Urinary C-peptide Creatinine Ratio Research Articles

Investigating the clinical application of urinary C-PEPTIDE creatinine ratio in patients with different types of diabetes at a large hospital in the southwest of Ireland

Investigating the clinical application of urinary C-PEPTIDE creatinine ratio in patients with different types of diabetes at a large hospital in the southwest of Ireland

Pregnancy induces longitudinal changes in Urinary C-peptide Creatinine Ratio in women with type 1 diabetes.

Changes in maternal serum C-peptide have been described during pregnancy in women with Type 1 diabetes. We aimed to determine whether in these women, C-peptide, as measured by the urinary C-peptide creatinine ratio (UCPCR), display changes during the course of pregnancy and in the postpartum period. In this longitudinal study including 26 women, UCPCR was measured in the first, second and third trimester of pregnancy, and postpartum, using a high sensitivity two-step chemiluminescent microparticle immunoassay. UCPCR was detectable in 7/26 (26.9%) participants in the first trimester, 10/26 (38.4%) in the second trimester, 18/26 (69.2%) in the third trimester. Changes in UCPCR concentrations were observed throughout pregnancy, significantly increasing from first to third trimester. UCPCR concentration in the three trimesters was associated with a shorter duration of diabetes, and, in the third trimester also with first trimester UCPCR. UCPCR detects longitudinal changes during pregnancy in women with type 1 diabetes mellitus, more marked in those with shorter diabetes duration.

1425-P: C-Peptide and Islet Autoantibodies at Diagnosis Predict Long-Term ß-Cell Function and Insulin Dependence in Pediatric Diabetes

We asked if assessment of islet autoimmunity and β cell function in children at diabetes diagnosis is useful for prognosis, using the “Aβ” system, [“A” representing autoimmunity (A+ = ≥1 autoantibody; A- = no antibodies), “β” representing β cell function (β+ = random serum C-peptide ≥0.6 ng/mL; β- = C-peptide <0.6 ng/mL)]. We followed β cell function longitudinally with 2h post-prandial urinary C-peptide-creatinine ratio (UCPCR) at 3-12 wk (V1) and 6-12 m (V2). We compared clinical characteristics, glycemia and β cell function at baseline and clinical outcomes at V2 between the groups. The cohort (n=74) was 50% female, 76% White, 22% non-Hispanic Black, 2% Other, 47% Hispanic. Median age (25p-75p) was 12.6 (8.5-14.6) years, median BMI 70.7 (16.7-96.1) %ile. Phenotypic frequencies were A+β- (36.5%), A-β+ (29.7%), A+β+ (31.1%) and A-β- (2.7%). Baseline serum C-peptide correlated with UCPCR at V1 (r=0.37, p=0.03). Adjusting for age, sex, race/ethnicity, and BMI, UCPCR at V2 was higher in A-β+ than A+β- (β=1.18, 95% CI:0.31-2.07, p=0.009). Fully 36% of A-β+ but none of A+β+ and A+β- were insulin-independent at V2 (p<0.001). The remaining results are shown in Table 1. The A-β+ phenotype at diagnosis predicts sustained β cell function and potential insulin-independence after 6-12 months. Random serum C-peptide at diagnosis correlates with 2h post-prandial UCPCR at 3-12 weeks. Disclosure M.Tosur: Advisory Panel; Provention Bio, Inc. A.Balasubramanyam: None. X.C.Huang: None. S.Deen: None. S.Uysal: None. M.Astudillo: None. W.Hagopian: Research Support; Janssen Research & Development, LLC, Provention Bio, Inc., Randox R & D. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. F.Jahoor: None. M.J.Redondo: None. Funding Texas Children's Hospital (to M.T.); Rutherford Fund (to A.B.); National Institutes of Health (K23DK129821 to M.T.)

Urinary c-peptide creatinine ratio (UCPCR) as a predictor of coronary artery disease in type 1 diabetes mellitus.

