):S14-S80.
  • 15. Dabelea D, Mayer-Davis EJ, Andrews JS, Dolan LM, Pihoker C, Hamman RF, Greenbaum C, Marcovina S, Fujimoto W, Linder B, Imperatore G, D’Agostino R Jr. Clinical evolution of beta cell function in youth with diabetes: the SEARCH for diabetes in youth study. Diabetologia. 2012;55(12):3359-3368.
  • 16. Hwang JW, Kim MS, Lee DY. Factors associated with C-peptide levels after diagnosis in children with type 1 diabetes mellitus. Chonnam Med J. 2017;53(3):216-222.
  • 17. Wilkin TJ. The accelerator hypothesis: Weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44(7):914-922.
  • 18. Poitout V, Robertson RP. Minireview: Secondary b-cell failure in type 2 diabetes - a convergence of glucotoxicity and lipotoxicity. Endocrinology. 2002;143:339-342.
  • 19. Redondo MJ, Rodriguez LM, Escalante M, O’Brian Smith E, Balasubramanyam A, Haymond MW. Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes. Pediatr Diabetes. 2012;13(7):564- 571.
  • 20. Ludvigsson J, Carlsson A, Deli A, Forsander G, Ivarsson SA, Kockum I, Lindblad B, Marcus C, Lernmark Å, Samuelsson U. Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents. Diabetes Res Clin Pract. 2013;100(2):203-209.
  • 21. Greenbaum CJ, Anderson AM, Dolan LM, Mayer-Davis EJ, Dabelea D, Imperatore G, Marcovina S, Pihoker C; SEARCH Study Group. Preservation of beta-cell function in autoantibody-positive youth with diabetes. Diabetes Care. 2009;32(10):1839-1844.
  • 22. Barker A, Lauria A, Schloot N, Hosszufalusi N, Ludvigsson J, Mathieu C, Mauricio D, Nordwall M, Van der Schueren B, Mandrup-Poulsen T, Scherbaum WA, Weets I, Gorus FK, Wareham N, Leslie RD, Pozzilli P. Age-dependent decline of β-cell function in type 1 diabetes after diagnosis: A multi-centre longitudinal study. Diabetes Obes Metab. 2014;16(3):262-267.
  • 23. Yu HW, Lee YJ, Cho WI, Lee YA, Shin CH, Yang SW. Preserved C-peptide levels in overweight or obese compared with underweight children upon diagnosis of type1 diabetes mellitus. Ann Pediatr Endocrinol Metab. 2015;20:92-97.
  • 24. Yuan JN, Zhang JW, Cutfield WS, Dong GP, Jiang YJ, Wu W, Huang K, Chen XC, Zheng Y, Liu BH, Derraik JGB, Fu JF. Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes. World J Pediatr. 2021;17(1):99-105.
  • 25. Dabelea D, D’Agostino RB Jr, Mayer-Davis EJ, Pettitt DJ, Imperatore G, Dolan LM, Pihoker C, Hillier TA, Marcovina SM, Linder B, Ruggiero AM, Hamman RF; SEARCH for Diabetes in Youth Study Group. Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes. Diabetes Care. 2006;29(2):290- 294.
  • 26. Cedillo M, Libman IM, Arena VC, Zhou L, Trucco M, Ize- Ludlow D, Pietropaolo M, Becker DJ. Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes. J Clin Endocrinol Metab. 2015;100(1):E82-86.
  • 27. https://www.cdc.gov/obesity/data/childhood.html
  • 28. Gong S, Wu C, Zhong T, Xie Y, Liu F, Li J, Li X, Zhou Z. Complicated curve association of body weight at diagnosis with C-peptide in children and adults with new-onset type 1 diabetes. Diabetes Metab Res Rev. 2020;36(4):e3285.

