Abstract
Type 2 diabetes mellitus (T2DM) is frequently misdiagnosed in children and treated as type 1 DM (T1DM) with insulin. Urinary C-peptide to creatinine ratio (UCPCR) can be used to measure ß cell function and endogenous insulin. We aimed to assess the value of UCPCR to differentiate T2DM from T1DM in pediatric patients. We assessed UCPCR from urine sample taken 2 h after lunch in 50 children with T1DM and 30 children with T2DM (duration of the disease ≥ 2 years and without renal impairment). Fasting and postprandial C-peptide levels were also evaluated in all included children. Receiver operating characteristic (ROC) curve was performed to assess the optimal UCPCR cutoff level to differentiate T2DM from T1DM in children. UCPCR was significantly lower in children with T1DM compared with those with T2DM (P < 0.001). There was a significant positive correlation between UCPCR and fasting C-peptide, postprandial C-peptide, and age of onset. There was a significant negative correlation between the UCPCR and both HbA1c and duration of DM in T1DM. Fasting C-peptide had a sensitivity of 63%, a specificity of 84% at a cutoff point ≥ 1.3 ng/ml to differentiate T2DM from T1DM. Postprandial C-peptide had a sensitivity of 87%, a specificity of 86% at a cutoff point ≥ 3.2 ng/ml to differentiate T2DM from T1DM. Finally, UCPCR had a sensitivity of 97%, a specificity of 88% at a cutoff point ≥ 0.28 nmol/nmol to differentiate T2DM from T1DM in pediatric patients.
Conclusion: UCPCR is an easy noninvasive reliable marker to differentiate T2DM from T1DM in pediatric patients.
What is Known: • Type 2 DM (T2DM) is frequently misdiagnosed in children and treated as type 1 DM (T1DM) with insulin. • Urinary C-peptide to creatinine ratio (UCPCR) can be used to measure ß cell function and endogenous insulin. | |
What is New: • We revealed that UCPCR had a sensitivity of 97%, a specificity of 88% at a cutoff point ≥ 0.28 nmol/nmol to differentiate T2DM from T1DM. • UCPCR is an easy noninvasive dependable marker to diagnose T2DM from T1DM in pediatric patients. |
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Abbreviations
- BMI:
-
Body mass index
- DM:
-
Diabetes mellitus
- ELIZA:
-
Enzyme-linked immunosorbent assay
- MODY:
-
Maturity onset diabetes of the young
- ROC:
-
Receiver operating characteristics
- SD:
-
Standard deviation
- SGOT:
-
Serum glutamic oxaloacetic transaminases
- SGPT:
-
Serum glutamic pyruvic transaminases
- T1DM:
-
Type 1 diabetes mellitus
- T2DM:
-
Type 2 diabetes mellitus
- UCPCR:
-
Urinary C-peptide creatinine ratio
References
Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME (2018) ISPAD Clinical Practice Consensus Guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 19(Suppl 27):7
Hanna XU, Verre MC (2018) Type 2 diabetes mellitus in children. Am Fam Physician 98(9):590–594
Craig ME, Jefferies C, Dabelea D, Balde N, Seth A, Donaghue KC (2014) Definition, epidemiology and classification of diabetes in children and adolescents. Pediatr Diabetes 15(S20):4–17
Leighton E, Sainsbury CAR, Jones GC (2017) A practical review of C-peptide testing in diabetes. Diabetes Ther 8(3):475–487
Hope SV, Knight BA, Shields BM, Hattersley AT, McDonald TJ, Jones AG (2016) Random non-fasting C–peptide: bringing robust assessment of endogenous insulin secretion to the clinic. Diabet Med 33:1554–1558
Ludvigsson J, Carlsson A, Forsander G, Ivarsson I, Kockum I, Lernmark A, Lindblad B, Marcus C, Samuelsson U (2012) C-peptide in classification of diabetes in children and adolescents. Pediatr Diabetes 13(1):45–50
Jones AG, Hattersley AT (2013) The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med 30:803–817
Besser RE (2013) Determination of C-peptide in children: when is it useful? Pediatr Endocrinol Rev 10:494–502
