Hip Fracture Risk According to Diabetic Kidney Disease Phenotype in a Korean Population

Abstract

Background: Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype.

Methods: In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU-GFR-), proteinuric DKD with normal eGFR (PU+GFR-), non-proteinuric DKD with reduced eGFR (PU-GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+).

Results: The cumulative incidence of hip fractures was highest in the PU+GFR+ group, followed by the PU-GFR+ group and the PU+GFR- group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU+GFR+ group. However, the PU+GFR- group had a higher HR for hip fracture than the PU-GFR+ group (PU+GFR+ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU+GFR- : HR, 1.37; 95% CI, 1.30 to 1.46; PU-GFR+ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU-GFR- group as the reference category).

Conclusion: The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

Keywords: Azotemia; Diabetes mellitus; Diabetic nephropathies; Hip fractures; Proteinuria.

Fig. 1

Flow chart of the study population. ESRD, end-stage renal disease; PU⁻GFR⁻, no diabetic kidney disease (DKD); PU⁺GFR⁻, proteinuric DKD with normal estimated glomerular filtration rate (eGFR); PU⁻GFR⁺, non-proteinuric DKD with reduced eGFR; PU⁺GFR⁺, proteinuric DKD with reduced eGFR.

Fig. 2

Cumulative incidence plot of hip fractures according to diabetic kidney disease (DKD) phenotype. PU⁻GFR⁻, no DKD; PU⁺GFR⁻, proteinuric DKD with normal estimated glomerular filtration rate (eGFR); PU⁻GFR⁺, non-proteinuric DKD with reduced eGFR; PU⁺GFR⁺, proteinuric DKD with reduced eGFR.

Fig. 3

Subgroup analyses according to age group, sex, and duration of diabetes. The analyses were adjusted with following covariates: age, sex, smoking, alcohol, exercise, income, hypertension, dyslipidemia, body mass index, stroke, proliferative diabetic retinopathy, insulin use, sulfonylurea use, thiazolidinedione use, renin-angiotensin system inhibitor use, and duration of diabetes (≥5 or <5 years). IR, incidence rate; PYs, person-years; HR, hazard ratio; CI, confidence interval; PU⁻GFR⁻, no diabetic kidney disease (DKD); PU⁺GFR⁻, proteinuric DKD with normal estimated glomerular filtration rate (eGFR); PU⁻GFR⁺, non-proteinuric DKD with reduced eGFR; PU⁺GFR⁺, proteinuric DKD with reduced eGFR.