Skin autofluorescence predicts cancer in subjects with type 2 diabetes

Abstract

IntroductionSubjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes.Research design and methodsFrom 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences.ResultsThe participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2–3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (χ2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045).ConclusionsSkin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.

Genome-wide association study identifies novel loci associated with skin autofluorescence in individuals without diabetes

“…Because of the growing interest to use SAF to screen for type 2 diabetes, diabetes complication risks, cardiovascular disease and mortality [12,37], more information on possible genetic determinants of SAF is warranted, especially because studies of serum AGEs have estimated heritability of 63-74% [14,15]. Understanding the genetics of a quantitative trait can improve performance of the tool.…”

Genome-wide association study identifies novel loci associated with skin autofluorescence in individuals without diabetes

“…Because of the growing interest to use SAF to screen for type 2 diabetes, diabetes complication risks, cardiovascular disease and mortality [12,37], more information on possible genetic determinants of SAF is warranted, especially because studies of serum AGEs have estimated heritability of 63-74% [14,15]. Understanding the genetics of a quantitative trait can improve performance of the Table 3 Linear regression models for lnSAF in R (GSA) tool.…”

“…In non-diabetic individuals SAF is a predictor for the development of type 2 diabetes, cardiovascular events and mortality and in individuals with both type 1 and type 2 diabetes SAF predicts diabetes-related complications and mortality [5][6][7][8][9][10][11]. A recent study reported that SAF may also predict the occurrence of cancer in individuals with type 2 diabetes, thereby suggesting the possibility that SAF may be used in selection of type 2 diabetes individuals for cancer screening [12].…”

AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers

“…Recently, the cutaneous accretion of these fluorescent AGEs arising from long-lived hyperglycemia in diabetics were assessed by measuring SAF with an AGE reader, using excitation and emission range of 300–420 nm and 420–600 nm, respectively, spanning different AGEs. Type-2 diabetic patients who had cancer or went onto develop new cancers had considerably higher initial SAF values than those who did not have or develop cancer [ 47 ]. SAF values greater than 2.6 projected a 2.6 fold increased risk of cancer with significant concomitance between AGEs and cancer incidence (shown in Table 2 ).…”