Our data indicate that youth with type 2 diabetes have significantly worse arterial stiffness measures than similar youth with type 1 diabetes. These differences are not accounted for by differences in demographic characteristics (age, sex, and race/ethnicity), diabetes duration, and A1C but are largely mediated through increased central adiposity and higher blood pressure levels in youth with type 2 diabetes. We also found a pattern of association of arterial stiffness measures with central adiposity (waist circumference) and blood pressure, independent of diabetes type. Thus, worse patterns of arterial stiffness seen in youth with type 2 diabetes are probably due to the higher prevalence of CVD risk factors seen in such subjects. The presence of CVD risk factors including hypertension, obesity, and subclinical hyperglycemia may contribute to vascular change before diagnosis of diabetes for patients with both type 1 and type 2 diabetes, although given the relatively acute onset of type 1 diabetes, this is more likely to occur in patients with type 2 diabetes.
These results suggest that increased adiposity may contribute to increased arterial stiffness in youth with diabetes, regardless of diabetes type. Other studies have also found a relationship between body size and vascular function in adults (13
) and youth with type 2 diabetes (15
), but data in youth with type 1 diabetes are limited (16
). Prevention and control of obesity in youth with both diabetes types may therefore play a significant role in reducing the risk of early vascular changes.
Blood pressure was also a significant independent correlate in our analyses, which is consistent with previous studies of arterial stiffness in adults. Evidence from such studies suggests that subclinical changes in blood pressure may have an impact on arterial stiffness before hypertension is clinically evident (5
We did not observe a cross-sectional association between glycemic control (A1C) and arterial stiffness in this study. Our data are similar to previous publications regarding the relationship between A1C and AIx in younger type 1 diabetic patients (18
). There are several possible explanations for this finding. First, our data only explore cross-sectional associations between a single A1C measure and arterial stiffness. Longitudinal studies of vascular changes in diabetic youth may provide further insight into how long-term glycemic control may affect arterial stiffness, even before clinical onset of chronic vascular complications. Second, the effects of hyperglycemia on the vasculature may not be seen with measures of arterial stiffness. However, studies of carotid intima-media thickness (cIMT) in youth with type 1 diabetes also did not show an association with A1C (19
). Hyperglycemia might not affect vascular structure and function measurably in persons with a relatively short duration of diabetes. In our cohort, the median (interquartile range) duration of diabetes was 4.75 (2.42–8.00) and 3.13 (2.08–4.54) years for patients with type 1 and type 2 diabetes, respectively. Parikh et al. (20
) noted an association between carotid distensibility and A1C in a cohort of adolescents with type 1 diabetes (aged 15.8 years) with longer diabetes duration (9.3 years). Worse glycemic control during the Diabetes Control and Complications Trial (DCCT) was associated with increased progression of cIMT (21
) and a higher incidence of CVD events in the Epidemiology of Diabetes Interventions and Complications (EDIC) study (22
). However, the DCCT findings were observed in older subjects (mean age 35 years) with longer diabetes duration (mean duration 13.8 years).
To our knowledge, this is the first study to compare measurements of arterial stiffness in youth with type 1 and type 2 diabetes. The cohort of 595 subjects is relatively large. Other studies of arterial stiffness (18
) and cIMT (19
) have been conducted in smaller cohorts of youth with type 1 diabetes. Moreover, our study included multiple methods to evaluate arterial stiffness (brachD, PWV, and AI75) and showed consistent results across all of these measures. Of the methods used in this study, PWV appeared to be the most robust. PWV was significantly higher in youth with type 2 diabetes even after adjustment for SBP and DBP, whereas differences in brachD and AI75 by diabetes type seemed to be more sensitive to adjustments for blood pressure.
Our study has limitations. A nondiabetic control group was not included, thus limiting our ability to compare these diabetic patients with the general population of healthy youth. Of note, data are sparse among nondiabetic youth of similar age (11
). Data were collected in only 60 subjects with type 2 diabetes. However, this relatively small sample is representative of youth with type 2 diabetes participating in the larger SEARCH study (24
), and only Urbina et al. (25
) have reported on arterial stiffness in a larger cohort of youth with type 2 diabetes; however, PWV and AI75 were not included in that study.
A potential methodological limitation for PWV is the distance measured externally on the body from the suprasternal notch to the femoral pulse. If the distance is longer for subjects with larger waist circumference, calculated PWV may be higher. We measured the distance from the suprasternal notch to the femoral pulse with a tape measure laid on the body to use the most reproducible technique. Alternatives include a measure over the body or intra-arterial measurement of the artery using imaging techniques. Measuring over the body was not done to avoid potential reproducibility issues. Imaging of the vascular segment to obtain a measurement was not feasible. Although other measurement techniques may have altered the findings for PWV, it is important to note that brachD and AI75, techniques not requiring such a measurement, showed a similar pattern of reduced difference in arterial stiffness by diabetes type after adjustment for waist circumference.
The cross-sectional design of this study also limits our ability to conclude which factors cause the development of altered arterial stiffness in diabetic patients. Longitudinal studies of vascular changes in diabetic patients are needed to further understand the role of glycemic control, blood pressure, and adiposity on arterial stiffness over time.
In summary, youth with type 2 diabetes have significantly worse arterial stiffness measures than youth with type 1 diabetes, probably because of their patterns of elevated blood pressure and central adiposity. Increased central adiposity and blood pressure levels are associated with measures of arterial stiffness, independent of diabetes type. Longitudinal studies are needed to determine whether increased arterial stiffness is an early sign of future progression to CVD in youth with diabetes. Further studies could potentially delineate key modifiable CVD risk factors and the utility of preventive interventions to decrease the rates of CVD in patients with youth-onset type 1 and type 2 diabetes.