Urinary C-peptide Research Articles

A Position Statement on Diabetes with β-Cell Failure

Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided.

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 and delivery in an advanced cancer survivor with immune checkpoint inhibitor-induced type 1 diabetes: a case report

PurposeGiven the rarity and elderly onset of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (ICI-T1DM), cases leading to delivery are rare.MethodTo our knowledge, this is the first case report of childbirth in a patient with ICI-T1DM after cancer survival. A 32-year-old woman was started on Nivolumab for metastatic parotid cancers one year after total parotidectomy.ResultThe patient developed ICI-T1DM after 43 cycles and started multiple daily insulin therapy and self-monitoring of blood glucose. Complete response was maintained for 2 years by nivolumab, and she finished nivolumab in 77 cycles to attempt pregnancy. During the follow-up period, she began using a sensor-augmented pump (SAP). She had undetectable serum and urinary C-peptide when she started SAP. Her HbA1c level decreased from 7.8 to 6.6% without increasing hypoglycemia in one year. The patient remained in complete response after ICI discontinuation, and embryo transfer was initiated. Pregnancy was confirmed after a second embryo transfer (21 months after ICI discontinuation). At 36 weeks and 6 days, an emergency cesarean section was performed due to the onset of preeclampsia. The baby had hypospadias and bifid scrotum but no other complications or neonatal intensive care unit admission.ConclusionBecause ICI discontinuation and ICI-T1DM carry risks for the patient and child, the decision regarding pregnancy warrants careful consideration. Diabetologists should collaborate with patients and other clinical departments to develop a treatment plan for childbirth.

Abnormal Urinary C-Peptide Levels in a Patient with Type 2 Diabetes and Heart Failure Treated with GLP-1 Receptor Agonists and an ARNI

Abnormal Urinary C-Peptide Levels in a Patient with Type 2 Diabetes and Heart Failure Treated with GLP-1 Receptor Agonists and an ARNI

The effects of endurance physical exercise with fat-free milk intake as a therapy for metabolic syndrome and/or sarcopenia

Background: Nutrition and exercise are important factors for addressing metabolic syndrome and sarcopenia as they are related to insulin secretion. Proteins, particularly branched-chain amino acids (BCAAs), have insulinotropic effects, while exercise reduces insulin secretion. It is thus important to investigate the effects of protein intake and exercise alone and in combination to determine suitable dietary and exercise therapies for treating metabolic syndrome and sarcopenia. Methods: Eight healthy young adult female volunteers participated in a crossover trial consisting of two 5-day experiments. Days 1 and 2 comprised a body-weight-maintained adjustment period during which the participants consumed control diets (energy, 2,010 kcal; protein, 51.9 g). Days 3 to 5 comprised the treatment period during which the participants consumed experimental diets (energy, 2,010 kcal; protein 82.3 g) containing 402 kcal of fat-free milk, and either performed only normal daily activities (non-Ex) or performed normal daily activities and exercised on a bicycle with an ergometer at a target intensity of about 50% of the maximal oxygen intake, expending 402 kcal of additional energy (Ex). Total urine samples were collected during the daytime (6:45 to 18:45) and nighttime (18:45 to 6:45 the next morning). Fasting blood samples were collected early in the morning before and after the treatment period. Results: Plasma valine, leucine, and BCAA levels were significantly elevated after both the non-Ex and Ex periods. Serum insulin levels were significantly elevated only after the non-Ex period. Urinary C-peptide immunoreactivity excretion levels increased significantly during the non-Ex period, but they decreased significantly during the Ex period. After the Ex period, the serum triglyceride and remnant lipoprotein-cholesterol (RLP-C) levels were significantly decreased. Homeostatic model assessment for insulin resistance (HOMA-IR) and atherosclerosis index (AI) values were slightly, yet significantly, increased after the non-Ex period, but were unchanged after the Ex period. The degree of change (Δ) in the RLP-C level significantly and positively correlated with the Δ HOMA-IR and Δ AI.

