Cross-Sectional Evaluation of Noninvasively Detected Skin Intrinsic Fluorescence and Mean Hemoglobin A1c in Type 1 Diabetes
ABSTRACT Abstract 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 m(2) 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.
SourceAvailable from: K M V Narayan[Show abstract] [Hide abstract]
ABSTRACT: The albumin-to-creatinine ratio (ACR) reflects urinary albumin excretion and is increasingly being accepted as an important clinical outcome predictor. Because of the great public health need for a simple and inexpensive test to identify individuals at high risk for developing type 2 diabetes, it has been suggested that the ACR might serve this purpose. We therefore determined whether the ACR could predict incident diabetes in a well-characterized cohort of pre-diabetic Americans. A total of 3,188 Diabetes Prevention Program (DPP) participants with a mean BMI of 34 kg/m(2) and elevated fasting glucose, impaired glucose tolerance, and baseline urinary albumin excretion measurements were followed for incident diabetes over a mean of 3.2 years. Of the participants, 94% manifested ACR levels below the microalbuminuria range and 21% ultimately developed diabetes during follow-up. Quartiles of ACR (median [range] within quartiles: 1, 3.0 [0.7-3.7]; 2, 4.6 [3.7-5.5]; 3, 7.1 [5.5-9.7]; and 4, 16.5 [9.7-1,578]) were positively associated with age, markers of adiposity and insulin secretion and resistance, blood pressure, and use of antihypertensive agents with antiproteinuric effects and inversely related to male sex and serum creatinine. An elevated hazard rate for developing diabetes with doubling of ACR disappeared after adjustment for covariates. Within the DPP intervention groups (placebo, lifestyle, and metformin), we found no consistent trend in incident diabetes by quartile or decile of ACR. An ACR at levels below the microalbuminuria range does not independently predict incident diabetes in adults at high risk of developing type 2 diabetes.Diabetes care 10/2008; 31(12):2344-8. DOI:10.2337/dc08-0148 · 8.57 Impact Factor
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ABSTRACT: Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.Annals of internal medicine 05/2009; 150(9):604-12. · 16.10 Impact Factor
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ABSTRACT: Considerable progress has been made in our understanding of nonenzymatic glycation of collagen, and the relationship between glycation of collagen and changes in connective tissue associated with aging and diabetes. Recent studies surveyed in this review suggest the following conclusions: 1. Collagen content of early glycation products does not appear to increase throughout the life span in normal human subjects, although small increases may occur that are linked to glycemic changes. These products are increased, relative to age-matched controls, in experimental diabetes and in diabetes mellitus in collagen from virtually all tissues analyzed. 2. Collagen content of browning products increases with aging and appears to be higher in diabetic subjects than in age-matched controls. Rates of accumulation may be accelerated in subpopulations of diabetic subjects at high risk for developing complications. 3. Increases in early glycation products do not appear to be associated with alterations in collagen solubility, thermal rupture time, or mechanical strength, nor is there an association with most diabetic complications. Alterations in these products may, however, affect conformation, ligand binding, lysyl oxidase-mediated cross-linking, and interactions between collagen and other macromolecules in the extracellular matrix. 4. Increased content of browning products is associated with many physicochemical changes in collagen as well as with long-term complications in diabetes mellitus. 5. Regulatory mechanisms have been identified in vivo that may serve to control or limit the formation of glycation products. 7. Pharmacologic agents have been identified that may be able to reduce collagen content of late glycation products. Despite the progress that has been made in this field, many areas of uncertainty and controversy exist. For example, there is not yet a consensus that the browning products associated with collagen exclusively comprise advanced Maillard products derived from nonenzymatically glycated residues. There is evidence that oxidative reactions involving lipids also play a role in generating fluorophores and chromophores that may alter properties of collagen. Thus, in the extracellular matrix collagen may be continuously modified by at least three very different processes: Maillard reactions, interactions with oxidizing lipids, and enzymatically mediated cross-linking. The interrelationships between these and possibly other posttranslational modifications remain a poorly understood area of great complexity.Proceedings of The Society for Experimental Biology and Medicine 02/1991; 196(1):17-29. DOI:10.3181/00379727-218-44264