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Background To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 ( ICAM-1) and myeloperoxidase ( MPO), are increased in youth with obesity and in those with type 1 diabetes ( T1D) at similar levels, and whether their levels are associated with markers of renal function. Methods A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index ( BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: −0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate ( AER). Results Levels of ICAM-1 and MPO were significantly higher in obese [ ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function ( AER: β = 0.21, p = 0.03; e- GFR: β = 0.19, p = 0.04), after adjusting for BMI. Conclusions Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e- GFR and AER confirm the known the association between general endothelial and renal dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To perform a cross-sectional comparison of endogenous markers of glomerular filtration rate (GFR) (plasma symmetric dimethylarginine (SDMA) and estimated GFR (eGFR)) with a direct measure of GFR (using the plasma clearance of Inutest (In-GFR)), and a longitudinal evaluation of these markers in relation to the development of microalbuminuria, in young people with type 1 diabetes (T1D).Methods: Longitudinal stored blood samples (n=1105) were available from 417 young people from the Oxford Regional Prospective Study (an inception cohort of 527 children followed for a median of 10.3 (interquartile range 7.1-12.3) years), for measurement of SDMA and creatinine. Additional annually collected data on anthropometric parameters, HbA1c, insulin dose and three early morning albumin:creatinine ratios were available. In-GFR was measured in a representative subgroup of 183 subjects.Main Outcome Measures: SDMA and eGFR.Results: SDMA and eGFR were significantly and similarly associated with In-GFR (r=-0.38 and r=0.36, p<0.001). Overall SDMA levels were lower in microalbuminuric (n=116) than normoalbuminuric subjects (n=301) (0.385 + or - 0.063 vs 0.412 + or - 0.059 micromol/l, p<0.001), probably reflecting hyperfiltration. The pattern of change in SDMA levels with age differed between microalbuminuric and normoalbuminuric subjects. Whereas SDMA levels declined in both groups until the age of 16 years, thereafter they tended to rise only in microalbuminuric subjects, probably reflecting a decline in renal function.Conclusions: In this longitudinal study of young people with T1D, measurement of SDMA, in contrast to eGFR, proved to be a reliable marker in identifying changes in filtration rates associated with the development of microalbuminuria (MA). [ABSTRACT FROM AUTHOR]

OBJECTIVES: To perform a longitudinal evaluation of high-sensitivity C-reactive protein (hs-CRP) in young people with type 1 diabetes in relation to the development of microalbuminuria (MA). RESEARCH DESIGN AND METHODS: hs-CRP was measured in 329 blood samples collected from 49 subjects with type 1 diabetes with MA and 49 normoalbuminuric subjects matched for age, sex, and duration of diabetes. RESULTS: In subjects developing MA, a progressive rise in hs-CRP was detected with levels significantly higher in the years after the onset of MA when compared with levels before MA onset (P = 0.003; age-adjusted P = 0.06). After the onset of MA, hs-CRP levels were significantly higher in subjects with MA when compared with normoalbuminuric subjects (median 1.9 mg/l [range 0.2-9.8] vs. 1.1 mg/l [0.2-6.4]; P = 0.02; adjusted P = 0.036). CONCLUSIONS: In this population of young subjects with type 1 diabetes, there was a significant increase in hs-CRP levels after the onset of MA, likely reflecting a general state of inflammation. [ABSTRACT FROM AUTHOR]