Skin Intrinsic Fluorescence and Age-Related Macular Degeneration: The Beaver Dam Eye Study.

Purpose: To determine if skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation endproducts and oxidative stress in skin is associated with AMD. Methods: SIF was measured with the SCOUT DS skin fluorescence spectrometer in a cross-sectional cohort study of 969 persons aged 68 to 102 years from the 1181 who participated in the 25-year follow-up examination in the Beaver Dam Eye Study (BDES) in 2014 to 2016. The SCOUT DS skin fluorescence spectrometer uses five light-emitting diodes, centered at 375 nm to 456 nm. AMD was assessed by grading of digital color 45° stereoscopic fundus photographs of the macula using the Wisconsin Age-Related Maculopathy grading scheme. Analyses included logistic regression with generalized estimating equations to account for correlation between the eyes of a person. Results: There were data for 1827 eyes for analyses. Early AMD was present in 22% and late AMD in 4% of the eyes. While adjusting for age, sex, smoking status, and history of cardiovascular disease, there were no significant associations of any SIF measure with any AMD or exudative AMD. SIF01 (odds ratio per 1 SD difference on the log scale, 95% confidence interval) (1.66, 1.00-2.74, P = 0.05) and SIF03 (1.81, 1.16-2.81, P = 0.008) were associated with geographic atrophy. Conclusions: There was a suggestive relationship of two SIF measures, SIF01 and SIF03, using different correction factors from the excitation centered at 375 nm, with the prevalence of geographic atrophy in the BDES. Longitudinal follow-up is indicated to assess a temporal relationship.

White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes.

OBJECTIVE: Although microvascular complications are common in type 1 diabetes mellitus (T1DM), few studies have quantified the severity, risk factors, and implications of cerebral microvascular damage in these patients. As life expectancy in patients with T1DM increases, patients are exposed to age- and disease-related factors that may contribute to cerebral microvascular disease. METHODS: Severity and volume of white matter hyperintensities (WMH) and infarcts were quantified in 97 middle-aged patients with childhood-onset T1DM (mean age and duration: 50 and 41 years, respectively) and 81 non-T1DM adults (mean age: 48 years), concurrent with cognitive and health-related measures. RESULTS: Compared with non-T1DM participants, patients had more severe WMH (Fazekas scores 2 and 3 compared with Fazekas score 1, p < 0.0001) and slower information processing (digit symbol substitution, number correct: 65.7 ± 10.9 and 54.9 ± 13.6; pegboard, seconds: 66.0 ± 9.9 and 88.5 ± 34.2; both p < 0.0001) independent of age, education, or other factors. WMH were associated with slower information processing; adjusting for WMH attenuated the group differences in processing speed (13% for digit symbol, 11% for pegboard, both p ≤ 0.05). Among patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. Associations between measures of blood pressure or hyperglycemia and WMH were not significant. CONCLUSIONS: Clinically relevant WMH are evident earlier among middle-aged patients with childhood-onset T1DM and are related to the slower information processing frequently observed in T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage. Longitudinal studies are warranted to fully characterize WMH development, risk factors, and long-term effects on cognition.

Noninvasive skin fluorescence spectroscopy is comparable to hemoglobin A1c and fasting plasma glucose for detection of abnormal glucose tolerance.

AIM: We compare performance of noninvasive skin fluorescence spectroscopy (SFS), fasting plasma glucose (FPG), and hemoglobin A1c (A1C) for detection of abnormal glucose tolerance (AGT). METHODS: The NSEEDS trial evaluated SFS, FPG, and A1C in an at-risk population of 479 previously undiagnosed subjects from nine US centers, each of whom received a 75 g, 2 h oral glucose tolerance test (OGTT). Skin fluorescence spectra were collected and analyzed with SCOUT DS® devices. Disease truth was AGT, defined as OGTT ≥140 mg/dl. Abnormal glucose tolerance sensitivity, false positive rate (FPR), and receiver operating characteristic (ROC) curves were computed for each measurement technique. Skin fluorescence spectroscopy reproducibility was also assessed. RESULTS: The AGT sensitivity of SFS was 68.2%, higher than that of FPG (thresholds of 100 and 110 mg/dl) and A1C (thresholds of 5.7% and 6.0%). The FPR of SFS was 37.7%, comparable to A1C at the 5.7% threshold (30.7%). Partial ROC areas of SFS, FPG, and A1C were similar for FPRs of 20-50% (average sensitivities of 64.0%, 59.0%, and 68.6%, respectively). The interday coefficient of variation for SFS was 7.6%. CONCLUSIONS: Skin fluorescence spectroscopy has similar screening performance to FPG and A1C and is a viable approach for detection of AGT.