Elevated C-peptide has been suggested as a risk factor for coronary artery disease (CAD). Elevated urinary C-peptide to creatinine ratio (UCPCR) as an alternative measurement is shown to be related to insulin secretion dysfunction; however, data regarding UCPCR predictive value for CAD in diabetes mellitus (DM) are scarce. Therefore, we aimed to assess the UCPCR association with CAD in type 1 DM (T1DM) patients. 279 patients previously diagnosed with T1DM included and categorized into two groups of CAD (n=84) and without-CAD (n=195). Furthermore, each group was divided into obese (body mass index (BMI) ≥ 30) and non-obese (BMI < 30) groups. Four models utilizing the binary logistic regression were designed to evaluate the role of UCPCR in CAD adjusted for well-known risk factors and mediators. Median level of UCPCR was higher in CAD group compared to non-CAD group (0.07 vs. 0.04, respectively). Also, the well-acknowledged risk factors including being active smoker, hypertension, duration of diabetes, and body mass index (BMI) as well as higher levels of haemoglobin A1C (HbA1C), total cholesterol (TC), low-density lipoprotein (LDL) and estimated glomeruli filtration rate (e-GFR) had more significant pervasiveness in CAD patients. Based on multiple adjustments by logistic regression, UCPCR was a strong risk factor of CAD among T1DM patients independent of hypertension, demographic variables (gender, age, smoking, alcohol consumption), diabetes-related factors (diabetes duration, FBS, HbA1C), lipid profile (TC, LDL, HDL, TG) and renal-related indicators (creatinine, e-GFR, albuminuria, uric acid) in both patients with BMI≥30 and BMI < 30. UCPCR is associated with clinical CAD, independent of CAD classic risk factors, glycaemic control, insulin resistance and BMI in type 1 DM patients.

Application of urine C-peptide creatinine ratio in type 2 diabetic patients with different levels of renal function.

This study aims to investigate the effect of single urine C peptide/creatinine (UCPCR) in assessing the islet β Cell function of type 2 diabetes mellitus (T2DM) patients with different renal function. A total of 85 T2DM patients were recruited in this study, all the patients were assigned to one group with estimated glomerular filtration rate (eGFR)≤60 ml·min-1·1.73 m-2 and another group complicated with eGFR>60 ml·min-1·1.73 m-2. Serum creatinine, urine creatinine, serum fasting C-peptide (FCP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C) and 24-hour urinary C-peptide (24hUCP) were measured. The modified homeostasis model assessment-islet β cell function [HOMA-islet (CP-DM)], the modified homeostasis model assessment-insulin resistance [HOMA-IR(CP)] and UCPCR were calculated. When compared with group eGFR ≤60 ml·min-1·1.73 m-2, the levels of UCPCR, FCP, the modified HOMA-IR(CP) and HOMA-islet (CP-DM) were promoted and the concentrations of HbA1C, FPG, creatinine were decreased in the patients of eGFR>60 ml·min-1·1.73 m-2 (P<0.05); FCP was uncorrelated with 24hUCP while associated with UCPCR in the patients of eGFR ≤ 60 ml·min-1·1.73 m-2; UCPCR was positively correlated with FCP and HOMA-IR(CP) in the T2DM patients with different levels of renal function; the cut-off (UCPCR ≤ 1.13 nmol/g) had 88.37% sensitivity and 95.24% specificity [95% confidence interval (CI):0.919-0.997] for identifying severe insulin deficiency in T2DM patients[area under the curve (AUC) 0.978]. UCPCR can be used to evaluate islets β Cell function in T2DM patients with different renal function status.

Casual C peptide index: Predicting the subsequent need for insulin therapy in outpatients with type 2 diabetes under primary care.

