Danish Medical Bulletin - No. 3. September 2004. Vol. 51 Page 298.

ABSTRACT OF PhD DISSERTATION

Lens fluorescence as a marker of ageing in relation to
heritability, diabetes mellitus, and ischaemic heart disease

Line Kessel

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This PhD dissertation was accepted by the Faculty of Health Sciences of the University of Copenhagen, and defended on June 4, 2004.

Official opponents: Jens Christian Nørregaard, Jesper Hjortdal, Allan Vaag.

Tutors: Michael Larsen, Lennart B-Å Johansson (Sweden), Lars Lindvold.

Correspondence: Line Kessel, IP Hansensvej 13, DK-4000 Roskilde.
E-mail: line.kessel@dadlnet.dk

Dan Med Bull 2004;51:298.

ABSTRACT

The PhD project was performed during my position as a research fellow at the Department of Ophthalmology at Herlev Hospital from August 2000 to August 2003. The PhD dissertation consists of 5 original scientific papers.

The aim of the PhD project was to examine the relationship between the ageing process of the lens in the human eye and general health status with special emphasis on diabetes mellitus and ischaemic heart disease. Lens ageing was quantified by lens autofluorometry. The basic concept of lens autofluorometry is that metabolic and oxidative stress induce changes on lens proteins. These changes give rise to a physical phenomenon, fluorescence, which can be quantified objectively and non-invasively in vivo. There is no degradation of lens proteins, the concentration of fluorophores in the lens thus reflects a life-time index of metabolic and oxidative stress.

The phd-project is based on clinical, epidemiological studies. The first study, a twin study, showed that the ageing process in the lens was influenced by genetic and environmental factors of which glucose metabolism and tobacco smoking were the most conspicuous. The second study investigated the long-term relationship between lens ageing and metabolic control. It demonstrated that rate of lens ageing reflects a long-term glycaemic index. In the third study, the relationship between lens ageing and long-term glycaemia was used to produce a mathematical model describing the prediagnostic glycaemic load, and hence derives the prediagnostic duration, in patients recently diagnosed with type 2 diabetes mellitus. In the fourth study, the model from study three was used to estimate the prediagnostic duration of type 2 diabetes mellitus in a group of patients diagnosed with type 2 diabetes mellitus as a result of systematic screening. The prediagnostic duration of type 2 diabetes mellitus was found to be 2 years. The fifth and last study showed that the ageing process of the lens was accelerated in subjects with a high risk of developing ischaemic heart disease. The association between lens ageing and ischaemic heart disease risk was attributable to the effects of glucose metabolism and tobacco smoking.

The fluorescence of the human lens is caused by accumulation of advanced glycation end products formed by non-enzymatic glycation on lens proteins. Advanced glycation end products are important for the pathogenesis of diabetic long-term complications. Lens fluorescence may thus serve as a biomarker of the extent of tissue-damage related to advanced glycation end products which may be of importance for the management of diabetic patients.
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