Increased skin autofluorescence of children and adolescents with type 1 diabetes despite a well-controlled HbA1c: results from a cohort study.

BACKGROUND: Early identification of children and adolescents with type 1 diabetes at high risk for development of complications is important, as early intervention may prevent further deterioration. Here we investigate the applicability of assessing skin advanced glycation end products (sAGEs) by skin autofluorescence (SAF) as a potential surrogate risk marker. METHODS: This study included a cross-sectional analysis of SAF in 77 patients with type 1 diabetes mellitus and 118 healthy controls across age categories (11-12, 13-14, 15-16, and 17-19 years old). In patients, the impact of current and historical glycated hemoglobin (HbA1c) values, age, and duration of diabetes on SAF was studied in a retrospective cohort study and analyzed with multivariable analyses. RESULTS: SAF was significantly and similarly higher in patients when compared with controls across all age categories (P ≤0.009). For patients, age, duration of diabetes, and current and historical HbA1c were associated with SAF in univariate analysis. Multivariate analysis showed no association between HbA1c and SAF. A subgroup of patients with a HbA1c-within-target (≤7.5 %/59 mmol/mol) were observed to have high SAF. CONCLUSION: Children and adolescents with type 1 diabetes show higher SAF than controls. The presumed correlation of high HbA1c with high SAF does not exist in all patients. Thus, use of this non-invasive measure may provide a surrogate marker for diabetic complications, additional to HbA1c.

Erythrocyte-associated apolipoprotein B and its relationship with clinical and subclinical atherosclerosis.

BACKGROUND: Apolipoprotein (apo) B-containing lipoproteins are closely linked to atherogenesis. These lipoproteins are transported in plasma and are also associated with blood leucocytes. Our aim was to investigate whether apoB-containing lipoproteins are also present on the surface of erythrocytes and investigate the relationship with the presence of atherosclerosis in a cross-sectional study. MATERIALS AND METHODS: Erythrocyte-bound apoB (ery-apoB) was measured by flowcytometry in subjects with (CAD+) and without coronary artery disease (CAD-), based on coronary angiography or on a history of cardiovascular disease. Intima media thickness (IMT) measurements were carried out using B-mode ultrasound. The relationship between ery-apoB and clinical and subclinical atherosclerosis was evaluated with binary logistic regression. RESULTS: A total of 166 subjects were included (40 CAD+ and 126 CAD-). ApoB was detected on freshly isolated erythrocytes (range: 0·1-5·5 au; mean ± SEM 0·86 ± 0·09 au) in all but nine subjects (four CAD+ and five CAD-). Ery-apoB was lower in CAD+ (0·62 ± 0·09 au) compared to CAD- (1·18 ± 0·10 au; P < 0·001). Higher ery-apoB was associated with a lower risk of CAD (adjusted OR: 0·003 (95% CI: 0·001-0·08; P < 0·001), but the protective effect was diminished with increasing age (adjusted OR: 1·10 (95% CI: 1·04-1·16; P < 0·001). IMT was increased in CAD+ subjects (0·77 ± 0·13 mm) compared to CAD- (0·57 ± 0·14 mm; P < 0·001). A significant negative association was found between ery-apoB and IMT (ß = -0·214: 95% CI -0·284 to -0·145; P < 0·001). There was no association between ery-apoB and plasma apoB (Pearson's r = -0·45; P = 0·57). CONCLUSIONS: Human erythrocytes carry apoB-containing lipoproteins. Subjects with atherosclerosis have lower ery-apoB. High ery-apoB may be protective against atherosclerosis and may reflect an alternative blood cell-mediated lipoprotein transport system in the circulation, in which these lipoproteins less likely interact with the endothelium.

Effects of Peri-Conception and Pregnancy Glycemic Variability on Pregnancy and Perinatal Complications in Type 1 Diabetes: A Pilot Study.

