Biochemical and Molecular Markers Among Prediabetic and Type 2 Diabetes Mellitus Patients.

Background: Type 2 diabetes mellitus (T2DM) progresses through prediabetes (PD), which is characterized by insulin resistance and β-cell dysfunction. More than 50% of T2DM cases remain undiagnosed, underscoring the need for specific molecular markers beyond standard diagnostic tests. Objectives: This study aimed to compare sociodemographic, biochemical, and molecular profiles among groups to improve risk stratification. Methods: This cross-sectional study recruited 90 participants, including healthy controls (HC), individuals with PD, and patients with T2DM (n = 30 each), at Smart Health Tower, Sulaymaniyah, Iraq, from January to June 2025. Approximately 6.0 mL of blood was collected from each participant and analyzed for glycated hemoglobin (HbA1C), random blood glucose (RBG), C-peptide, lipid profile, urea, and creatinine, as well as molecular markers, including micro-ribonucleic acids (miRNAs) such as miRNA-126 and miRNA-132. Variables were subsequently compared among the groups. Results: Glycemic markers differed markedly among groups, with HbA1C and RBG highest in T2DM (P < 0.050). In PD, C-peptide (3.04 ± 1.33 ng/mL, P < 0.010) and high-density lipoprotein (HDL) (48.2 ± 12.3 mg/dL, P = 0.028) were highest. Renal markers showed the lowest creatinine level in T2DM (0.72 ± 0.18 mg/dL, P < 0.010), whereas urea levels were comparable among groups (P > 0.05). In patients with T2DM, correlations were observed between RBG and HbA1C (r = 0.792, P < 0.001), C-peptide and triglycerides (r = 0.598, P < 0.001), and HbA1C and creatinine (r = -0.452, P = 0.012). In the PD group, RBG correlated with C-peptide (r = 0.387, P = 0.035). In contrast, miRNA-132 expression was lowest in HC (0.90 ± 0.63; 95% CI, 0.67 - 1.14), significantly increased in PD (2.50 ± 1.86; 95% CI, 1.74 - 3.26), and highest in T2DM (3.56 ± 2.04; 95% CI, 2.80 - 4.32), with highly significant differences between HC and PD and between HC and T2DM (P < 0.001), as well as between PD and T2DM (P = 0.045). Additionally, miRNA-126 expression was lowest in HC (1.22 ± 0.52; 95% CI, 1.03 - 1.42), moderately elevated in T2DM (1.29 ± 0.85; 95% CI, 0.97 - 1.61), and highest in PD (1.70 ± 0.74; 95% CI, 1.41 - 1.98), with significant differences between PD and HC (P = 0.021) and between PD and T2DM (P = 0.029), while no significant difference was observed between HC and T2DM (P = 0.252). Conclusions: The identified interconnections among glycemic, lipid, and renal indicators underscore the importance of early identification, comprehensive biochemical evaluation, and timely care during the PD phase to prevent progression to overt DM and its associated complications.