Yeni Tanı Tip 1 Diyabetli Çocuklarda Korunmuş C-Peptid Düzeyleri: Vücut Kütle İndeksine Dayalı Bir Karşılaştırma

Year 2022, , 32 - 38, 30.04.2022
https://doi.org/10.25048/tudod.1059061

Abstract

Amaç: Çocuklarda tip 1 diyabet (T1D) ve obezite prevalansındaki eşzamanlı artış, aşırı kilonun beta hücre fonksiyonu ve T1D'nin ortaya
çıkışı üzerine etkilerine dair çelişkili raporlara yol açmıştır. Yeni tanı T1D’li çocuklardan oluşan geniş bir kohortta vücut kütle indeksi
(VKİ) ile beta hücre fonksiyonu arasındaki ilişkiyi incelemeyi amaçladık.
Gereç ve Yöntemler: Bu çalışmaya 1-18 yaş arası T1D tanılı 204 ardışık çocuk dahil edildi. Tıbbi verileri geriye dönük olarak inceledik.
Korunmuş C-peptid düzeyi ≥0.6 ng/mL olarak tanımlandı. Değişkenlerin gruplar arası karşılaştırmaları uygun istatistiksel prosedürler
kullanılarak yapıldı.
Bulgular: Çocukların %18'i aşırı kilolu veya obezdi. Fazla kilo/obezite, tanı anında önemli ölçüde daha yüksek C-peptid seviyeleri ile
ilişkiliydi [0.57 (0.05-2.99)'ye karşı 0.41 (0.05-2.58) ng/ml, p=0.01]. Hastaların %67'sinde C-peptid düzeylerinin korunduğu gözlendi.Korunmuş C-peptid düzeyi grubundaki hastalar tanı anında daha ileri yaştaydı [10.4 (1.9-16.5)'e karşı 7.5 (1.1-17.3) yıl, p<0.001],
pubertal olma olasılıkları daha yüksekti (%61.2'ye karşı %22.6, p<0.001) ve daha yüksek VKİ SDS'e sahipti. (0.03±1.37 vs -0.67±1.47,
p=0.001). Korunmuş C-peptid seviyelerine sahip olguların oranı, artan VKİ ile artmaktaydı ancak fark istatistiksel anlamlılığa ulaşmadı
(%29.9 ila %45.9, p=0.06). VKİ SDS ile C-peptid seviyeleri arasında pozitif korelasyon varken (rs=0.24, p=0.001) HbA1c seviyeleri VKİ
SDS ile negatif korelasyon gösterdi (r=-0.16, p=0.025).
Sonuç: Fazla kilo/obezite, çalışma popülasyonunun önemli bir kısmında mevcuttu. Obez ve fazla kilolu çocuklar, T1D başlangıcında
daha fazla rezidüel beta hücre fonksiyonuna sahipti. Bu çocukların beta hücre hasarının daha erken bir aşamasında tanı aldıkları
söylenebilir.

