Lens ageing as an indicator of tissue damage associated with smoking and non-enzymatic glycation - a twin study

Kessel, Line; Hougaard, Jesper Leth; Sander, Birgit; Kyvik, Kirsten Ohm; Sørensen, Thorkild I A; Larsen, Michael

doi:10.1007/s00125-002-0925-3

Cited by 34 publications

(5 citation statements)

References 22 publications

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“…Some previous studies suggested that genetics play a role in skin and lens fluorescence 38 39 . Indeed, a recent genome-wide association study has reported an association between N -acetyltransferase 2 (NAT2) acetylation status and SAF in people with and without diabetes of European decent 40 .…”

Section: Discussionmentioning

confidence: 99%

A new gender-specific model for skin autofluorescence risk stratification

Ahmad

Damanhouri

Kimhofer

et al. 2015

Sci Rep

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Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79–4.84 AU) and 2.20 AU (0.75–4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis.

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Section: Discussionmentioning

confidence: 99%

A new gender-specific model for skin autofluorescence risk stratification

Ahmad

Damanhouri

Kimhofer

et al. 2015

Sci Rep

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“…A newly-described noninvasive method to assess tissue AGEs involves skin autofluorescence. This method is based on the specific fluorescence characteristics of AGEs and has been employed in both skin and lens [57, 58] . Studies by our group and others have shown that autofluorescence is increased in the presence of diabetes and may serve as a biomarker in identifying risks for microvascular complications in type 2 diabetic patients [14, 59] .…”

Section: Tissue Biomarkers In Diabetes: Skin and Retinamentioning

confidence: 99%

Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers

Lyons

Basu

2012

Translational Research

182

133

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Biomarkers are conventionally defined as ‘biological molecules that represent health and disease states.’ They typically are measured in readily available body fluids (blood or urine), lie outside the causal pathway, are able to detect sub-clinical disease, and are used to monitor clinical and sub-clinical disease burden and response to treatments. Biomarkers can be “direct” endpoints of the disease itself, or “indirect” or surrogate endpoints. New technologies (such as metabolomics, proteomics, genomics) bring a wealth of opportunity to develop new biomarkers. Other new technologies enable the development of non-molecular, functional or bio-physical tissue-based biomarkers. Diabetes mellitus is a complex disease affecting almost every tissue and organ system, with metabolic ramifications extending far beyond impaired glucose metabolism. Biomarkers may reflect the presence and severity of hyperglycemia (i.e. diabetes itself), or the presence and severity of the vascular complications of diabetes. Illustrative examples are considered in this brief review. In blood, hemoglobin A1c (HbA1c) may be considered as a biomarker for the presence and severity of hyperglycemia, implying diabetes or pre-diabetes, or, over time, as a “biomarker for a risk factor”, i.e. hyperglycemia as a risk factor for diabetic retinopathy, nephropathy, and other vascular complications of diabetes. In tissues, glycation and oxidative stress resulting from hyperglycemia and dyslipidemia lead to widespread modification of biomolecules by advanced glycation end products (AGEs). Some of these altered species may serve as biomarkers, whereas others may lie in the causal pathway for vascular damage. New non-invasive technologies can detect tissue damage mediated by AGE formation: these include indirect measures such as pulse wave analysis (a marker of vascular dysfunction) and more direct markers such as skin autofluorescence (a marker of long-term accumulation of AGEs). In the future, we can be optimistic that new blood and tissue-based biomarkers will enable the detection, prevention, and treatment of diabetes and its complications long before overt disease develops.

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“…A twin study has shown that lens fluorescence is significantly heritable [21]. However, the specific genetic determinants of SF are unknown.…”

Section: Introductionmentioning

confidence: 99%

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence

et al. 2014

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Aims/hypothesisSkin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.MethodsCohort 1 included 1,082 participants, 35–67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18–90 years.Resultsrs1495741 was significantly associated with SF in Cohort 1 (p < 6 × 10−10), which is known to tag the NAT2 acetylator phenotype. The fast acetylator genotype was associated with lower SF, explaining up to 15% of the variance. In Cohort 2, the top signal associated with SF (p = 8.3 × 10−42) was rs4921914, also in NAT2, 440 bases upstream of rs1495741 (linkage disequilibrium r2 = 1.0 for rs4921914 with rs1495741). We replicated these results in two additional cohorts, one with and one without type 1 diabetes. Finally, to understand which compounds are contributing to the NAT2–SF signal, we examined 11 compounds assayed from skin biopsies (n = 198): the fast acetylator genotype was associated with lower levels of the AGEs hydroimidazolones of glyoxal (p = 0.017).Conclusions/interpretationWe identified a robust association between NAT2 and SF in people with and without diabetes. Our findings provide proof of principle that genetic variation contributes to interindividual SF and that NAT2 acetylation status plays a major role.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3286-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Lens ageing as an indicator of tissue damage associated with smoking and non-enzymatic glycation - a twin study

Cited by 34 publications

References 22 publications

A new gender-specific model for skin autofluorescence risk stratification

A new gender-specific model for skin autofluorescence risk stratification

Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence

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