FRI619 Kidney Magnetic Resonance Imaging Reveals Altered Tissue Architecture In Young Persons With Type 1 And 2 Diabetes
Authors: Wing-yiu Poon Sarah , Nash Kelly , Ji Choi Ye , Li Lu-Ping , Prasad Pottumarthi V , van Raalte Daniël H , Karihaloo Anil , Sawyer Alexandra , Bjornstad Petter 
Published: October 2023

Disclosure: S. Poon: None. K. Nash: None. Y. Choi: None. L. Li: None. P. Prasad: None. D. Raalte: Other; Self; consulting relationships with Boehringer Ingelheim, Eli Lilly, Merck and Sanofi, and receives research operating funding from AstraZeneca, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, MSD. A. Karihaloo: Employee; Self; Novo Nordisk. A. Sawyer: None. P. Bjornstad: Advisory Board Member; Self; AstraZeneca, Bayer, Lilly, Boehringer Ingelheim, Novo Nordisk, and XORTX. Other; Self; PB reports serving or having served as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, LG Chemistry, Sanofi, Novo Nordisk, and Horizon Pharma.

Background: Apparent diffusion coefficient (ADC) by magnetic resonance imaging (MRI) provides information about the microstructure and cellular organization of the kidney, and has been linked with kidney function decline in adults with chronic kidney disease. However, it is unclear whether alterations in tissue architecture or cellular density are also present in young persons with type 1 and 2 diabetes. Accordingly, the objective of this analysis was to determine early changes in ADC among young persons with and without diabetes. Materials and Method: Kidney MRIs were performed in 37 lean controls (age: 18±6 years, 54% female, eGFR: 106±19 ml/min/1.73m2), 28 participants with youth-onset T1D (age: 20±4 years, 50% female, diabetes duration: 9±6 years, HbA1c: 8.3±1.3%, eGFR: 110±19 ml/min/1.73m2) and 30 participants with youth-onset T2D (age: 17±4 years, 62% female, diabetes duration: 2±2 years, HbA1c: 7.4±2.2%, eGFR: 127±24 ml/min/1.73m2). All scans were performed on 3T whole-body scanners. A single reader at The NorthShore University HealthSystem analyzed all images while blinded to participants’ clinical information. Lower values of cortical ADC on diffusion-weighted MRI may indicate increased cellular density and are often used to estimate fibrosis. Estimated GFR (eGFR) were calculated by Full Age Spectrum serum creatinine equation. We performed multivariable linear regression models adjusted for age and sex. Results: Compared to lean controls (age and sex-adjusted means ± standard errors (SE): (1722±22 × 10−6 mm2/s), young persons with T1D (1636±28 × 10−6 mm2/s, p=0.02) and T2D (1612±27 × 10−6 mm2/s, p=0.002) exhibited lower cortical ADC. Despite younger age and shorter diabetes duration, young persons with T2D had numerically lower cortical ADC compared to those with T1D, although the difference did not reach statistical significance. Higher age and male sex were associated with lower cortical ADC (β±SE: −7.5±2.8 x 10−6 mm2/s per 1 year of age, p=0.009; β±SE: −71.1±28.5 x 10−6 mm2/s per 1 year for male sex, p=0.008) in multivariable models. Lower eGFR was associated with lower cortical ADC (β±SE: 2.3±0.8 x 10−6 mm2/s per 1 ml/min/1.73m2 increment eGFR, p=0.005). HbA1c and urine albumin-to-creatinine ratio did not associate significantly with cortical ADC in multivariable models. Conclusion: Young persons with diabetes exhibit lower cortical ADC compared to healthy lean controls, suggesting alternations in microstructure and cellular density and potentially early signs of fibrosis. Additionally, despite shorter duration of disease and younger age, participants with T2D had the lowest cortical ADC values among the 3 groups. Further research is needed to investigate the role of cortical ADC in predicting kidney function decline in young individuals with diabetes, as well as molecular determinants of the alterations in microstructure and cellular density.

Presentation: Friday, June 16, 2023