Cross-sectional evaluation of noninvasively detected skin intrinsic fluorescence and mean hemoglobin a1c in type 1 diabetes.

BACKGROUND: This study evaluated the relationship between skin intrinsic fluorescence (SIF) and long-term mean hemoglobin A1c (HbA1c) in individuals with type 1 diabetes. SUBJECTS AND METHODS: We undertook a cross-sectional analysis of 172 individuals with type 1 diabetes followed longitudinally with HbA1c data available over an average of 16.6 years. SIF was evaluated cross-sectionally using the SCOUT DS device (VeraLight Inc., Albuquerque, NM) and correlated with most recent HbA1c and long-term mean HbA1c. Potential determinants of this relationship, including age, gender, smoking status, duration of diabetes, and renal function, were also evaluated. RESULTS: Age-adjusted skin intrinsic fluorescence significantly correlated with long-term mean HbA1c (R=0.44, P<0.0001). In contrast, there was no significant relationship between SIF and most recent HbA1c (R=0.14, P=0.075). The best-fit model describing the relationship between SIF and mean HbA1c controlled for factors of age, duration of disease, renal function, and site of study conduct. Controlling for these factors was also important in understanding the relationship between most recent HbA1c and SIF. Evaluating longer-term HbA1c data also strengthened the relationship between SIF and mean HbA1c. In the presence of renal dysfunction or damage, as indicated by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or presence of gross proteinuria, there was no significant correlation between SIF and mean HbA1c. CONCLUSIONS: Noninvasive detection of SIF significantly correlates with long-term mean HbA1c, providing insight into long-term glycemic exposure. Age, duration of diabetes, and renal function are potential contributors to this relationship.

Noninvasive optical screening for diabetes.

BACKGROUND: Advanced glycation end products (AGEs) are implicated in the complications of diabetes. Advanced glycation end products also accumulate in the skin and are sensitive biomarkers for the risk of developing diabetes and related complications. Some AGEs fluoresce and can be measured noninvasively by optical spectroscopy. METHODS: Noninvasive screening for diabetes has been evaluated in an 18-site study involving a cohort of 2793 subjects meeting American Diabetes Association-based screening criteria. Subjects were measured with a specialized skin fluorimeter and also received traditional blood glucose and glycated hemoglobin tests. RESULTS: Retrospective results indicated that the noninvasive technology measuring dermal fluorescence is more sensitive at detecting abnormal glucose tolerance than either fasting plasma glucose or glycated hemoglobin A1C. CONCLUSIONS: These results suggest that noninvasive measurement of dermal fluorescence may be an effective tool to identify individuals at risk for diabetes and its complications. The noninvasive technology yields immediate results, and since measuring dermal fluorescence requires no blood draws or patient fasting, the instrument may be well suited for opportunistic screening.

Noninvasive type 2 diabetes screening: superior sensitivity to fasting plasma glucose and A1C.

OBJECTIVE: This study compared the performance of a novel noninvasive technology to fasting plasma glucose (FPG) and A1C tests for detecting undiagnosed diabetes and impaired glucose tolerance. RESEARCH DESIGN AND METHODS: The design was a head-to-head evaluation in a naïve population. Consented subjects received FPG and A1C tests and an oral glucose tolerance test (OGTT). Subjects were also measured by a noninvasive device that detects the fluorescence of skin advanced glycation end products. A total of 351 subjects participated. RESULTS: Subjects with 2-h OGTT values > or = 140 mg/dl defined the positive screening class. A total of 84 subjects (23.9% prevalence) screened positive. The performances of the noninvasive device, FPG, and A1C were evaluated for sensitivity and specificity against this classification. At the impaired fasting glucose threshold (FPG = 100 mg/dl), the FPG testing sensitivity was 58% and the specificity was 77.4%. At that same specificity, the sensitivity for A1C testing was 63.8%, while the noninvasive testing sensitivity was 74.7%. The sensitivity advantage of the noninvasive device over both blood tests for detecting diabetes and precursors was statistically significant (P < 0.05). CONCLUSIONS: The noninvasive technology showed clinical performance advantages over both FPG and A1C testing. The sensitivity differential indicated that the noninvasive device is capable of identifying 28.8% more individuals in the OGTT-defined positive screening class than FPG testing and 17.1% more than A1C testing. The combination of higher sensitivity and greater convenience--rapid results with no fasting or blood draws--makes the device well suited for opportunistic screening.