The levels of the α-klotho protein could have a useful role as a biomarker to help identify patients with type 1 diabetes who are at increased risk of developing arteriosclerosis and thus increased cardiovascular risk. This is suggested by a study published in the journal Cardiovascular Diabetology, led by CIBERDEM researchers from the Endocrinology, Diabetes and Nutrition Research Group of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, directed by Dr. Dídac Mauricio, head of the Endocrinology Service of the same hospital.

Patients with diabetes have a higher risk of developing arteriosclerosis, especially those who also have kidney problems. Previous studies had already detected that these patients had altered levels of α-klotho. This protein is one of the main molecules involved in mineral metabolism, but until now its circulating levels had been found to be reduced in early stages of renal dysfunction, which had been associated with an increased risk of developing cardiovascular diseases.

“In people with diabetes, atherosclerosis is more frequent compared to the non-diabetic population. For this reason, it is very important to anticipate the development of atherosclerotic plaques subclinically, that is, when they have not yet caused symptoms”, explains Josep Julve, one of the main authors of the study at the IIB Sant Pau.

In this study, the researchers analyzed the relationship between circulating levels of different determinants of mineral metabolism related to calcium/phosphorus metabolism in relation to the burden of subclinical carotid arteriosclerosis in patients with type 1 diabetes. The results show that the proteins FGF23 and α-klotho present alterations associated with the progression of chronic kidney disease.

In this new investigation, unlike previous studies, the relationship between α-klotho levels in patients with type 1 diabetes without chronic kidney disease was analyzed. The results demonstrate, for the first time, that serum levels of this protein are increased in diabetics with subclinical arteriosclerotic disease. Furthermore, circulating levels of α-klotho were also related to the number of subclinical arteriosclerotic plaques in people without diabetes, postulating it as an independent risk factor and thus a potential biomarker.

The researcher comments that “one of the most relevant aspects of this study is that the association between high levels of α-klotho and the development of atherosclerotic plaque was observed in the absence of impaired renal function or established diabetic nephropathy.”

From these results, new research questions are derived that will give rise to new studies, both clinical and translational, to confirm the importance of this protein as an early risk factor for subclinical arteriosclerosis in patients with type 1 diabetes.

CIBERDEM researchers from the Endocrinology and Nutrition Service of the Hospital Universitario Arnau de Vilanova – Institut d’Investigació Biomédica de Lleida (IRB Lleida) and the Washington University School of Medicine, in Saint Louis, Missouri (United States) also collaborated in the development of this study. ).

Reference Article

Castelblanco E, Hernández M, Alonso N, Ribes-Betriu A, Real J, Granado-Casas M, Rossell J, Rojo-López MI, Dusso AS, Julve J, Mauricio D. Association of α-klotho with subclinical carotid atherosclerosis in subjects with type 1 diabetes mellitus. Cardiovasc Diabetol. 2022 Oct 11;21(1):207. doi: 10.1186/s12933-022-01640-3. PMID: 36221075; PMCID: PMC9554979

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