Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria

Diabetologia. 2017 May;60(5):911-914. doi: 10.1007/s00125-017-4219-1. Epub 2017 Feb 13.

Abstract

Aims/hypothesis: Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown.

Methods: In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin-angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs). All participants had an eGFR >45 ml/min, duration of diabetes >20 years and no history of CVD. Serum soluble Klotho levels were measured by a validated immunoassay.

Results: Participants with microalbuminuria had significantly lower levels of serum Klotho compared with those without microalbuminuria (median [interquartile range], 659.3 [525.3, 827.6] vs 787.7 [629.5, 1007]; p = 0.023). This difference persisted after adjustment for variables including age and eGFR. In a subgroup of 30 individuals with and without microalbuminuria, other markers of phosphate balance were not significantly different.

Conclusions/interpretation: In individuals with type 1 diabetes, microalbuminuria is associated with soluble Klotho deficiency. Further studies are required to determine whether soluble Klotho is causally related to the development of cardio-renal disease in type 1 diabetes.

Keywords: Microalbuminuria; Soluble Klotho; Type 1 diabetes.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Albuminuria / blood*
  • Albuminuria / physiopathology
  • Albuminuria / prevention & control
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Female
  • Glomerular Filtration Rate / physiology
  • Glucuronidase / blood*
  • Humans
  • Immunoassay
  • Klotho Proteins
  • Male
  • Middle Aged

Substances

  • Glucuronidase
  • Klotho Proteins