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Higher circulating levels of non-esterified fatty acids are associated with faster kidney function decline in post-menopausal women with type 2 diabetes: a pilot prospective study

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Abstract

Aims

Currently, there is little and inconsistent evidence regarding the possible adverse effects of circulating levels of non-esterified fatty acids (NEFA) on kidney function decline in patients with type 2 diabetes mellitus (T2DM).

Methods

We followed for a median of 4.6 years 85 post-menopausal women with non-insulin-treated T2DM and preserved kidney function at baseline. Serum NEFA concentrations were measured using an enzymatic colorimetric method. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Results

Enrolled patients had a baseline mean eGFRCKD-EPI of 83 ± 12 mL/min/1.73 m2 and a median serum NEFA concentration of 662 uEq/L (interquartile range 524–842 uEq/L). During the follow-up period, 13 patients developed kidney function decline at follow-up (defined as an eGFRCKD-EPI decline ≥ 30% from baseline). In Cox proportional hazards regression analyses, higher serum NEFA levels were significantly associated with an increased risk of developing kidney function decline (adjusted-hazard ratio 3.67, 95% CI 1.64–8.22, p < 0.001; for each 1-SD increment, i.e., 262 uEq/L), even after adjustment for waist circumference, hemoglobin A1c, C-reactive protein, HOMA-estimated insulin resistance, hypertension, dyslipidemia, microalbuminuria, baseline eGFRCKD-EPI, as well as temporal changes in HbA1c levels or the use of renin-angiotensin system inhibitors over the follow-up.

Conclusions

The findings of this exploratory prospective study show that in post-menopausal women with T2DM and preserved kidney function at baseline, higher circulating levels of NEFA were strongly associated with a faster kidney function decline, even after adjustment for established renal risk factors and potential confounders.

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Data availability

Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will, on request, detail the restrictions and any conditions under which access to some data may be provided.

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Funding

GT is partly supported by grants from the University School of Medicine of Verona, Verona, Italy.

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Authors and Affiliations

  1. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126, Verona, Italy

    Alessandro Mantovani, Alessandro Csermely, Davide Cappelli, Antonio Taverna, Elena Sani, Emigela Shtembari, Micol Pagani & Giovanni Targher

  2. IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella, Italy

    Giovanni Targher

Authors
  1. Alessandro Mantovani
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  2. Alessandro Csermely
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  3. Davide Cappelli
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  4. Antonio Taverna
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  5. Elena Sani
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  6. Emigela Shtembari
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  7. Micol Pagani
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  8. Giovanni Targher
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Corresponding author

Correspondence to Alessandro Mantovani.

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All authors do not have any conflicts of interest to declare.

Ethical approval

The study was performed according to the Declaration of Helsinki. The local Ethics Committee approved the study protocol. All participants gave their written informed consent for participation in this research.

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This article belongs to the Topical Collection “Diabetic Nephropathy”, managed by Giuseppe Pugliese.

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Mantovani, A., Csermely, A., Cappelli, D. et al. Higher circulating levels of non-esterified fatty acids are associated with faster kidney function decline in post-menopausal women with type 2 diabetes: a pilot prospective study. Acta Diabetol 61, 281–288 (2024). https://doi.org/10.1007/s00592-023-02198-6

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  • DOI: https://doi.org/10.1007/s00592-023-02198-6

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