Jones AG, Besser RE, McDonald TJ, Shields BM, Hope SV, Bowman P, Oram RA, Knight BA, Hattersley AT (2011) Urine C-peptide creatinine ratio is an alternative to stimulated serum C-peptide measurement in late-onset, insulin-treated diabetes. Diabet Med 28:1034–1038
McDonald TJ, Knight BA, Shields BM, Bowman P, Salzmann MB, Hattersley AT (2009) Stability and reproducibility of a single-sample urinary C-peptide/creatinine ratio and its correlation with 24-h urinary C-peptide. Clin Chem 55:2035–2039
Kuhtreiber WM, Washer SLL, Hsu E, Zhao M, Reinhold P, Burger D, Zheng H, Faustman DL (2015) Low levels of C-peptide have clinical significance for established type 1 diabetes. Diabet Med 32(10):1346–1353
Cho MJ, Kim MS, Kim CJ, Kim EY, Kim JD, Kim EY, Lee DY (2014) Fasting serum C-peptide is useful for initial classification of diabetes mellitus in children and adolescents. Ann Pediatr Endocrinol Metab 19(2):80–85
D’Adamo E, Caprio S (2011) Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care 34(S2):S161–S165
Wahren J, Kallas A, Sima AA (2012) The clinical potential of C-peptide replacement in type 1 diabetes. Diabetes 61:761–772
Besser REJ, Shields BM, Hammersley SE, Colclough K, McDonald TJ, Gray Z, Heywood JJN, Barrett TG, Hattersley AT (2013) Home urine C-peptide creatinine ratio testing can identify type 2 and MODY in pediatric diabetes. Pediatr Diabetes 14(3):181–188
Besser REJ, Ludvigsson J, Jones AG, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2011) Urine C-peptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes. Diabetes Care 34:607–609
Bowman P, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2012) Validation of a single-sample urinary C-peptide creatinine ratio as a reproducible alternative to serum C-peptide in patients with type 2 diabetes. Diabet Med 29:90–93
Oram RA, Rawlingson A, Shields BM, Bingham C, Besser REJ, McDonald TJ, Knight BA, Hattersley AT (2013) Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study. BMJ 3(12):e003193
Yilmz Agladioglu S, Sagsak E, Aycan Z (2015) Urinary C-peptide/creatinine ratio can distinguish maturity-onset diabetes of the young from type 1 diabetes in children and adolescents: a single-center experience. Horm Res Paediatr 84(1):54–61
Besser REJ, Shepherd MH, McDonald TJ, Shields BM, Knight BA, Ellard S, Hattersley AT (2011) Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-a/hepatocyte nuclear factor 4-a maturity-onset diabetes of the young from long-duration type 1 diabetes. Diabetes Care 34:286–291
Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, Lachin JM, Polonsky KS, Pozzilli P, Skyler JS, Steffes MW (2004) C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve b-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes 53:250–264
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Wafaa Elzahar: collecting the study data, writing the manuscript, doing the statistical analysis, recruitment of patients. Ahmed Arafa: collecting the study data, writing the manuscript, doing the statistical analysis, recruitment of patients. Doaa El Amrousy: writing the manuscript, doing the statistical analysis. Amira Youssef: doing the laboratory investigation of the study, help in writing the manuscript. Adel Erfan: the idea of the research, supervising the work of research, revising and approval of the manuscript.
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The study was approved by local Ethics Committee of faculty of Medicine of our University and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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Elzahar, W., Arafa, A., Youssef, A. et al. Urinary C-peptide creatinine ratio to differentiate type 2 diabetes mellitus from type 1 in pediatric patients. Eur J Pediatr 179, 1115–1120 (2020). https://doi.org/10.1007/s00431-020-03606-7
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DOI: https://doi.org/10.1007/s00431-020-03606-7