BackgroundEvaluation of residual beta cell function is indispensable in patients with type 2 diabetes as it informs not only diagnoses but also appropriate treatment modalities. However, there is a lack of convenient biomarkers for residual beta cell function. Therefore, we evaluated endogenous insulin level as a biomarker in outpatients who were being treated with insulin therapy and in patients who were introduced to insulin therapy after 4 years.MethodsData of 174 outpatients with type 2 diabetes (50% male) whose glycemia was moderately controlled (glycated A1c 7.3% [5.2%–14.8%]) were reviewed. Twenty patients whose estimated glomerular filtration rate was lower than 30 ml/min/1.73 m2 were excluded from the evaluation of endogenous insulin level with both casual C‐peptide index (C‐CPI) and urinary C‐peptide/creatinine ratio (determined at any time, generally 1–2 h after breakfast). Patients were stratified based on the provision of insulin therapy.ResultsC‐CPI and UCPCR were significantly lower in the insulin‐treated patients than in the insulin‐untreated patients (0.9 vs. 2.2, p < 0.0001; 24.7 vs. 75.5, p = 0.0003, respectively). Moreover, C‐CPI were significantly lower in the insulin‐requiring patients for 4 years than in the insulin‐unrequiring patients (1.0 vs. 1.7, p = 0.0184). The multivariate logistic regression analysis revealed that both indicators of insulin secretion influenced the requirement for insulin therapy, but C‐CPI could serve as the most convenient and useful biomarker for not only current insulin therapy requirements (p = 0.0002) but also the subsequent requirement for insulin therapy (p = 0.0008).ConclusionsC‐CPI could be determined easily, and it was found to be a more practical marker for outpatients; therefore, our findings would have critical implications for primary care.

Urinary C-peptide creatinine ratio is a significant indicator of non-alcoholic fatty liver disease in children with obesity.

Nonalcoholic fatty liver disease (NAFLD) is the commonest etiology of chronic hepatic problems in children with obesity. This study aimed to assess whether urinary C-peptide creatinine ratio (UCPCR) might be a potential indicator of NAFLD in obese children. The study included 240 children with simple obesity. Hepatic ultrasonic examination, anthropometric and laboratory measurements including fasting plasma glucose, fasting insulin, fasting C peptide, liver, renal profile, lipid profile, and UCPCR were obtained in all cases. According to the results of the hepatic ultrasonography, cases were classified into two categories, those with NAFLD (n=98) and without NAFLD (n= 142). In cases with NAFLD, UCPCR was significantly higher than those without NAFLD (P &amp;lt; 0.001). A significant positive correlation between UCPCR and waist circumference (WC SDS), triglyceride, fasting C-peptide, HOMA-IR and alanine aminotransferase (ALT) was found (P &amp;lt; 0.001 for each). Adjusting for other variables, UCPCR was the most significant predictor of NAFLD in children with obesity with higher odds ratio (OR = 3.26) than fasting C peptide (OR = 2.87), triglyceride (OR = 1.89), ALT (OR = 2.20), WC SDS (OR = 1.32) and age (OR=1.27) . UCPCR cut-off value of 0.755 nmol/mmol was able to discriminate cases with NAFLD from those without NAFLD with a sensitivity of 95%, a specificity of 87%. We concluded that UCPCR is a useful, practical and non-invasive predictor of NAFLD in children with obesity with high sensitivity and specificity.

Diagnostic Test Accuracy of Urine C-peptide Creatinine Ratio for the Correct Identification of the Type of Diabetes: A Systematic Review

Objective: To examine the accuracy of urine c-peptide creatinine ratio (UCPCR) for identifying the type of diabetes in appropriate clinical settings. Design: Systematic review of test accuracy studies on patients with different forms of diabetes. Data sources: Medline, Embase and Cochrane library databases from 1 January 2000 to 15 November 2020. Eligibility criteria: Studies reporting the use of UCPCR for diagnosing patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and monogenic forms of diabetes (categorized as maturity-onset diabetes of the young [MODY]). Study selection and data synthesis: Two reviewers independently assessed articles for inclusion and assessed the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, with input from a third reviewer to reach consensus when there was a dispute. Meta-analysis was performed with the studies reporting complete data to derive the pooled sensitivity, specificity and diagnostic odds ratio (DOR), and narrative synthesis only for those with incomplete data. Results: Nine studies with 4,488 patients were included in the qualitative synthesis, while only four of these (915 patients) had complete data and were included in the quantitative synthesis. All the studies had moderate risk of bias and applicability concerns. Meta-analysis of three studies (n=130) revealed sensitivity, specificity and DOR of 84.4% (95% confidence interval [CI] 68.1–93.2%), 91.6% (82.8–96.1%) and 59.9 (32.8–106.0), respectively, for diagnosing T1DM using a UCPCR cut-off of <0.2 nmol/mmol. For participants with T2DM (three studies; n=739), UCPCR >0.2 nmol/mmol was associated with sensitivity, specificity and DOR of 92.8% (84.2–96.9%), 81.6% (61.3–92.5%) and 56.9 (31.3–103.5), respectively. For patients with MODY in the appropriate clinical setting, a UCPCR cut-off of >0.2 nmol/mmol showed sensitivity, specificity and DOR of 85.2% (73.1–92.4%), 98.0% (92.4–99.5%) and 281.8 (57.5–1,379.7), respectively. Conclusions: Based on studies with moderate risk of bias and applicability concerns, UCPCR confers moderate to high sensitivity, specificity, and DOR for correctly identifying T1DM, T2DM and monogenic diabetes in appropriate clinical settings. Large multinational studies with multi-ethnic participation among different age groups are necessary before this test can be routinely used in clinical practice. Study registration: Protocol was registered as PROSPERO CRD42017060633.

