Skin Intrinsic Fluorescence Is Associated With Hemoglobin A1c and Hemoglobin Glycation Index but Not Mean Blood Glucose in Children With Type 1 Diabetes

Abstract

OBJECTIVETo evaluate the relationship between skin advanced glycation end products (sAGEs) with mean blood glucose (MBG), hemoglobin A1c (HbA1c), and MBG-independent, between-patient differences in HbA1c among children with type 1 diabetes.RESEARCH DESIGN AND METHODSChildren aged 5 to 20 years with type 1 diabetes of at least 1 year duration participated. At a clinic visit, sAGE was estimated noninvasively by measurement of skin intrinsic fluorescence (SIF). SIF data were adjusted to correct for variation in skin pigmentation. MBG-independent, between-patient differences in HbA1c were examined by statistically controlling HbA1c for MBG or alternatively by use of a hemoglobin glycation index (HGI). Results were similar whether HbA1c, MBG, and HGI were analyzed as single values from the time of the SIF examination visit or as the mean values from all available visits of the patient.RESULTSHbA1c was correlated with MBG (r = 0.5; P < 0.001; n = 110). HbA1c and HGI, but not MBG, were statistically associated with SIF after adjustment for age, duration of diabetes, race, sex, and BMI z-score. SIF increased with age and duration of diabetes and was higher in girls than boys.CONCLUSIONSsAGE levels estimated by SIF increase with age, duration of diabetes, and female sex. sAGE is correlated with MBG-independent biological variation in HbA1c, but not with MBG itself. These results suggest that factors besides MBG that influence HbA1c levels also contribute to accumulation of sAGE.

Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals

“…HGI has been shown to reflect the burden of AGEs in the tissues [38], raising the possibility that subjects with high HGI have increased levels of AGEs in the liver. There is accumulating evidence that activation of RAGE downstream pathway by AGEs may promote pro-inflammatory reactions and impair insulin signaling, thus contributing to the development and progression of NAFLD [23,24].…”

Cross-Sectional Evaluation of Noninvasively Detected Skin Intrinsic Fluorescence and Mean Hemoglobin A1c in Type 1 Diabetes

“…It is interesting that in children there was also an influence of gender on SIF, with higher levels in females at all ages than males, which we did not find in our adult cohort. In this study by Felipe et al, 20 which had 29% black or African American participants, race was also an influence on SIF, with SIF levels being higher in blacks than in whites. In our model, ethnicity was not a significant contributor, although our population was predominantly white.…”

“…In our model, ethnicity was not a significant contributor, although our population was predominantly white. The study by Felipe et al 20 found no significant association between mean blood glucose or mean blood glucose over time with SIF, suggesting factors other than mean blood glucose might influence nonenzymatic glycation and formation of AGEs.…”

“…5,[17][18][19][20] AGEs are formed from nonenzymatic glycation of tissue proteins and are found in a variety of tissues, including skin, tracheal cartilage, tendons, ligaments, cortical bone, aorta, cardiac muscle, lung, liver, kidney, lens, red blood cells, and blood proteins. 17 In skin biopsy studies, Dyer 21 previously showed that concentrations of AGEs such as N'-(carboxymethyl)lysine and pentosidine, as well as AGE-associated skin fluorescence, increase in human skin collagen with age and that the rate of their increase is accelerated in diabetes.…”

“…Finally, this study focused on long-term mean HbA1c as an indicator of glycemia, comparable to that used in the UKPDS. 2 However, other variables of interest to evaluate chronic glycemic exposure may have included mean blood glucose, 20 which was not available for this study.…”