Use of a Miniaturized Near-Infrared Spectroscopy Device for Type 2 Diabetes Mellitus Screening: Pooled Analysis of the Pilot ANODE01 and ANODE02 Studies

Abstract

Background: Current diabetes screening methods are complex, inefficient, and inconvenient, requiring resource-intensive blood sampling. With the increasing prevalence of underdiagnosed type 2 diabetes mellitus (T2DM) worldwide, particularly in low-resource settings and underserved populations, affordable and sustainable mass-screening tools are crucial.

Methods: The accuracy and safety of the miniaturized near-infrared (NIR), full-spectrum spectroscopy Glyconics-DS System in detecting T2DM risk status was assessed by pooling data from two independent pilot studies: ANODE01 and ANODE02. Rapid NIR assessments of glycated nail keratin in 60 repeated spectral readings of fingernails from individuals with or without T2DM focused on detecting dichotomized diabetes risk status (glycated hemoglobin [HbA_1c] <6.5%) based on chemometric prediction models, clinical specificity/sensitivity, and true/false positive outcomes. An HbA_1c point-of-care assay served as an internal control.

Results: Over 12 000 NIR spectral readings were collected in a female-dominant (58.5%), mostly non-smoking (80.0%), diverse cohort of 200 participants (n = 100 with/n = 100 without T2D). The selected chemometrics prediction model on a diagnostic HbA_1c cut-off of 6.5% showed a specificity of 92.9% (95% confidence interval [CI] = 88.5-97.4) and a sensitivity of 34.2% (95% CI = 23.4-45.1), with 71.5% concordance. Chemometric predictions were consistent and reproducible with no relevant impact of anthropometric variables, concomitant conditions/medications, smoking status, and number of spectral assessments/nail or hand dominance on NIR assessment. No adverse events or suspected de novo T2D cases were reported.

Conclusions: This pooled analysis of two independent studies demonstrates the clinical feasibility and high specificity of rapid NIR spectral assessment of T2DM risk, with potential for screening, early detection, and sustainable management across health care settings.

Keywords: glycated keratin; hemoglobin; near-infrared spectroscopy; screening; specificity; type 2 diabetes.

Figure 1.

Optimization process for staged data analysis and preclinical validation of the algorithm in the ANODE01 and 02 studies. Abbreviation: ROI, region of interest. Adapted from Lazaro-Pacheco D et al.

Figure 2.

ROC analysis for (a) <6.5% and (b) <6.0% HbA_1c cut-off values. (a) <6.5% HbA_1c threshold. (b) <6.0% HbA_1c threshold. Abbreviations: HbA_1c, glycated hemoglobin; ROC, receiver operating characteristic.