The effect of diabetes and the diabetogenic TBC1D4 p.Arg684ter variant on kidney function in Inuit in Greenland

• Published in: International journal of circumpolar health Vol. 82; no. 1; p. 2191406
• Main Authors: Overvad, Maria, Díaz, Lars Jorge, Bjerregaard, Peter, Pedersen, Michael Lynge, Larsen, Christina Viskum Lytken, Grarup, Niels, Hansen, Torben, Rossing, Peter, Jørgensen, Marit Eika
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.12.2023; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Albuminuria - complications; CKD; complications; Diabetes; Diabetes Mellitus - genetics; genetics; Greenland; Greenland - epidemiology; GTPase-Activating Proteins - genetics; Humans; Inuit; Inuit - genetics; Kidney; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - genetics; Greenland; genetics; complications; CKD; diabetes; Greenland
• ISSN: 2242-3982; 1239-9736; 2242-3982
• DOI: 10.1080/22423982.2023.2191406

The aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting. Health survey data and TBC1D4 genotypes from 5,336 Greenlanders were used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR <60 ml/min/1.73m 2 ), comparing individuals with and without diabetes, including the effect of TBC1D4 variant. Of the 3,909 participants with complete data, 9.3% had diabetes. Albuminuria was found in 27.6% and 9.5% and CKD was found in 10.8% and 6.3% among those with and without diabetes, respectively. Diabetes was cross-sectionally associated with an increased risk of albuminuria (OR (95% CI) = 2.37 (1.69,3.33); p < 0.001) and the TBC1D4 variant protected against albuminuria (OR (95% CI) = 0.44 (0.22,0.90); p = 0.02) in a multivariable model. Neither diabetes nor the TBC1D4 variant significantly associated with CKD. The presence/absence of diabetes did not predict changes in eGFR and UACR in longitudinal analyses. Diabetes conferred an increased risk of albuminuria, and the TBC1D4 variant was associated with a decreased risk of albuminuria, but neither was associated with CKD. The potential renoprotective association of the TBC1D4 variant on albuminuria calls for further studies.