Abstract

Background & ObjectivePatients with type-1-diabetes (T1D) are at risk of long-term micro and macrovascular complications causing significant morbidity and mortality. Overt complications are not common in childhood; however, subclinical impairments in endothelial function, may be found. Better understanding of the timeline for the appearance of diabetic complications and identifying individuals at increased risk is key for developing prevention strategies. We aimed to study endothelial function and it’s determinants in adolescents with T1D at different time points from diagnosis.MethodsForty adolescents 11-20 years of age with T1D followed at our pediatric diabetes clinic and 18 healthy control subjects were included. Two groups of patients were recruited based on time from T1D diagnosis; 20 individuals were diagnosed 2-4 months prior to the study visit and 20 at least 7 years prior to the visit. Investigations included: i) medical and demographic data ii) anthropometrics iii) fasting blood samples iv) EndoPAT testing of endothelial function and heart rate variability (Itamar Medical Ltd., Israel) v) Carotid intima media thickness (CIMT).ResultsMean age differed slightly between groups being 14.1±2.0years in individuals with recent-onset T1D, 16.2±2.5 in those with prolonged T1D, and 14.8±2.3 in the control group (p=0.02). There were no significant differences in pubertal stage or in BMI z-score between groups. Thirty-three (57%) females participated. No patient suffered from diabetic complications. Mean CIMT was significantly higher in individuals with prolonged T1D (0.49±0.07mm) compared to control subjects (0.43±0.05mm; p=0.013) and did not differ significantly between patients with recent-onset T1D (0.45±0.07mm) and controls. This difference remained significant when age and sex were included in the model. EndoPAT measures of endothelial function and heart rate variability did not differ significantly between groups. Mean HbA1c at the time of the visit differed between groups (6.7%±0.7, 9.6%±1.8, 5.4%±0.3, p<0.001). However, the average of HbA1c reflecting the 6-7 months prior to the visit did not differ significantly between subjects with recent onset T1D (9.8%±1.3) and those with prolonged T1D (9.5%±1.7). LDL was higher in subjects with prolonged T1D (114±28mg/dl) compared to either controls (93±26mg/dl) or recent onset T1D (88±19mg/dl),p=0.002. Diastolic blood pressure was higher in subjects with prolonged T1D (70±6mmHg) than in controls (61±6, p=0.007).ConclusionsOur results demonstrate disease duration to be an important factor in the development of subclinical arterial damage in the pediatric age group. Early in the course of T1D, CIMT results were similar in patients and control subjects, suggesting an important window for prevention. Larger studies could shed light on the precise timeline of endothelial impairment.

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