Effects of Different Exogenous Insulin Analog Treatments on the Evaluation of Pancreatic Islet Function in Diabetes.

AIMS: Most current domestic and international studies on the effects of different exogenous insulin analogues on insulin detection results have been conducted through in vitro experiments, while relevant in vivo studies are rarely reported. Therefore, this study investigated the impact of different exogenous insulins on insulin detection levels in diabetic patients through in vivo experiments, analyzing the interference of various exogenous insulins with insulin detection by the electrochemiluminescence immunoassay (ECLIA). METHODS: A total of 495 diabetic patients hospitalized in the Department of Endocrinology and Metabolism at the First People's Hospital of Yunnan Province from January 2018 to October 2025 and undergoing pancreatic islet function testing (using a steamed bun meal test) were selected as study subjects. All subjects met the criterion of fasting C-peptide (FCP) level < 0.2 nmol/L. Based on the hypoglycemic regimen administered the day before the steamed bun meal test, all subjects were divided into five groups: the continuous subcutaneous insulin infusion (CSII) groups (insulin aspart [aspart] and insulin lispro [lispro]) and the subcutaneous insulin injection at bedtime groups (insulin glargine [glargine], insulin degludec [degludec], and insulin detemir [detemir]). Data was collected on the following characteristics for the five patient groups: gender, age, disease duration, height, weight, body mass index (BMI), and diabetes-related antibody test results (including IAA, IA-2A, ICA, GADA, and ZnT8). Measure C-peptide (CP) and insulin levels in fasting blood samples and in samples taken 0.5, 1, 2, and 3 h after a steamed bun meal using an ECLIA. Also measure fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG) on the day of islet function testing. Record the exogenous insulin dose (EINS) and the EINS/weight, as well as the proportion of fasting insulin (INS0h) > 2.5  μIU/mL. A statistical analysis was performed. RESULTS: There were no significant differences among the five groups in terms of gender, age, height, weight, BMI, disease duration, FBG, PBG, FCP, C-peptide 0.5 h postprandial (CP0.5h), C-peptide 1 h postprandial (CP1h), C-peptide 2 h postprandial (CP2h), C-peptide 3 h postprandial (CP3h), FCP/FBG, CP2h/PBG, EINS, and EINS/weight (p > 0.05). There were no statistically significant differences in diabetes-related antibody positivity rates among the five groups (p > 0.05). INS0h/FBG and INS2h/PBG in the glargine group were significantly higher than in the other four groups (p < 0.05). INS0h, insulin levels at all time points after the steamed bun meal, the area under the insulin curve (AUC-INS), and the proportion of INS0h > 2.5  μIU/mL were all significantly higher in the glargine group than in the other four groups (p < 0.05). INS0h in the glargine group showed a positive correlation with EINS/weight levels (R = 0.2959, p < 0.001). CONCLUSION: Insulin glargine can be detected by ECLIA, which causes significant positive interference in insulin test results. The degree of interference positively correlates with EINS/weight. For patients using insulin glargine, INS0h test results may reflect the sum of suppressed endogenous insulin and exogenous insulin. In contrast, ECLIA is virtually incapable of detecting aspart insulin, lispro insulin, deglutamate insulin, and detemir insulin; these analogs exhibit low cross-reactivity with the ECLIA detection antibodies, resulting in underestimation of insulin levels. Consequently, the true basal level of pancreatic islet function in patients using these insulins may be underestimated.