Urinary C-peptide and urinary C-peptide creatinine ratio as markers for insulin resistance in obese children and adolescents.

Obesity is associated with insulin resistance (IR). Identifying high-risk obese children affected with IR is crucial to apply preventive management. We aimed to assess the diagnostic value of urinary C-peptide (UCP) and urinary C-peptide creatinine ratio (UCPCR) to diagnoseIR in obese children. This prospective cross-sectional study was performed on 60 children with obesity as the study group. Sixty healthy children of matched age and sex with normal body mass index (BMI) served as the control group. Hemostasis model for the assessment of IR (HOMA-IR), glycated hemoglobin (HbA1c), fasting blood glucose and insulin, UCP, and UCPCR were assessed in all included children. UCP and UCPCR were significantly higher in children with obesity (2.075 ± 0.783) ng/ml, (0.200 ± 0.021) nmol/mmol compared to the control group (1.012 ± 0.465) ng/ml, (0.148 ± 0.016) nmol/mmol, respectively. Both UCP and UCPCR were positively correlated with each other and with HOMA-IR, HbA1c, acanthosis nigricans, waist circumference, and BMI. At cutoff ≥2.45, the sensitivity of UCP to diagnose IR in obese children was 71.4%. At cutoff ≥0.20, the sensitivity of UCPCR to diagnose IR in obese children was 87.6%. UCP and UCPCR are promising surrogate markers of IR in children and adolescents with obesity. However, UCPCR is a better marker than UCP. Obesity is associated with IR. Identifying high-risk obese children affected with IR is crucial to apply preventive management. We aimed to assess the diagnostic value of UCP and UCPCR to detect IR in obese children. To the best of our knowledge, we are the first to use UCP and UCPCR to assess IR in obese children. We found that UCP and UCPCR are practical, easy, dependable noninvasive markers to assess IR in children with obesity and could potentially be useful in epidemiological studies and clinical practice.

Urinary C-peptide Creatinine Ratio and Its Correlation with Parameters of Metabolic Syndrome

To assess the correlation between urinary C peptide creatinine ratio with serum C peptide, serum insulin and its correlation with clinical and biochemical parameters of metabolic syndrome. A total of 100 subjects more than 18 years of age with metabolic syndrome according to ATP III criteria with 100 controls were included in a prospective observational study for a period of 1.5 years. Individual parameters of metabolic syndrome was higher in females with hypertriglyceridemia was most common and hyperglycaemia least common parameter of metabolic syndrome. Fasting urinary C peptide creatinine ratio and Stimulated urinary C peptide correlate significantly with fasting serum C peptide (p&lt;0.01),stimulated serum C peptide (p&lt;0.01), serum fasting insulin (p&lt;0.01) and HOMA IR (p&lt;0.01). A fasting urinary C peptide creatinine ratio of more than 1.8 nmol/mmol, stimulated urinary C peptide creatinine ratio more than 2.8 nmol/mmol and HOMA IR &gt;2.7 can be used as a parameter to distinguish individual with and without metabolic syndrome. Urinary C peptide creatinine ratio correlate with serum C peptide and parameters of metabolic syndrome and can be used as a non-invasive simple tool to assess insulin resistance and also to distinguish patients with and without metabolic syndrome.

Urinary C-peptide/creatinine ratio: A useful biomarker of insulin resistance and refined classification of type 2 diabetes mellitus.

The urinary C-peptide/creatinine ratio (UCPCR) is low in patients with type 1 diabetes mellitus, but it has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We aimed to measure the UCPCRs in patients with T2DM and explore the relationships among UCPCR, insulin resistance (IR), and chronic vascular complications of diabetes. A cross-sectional study was performed of 1299 Chinese hospitalized patients with T2DM. Binary logistic regression was used to evaluate the relationships between the chronic vascular complications of diabetes and UCPCR. K-means analysis was used to allocate participants to subgroups with five to six variables (age at diagnosis, body mass index [BMI], glycosylated hemoglobin, homoeostasis model assessment 2-estimated beta-cell function (HOMA2-B), and HOMA2-insulin resistance (HOMA2-IR), with or without UCPCR). UCPCR positively correlated with HOMA2-IR (r=0.448, P < .001). After adjustment for sex, age, duration of diabetes, and other cardiovascular risk factors, UCPCR was positively associated with diabetic kidney disease (DKD) (odds ratio [OR]=1.198, 95% CI 1.019-1.408, P=.029) and coronary heart disease (CHD) (OR=1.312, 95% CI 1.079-1.594, P=.006). When UCPCR was added, cluster analysis using the six variables identified five subgroups of T2DM, characterized by differing age at diagnosis, BMI, beta-cell function, IR, and prevalence of vascular complications. UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.

501-P: Urinary C-Peptide Creatinine Ratio: A New Marker of Insulin Resistance and Diabetic Kidney Disease

Introduction: Urinary C-peptide creatinine ratio (UCPCR) is used to access β cell function, but rare study had explored UCPCR in conditions with insulin resistance (IR). Some studies indicated the positive correlation between diabetic kidney disease (DKD) and IR. This study aims to explore the correlation among UCPCR,IR and DKD. Methods: Chinese hospitalized patients with type 2 diabetes were included (n=1299). Fasting UCPCR was collected in the morning. We divided patients into three groups by the tertile of UCPCR, the characteristics of three groups were compared. Results: In patients with the highest tertile of UCPCR, they had the lowest percentage of male (223 [51.6%] vs.294 [68.1%] vs. 302 [70.1%], P&amp;lt;0.001), highest homoeostasis model assessment 2 estimates of insulin resistance (HOMA2-IR) (2.0 [1.5,2.6] vs. 1.6 [1.2,2.2] vs. 1.5 [1.0,2.0], P&amp;lt;0.001), urinary albumin creatinine ratio (9.58 [4.67,36.42] vs. 7.14 [4.10,22.43] vs. 6.87 [3.60,22.94]mg/g, P=0.003) level,highest percentage of diabetic kidney disease (DKD) (121 [27.9%] vs. 95 [21.9%] vs. 98 [22.7%], P=0.078), coronary heart disease (CHD) (75 [17.4%] vs. 61 [14.1%] vs. 36 [8.4%], P&amp;lt;0.001) and stroke (77 [17.8%] vs. 55 [12.7%] vs. 46 [10.7%], P=0.007). After the adjustment for sex, age, duration, SBP, DBP, BMI, UA,TG, LDL-c, HbA1c, the history of smoke, hypertension and hyperlipidemia, UCPCR level had a positive correlation with the risk of DKD (OR=1.207,95%CI [1.026,1.419], P=0.023) and CHD (OR=1.302, 95%CI [1.069,1.587], P=0.009). Conclusions: UCPCR is a practical and non-invasive marker of insulin resistance and associated with increased risk of DKD and CHD. Disclosure Y. Wang: None. X. Cai: None. L. Ji: None.

Post-meal Urinary C-peptide creatinine ratio is a moderate measure of insulin secretion in diabetes patients in Cameroon: results from a cross-sectional study

Introduction: Urinary C-peptide creatinine ratio (UCPCR) measured in urine collected at home after a meal has been shown to correlate strongly with stimulated blood C-peptide in European populations. This association and the clinical utility of UCPCR in a sub-Saharan African clinical setting has not been described before. We aimed to assess the performance of UCPCR as a measure of endogenous insulin secretion in Cameroon.

Urinary C-Peptide Creatinine Ratio as a Non-Invasive Tool for Identifying Latent Autoimmune Diabetes in Adults (LADA).

PurposeLatent autoimmune diabetes in adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of both type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), meaning that accurate and early diagnosis of this subtype of diabetes is critical for optimal long-term management. Urinary C-peptide creatinine ratio (UCPCR) represents a non-invasive and practical method for assessing endogenous insulin production to facilitate diabetes classification. However, no study to date has reported the use of UCPCR in identifying LADA.Patients and methodsA total of 574 subjects were included in our study (42 LADA, 61 T1DM, 471 T2DM). All participants were evaluated for UCPCR and underwent clinical and laboratory evaluations. UCPCR was compared among different subtypes of diabetes using multinomial regression analysis, and a receiver operating characteristic (ROC) curve was used to identify its performance in diagnosing LADA.ResultsUCPCR was lower in LADA (0.4±0.6 nmol/mmol) compared with T2DM (1.2±0.9 nmol/mmol), but higher than in T1DM (0.2±0.3 nmol/mmol) (p<0.05). The association between UCPCR and LADA remained significant after adjusting for gender, age, age at diagnosis, body mass index, high-density lipoprotein cholesterol, and triglyceride (OR, 95% confidence interval (CI), 0.29 (0.09, 0.95)). The ROC curve revealed an area under the curve of 0.835 (95% CI (0.742–0.928), p<0.001). The cut-off point for UCPCR ≤ 0.46 nmol/mmol was 82.1% for sensitivity and 76.7% for specificity in the diagnosis of LADA.ConclusionUCPCR may represent a non-invasive, simple, and practical measurement of insulin secretion for early discrimination of LADA in routine clinical practice.

Screening of Siblings of Diabetic Children for Prediction of Developing T1DM by Use of Urinary C-Peptide Creatinine Ratio

AbstractBackground: Diabetes Mellitus is considered an epidemic with increasing incidence over years. UCPCR above 0.2nmol/ mmol is suggestive of remaining pancreatic reserve and is also safe and noninvasive. Screening for type 1 diabetes in siblings of children with T1DM is recommended.Aim of Study: To screen the siblings of children with T1DM for risk of development of diabetes by using Urinary c-peptide creatinine ratio.Patients and Methods: A prospective case control study was carried out on 43 child who were classified into two groups: 21 children as a control group and 22 siblings of children with T1DM. These diabetic children were diagnosed and followed-up at Endocrinology Unit, Pediatric Department, Tanta University Hospitals. The duration of the study was one year.Results: Study showed that one child had a diabetic level of fasting blood glucose. It forms 4.5% of siblings of diabetic children. UCPCR for siblings ranged between 0.052-1.393 with a mean 0.23 and SD ±0.29, while it ranged between 0.159-1.69 with a mean 0.49 and SD ±0.35 in control. The UCPCR was statistically significant (p=0.009*). Negative correlation between fasting blood glucose and UCPCR had a cut off 0.17 with 60% sensitivity and 95% specificity.In Conclusion: C-peptide is a useful indicator of beta cell function, and production of insulin. Urinary C-peptide creat-inine ratio may be used as screening test to predict childrende-veloping type 1 diabetes mellitus.

Clinical Implications of Urinary C-Peptide Creatinine Ratio in Patients with Different Types of Diabetes

Introduction Urinary C-peptide creatinine ratio (UCPCR) is used as a marker of endogenous insulin secretion. This study aims to assess the effectiveness of UCPCR for distinguishing between type 1 diabetes (T1DM) and non-T1DM (monogenic diabetes and T2DM) and predicting therapeutic choices in type 2 diabetes (T2DM) patients. Methods Twenty-three patients with genetically confirmed monogenic diabetes (median age 35.0 years (interquartile range 30.0-47.0), 13 (56.5%) men), 56 patients with T1DM (median age 46.0 years (interquartile range 26.5-59.5), 28 (50.0%) men), 136 patients with T2DM (median age 53.0 years (interquartile range 42.0-60.0), 87 (64.0%) men), and 59 healthy subjects (median age 36.0 years (30.0-42.0), 26 (44.1%) men) were included. UCPCR was collected in the morning. Receiver operating characteristic (ROC) curves were used to identify optimal UCPCR cut-off values to differentiate T1DM from non-T1DM. This UCPCR cut-off was used to divide T2DM patients into two groups, and the two groups were compared. Results The UCPCR was lower in patients with T1DM compared with T2DM, monogenic diabetes, and healthy subjects, while the UCPCR was similar in T2DM and monogenic diabetes. A UCPCR cut-off of ≥0.21 nmol/mmol distinguished between monogenic diabetes and T1DM (area under the curve [AUC], 0.949) with 87% sensitivity and 93% specificity. UCPCR ≥ 0.20 nmol/mmol had 82% sensitivity and 93% specificity for distinguishing between T2DM and T1DM, with an AUC of 0.932. UCPCR was not reliable for distinguishing between monogenic diabetes and T2DM (AUC, 0.605). Twenty-five of 136 (18.4%) T2DM patients had UCPCR ≤ 0.20 nmol/mmol. Compared with T2DM patients with a UCPCR > 0.20 nmol/mmol, T2DM patients with UCPCR ≤ 0.20 nmol/mmol had a lower serum C-peptide (fasting C-peptide, 0.39 nmol/L vs. 0.66 nmol/L, P < 0.001; postprandial C-peptide, 0.93 nmol/L vs. 1.55 nmol/L, P < 0.001), lower BMI (22.8 kg/m2 vs. 25.2 kg/m2, P = 0.006), and higher percentage of insulin or secretagogue therapy (92.0% vs. 59.5%, P = 0.002). Conclusions UCPCR is a practical and noninvasive marker that can distinguish between TIDM and T2DM or monogenic diabetes. UCPCR ≤ 0.20 nmol/mmol reflects severe impaired beta cell function and the need for insulin or secretagogue therapy in T2DM patients.

294-OR: Type 1 Diabetes Patients with Residual Beta-Cell Function Display Improved Time in Euglycemia and Less Glycaemic Fluctuation after Exercise

Aims: Exercise can disrupt glycemia in individuals with type 1 diabetes (T1D). A large inter-individual variability in the glucose responses to exercise exists. It is not known how residual beta-cell function in long duration T1D influences glycaemia around exercise. Methods: Individuals with T1D completed a postprandial urine C-peptide creatinine ratio test (UCPCR), and 25 participants (M/F 14/11, 39.4±12.4 years, HbA1c 58.8±9.3 mmol/mol-1, BMI 25.6±4.0 kg/m2, diabetes duration 21.4±13.7 years) with a range of UCPCR were recruited. Participants were split into undetectable, microsecretors and clinically significant C-peptide groups (&amp;lt;0.001, 0.001-0.2 and &amp;gt;0.2 nmol/mmol, respectively). After a maximum exercise test, participants attended the second visit whereby they completed 45 minutes of walking at 60%VO2peak. Participants then left the laboratory, with the remainder of the trial under free-living control. Blinded continuous glucose monitoring (CGM) was captured for 12 hours before exercise and for 3 days afterwards. Data (mean±SD) were analysed by one way ANOVA with significance accepted at p ≤0.05. Results: CGM data were successfully captured for 22/25 participants. In the 12 hours prior to exercise, there was no significant differences in CGM between groups. In the first 12 hours post-exercise, the clinical C-peptide group spent significantly more time (83.7±23.2%) in time in euglycemia (3.9-10 mmol/l) compared to the microsecretors (38.8±16.9%, p =0.002) and undetectable participants (40.5±23.3%, p =0.005). The clinical group had lower post exercise SD (1.95±1.26) than the microsecretors (3.56±1.09 p =0.045) and tended to be lower than the undetectable (3.54±1.10 p =0.07). Conclusion: Residual beta-cell function may offer protection against exercise induced dysglycemia. C-peptide could potentially be a method of stratifying the amount of exercise related support patients need to manage glucose around exercise. Disclosure G.S. Taylor: None. K. Smith: None. J. Scragg: None. A. Bashir: None. R.A. Oram: Other Relationship; Self; Randox Laboratories Ltd. T.J. McDonald: None. E.J. Stevenson: None. J.A. Shaw: Advisory Panel; Self; Sanofi. Other Relationship; Self; Novo Nordisk A/S. D.J. West: Research Support; Self; Arla Foods Ingredients, Dexcom, Inc. Funding Diabetes Research &amp; Wellness Foundation

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

Background/Aims: Maturity onset diabetes of the young (MODY) is a rare condition often misdiagnosed as type 1 diabetes (T1D). The purposes of this study were: to identify any patients followed in a large Turkish cohort as T1D, with an atypical natural history, who may in fact have MODY, and to define the criteria which would indicate patients with likely MODY as early as possible after presentation to allow prompt genetic testing. Methods: Urinary C-peptide/creatinine ratio (UCPCR) was studied in 152 patients having a diagnosis of T1D for at least 3 years. Those with a UCPCR ≥0.2 nmol/mmol were selected for genetic analysis of the Glucokinase (GCK), Hepatocyte nuclear factor 1a (HNF1A), Hepatocyte nuclear factor 4a (HNF4A), and Hepatocyte nuclear factor 1b (HNF1B) genes. This UCPCR cut-off was used because of the reported high sensitivity and specificity. Cases were also evaluated using a MODY probability calculator. Results: Twenty-three patients from 152 participants (15.1%) had a UCPCR indicating persistent insulin reserve. The mean age ± SD of the patients was 13.6 ± 3.6 years (range 8.30–21.6). Of these 23, two (8.7%) were found to have a mutation, one with HNF4A and one with HNF1B mutation. No mutations were detected in the GCK or HNF1A genes. Conclusion: In Turkish children with a diagnosis of T1D but who have persistent insulin reserve 3 years after diagnosis, up to 9% may have a genetic mutation indicating a diagnosis of MODY.

C-Peptide Decline in Type 1 Diabetes Has Two Phases: An Initial Exponential Fall and a Subsequent Stable Phase.

The decline in C-peptide in the 5 years after diagnosis of type 1 diabetes has been well studied, but little is known about the longer-term trajectory. We aimed to examine the association between log-transformed C-peptide levels and the duration of diabetes up to 40 years after diagnosis. We assessed the pattern of association between urinary C-peptide/creatinine ratio (UCPCR) and duration of diabetes in cross-sectional data from 1,549 individuals with type 1 diabetes using nonlinear regression approaches. Findings were replicated in longitudinal follow-up data for both UCPCR (n = 161 individuals, 326 observations) and plasma C-peptide (n = 93 individuals, 473 observations). We identified two clear phases of C-peptide decline: an initial exponential fall over 7 years (47% decrease/year [95% CI -51, -43]) followed by a stable period thereafter (+0.07%/year [-1.3, +1.5]). The two phases had similar durations and slopes in patients above and below the median age at diagnosis (10.8 years), although levels were lower in the younger patients irrespective of duration. Patterns were consistent in both longitudinal UCPCR (n = 162; ≤7 years duration: -48%/year [-55, -38]; >7 years duration -0.1% [-4.1, +3.9]) and plasma C-peptide (n = 93; >7 years duration only: -2.6% [-6.7, +1.5]). These data support two clear phases of C-peptide decline: an initial exponential fall over a 7-year period, followed by a prolonged stabilization where C-peptide levels no longer decline. Understanding the pathophysiological and immunological differences between these two phases will give crucial insights into understanding β-cell survival.

Urinary C peptide creatinine ratio in pregnant women with normal glucose tolerance and type 1 diabetes: evidence for insulin secretion

HypothesisIn pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes.Research design and methodsUCPCR and serum C peptide were...