Fasted C-Peptide Distribution and Associated Clinical Factors in Adults With Longstanding Type 1 Diabetes: Analysis of the Canadian Study of Longevity in Type 1 Diabetes

ObjectiveAlthough insulin production is reportedly retained in many people with longstanding type 1 diabetes (T1D), the magnitude and relevance of connecting peptide (C-peptide) production are uncertain. In this study, we aimed to define fasted C-peptide distributions and associated clinical factors. MethodsIn a cross-sectional analysis of the Canadian Study of Longevity, fasted serum and urinary C-peptide was measured in 74 patients with longstanding T1D (duration ≥50 years) and 75 age- and sex-matched controls. Extensive phenotyping for complications was performed and patient-reported variables were included. C-peptide distributions were analyzed, and multivariable logistic regression was used to assess the variable association in participants with T1D. ResultsThe 74 participants with T1D had a mean age of 66±8 years, a disease duration of 54 (interquartile range 52 to 58) years, and a glycated hemoglobin (A1C) of 7.4%±0.8% (56.8±9.15 mmol/mol). The 75 controls had a mean age of 65±8 years and an A1C of 5.7%±0.4% (38.4±4.05 mmol/mol). Participants with T1D had lower fasted serum C-peptide than controls (0.013±0.022 vs 1.595±1.099 nmol/L, p<0.001). Of the participants with T1D, C-peptide was detectable in 30 of 73 (41%) serum samples, 32 of 74 (43%) urine samples, and 48 of 74 (65%) for either serum or urine. The variables independently associated with detectable serum or urinary C-peptide were lower total daily insulin requirement (odds ratio 2.351 [for 1 lower unit/kg], p=0.013) and lower hypoglycemia worry score (odds ratio 1.059 [for 1 point lower on the worry subscore of the Hypoglycemia Fear Survey], p=0.030). ConclusionsAlthough detectable C-peptide in longstanding diabetes was common, the magnitude of concentration was extremely low when compared with age- and sex-matched controls. Despite minimal detectability, its presence is validated by lower insulin requirements and strongly associated with lower hypoglycemia worry.

Urinary C-peptide and total triiodothyronine as energetic biomarkers for studies of lemurs.

Measuring energy balance and energy metabolism can provide crucial information for understanding the ecological and behavioral drivers of an animal's energetic and physiological condition. Both urinary C-peptide (uCP) of insulin and urinary total triiodothyronine (uTT3) have been validated as noninvasive biomarkers of energy balance and metabolic activity in haplorrhine primates. This study attempts to validate uCP and uTT3 measures in strepsirrhines, a phylogenetically distinct primate clade, using the ruffed lemur (genus Varecia) as a model. We experimentally manipulated the diet of captive black-and-white (Varecia variegata) and red (Varecia rubra) ruffed lemurs at Duke Lemur Center across a 4-week period. We collected urine samples from subjects (n = 5) each day during 1 week of control diet, 2 weeks of calorie-restricted diet and 1 week of refeeding, designed to temporarily reduce energy balance and metabolism. We also tested the outcome of filter paper as a storage method by comparing to controls (frozen at -20°C) to assess its suitability for studies of wild populations. We successfully measured uCP and uTT3 levels in frozen urine samples using commercial enzyme immunoassay kits and found that both biomarkers were excreted at lower concentrations (C-peptide: 1.35 ng/mL, 54% reduction; TT3: 1.5 ng/mL, 37.5% reduction) during calorie-restricted periods compared to normal diet periods. Filter paper recovery for uCP was 19%, though values were significantly positively correlated with frozen control samples. uTT3 could not be recovered at measurable concentrations using filter paper. These methods enable noninvasive measurement of energetic conditions in wild strepsirrhines and subsequent assessment of relationships between energy balance and numerous socioecological drivers in primate populations.

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.

