Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathyReportar como inadecuado

Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cardiovascular Diabetology

, 12:116

First Online: 14 August 2013Received: 22 May 2013Accepted: 12 August 2013


BackgroundDiabetes is associated with a high incidence of macrovascular disease MVD, including peripheral and coronary artery disease. Circulating soluble-Klotho sKlotho is produced in the kidney and is a putative anti-aging and vasculoprotective hormone. Reduced Klotho levels may therefore increase cardiovascular risk in diabetes. We investigated if sKlotho levels are decreased in type 2 diabetes and associate with MVD in the absence of diabetic nephropathy, and whether hyperglycemia affects renal Klotho production in vitro and in vivo.

MethodssKlotho levels were determined with ELISA in diabetic and non-diabetic patients with and without MVD, and healthy control subjects. Human renal tubular epithelial cells TECs were isolated and exposed to high glucose levels 15 and 30 mM in vitro and Klotho levels were measured with qPCR and quantitative immunofluorescence. Klotho mRNA expression was quantified in kidneys obtained from long term 3 and 8 months diabetic Ins2 mice and normoglycemic control mice.

ResultsNo significant differences in sKlotho levels were observed between diabetic patients with and without MVD 527 433–704 pg-mL, n = 35, non-diabetic MVD patients 517 349–571 pg-mL, n = 27, and healthy control subjects 435 346–663 pg-mL, n = 15. High glucose 15 and 30 mM did not alter Klotho expression in TECs. Long-term hyperglycemia in diabetic Ins2 mice characterized by increased HbA1c levels 12.9 ± 0.3% 3 months and 11.3 ± 2.0% 8 months, p < 0.05 vs. non-diabetic mice did not affect renal Klotho mRNA expression.

ConclusionsThese data indicate that sKlotho levels are not affected in type 2 diabetes patients with and without MVD. Furthermore, hyperglycemia per se does not affect renal Klotho production. As type 2 diabetes does not alter sKlotho levels, sKlotho does not seem to play a major role in the pathogenesis of MVD in type 2 diabetes.

KeywordsAtherosclerosis Coronary artery disease Klotho Macrovascular disease Peripheral artery disease Type 2 diabetes AbbreviationsADAMA Disintegrin and metalloproteinase domain-containing protein

BUNBlood urea nitrogen

CADCoronary artery disease

CKDChronic kidney disease

CVDCardiovascular disease

eGFREstimated glomerular filtration rate

EMAEpithelial membrane antigen

FGF23Fibroblast growth factor 23

FGFR1Fibroblast growth factor receptor 1

MVDMacrovascular disease

PADPeripheral artery disease

sKlothoSoluble Klotho

TECTubular epithelial cell

WBCWhite blood cells.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2840-12-116 contains supplementary material, which is available to authorized users.

An erratum to this article is available at

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Autor: Joris van Ark - Hans-Peter Hammes - Marcory C R F van Dijk - Marc G Vervloet - Bruce H R Wolffenbuttel - Harry van Goo


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