Project Number

-

References

  • 1. Ludvigsson J, Carlsson A, Forsander G, Ivarsson S, Kockum I, Lernmark A, Lindblad B, Marcus C, Samuelsson U. C-peptide in the classification of diabetes in children and adolescents. Pediatr Diabetes. 2012 Feb;13(1):45-50.
  • 2. Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26:832-6.
  • 3. Panero F, Novelli G, Zucco C, Fornengo P, Perotto M, Segre O, Grassi G, Cavallo-Perin P, Bruno G. Fasting plasma C-peptide and micro- and macrovascular complications in a large clinic-based cohort of type 1 diabetic patients. Diabetes Care. 2009 Feb;32(2):301-5.
  • 4. Lachin JM, McGee P, Palmer JP; DCCT/EDIC Research Group. Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes 2014;63:739–748.
  • 5. Besser RE. Determination of C-peptide in children: when is it useful? Pediatr Endocrinol Rev 2013;10:494-502.
  • 6. Li X, Cheng J, Huang G, Luo S, Zhou Z. Tapering decay of β-cell function in Chinese patients with autoimmune type 1 diabetes: A four-year prospective study. J Diabetes. 2019 Oct;11(10):802-808.
  • 7. Pinhas-Hamiel O, Levek-Motola N, Kaidar K, Boyko V, Tisch E, Mazor-Aronovitch K, Graf-Barel C, Landau Z, Lerner-Geva L, Frumkin Ben-David R. Prevalence of overweight, obesity and metabolic syndrome components in children, adolescents and young adults with type 1 diabetes mellitus. Diabetes Metab Res Rev. 2015 Jan;31(1):76-84.
  • 8. Sosenko JM, Geyer S, Skyler JS, Rafkin LE, Ismail HM, Libman IM, Liu YF, DiMeglio LA, Evans-Molina C, Palmer JP. The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1. Pediatr Diabetes. 2018 May;19(3):403-409.
  • 9. Lauria A, Barker A, Schloot N, Hosszufalusi N, Ludvigsson J, Mathieu C, Mauricio D, Nordwall M, Van der Schueren B, Mandrup-Poulsen T, Scherbaum WA, Weets I, Gorus FK, Wareham N, Leslie RD, Pozzilli P. BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children. Eur J Endocrinol. 2015 Feb;172(2):107-13.
  • 10. Demir K, Özen S, Konakçı E, Aydın M, Darendeliler F. A comprehensive online calculator for pediatric endocrinologists: ÇEDD Çözüm/TPEDS metrics. J Clin Res Pediatr Endocrinol 2017;9:182–4.
  • 11. Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2018 Oct;19 Suppl 27(Suppl 27):7-19.
  • 12. Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, Sperling MA, Codner E. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19(Suppl 27):155- 177.
  • 13. The Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med. 1998;128:517-523.
  • 14. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care. 2014;37(Suppl. 1):S14-S80.
  • 15. Dabelea D, Mayer-Davis EJ, Andrews JS, Dolan LM, Pihoker C, Hamman RF, Greenbaum C, Marcovina S, Fujimoto W, Linder B, Imperatore G, D’Agostino R Jr. Clinical evolution of beta cell function in youth with diabetes: the SEARCH for diabetes in youth study. Diabetologia. 2012;55(12):3359-3368.
  • 16. Hwang JW, Kim MS, Lee DY. Factors associated with C-peptide levels after diagnosis in children with type 1 diabetes mellitus. Chonnam Med J. 2017;53(3):216-222.
  • 17. Wilkin TJ. The accelerator hypothesis: Weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44(7):914-922.
  • 18. Poitout V, Robertson RP. Minireview: Secondary b-cell failure in type 2 diabetes - a convergence of glucotoxicity and lipotoxicity. Endocrinology. 2002;143:339-342.
  • 19. Redondo MJ, Rodriguez LM, Escalante M, O’Brian Smith E, Balasubramanyam A, Haymond MW. Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes. Pediatr Diabetes. 2012;13(7):564- 571.
  • 20. Ludvigsson J, Carlsson A, Deli A, Forsander G, Ivarsson SA, Kockum I, Lindblad B, Marcus C, Lernmark Å, Samuelsson U. Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents. Diabetes Res Clin Pract. 2013;100(2):203-209.
  • 21. Greenbaum CJ, Anderson AM, Dolan LM, Mayer-Davis EJ, Dabelea D, Imperatore G, Marcovina S, Pihoker C; SEARCH Study Group. Preservation of beta-cell function in autoantibody-positive youth with diabetes. Diabetes Care. 2009;32(10):1839-1844.
  • 22. Barker A, Lauria A, Schloot N, Hosszufalusi N, Ludvigsson J, Mathieu C, Mauricio D, Nordwall M, Van der Schueren B, Mandrup-Poulsen T, Scherbaum WA, Weets I, Gorus FK, Wareham N, Leslie RD, Pozzilli P. Age-dependent decline of β-cell function in type 1 diabetes after diagnosis: A multi-centre longitudinal study. Diabetes Obes Metab. 2014;16(3):262-267.
  • 23. Yu HW, Lee YJ, Cho WI, Lee YA, Shin CH, Yang SW. Preserved C-peptide levels in overweight or obese compared with underweight children upon diagnosis of type1 diabetes mellitus. Ann Pediatr Endocrinol Metab. 2015;20:92-97.
  • 24. Yuan JN, Zhang JW, Cutfield WS, Dong GP, Jiang YJ, Wu W, Huang K, Chen XC, Zheng Y, Liu BH, Derraik JGB, Fu JF. Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes. World J Pediatr. 2021;17(1):99-105.
  • 25. Dabelea D, D’Agostino RB Jr, Mayer-Davis EJ, Pettitt DJ, Imperatore G, Dolan LM, Pihoker C, Hillier TA, Marcovina SM, Linder B, Ruggiero AM, Hamman RF; SEARCH for Diabetes in Youth Study Group. Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes. Diabetes Care. 2006;29(2):290- 294.
  • 26. Cedillo M, Libman IM, Arena VC, Zhou L, Trucco M, Ize- Ludlow D, Pietropaolo M, Becker DJ. Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes. J Clin Endocrinol Metab. 2015;100(1):E82-86.
  • 27. https://www.cdc.gov/obesity/data/childhood.html
  • 28. Gong S, Wu C, Zhong T, Xie Y, Liu F, Li J, Li X, Zhou Z. Complicated curve association of body weight at diagnosis with C-peptide in children and adults with new-onset type 1 diabetes. Diabetes Metab Res Rev. 2020;36(4):e3285.
There are 28 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Emine Ayça Cimbek 0000-0002-7866-9228