Impact of the angiotensin receptor-neprilysin inhibitor in clinical diabetes management: Potential benefits and pitfalls.

The possible mechanism of increased urinary C-peptide due to neprilysin inhibitors is investigated. Neprilysin inhibition blocks degradation of natriuretic peptides, and elicits a natriuretic and antihypertensive effect. Neprilysin inhibition might similarly block degradation of C-peptides in the kidney and thus increase the urinary C-peptide level.

1657-P: Post–Mixed Meal Glucagon Secretion Is Not Influenced by Residual Beta-Cell Function in Type 1 Diabetes

Aims: Postprandial glucose excursions contribute to dysglycemia in type 1 diabetes (T1D). Hyperglucagonaemia may play a role but the relationship between beta and alpha-cell dysfunction together with incretin response remains unclear. We sought to elucidate this in people with established T1D with and without C-peptide. Methods: Participants (n=29, age 38 ± 12 years, HbA1c 57 ± 9 mmol/mol, T1D duration 20 ± 13 years) with a range of postprandial urine C-peptide were recruited. A Meal Tolerance Test (MTT, 240 mL Fortisip: 360kcal, 14.4g protein, 13.92g fat, 44.16g carbohydrate) was completed after an overnight fast, maintaining normal basal insulin, without an insulin bolus. Blood samples were taken pre and 30min intervals for 180 minutes post-drink and analysed for glucose, C-peptide, glucagon, proinsulin, GLP-1 and GIP. Participants were grouped by peak C-peptide (high &amp;gt;200 pmol/L, low 3-200pmol/L, undetectable). [Incremental] area under the curves ([i]AUC) were compared by one way ANOVA, Spearman's correlation and multiple regression with significance accepted p≤0.05. Results: Ten participants had high peak C-peptide (680 ± 426 pmol/L), 8 low (39 ± 34 pmol/L), and 11 undetectable. Glucagon was comparable in all groups with mean AUC 1721 ± 890 pmol/L*180min (p=0.84). Glucagon correlated with GLP-1 (r=0.81, p&amp;lt;0.01) and GIP (r=0.43, p=0.02) response, but not C-peptide (R=-0.10, p=0.61), proinsulin (r=-0.18, p=0.35) or proinsulin/C-peptide ratio (r=0.04, p=0.85). C-peptide predicted glucose AUC using multiple regression (R2 = 44.3%, F(1, 27) = 21.4, p&amp;lt;0.01). C-peptide in combination with glucagon predicted glucose iAUC (R2 = 41.1% F(2, 26) = 9.1, p&amp;lt;0.01). Conclusion: Residual C-peptide is a predictor of MTT glucose excursions but not glucagon response in established T1D. Postprandial glucagon contributed to glucose excursion as well as correlating with incretin response. This supports altered alpha-cell phenotype in T1D, aberrantly responding to or secreting incretin. Disclosure G.Taylor: None. K.Smith: None. A.Bashir: None. T.J.Mcdonald: None. E.J.Stevenson: None. J.A.Shaw: Advisory Panel; Betalin Therapeutics, Provention Bio, Inc., Consultant; Mogrify. D.J.West: None. Funding Diabetes Research and Wellness Foundation (SCA/OF/12/15); Francis James Bell Endowment Fund; Country Durham Community Foundation

Development of Fulminant Type 1 Diabetes Mellitus in the Course of Treatment with Atezolizumab for Hepatocellular Carcinoma.

A 71-year-old woman with recurring stage IV hepatocellular carcinoma (HCC) was admitted to our hospital while being treated with atezolizumab and bevacizumab and complained of fatigue, vomiting, and appetite loss. The following were noted on admission: serum glucose level, 633 mg/dL; metabolic acidemia (HCO3- of 19.5 mmol/L); remarkably low serum and urinary C-peptide levels (0.16 ng/mL and ≤1.5 μg/day, respectively); and urinary ketone body level, 4,197 μmol/L. She was diagnosed with atezolizumab-induced fulminant type 1 diabetes mellitus (T1DM), and insulin therapy improved the symptoms. To our knowledge, this a novel report of atezolizumab-induced fulminant T1DM in an HCC patient.

