OBJECTIVETo determine whether skin intrinsic fluorescence (SIF) is associated with long-term complications of type 1 diabetes (T1D) and, if so, whether it is independent of chronic glycemic exposure and previous intensive therapy.RESEARCH DESIGN AND METHODSWe studied 1,185 (92%) of 1,289 active Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) participants from 2010 to 2011. SIF was determined using a fluorescence spectrometer and related cross-sectionally to recently determined measures of retinopathy (stereo fundus photography), cardiac autonomic neuropathy (CAN; R-R interval), confirmed clinical neuropathy, nephropathy (albumin excretion rate [AER]), and coronary artery calcification (CAC).RESULTSOverall, moderately strong associations were seen with all complications, before adjustment for mean HbA1c over time, which rendered these associations nonsignificant with the exception of sustained AER >30 mg/24 h and CAC, which were largely unaffected by adjustment. However, when examined within the former DCCT treatment group, associations were generally weaker in the intensive group and nonsignificant after adjustment, while in the conventional group, associations remained significant for CAN, sustained AER >30 mg/24 h, and CAC even after mean HbA1c adjustment.CONCLUSIONSSIF is associated with T1D complications in DCCT\EDIC. Much of this association appears to be related to historical glycemic exposure, particularly in the previously intensively treated participants, in whom adjustment for HbA1c eliminates statistical significance.

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.

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 6 10.9 and 54.9 6 13.6; pegboard, seconds: 66.0 6 9.9 and 88.5 6 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. Patients with type 1 diabetes mellitus (T1DM) develop slower information processing speed earlier than adults without diabetes.1 In nondiabetic populations, slower information processing speed is strongly associated with white matter hyperintensities (WMH).2,3 Few studies, however, have characterized WMH in patients with T1DM. 4 Most of the knowledge about WMH comes from older populations without diabetes: WMH 5 are common in individuals older than 65 years, 6 with a prevalence ranging from 60% to 100%, 7 and are less frequent in middle-aged adults, with prevalence ranging from 0% to 50%. 8 Although they can remain silent, WMH predict greater incidence of stroke, dementia, disability, and death.2,9-11 In addition to older age, chronic exposure to hypertension and hyperglycemia are known risk factors for WMH in adults without diabetes, conditions that may predispose patients with T1DM to develop WMH. Considering the increasing life expectancy in T1DM 12 and the 1.5% to 3.0% annual increase in T1DM incidence, 13 determining the severity of, and risk factors for, WMH in patients with T1DM who are now aging deserves prompt...

Background: Coronary artery calcification (CAC) is more severe and occurs at an earlier age in type 1 diabetes. Risk factors for this subclinical marker of atherosclerotic burden, like coronary artery disease (CAD) itself, are not fully identified. One postulated mechanism for the increased CAC observed in type 1 diabetes is the accumulation of advanced glycation end products (AGEs). As certain collagen AGEs fluoresce, skin intrinsic fluorescence (SIF) can act as a novel marker of levels of collagen AGEs. We thus sought to determine the relationship between skin intrinsic fluorescence and CAC in type 1 diabetes. Methods: One hundred five participants in the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset (age <17 years) type 1 diabetes who had previously undergone electron beam tomography scanning for CAC (80 of whom had follow-up data) had SIF measurements taken using the SCOUT DM Ò (VeraLight, Inc., Albuquerque, NM). Mean age and diabetes' duration were 49 and 40 years, respectively, at the time of SIF measurement. Results: Seventy-one percent of the study participants had some measurable CAC that was univariately (but not after age adjustment) cross-sectionally associated with SIF (odds ratio ¼ 2.51, 1.37-4.59). However, for CAC severity using natural logarithmically transformed scores, SIF was both univariately (P < 0.0001) and multivariably (P ¼ 0.03) associated with CAC. This relationship was independent of age, a history of CAD, renal function, or renal damage. Receiver operator characteristic analyses revealed that the discriminative ability of SIF to detect CAC went from an area under the curve of 71% for the presence of any CAC to 85% for those with a CAC score >400. Conclusions: The relationship between SIF and CAC appears stronger with more severe calcification. Given the strong relationship of CAC with CAD this finding has important implications and suggests that SIF maybe a useful marker of CAC=CAD risk and potentially a therapeutic target.

SIF reflects age, mean HbA1c over time, smoking, and renal damage, which are known risk factors for diabetes complications.