Objective: In health, circulating growth differentiation factor (GDF)-15 is low, and concentrations are thought to increase rapidly in response to cardiac and renal injuries. GDF-15 is secreted in response to inflammation, oxidative stress and hypoxia, and therefore may be a biomarker of subclinical vascular disease. Yet, the relationships between GDF-15, coronary artery disease and diabetic kidney disease (DKD) remain incompletely understood. Accordingly, the objective of this study was to delineate these relationships in adults with T1D.

Methods: Participants with (n=377, HbA1c 7.8±1.3%, duration 37.1±8.6 years) and without T1D (n=456) in the Coronary Artery Calcification in type 1 diabetes (CACTI) study were assessed for serum GDF-15, coronary artery calcification (CAC) measured using 128-slice spiral CT, urinary albumin-to-creatinine ratio (UACR) and eGFR calculated by CKD-EPI creatinine. Impaired GFR was defined as eGFR <60mL/minutes/1.73m2, albuminuria as UACR ≥30 mg/g, high and very high CAC score as ≥100 and ≥300 AU. Multivariable (age, sex, HbA1c, and antihypertensive medication use) logistic models were applied to examine the relationships.

Results: Participants with T1D had greater GDF-15 concentrations than nondiabetics (666.4 [95% CI 633.9-700.5] vs. 579.1 [558.7-600.4] ng/l, p<0.0001). In participants with type 1 diabetes, higher GDF-15 was associated with greater odds of impaired GFR (OR: 4.40, 95% CI 2.51-7.73, p<0.0001), albuminuria (2.47, 1.60-3.80, p<0.0001), high CAC (1.67, 1.16-2.41, p=0.006) and very high CAC (1.62, 1.01-2.58, p=0.04) in multivariable models (per 1 SD increase in natural log GDF-15).

Conclusion: In this cross-sectional analysis, GDF-15 was strongly associated with DKD and coronary atherosclerosis in adults with T1D, independent of glycemic control. As a biomarker, GDF-15 holds promise to aid in risk stratification and clinical trial enrichment.


P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. R.M. Sippl: None. M. Rewers: None. J.K. Snell-Bergeon: None.


National Institutes of Health; JDRF

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