Mehmet Aykut Öztürk This is me 0000-0002-3681-6752

Gülay Karagüzel 0000-0003-4116-5365

Project Number -
Publication Date April 30, 2022
Acceptance Date March 17, 2022
Published in Issue Year 2022

Cite

APA Cimbek, E. A., Öztürk, M. A., & Karagüzel, G. (2022). Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index. Turkish Journal of Diabetes and Obesity, 6(1), 32-38. https://doi.org/10.25048/tudod.1059061
AMA Cimbek EA, Öztürk MA, Karagüzel G. Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index. Turk J Diab Obes. April 2022;6(1):32-38. doi:10.25048/tudod.1059061
Chicago Cimbek, Emine Ayça, Mehmet Aykut Öztürk, and Gülay Karagüzel. “Preservation of C-Peptide Levels in Children With New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index”. Turkish Journal of Diabetes and Obesity 6, no. 1 (April 2022): 32-38. https://doi.org/10.25048/tudod.1059061.
EndNote Cimbek EA, Öztürk MA, Karagüzel G (April 1, 2022) Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index. Turkish Journal of Diabetes and Obesity 6 1 32–38.
IEEE E. A. Cimbek, M. A. Öztürk, and G. Karagüzel, “Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index”, Turk J Diab Obes, vol. 6, no. 1, pp. 32–38, 2022, doi: 10.25048/tudod.1059061.
ISNAD Cimbek, Emine Ayça et al. “Preservation of C-Peptide Levels in Children With New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index”. Turkish Journal of Diabetes and Obesity 6/1 (April 2022), 32-38. https://doi.org/10.25048/tudod.1059061.
JAMA Cimbek EA, Öztürk MA, Karagüzel G. Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index. Turk J Diab Obes. 2022;6:32–38.
MLA Cimbek, Emine Ayça et al. “Preservation of C-Peptide Levels in Children With New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index”. Turkish Journal of Diabetes and Obesity, vol. 6, no. 1, 2022, pp. 32-38, doi:10.25048/tudod.1059061.
Vancouver Cimbek EA, Öztürk MA, Karagüzel G. Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index. Turk J Diab Obes. 2022;6(1):32-8.

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