Noninvasive skin fluorescence spectroscopy for detection of abnormal glucose tolerance.

The ENGINE study evaluated noninvasive skin fluorescence spectroscopy (SFS) for detection of abnormal glucose tolerance (AGT). The AGT detection performance of SFS was compared to fasting plasma glucose (FPG) and hemoglobin A1C (A1C). The study was a head-to-head comparison of SFS to FPG and A1C in an at-risk population of 507 subjects, with no prior diagnosis of diabetes, each of whom received a 75 g, two-hour oral glucose tolerance test (OGTT). Subjects were measured by SFS on multiple days in fasting and non-fasting states. SFS data were acquired and analyzed with the SCOUT DS® device (VeraLight, Albuquerque, NM, USA). Disease truth was AGT, defined as OGTT ≥ 7.8 mmol/L. Sensitivity, false positive rate (FPR), ROC area, and equal error rate (EER) for detection of AGT were computed. The reproducibility of SFS and FPG was assessed. The AGT sensitivity of SFS at the device's recommended screening threshold of 50 was 75.2%, higher than that of FPG (thresholds of 5.6 mmol/L or 6.1 mmol/L) and A1C (thresholds of 5.7% or 6.0%). The SFS FPR was 42.1%, comparable to an A1C threshold of 5.7% (FPR = 43.5%). The EERs of SFS, FPG and A1C were similar, as were the partial ROC areas for FPRs of 20-50%. The reproducibility of SFS was 7.7% versus 8.1% for FPG. SFS had similar AGT detection performance to FPG and A1C and is a viable alternative to screening individuals for AGT.

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.

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.

Reflectance-based determination of optical properties in highly attenuating tissue.

Accurate data on in vivo tissue optical properties in the ultraviolet A (UVA) to visible (VIS) range are needed to elucidate light propagation effects and to aid in identifying safe exposure limits for biomedical optical spectroscopy. We have performed a preliminary study toward the development of a diffuse reflectance system with maximum fiber separation distance of less than 2.5 mm. The ultimate objective is to perform endoscopic measurement of optical properties in the UVA to VIS. Optical property sets with uniformly and randomly distributed values were developed within the range of interest: absorption coefficients from 1 to 25 cm(-1) and reduced scattering coefficients from 5 to 25 cm(-1). Reflectance datasets were generated by direct measurement of Intralipid-dye tissue phantoms at lambda=675 nm and Monte Carlo simulation of light propagation. Multivariate calibration models were generated using feed-forward artificial neural network or partial least squares algorithms. Models were calibrated and evaluated using simulated or measured reflectance datasets. The most accurate models developed-those based on a neural network and uniform optical property intervals-were able to determine absorption and reduced scattering coefficients with root mean square errors of +/-2 and +/-3 cm(-1), respectively. Measurements of ex vivo bovine liver at 543 and 633 nm were within 5 to 30% of values reported in the literature. While our technique for determination of optical properties appears feasible and moderately accurate, enhanced accuracy may be achieved through modification of the experimental system and processing algorithms.

Selective detection of fluorophore layers in turbid media: the role of fiber-optic probe design.

Experimental verification of the ability to alter the sensitivity to fluorophore layers in turbid media by varying illumination-collection geometry is presented. Fiber-optic probes and two-layer, fluorophore-doped, turbid phantoms are used to elucidate the roles of spot size, illumination-collection fiber separation, and probe-sample spacing. Variations in single- and multiple-fiber probe design parameters produce significant changes in the relative sensitivity to sample layers in a manner that agrees with prior computational studies.

In vivo assessment of diabetic lenses using dynamic light scattering.

One of the most threatening aspects of diabetes mellitus is the development of visual impairment. For example, cataracts are 1.6 times more common in people with diabetes than in those without diabetes. Cataract extraction is the only treatment. In many cases, diabetes-related ocular pathologies go undiagnosed until visual function is compromised. This paper compares and contrasts the ocular changes observed using dynamic light scattering (DLS) and conventional ophthalmic techniques during long-term maintenance of the sand rat (Psammomys obesus) on a high caloric diet. P. obesus is a wild rodent in the subfamily Gerbillinae that inhabits the desert areas of the Middle East and Africa. This animal is unique in that it develops mild to moderate obesity, hyperglycemia, pancreatic atrophy, impaired renal function, ketoacidosis, vision loss, and other diabetic complications when it consumes a high caloric diet. In this study, five animals were fed Purina sand rat chow and thus served as normal control animals. Five animals were fed a commercially prepared rodent diet (Purina 5002) consisting of only 4-5% fiber and a grain-based rabbit supplement (BioServe Rabbit Stix Appetite Stimulant) consisting of 50% carbohydrate to provide a high caloric (diabetogenic) diet and thus induce diabetes. Blood samples for the biochemical analyses, DLS, and other optical examinations were obtained on alternate weeks. Our preliminary results have demonstrated subtle changes in the lens of the diabetic sand rats as early as 2 months on a diabetogenic diet. This is an ongoing joint project with Food and Drug Administration and the National Aeronautics and Space Administration. This technique is proving to be a practical, sensitive, noninvasive diagnostic tool useful for the early detection of ocular pathologies and understanding the mechanism of cataract formation.

Multiple-fiber probe design for fluorescence spectroscopy in tissue.

The fiber-optic probe is an essential component of many quantitative fluorescence spectroscopy systems, enabling delivery of excitation light and collection of remitted fluorescence in a wide variety of clinical and laboratory situations. However, there is little information available on the role of illumination--collection geometry to guide the design of these components. Therefore we used a Monte Carlo model to investigate the effect of multifiber probe design parameters--numerical aperture, fiber diameter, source--collection fiber separation distance, and fiber-tissue spacer thickness--on light propagation and the origin of detected fluorescence. An excitation wavelength of 400 nm and an emission wavelength of 630 nm were simulated. Noteworthy effects included an increase in axial selectivity with decreasing fiber size and a transition with increasing fiber-tissue spacer size from a subsurface peak in fluorophore sensitivity to a nearly monotonic decrease typical of single-fiber probes. We provide theoretical evidence that probe design strongly affects tissue interrogation. Therefore application-specific customization of probe design may lead to improvements in the efficacy of fluorescence-based diagnostic devices.