Refining diagnosis of Latent Autoimmune Diabetes Of Adults: Oral glucose stimulated C-peptide assay augments specificity of clinical risk scores in non-obese Indian cohort Priyadarshini.K.S. et al 2026

Latent autoimmune diabetes in adults (LADA) overlaps with presenting features of type 2 diabetes mellitus (T2DM), leading to misclassification as diagnosis relies primarily on plasma glucose levels. Autoantibody testing, although confirmatory, is costly, variably standardized, and inaccessible in resource-limited settings. Measurement of stimulated C-peptide can provide a practical metabolic surrogate of β-cell reserve to improve LADA identification. The present study was conducted as a cross-sectional observational analytical study in a tertiary care centre. It was approved by the institutional review board, and it complied with the principles embodied in the Declaration of Helsinki. A total of 1000 adult diabetes patients were targeted for recruitment. The final analysed dataset comprised 1011 subjects, divided into potential LADA cases (n = 500) and healthy controls (n = 511), by consecutive convenience sampling to remove selection bias. Procedure for OGSC test was as follows: (1) 8 to 10 hours fasting venous blood sample was first collected for fasting plasma glucose (FPG) and fCP levels. (2) Subjects were given 50grams of anhydrous glucose dissolved in 100 ml of water. One hour after glucose administration, another venous blood sample was collected for the measurement of both stimulated plasma glucose (SPG) and stimulated serum C-peptide levels.Whole blood was collected in vacutainers with no anticoagulants (red-capped) and EDTA (purple-capped), then centrifuged to separate serum and plasma, respectively. Specimens were refrigerated at 2-8°C for up to five days or stored at -20°C for longer periods, avoiding repetitive freeze-thaw cycles. Specimens with C-peptide concentrations >3.3 nmol/L (10ng/mL) were diluted and re-assayed. C-peptide measurement was performed using chemiluminescent immunoassay in Beckman Coulter Access-2 autoanalyzer. Plasma glucose and serum C-Peptides were measured and data analysed in conventional units and then converted to SI units. Statistical analysis was performed using SPSS software version 20.0. Descriptive statistics were used to characterise the distribution of continuous variables, with results expressed as mean with standard deviation (SD) or median and interquartile range (IQR) depending on data distribution. Generalized Estimating Equations (GEE) were used to compare the overall change in plasma glucose and C-peptide over time between the two groups. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy, sensitivity, and specificity of fasting and stimulated C-peptide parameters. Multivariable regression analysis was used to identify independent predictors of LADA status, with p-values <0.05 considered statistically significant.