Prospective Analysis of HbA1c Trajectories and Their Association with Diabetic Nephropathy Outcomes

Palyam Dinesh Kumar1, Hanumanthakari Prudhvirajrana2*, Saketh Ramineni3

1Junior Resident, Department of General Medicine, Sree Balaji Medical College and Hospital, India
2*Senior Resident, Department of General Medicine, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
Email: Prudhvirajrana991@gmail.com
(Corresponding Author)
3Senior Resident, Department of General Medicine, Sree Balaji Medical College and Hospital, India

Received: ; Revised: ; Accepted: ; Available Online:

ABSTRACT

Background: Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease worldwide. While glycated haemoglobin (HbA1c) is an established marker of glycaemic control, the longitudinal trajectories of HbA1c and their differential impact on DN progression are insufficiently understood.

Objective: To identify distinct HbA1c trajectories over a five-year follow-up period and evaluate their association with the development and progression of diabetic nephropathy.

Methods: This prospective cohort study enrolled 846 patients with type 2 diabetes mellitus (T2DM) from three tertiary care hospitals between December 2023 to January 2026. HbA1c was measured quarterly. Group-based trajectory modelling (GBTM) was used to identify distinct HbA1c trajectory groups. The primary outcome was incident DN or progression to advanced DN stages, assessed by estimated glomerular filtration rate (eGFR) decline and albuminuria staging. Cox proportional hazards models were employed to assess associations.

Results: Four distinct HbA1c trajectories were identified: stable-low (mean HbA1c <7.0%; n=268, 31.7%), moderate-stable (7.0–8.0%; n=243, 28.7%), moderate-increasing (7.5–9.5%; n=198, 23.4%), and high-persistent (>9.0%; n=137, 16.2%). Over median follow-up of 4.6 years, the high-persistent group had a significantly greater incidence of DN (HR 3.42, 95% CI 2.18–5.36, p<0.001) compared to the stable-low group. The moderate-increasing trajectory also conferred elevated risk (HR 2.15, 95% CI 1.41–3.28, p<0.001). Annual eGFR decline was steepest in the high-persistent group (−4.8 mL/min/1.73 m²/year).

Conclusion: Distinct HbA1c trajectories are independently associated with DN risk. Patients with persistently elevated or progressively increasing HbA1c face substantially higher nephropathy risk, underscoring the importance of sustained glycaemic control rather than isolated measurements.

Keywords: HbA1c trajectory; diabetic nephropathy; glycaemic control; type 2 diabetes; group-based trajectory modelling; chronic kidney disease

How to cite this article: Kumar PD, Prudhvirajrana H, Ramineni S, Prospective Analysis of HbA1c Trajectories and Their Association with Diabetic Nephropathy Outcomes. Int J Drug Deliv Technol. 2026;16(4s): 447-453; DOI: 10.25258/ijddt.16.4s.55