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Lymphocytes of type 2 diabetic women carry a high load of stable chromosomal aberrations: A novel risk factor for disease-related early death

¹Division of Endocrinology and Diabetes, Graduate School Molecular Endocrinology and Diabetes, Ulm University, Germany
²Institute of Pathology, Ulm University, Ulm, Germany
³Institute of Human Genetics, Ulm University, Ulm, Germany
⁴Cardiology Group, Frankfurt-Sachsenhausen, Germany
⁵Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
⁶LURIC Study nonprofit LLC, Freiburg, Germany

Objective: Diabetes mellitus is associated with an increased risk of death in women. Oxidative stress due to chronic hyperglycemia leads to the generation of reactive oxygen species and loss of chromosomal integrity. To clarify whether diabetes is a premature aging syndrome, we determined telomere erosion dynamics and occurrence of structural chromosomal aberrations in women of the LURIC study.

Research Design and Methods: Telomere lengths and karyotypes were examined in peripheral blood mononuclear cells. Regarding these parameters, surviving and deceased type 2 diabetes women of the LURIC study were compared to non-diabetic LURIC females with or without coronary heart disease, and to healthy female controls.

Results: Significantly enhanced telomere attrition was seen in all LURIC subjects compared to healthy controls. Although the average telomere length loss is equivalent to well above 10 years of healthy aging, telomere erosion was not associated with outcome within the LURIC cohort. However, strikingly high numbers of stable chromosomal aberrations were found in type 2 diabetes women but not in LURIC disease controls or in healthy individuals. Furthermore, within the younger age groups, deceased type 2 diabetes patients had significantly more marker chromosomes than the surviving type 2 diabetes patients.

Conclusions: All women at high risk for cardiovascular death have accelerated telomere erosion, obviously not caused by type 2 diabetes per se but likely linked to other risk factors, including dyslipidemia. By contrast, the occurrence of marker chromosomes is associated with type 2 diabetes and is a novel risk factor for type 2 diabetes-related early death.

Key Words: type 2 diabetes • dyslipidemia • oxidative stress • chromosomal aberrations • telomere length • telomere shortening

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