BACKGROUND: Not much is known about the effects of glycemic variability (GV) during the pre- and periconception period on pregnancy/perinatal complications. GV could potentially contribute to identification of high-risk pregnancies in women with type 1 diabetes. METHODS: An explorative retrospective cohort study was conducted between January 2014 and May 2019. Glucose data were retrieved from electronic patient charts. Pre-/periconceptional GV and GV during all three trimesters was expressed as mean glucose, standard deviation (SD), Coefficient of Variation (CV), High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI) and Average Daily Risk Range (ADRR). Maternal and neonatal complications were summarized using a composite total complication score. Binary logistic regression analyses were conducted to assess associations between the GV measures and a total complication score>3, a maternal complication score>1 and a neonatal complication score>1. RESULTS: Of 63 eligible women, 29 women (38 pregnancies) were included. Women in the group with a total complication score>3 had a significantly higher ADRR at conception (OR 1.1, CI 1.0-1.2, p=0.048). No statistically significant correlations between complication score and any other GV metric besides the ADRR were found. Although not significant, in the group with a complication score>3, odds ratios>1 were found for SD in trimester 1 (OR 1.6, CI 0.6-4.5, p=0.357) and trimester 2 (OR 1.8, CI 0.5-6.2, p=0.376). CONCLUSIONS: Presence of a positive association between GV and pregnancy and perinatal complications depends on which pregnancy period is assessed and the GV metrics that are used.

Losing Track of Lipids in Children and Adolescents with Type 1 Diabetes: Towards Individualized Patient Care.

AIM: To assess 1) the prevalence of children and adolescents with type 1 diabetes (T1D) changing from low-risk into borderline-high-risk lipid levels or from borderline-high-risk into high-risk lipid levels ('lose track of lipids') and 2) the power of a risk score including the determinants HbA1c, body mass index (BMI), gender, age, diabetes duration and ethnicity in predicting which patients lose track of lipids. METHODS: 651 children and adolescents with T1D were included in this longitudinal retrospective cohort study. Lipid dynamics and the impact of the risk score on losing track of lipids were evaluated. Kaplan-Meier analysis was used to estimate screening intervals. RESULTS: 31-43% percent of the patients had lost track of one or more lipids at the next lipid measurement. This happened more frequently in patients with a low-risk lipid level at start. Depending on the lipid parameter, 5% of patients with low-risk lipid levels lost track of lipids after 13-23 months. The risk score based on concomitant information on the determinants was moderately able to predict which patients would lose track of lipids on the short term. CONCLUSIONS: A considerable number of children and adolescents with T1D loses track of lipids and does so within a 2-year screening interval. The predictive power of a risk score including age, BMI, gender, HbA1c, diabetes duration and ethnicity is only moderate. Future research should focus on another approach to the determinants used in this study or other determinants predictive of losing track of lipids on the short term.

Do traditional cardiovascular risk factors solely explain intima-media thickening in youth with type 1 diabetes?

AIMS: The aim of this study was to assess age-specific carotid intima-media thickness (cIMT) in children and adolescents with type 1 diabetes and to investigate associations between cIMT, age, classical cardiovascular disease (CVD) and other risk factors. METHODS: This study included a cross-sectional analysis of cIMT in 178 patients with type 1 diabetes and 208 healthy controls across age categories. In patients, the impact of gender, socio-economic status, ethnicity, current and historical body mass index, blood pressure, hemoglobin A1c, high-density lipoprotein, and low-density lipoprotein cholesterol on cIMT was studied in a retrospective follow-up cohort study. RESULTS: Median cIMT was equally greater in patients versus controls across all age categories (P≤0.03). Regression models in patients confirmed a lack of association between cIMT and classical CVD risk factors. CONCLUSIONS: Children and adolescents with type 1 diabetes showed greater cIMT than controls in all age categories. Increased cIMT did not seem to be consistently associated with classical adult CVD risk factors, adding to the current debate in pediatrics about the impact on classical CVD risk factors to the development of subclinical atherosclerosis in type 1 diabetes. Future studies are warranted to determine if cIMT could assist in predicting macrovascular complications of type 1 diabetes.

Erythrocyte-bound apolipoprotein B in relation to atherosclerosis, serum lipids and ABO blood group.

INTRODUCTION: Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB) are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms. METHODS: Subjects with and without CVD were included (N = 398). Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤ 0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT) was determined as a measure of (subclinical) atherosclerosis. RESULTS: Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80 ± 0.09 mm, N = 140) compared to subjects with a normal CIMT (0.57 ± 0.08 mm, N = 258) (P = 0.007, adjusted P<0.001). CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021). A total of 55 subjects (13.6%) were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82). Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56 ± 0.94 a.u.) when compared to subjects with blood group A (0.89 ± 1.15 a.u), blood group B (0.73 ± 0.1.12 a.u.) or blood group AB (0.69 ± 0.69 a.u.) (P-ANOVA = 0.002). CONCLUSION: Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant.