Pregnancy induces longitudinal changes in urinary C-peptide creatinine ratio in women with type 1 diabetes.

AIMS: 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. METHODS: 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. RESULTS: UCPCR was detectable in 7/26 (26.9%) participants in the first trimester, 10/26 (38.4%) in the second trimester, and 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. CONCLUSION: UCPCR detects longitudinal changes during pregnancy in women with type 1 diabetes mellitus, more marked in those with shorter diabetes duration.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: UCPCR is associated with clinical CAD, independent of CAD classic risk factors, glycaemic control, insulin resistance and BMI in type 1 DM patients.

Stimulated UCPCR Levels Are Lower in People With Type 1 Diabetes Than in Other Diabetes Types in Sub-Saharan Africa: Results From a Preliminary Cross-Sectional Study.

Background: The clinical utility of Urinary C-Peptide to Creatinine Ratio (UCPCR) is well understood in people with different types of diabetes in Caucasian populations, but studies are lacking in African populations. We, therefore, aimed to examine Urinary C-Peptide to Creatinine Ratio levels among groups of people with different types of diabetes in a sub-Saharan African population. Methods: A total of 47 adults with diabetes; 10 with type 1 diabetes, 26 with type 2 diabetes, 11 with ketosis-prone diabetes, and 22 healthy control individuals, were recruited from Yaoundé Central Hospital in Cameroon. Fasting blood glucose and C-peptide were measured in venous blood and urine. Stimulated Urinary C-Peptide to Creatinine Ratio was determined in all subjects after ingestion of a standardized mixed meal. We compared the stimulated Urinary C-peptide to Creatinine Ration concentration in subjects with type 1 diabetes to the other groups. Results: The basal C-peptide and HOMA-ß were lower in T1D than in the T2D group [median 57 (34, 69) vs. 398 (335, 502) pmol/l; p ≤ 0.001] and [median 3.0 (1.63, 5.25) vs. 30.6 (17.94, 45.03); p < 0.001] respectively. Also, basal C-peptide and HOMA-ß were lower in T1D than in those with KPD [median 57 (34, 69) vs. 330 (265, 478) pmol/l; p = 0.003] and [median 3.0 (1.63, 5.25) vs. 47.1 (16.2, 63.1), p = 0.001] respectively. Basal C-peptide was not different between participants with T2D and KPD; 398 (335, 502) vs. 330 (265, 478) pmol/l, p = 0.19. Stimulated UCPCR was lower in T1D compared to T2D, KPD and control participants; [median 0.29 (0.14, 0.68) vs. 0.89 (0.40, 1.69) nmol/moll; p = 0.009], [median 0.29 (0.14, 0.68) vs. 1.33 (0.84, 1.59) nmol/mol; p = 0.006] and [median 0.29 (0.14, 0.68) vs. 1.21 (0.85, 1.21) nmol/mol; p = 0.005] respectively. However, stimulated UCPCR was similar between the T2D and KPD study participants; 0.89 (0.40, 1.69) vs. 1.33 (0.84, 1.59) nmol/mol, p = 0.36. Conclusions: Stimulated Urinary C-Peptide to Creatinine Ratio (UCPCR) is lower in participants with type 1 diabetes compared to those with other types of diabetes in this population. This means stimulated UCPCR could potentially differentiate type 1 diabetes from other diabetes types among people with diabetes in sub-Saharan Africa.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.

Maternal care according to offspring sex and maternal physical condition in mantled howler monkeys (Alouatta palliata).

The Trivers-Willard hypothesis (TWH) posits that maternal care will be biased in favor of the sex that provides the greatest fitness returns per unit of investment, depending on maternal physical condition. Our aim was to examine the TWH in mantled howler monkeys living at Los Tuxtlas (Veracruz, Mexico). The biological attributes of mantled howler monkeys (Alouatta palliata) meet the assumptions of TWH better than those of other explanations, so we expected that females in better physical condition should bias maternal care toward sons, whereas mothers in worse physical condition should bias care toward daughters. Between December 2017 and March 2019, we studied mother-infant interactions in 20 dyads with focal-animal sampling and continuous recording (N = 204 h). We performed genetic analysis to determine offspring sex (N = 7 daughters and 13 sons) and measured C-peptide in urine samples of mothers to assess their physical condition (N = 46 samples). Mothers in better physical condition spent less time in contact with their sons but more time in contact with their daughters. For proximity behavior, mothers in better physical condition spent more time near their sons and less time near their daughters. These results suggest a bias in maternal care towards daughters, contrary to our predictions. In light of current models of maternal investment, our results support that mothers obtain higher fitness returns through daughters.

Female reproductive energetics in mantled howler monkeys (Alouatta palliata): A follow-up study.

OBJECTIVE: Reproduction entails several challenges to primate females, among which energetic costs are remarkable at certain stages of the reproductive cycle. Still, females may use behavioral and physiological strategies to cope with those challenges. We had previously reported covariation between female energetic condition through the reproductive cycle and time-budget adjustments in mantled howler monkeys (Alouatta palliata). Accordingly, we suggested that behavioral flexibility allowed coping with the energetic challenges of reproduction. Subsequent evidence from the same population, however, suggested otherwise, so we performed a follow-up study on the variation in female reproductive energetics based on a larger sample of females. METHODS: We studied 48 free-ranging adult females at Los Tuxtlas (Mexico). We assessed energy balance via urinary C-peptide concentrations (2717 urine samples), behavioral energy intake and expenditure (5728 sampling hours), and physiological energy expenditure via fecal triiodothyronine metabolites (fTH3; 3138 fecal samples). RESULTS: We found that energy balance varied among reproductive states: (a) cycling was a period of low C-peptide concentrations; (b) the highest C-peptide concentrations occurred during gestation; and (c) the beginning of lactation marked a notable decrease in C-peptide concentrations, which then improved at mid-lactation to again decline at lactation offset. These peaks and valleys in energy balance did not seem to be associated with variation in energy acquisition but were rather mirrored by activity levels and fTH3 during lactation. DISCUSSION: Energy balance was not preserved through the reproductive cycle, supporting previous contentions that the reproductive performance of female mantled howler monkeys may be energetically constrained. The contrast between these and results that we have previously reported, highlights the importance of conducting follow-up studies to continually improve our understanding of the reproductive energetics of primate females.

Validation of a method for quantifying urinary C-peptide in platyrrhine monkeys.

Urinary C-peptide (UCP) is a biomarker for insulin that can be used as a non-invasive physiological measure of energy balance. Previous research has validated the use of UCP to quantify energy balance in catarrhines; however, there have been no such studies in platyrrhines. Validation is necessary in this lineage of primates as divergent evolution has resulted in varied organization of insulin genes. Here, we evaluate a method for quantifying UCP in platyrrhines to measure energetic expenditure, a key component of calculating energy balance. Urine samples were opportunistically collected from laboratory-housed tufted capuchins (Sapajus apella) during exercise activities. To examine the efficacy of using UCP as a means for assessing energetic condition, we analyzed urine samples collected before and after exercise. Urinary C-peptide concentrations were measured using a commercial C-peptide radioimmunoassay. We found that on average, UCP concentrations were 0.34 ng/mL lower after exercise than they were prior to exercise (range =0.04 to 0.71 ng/mL). The rateofenergy expenditureper unit time was greater when capuchins were exercising at faster speeds. Concordantly, UCP concentrations decreased more following exercise at those faster speeds. Parallelism of serial dilutions of samples was calculated to assess the precision of UCP concentrations produced using these methods. Measured UCP concentrations decreased at expected intervals in accordance with each dilution factor. Our results provide biological validation of the use of a commercial assay for quantifying UCP as a measure of energy expenditure in this platyrrhine species.

Energetics at the urban edge: Environmental and individual predictors of urinary C-peptide levels in wild chacma baboons (Papio ursinus).

As human-modified landscapes encroach into natural habitats, wildlife face a reduction in natural food sources but also gain access to calorie-rich, human-derived foods. However, research into the energetics of wildlife living within and adjacent to urban and rural landscapes is lacking. C-peptide - a proxy for insulin production and a diagnostic tool for assessing pancreatic function in humans and domestic animals - can be quantified non-invasively from urine (uCP) and may provide a way to investigate the energetic correlates of living in human-altered landscapes. UCP is increasingly used in studies of primate energetics, and here we examine predictors of variation in uCP levels in n = 17 wild chacma baboons (Papio ursinus) living at the urban edge on the Cape Peninsula, South Africa. We find that uCP was positively associated with food provisioning and negatively with night fasting. UCP levels were comparable between winter and summer but significantly lower during spring, possibly driven by consumption of energy-rich seeds during summer and more human-derived foods during winter. UCP was elevated in pregnant females and similar for lactating and cycling females. We find no effect of dominance rank on uCP. Samples collected with synthetic Salivettes had significantly lower uCP levels than directly pipetted samples. Overall, our results indicate that uCP is a reliable, non-invasive measure of energy balance and intake in baboons, and suggest potential energetic benefits of living at the urban edge. More broadly, studies of uCP may offer unique insight into the environmental control of hormone-behaviour relationships in species crossing natural and urban environments.

Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications.

It is well known that type 2 diabetes mellitus (T2D) is a globally increasing health burden. Despite recent therapeutic advances and the availability of many different classes of antihyperglycemic therapy, a large proportion of people do not achieve glycemic control. A decline in pancreatic beta-cell function has been defined as a key contributing factor to progression of T2D. In fact, a significant proportion of beta-cell secretory capacity is thought to be lost well before the diagnosis of T2D is made. Several models have been proposed to explain the reduction in beta-cell function, including reduced beta-cell number, beta-cell exhaustion, and dedifferentiation or transdifferentiation into other cell types. However, there have been reports that suggest remission of T2D is possible, and it is believed that beta-cell dysfunction may be, in part, reversible. As such, the question of whether beta cells are committed to failure in people with T2D is complex. It is now widely accepted that early restoration of normoglycemia may protect beta-cell function. Key to the successful implementation of this approach in clinical practice is the appropriate assessment of individuals at risk of beta-cell failure, and the early implementation of appropriate treatment options. In this review, we discuss the progression of T2D in the context of beta-cell failure and describe how C-peptide testing can be used to assess beta-cell function in primary care practice. In conclusion, significant beta-cell dysfunction is likely in individuals with certain clinical characteristics of T2D, such as long duration of disease, high glycated hemoglobin (≥9%), and/or long-term use of therapies that continuously stimulate the beta cell. In these people, measurement of beta-cell status could assist with choice of appropriate therapy to delay or potentially reverse beta-cell dysfunction and the progression of T2D.

Urinary C-peptide creatinine ratio to differentiate type 2 diabetes mellitus from type 1 in pediatric patients.

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.

Energy balance but not competitive environment corresponds with allostatic load during development in an Old World monkey.

Primates develop slowly relative to their body size, a pattern posited to result from ecological risk aversion. Little is known, however, about how energy balance contributes to allostatic load in juveniles. Using data collected over 8 consecutive months, we examined variation in energy balance (as measured by urinary C-peptide) and how energy balance, life history status, and social competition related to allostatic load (as measured by deviation from baseline fecal glucocorticoid metabolites, dfGCs) in 41 wild juvenile blue monkeys from 3 social groups. Juvenile energy balance was higher among females, older juveniles, when ripe fruit was more available, and when rainfall was lower. Energy balance, but not life history or competitive environments, predicted dfGC concentrations, such that juveniles generally had lower mean dfGCs when they had higher energy balance. An additional exploratory analysis of how dfGCs relate to social strategies revealed that subjects had lower dfGCs when they groomed less, and played more. Time spent grooming interacted with energy balance in predicting dfGC concentrations, so that individuals that groomed more actually had higher dfGCs when they had higher energy balance. Together these results reveal that energetic deficiencies are a true ecological risk factor in blue monkeys, and suggest that navigating the social environment via overt affiliative behavior is potentially both a stress-relieving and stress-inducing endeavor during development.

Urinary total T3 levels as a method to monitor metabolic changes in relation to variation in caloric intake in captive bonobos (Pan paniscus).

Monitoring metabolic activity in wild living animals has become of particular interest in the field of ecological research. Methods for the repeated non-invasive sampling of individuals are needed. Thyroid hormones (TH) are involved in the regulation of metabolic activity, and their measurement can be used as a proxy to monitor metabolic changes. During periods of low energy intake, serum TH levels are reduced, leading to a decrease in metabolic activity. Using urine samples collected during a food restriction experiment in captive bonobos we validated a total triiodthyronin (TT3) enzyme immunoassay (EIA) for the monitoring of metabolic changes. We found that the majority of immune reactivity of the assay in the urine samples could be explained through immunoreactivity to T3. Furthermore, urinary T3 was stable through repeated freeze-thaw cycles but prolonged exposure to room temperature lead to degradation. Most importantly, we found that for all animals urinary total T3 levels were higher when more digestible energy was consumed. We concluded that urinary total T3 measurements are a suitable method for monitoring metabolic changes in bonobos and potentially in a wide range of animal species.

Non-invasive estimation of the costs of feeding competition in a neotropical primate.

A key goal in behavioral ecology is to investigate the factors influencing the access to food resources and energetic condition of females, which are strong predictors of their reproductive success. We aimed to investigate how ecological factors, social factors, and reproductive state are associated with energetic condition in a wild neotropical primate using non-invasive measures. We first assessed and compared urinary C-peptide levels (uCP), the presence of urinary ketones (uKet), and behaviorally assessed energy balance (bEB) in female white-faced capuchin monkeys (Cebus imitator) living in Santa Rosa, Costa Rica. Then, we assessed how these measures were associated with feeding competition, dominance rank, and reproductive state. As predicted, uCP and bEB were positively associated with each other, and bEB was negatively associated with uKet. However, we did not find a relationship between uCP and uKet. Females showed lower uCP and bEB values during periods of intense feeding competition, but this relationship was not dependent on dominance rank. Furthermore, rank was not directly associated with uCP and bEB. Urinary ketones, on the other hand, were only produced in the most adverse conditions: by low-ranking, lactating females during periods of intense feeding competition. Behavioral strategies are assumed to maximize reproductive success and not energetic condition per se, which might explain why rank was not generally associated with energetic condition in our study population. This highlights the importance of considering potential differences between reproductive success and proxies of reproductive success, such as energetic condition or food intake, when investigating predictions of socioecological models.

Size-Controllable Synthesis of Uniform Spherical Covalent Organic Frameworks at Room Temperature for Highly Efficient and Selective Enrichment of Hydrophobic Peptides.

Covalent organic frameworks (COFs) represent a new class of porous crystalline polymers with a diversity of applications. However, synthesis of uniform spherical COFs poses a great challenge. Here, we present size-controllable synthesis of uniform spherical COFs from nanometer to micrometer scale by a facile approach at room temperature. The as-prepared spherical COFs with different sizes exhibited ultrahigh surface area, good crystallinity, and chemical/thermal stability. Multifarious microscopic and spectroscopic techniques were performed to understand the formation mechanism and influencing factors of the spherical COFs. Moreover, the general applicability for room-temperature synthesis of the spherical COFs was demonstrated by varying different building blocks. Spherical COFs, because of the advantageous nature of their surface area, hydrophobicity, and mesoporous microenvironment, serve as an attractive restricted-access adsorption material for highly selective and efficient enrichment of hydrophobic peptides and size exclusion of macromolecular proteins simultaneously. On this basis, the spherical COFs were successfully applied to the specific capture of ultratrace C-peptide from human serum and urine samples. This research provides a new strategy for room-temperature controllable synthesis of uniform spherical COFs with different sizes and extends the application of COFs as an attractive sample-enrichment probe for clinical analysis.

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.

Development of a double-antibody sandwich ELISA for rapid detection to C-peptide in human urine.

C-peptide level is recognized as an important indicator of diabetes diagnosis. A sensitive and specific double-antibody sandwich enzyme-linked immunosorbent assay for the detection of C-peptide based on double antibody sandwich method was studied in this paper. The rabbit and hen were innunized with PLL-C-peptide and BSA-C-peptide respectively to obtain specific Yolk antibody (IgY) and polyclonal antibody used to construct the sandwich ELISA for the measurement of C-peptide. The limit of detection was 0.51 µg/mL and the half maximal inhibitory concentration (IC50) was 3.26 µg/mL. The method developed in the study showed no evident cross-reactivity with other similar analogs. The detection standard curve of C-peptide exhibited a good linearity (R2 = 0.9896, n = 15). 17 types of the urine of diabetes patients on c-peptide levels compared with the hospital type of diabetes information, with a conclusion of a high consistent rate. Therefore, the methods could be selectively used for rapid screening of C-peptide in human urine, and the type of diabetes has some referential significance.

Fulminant Type 1 Diabetes Mellitus Presenting 15 Days after Delivery Diagnosed in Cooperation with Obstetricians.

The patient was a 32-year-old Japanese woman who was given a 75-g oral glucose tolerance test at the 35th week of pregnancy and was normoglycemic. She had excessive thirst and polyuria from 15 days after delivery. When she visited for the 1-month postpartum checkup, her plasma glucose level was 479 mg/dL, HbA1c was 7.4%, and urinary C-peptide was 1.1 µg/mL; she was therefore diagnosed with fulminant type 1 diabetes mellitus associated with pregnancy. All physicians should be aware of this disease so as to provide a prompt diagnosis and emergency treatment and consequently improve the maternal prognosis.

Insulin sensitivity assessed using urine C peptide creatinine ratio (UCPCR) in pregnancy: cross-sectional analysis of an English multiethnic cohort.

AIMS: To assess urinary C peptide creatinine ratio (UCPCR) used in a modified Matsuda equation to measure insulin sensitivity (IS) in pregnancy. RESEARCH AND DESIGN METHODS: In this cross-sectional study, two IS measurements were calculated in 73 pregnant women at ~28 weeks of gestation by two separate methods using modified Matsuda equations. The first using the 0 and 120 min serum C peptide concentration during a 75 g oral glucose tolerance test (OGTT) and the second using the 0 and 120 min UCPCR values. The calculated IS measurements from the two methodologies were evaluated using Person's test and linear regression analysis. The relationship between ISOGTT UCPCR and the fasting second void UCPCR and 120 min UCPCR was assessed using Pearson correlation and linear regression analysis after logarithmic transformation of the variables. Statistical analysis was performed using SPSS V.22. RESULTS: The IS measured using serum C peptide (ISOGTTc-pep) in the modified Matsuda equation correlated with the IS measurement using serum UCPCR (ISOGTT-UCPCR) (r 0.704, p<0.0001). A strong correlation was found between the ISOGTT-UCPCR and the fasting UCPCR (r -0.916, p<0.0001), displaying a hyperbolic relationship. CONCLUSION: The UCPCR provides a practical methodology to assess IS and ß-cell function in pregnancy.

Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid Diagnosis of Monogenic Diabetes in Young-Onset Patients.

OBJECTIVE: Monogenic diabetes, a young-onset form of diabetes, is often misdiagnosed as type 1 diabetes, resulting in unnecessary treatment with insulin. A screening approach for monogenic diabetes is needed to accurately select suitable patients for expensive diagnostic genetic testing. We used C-peptide and islet autoantibodies, highly sensitive and specific biomarkers for discriminating type 1 from non-type 1 diabetes, in a biomarker screening pathway for monogenic diabetes. RESEARCH DESIGN AND METHODS: We studied patients diagnosed at age 30 years or younger, currently younger than 50 years, in two U.K. regions with existing high detection of monogenic diabetes. The biomarker screening pathway comprised three stages: 1) assessment of endogenous insulin secretion using urinary C-peptide/creatinine ratio (UCPCR); 2) if UCPCR was ≥0.2 nmol/mmol, measurement of GAD and IA2 islet autoantibodies; and 3) if negative for both autoantibodies, molecular genetic diagnostic testing for 35 monogenic diabetes subtypes. RESULTS: A total of 1,407 patients participated (1,365 with no known genetic cause, 34 with monogenic diabetes, and 8 with cystic fibrosis-related diabetes). A total of 386 out of 1,365 (28%) patients had a UCPCR ≥0.2 nmol/mmol, and 216 out of 386 (56%) were negative for GAD and IA2 and underwent molecular genetic testing. Seventeen new cases of monogenic diabetes were diagnosed (8 common Maturity Onset Diabetes of the Young [Sanger sequencing] and 9 rarer causes [next-generation sequencing]) in addition to the 34 known cases (estimated prevalence of 3.6% [51/1,407] [95% CI 2.7-4.7%]). The positive predictive value was 20%, suggesting a 1-in-5 detection rate for the pathway. The negative predictive value was 99.9%. CONCLUSIONS: The biomarker screening pathway for monogenic diabetes is an effective, cheap, and easily implemented approach to systematically screening all young-onset patients. The minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed at age 30 years or younger.

Preparation, calibration and evaluation of the First International Standard for human C-peptide.

BACKGROUND: Measurement of C-peptide by immunoassay contributes to the diagnosis of a number of disorders related to ß cell function. Stocks of the current international reference reagent (IRR) for C-peptide, used to calibrate these immunoassays, are exhausted, and this report summarises the international study to establish a replacement World Health Organization (WHO) international standard (IS) to maintain the availability of a globally available reference material and support efforts to standardise C-peptide assays. METHODS: The study was conducted in three phases; phase I involved the assignment of a value to a primary calibrant in mass units by amino acid analysis and phase II applied this value to the calibration of a candidate standard, 13/146, by reversed phase high-performance liquid chromatography (RP-HPLC) assay. In phase III, the candidate standard was compared to the first IRR by current immunoassays to assess its suitability to serve as an IS. RESULTS: Calibration of the candidate standard by RP-HPLC gave a final estimated content of 8.64 µg/ampoule with expanded uncertainty of 8.21-9.07 µg/ampoule (95% confidence; k=2.45). The candidate standard also appears sufficiently stable to serve as an IS, based on HPLC analysis of accelerated thermal degradation samples of 13/146, and was also shown to have appropriate immunological activity. A difference in bias approach was used to assess the commutability of 13/146 with human serum and urine samples. With the exception of two laboratories, the candidate standard demonstrated commutability with respect to the serum and urine samples included in this study. CONCLUSIONS: The candidate standard, 13/146, is suitable to serve as the First International Standard for human C-peptide, and it has been formally adopted by the Expert Committee on Biological Standardisation of the WHO.