Urinary C-peptide to creatinine ratio (UCPCR) as indicator for metabolic risk in apparently healthy adults - a BioPersMed cohort study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Urinary C-Peptide to Creatinine Ratio (UCPCR) as Indicator for Metabolic Risk in Apparently Healthy Adults—A BioPersMed Cohort Study

Background: C-peptide is produced in equimolar amounts with insulin from pancreatic beta cells, and thus is a fundamental biomarker for beta cell function. A non-invasive urinary C-peptide-to-creatinine ratio (UCPCR) has attracted attention as a biomarker for metabolic conditions. However, the UCPCR as an indicative risk predictor for prediabetes is still being investigated. Methods: We aimed to characterize UCPCRs in healthy people using American Diabetes Association (ADA) criteria and to evaluate their metabolic outcomes over time. A total of 1022 participants of the Biomarkers in Personalized Medicine cohort (BioPersMed) were screened for this study. Totals of 317 healthy with normal glucose metabolism, 87 prediabetic, and 43 diabetic subjects were included. Results: Prediabetic participants had a significantly higher UCPCR median value than healthy participants (p &lt; 0.05). Dysglycaemia of healthy baseline participants was measured twice over 4.5 ± 0.9 years; 25% and 30% were detected with prediabetes during follow-ups, predicted by UCPCR both for the first (p &lt; 0.05) and the second visit (p &lt; 0.05), respectively. This is in good agreement with the negative predictive UCPCR value of 60.2% based on logistic regression. UCPCR levels were equal in both sexes. Conclusion: UCPCR measurements provide an indicative approach for metabolic risk, representing a potential use for prevention and monitoring of impaired glucose metabolism.

Effects of accelerometry-derived physical activity energy expenditure on urinary C-peptide levels in a wild primate (Papio ursinus)

Animals have finite energy reserves for growth, survival, and reproduction and must maintain a stable energy balance. Measuring energy balance in the wild, however, is beset with methodological challenges. Quantification of urinary C-peptide (uCP), a proxy for insulin secretion, has enabled researchers to non-invasively estimate energy balance, and positive relationships between uCP levels and energy intake have been documented in numerous non-human primates. Comparatively few studies show that, consistent with insulin physiology, energy expenditure also alters levels of uCP. The timescale and extent of this relationship, however, remains unclear given the reliance on crude measures of activity and inferred energy expenditure. Here, for the first time, we test for effects of accelerometer-derived Vectorial Dynamic Body Acceleration (VeDBA) - a continuous measure of physical activity energy expenditure - on urinary C-peptide (uCP) levels in n = 12 wild chacma baboons (Papio ursinus). Applying a model selection approach, we show that VeDBA summed over short timescales (30 min to 1 h) prior to urine collection was negatively associated with uCP levels. Using the acceleration-based time individuals spent ‘non-stationary’ (i.e. locomoting) prior to urine collection as a predictor - instead of summed VeDBA - revealed similar but less clear results. Overall, the negative relationship between VeDBA and uCP levels highlights the importance of quantifying physical activity energy expenditure when using uCP measures to estimate energy balance and has potential implications for the field of energetics accelerometry.

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.

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas.

To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.

Molecularly imprinted and cladded polymers for constructing a portable plasmonic immunoassay for peptides in biofluids.

Using two molecularly imprinted and cladded polymers (cMIPs), an inexpensive, fast and portable plasmonic immuno-sandwich assay (PISA) was rationally developed for high-specificity and ultra-sensitive detection of C-peptide in urine. The dual cMIPs-based PISA allowed healthy individuals to be distinguished from diabetes patients and exhibited several significant merits over existing immunoassays, holding great promise in clinical diagnosis.

PS-C29-7: ASSOCIATION OF SERUM LEPTIN TO ADIPONECTIN RATIO AND CARDIOVASCULAR STRUCTURAL INDICES IN ESSENTIAL HYPERTENSIVE PATIENTS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Dysregulated leptin and adiponectin profile is known to be associated with atherosclerotic disease. The evaluation of the leptin to adiponectin (L/A) ratio has been suggested as a powerful useful atherosclerotic index compared with adiponectin and leptin alone in patients with type 2 diabetes and obesity. In this study, we investigated the usefulness of L/A ratio for vascular structural abnormalities in essential hypertensive patients. Design and method: In 151 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion (UAE) less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), blood sampling, 24-hour urine collection, and 24-hour blood pressure monitoring were performed. Intima-media thickness of carotid artery (IMT) and minimal forearm vascular resistance (MVR) (wall to lumen ratio in resistance vessel) were also measured by using ultrasonography and strain-gauge plethysmography, respectively. Results: L/A ratio was higher in men than in women (1.23 ± 1.56 vs 0.73 ± 0.87, p &lt; 0.05). There was no correlation between L/A ratio and systolic and diastolic blood pressure, and pulse rate. L/A ratio correlated positively with body mass index, triglyceride, hemoglobin A1c, HOMA-R and urinary C-peptide excretion (r = 0.57, 0.20, 0.20, 0.31, 0.27, p &lt; 0.05, respectively) and negatively with HDL-cholesterol (r = -0.24, p &lt; 0.05). In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively)In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively), whereas these indices did not associated with leptin and adiponectin individually. In multiple regression analysis, L/A ratio was an independent determinant for UAE, IMT and MVR. Conclusions: In patients with essential hypertension, L/A ratio was associated with obesity, abnormal glucose and lipid metabolism, increase in microalbuminuria, and arterial and arteriolar sclerosis. L/A ratio was considered as a useful indicator of vascular structural abnormalities in patients with essential hypertension.

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.

Routine Islet Autoantibody Testing in Clinically Diagnosed Adult-Onset Type 1 Diabetes Can Help Identify Misclassification and the Possibility of Successful Insulin Cessation.

Recent joint American Diabetes Association and European Association for the Study of Diabetes guidelines recommend routine islet autoantibody testing in all adults newly diagnosed with type 1 diabetes. We aimed to assess the impact of routine islet autoantibody testing in this population. We prospectively assessed the relationship between islet autoantibody status (GADA, IA-2A, and ZNT8A), clinical and genetic characteristics, and progression (annual change in urine C-peptide-to-creatinine ratio [UCPCR]) in 722 adults (≥18 years old at diagnosis) with clinically diagnosed type 1 diabetes and diabetes duration <12 months. We also evaluated changes in treatment and glycemia over 2 years after informing participants and their clinicians of autoantibody results. Of 722 participants diagnosed with type 1 diabetes, 24.8% (179) were autoantibody negative. This group had genetic and C-peptide characteristics suggestive of a high prevalence of nonautoimmune diabetes: lower mean type 1 diabetes genetic risk score (islet autoantibody negative vs. positive: 10.85 vs. 13.09 [P < 0.001] [type 2 diabetes 10.12]) and lower annual change in C-peptide (UCPCR), -24% vs. -43% (P < 0.001).After median 24 months of follow-up, treatment change occurred in 36.6% (60 of 164) of autoantibody-negative participants: 22.6% (37 of 164) discontinued insulin, with HbA1c similar to that of participants continuing insulin (57.5 vs. 60.8 mmol/mol [7.4 vs. 7.7%], P = 0.4), and 14.0% (23 of 164) added adjuvant agents to insulin. In adult-onset clinically diagnosed type 1 diabetes, negative islet autoantibodies should prompt careful consideration of other diabetes subtypes. When routinely measured, negative antibodies are associated with successful insulin cessation. These findings support recent recommendations for routine islet autoantibody assessment in adult-onset type 1 diabetes.