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Association of Klotho with Coronary Artery Disease in Subjects with Type 2 Diabetes Mellitus and Preserved Kidney
Javier Donate-Correa1,2,3,4, Ernesto Martín-Núñez1,2, Carmen Mora-Fernández1,2,4
1Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain.
Insights
In type 2 diabetes mellitus (T2DM) patients with normal kidney function, higher circulating Klotho levels correlate with coronary artery disease (CAD) burden. This finding contrasts with general Klotho reduction in T2DM and kidney disease.
Area of Science:
- Endocrinology
- Cardiology
- Nephrology
Background:
- Circulating Klotho is reduced in type 2 diabetes mellitus (T2DM) and kidney disease.
- The role of Klotho in coronary artery disease (CAD) within T2DM patients with preserved kidney function is unclear.
Purpose of the Study:
- To investigate the association between serum Klotho levels and the extent of CAD in T2DM patients with normal kidney function.
Main Methods:
- Cross-sectional study of 133 T2DM patients and 200 non-diabetic controls undergoing coronary angiography.
- Measurements included serum Klotho, fibroblast growth factor 23, and inflammatory markers.
- Analysis of CAD burden using coronary angiography and correlation with Klotho levels.
Main Results:
- Serum Klotho was lower in the T2DM group compared to controls.
- Within the T2DM group, patients with significant CAD had higher Klotho levels than those without.
- Serum Klotho positively correlated with coronary stenosis severity in T2DM patients.
Conclusions:
- Higher circulating Klotho levels in T2DM patients with preserved kidney function are associated with the presence and severity of significant CAD.
- This suggests a complex, potentially protective role of Klotho in the context of diabetic cardiovascular complications.
Abstract:
Circulating Klotho levels are significantly reduced in subjects with type 2 diabetes mellitus (T2DM) and in kidney disease patients. In this work, the relationship between Klotho levels and the coronary artery disease (CAD) burden in subjects with T2DM and preserved kidney function was analyzed. For this, we performed a cross-sectional case-control study involving 133 subjects with T2DM and 200 age-, sex- and CAD-incidence-matched, non-diabetic patients undergoing non-emergency diagnostic coronary angiography. All of them were non-albuminuric and with normal glomerular filtration rates. The concentrations of serum Klotho, fibroblast growth factor 23, and inflammatory markers were also measured. As expected, the serum Klotho concentration was lower in the T2DM group (12.3% lower, p = 0.04). However, within the group of patients with T2DM, those subjects with CAD presented significantly higher Klotho levels than those without significant coronary stenosis (314.5 (6.15-562.81) vs. 458.97 (275.2-667.2) pg/mL; p = 0.02). Multiple regression analysis revealed that serum Klotho was positively related with stenosis values exclusively in subjects with T2DM (adjusted R2 = 0.153, p < 0.01). Moreover, logistic regression analysis showed that Klotho was positively associated with the presence of significant CAD in the group of T2DM patients (OR: 1.001; p = 0.041). Our data suggest that higher levels of circulating Klotho in subjects with T2DM and preserved kidney function are associated with the presence of significant CAD.
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