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

Abstract

Background: The urinary C-peptide/creatinine ratio (UCPCR) and fasting C-peptide level can assess beta-cell function in clinical practice. In the present study, the use of the UCPCR and fasting C-peptide levels was investigated in the differential diagnosis between maturity-onset diabetes of the young (MODY) and type 1 diabetes mellitus (T1DM). Methods: Twenty-seven patients with genetically confirmed MODY by next-generation sequence analysis and 42 children with T1DM were included. C-peptide levels were measured after an overnight fast before breakfast, and urine samples were collected 2 h after a standard lunch in the hospital. Results: The UCPCR in the T1DM group was 0.17 ± 0.5 nmol/mmol, and in the MODY group it was 1.27 ± 1.03 nmol/mmol (p = 0.001). The receiver operating characteristic (ROC) curves showed excellent discrimination (area under the curve 0.93). A UCPCR ≥0.22 nmol/mmol yielded a 96.3% sensitivity and an 85.7% specificity. The fasting C-peptide level in the T1DM group was lower than that in the MODY group (p = 0.001). The fasting C-peptide cutoff determined by ROC curve analysis was 0.62 ng/ml, with a sensitivity of 93% and a specificity of 90% for discriminating between MODY and T1DM. Conclusions: We showed that the UCPCR and fasting C-peptide levels in children and adolescents can distinguish patients with MODY from patients with T1DM with high specificity and sensitivity. A value of UCPCR ≥0.22 nmol/mmol may indicate further genetic testing for MODY.

Maturity Onset Diabetes of the Young due to Glucokinase, HNF1-A, HNF1-B, and HNF4-A Mutations in a Cohort of Turkish Children Diagnosed as Type 1 Diabetes Mellitus

“…Yılmaz Ağladıoğlu et al [24] used UCPCR to differentiate MODY from type 1 diabetes in a pediatric group of patients diagnosed at least 2 years earlier. They reported that at a level of 0.22 nmol/mmol, UCPCR exhibited 96.3% sensitivity and 85.7% specificity for identifying cases of MODY.…”

“…Values of 0.2 nmol/mmol or above were shown to be 97% sensitive and 96% specific for differentiating HNF1A and HNF4A cases from type 1 diabetes [7]. We adopted the UCPCR value used by this study because of its high sensitivity combined with high specificity [24, 25]. …”

Maturity onset diabetes of the young: Diagnosis and treatment options

“…This test was reported to have sensitivity up to 93% and specificity up to 90% for discriminating between MODY and T1DM. [44] MODY 1 HNF-4a regulates transcription of the insulin gene and other genes that are involved in glucose metabolism. If HNF-4a function is decreased then it affects the b-cells mainly by controlling HNF1a which is also a transcription factor for insulin.…”

C-Peptide and 24-Hour Urinary C-Peptide as Markers to Help Classify Types of Childhood Diabetes

“…The UCPCR provides another measure for beta-cell function in clinical practice [28]. In the Study by Yılmaz Agladioglu et al [29], the use of the UCPCR and fasting C-peptide levels was investigated in the differential diagnosis between MODY and T1DM. T1DM subjects received insulin treatment and had been diagnosed with diabetes for at least 2 years.…”

“…Biochemical markers of C-peptide and 24-hour urinary C-peptide add to the understanding of markers of diagnosis consistent with current theories of the pathogenesis of diabetes. The paper by Yılmaz Agladioglu et al [29] suggests that UCPCR and fasting C-peptide testing after 2 years of diagnosis in children and adolescents is able to distinguish patients with MODY from patients with T1DM with a high specificity and sensitivity. Further studies in larger samples with a wider distribution of patients with specific MODY mutations are indicated.…”