We found that in youth with type 1 diabetes and relatively short disease duration (mean 4.2 years) mean lipid levels and prevalence of lipid abnormalities are substantially influenced by glycemic control. Youth with type 1 diabetes and optimal A1C levels have lipid profiles that are similar (total and LDL cholesterol) or even less atherogenic (HDL cholesterol, triglyceride, and triglyceride-to-HDL ratio) than those observed in nondiabetic youth. In contrast, youth with type 1 diabetes and suboptimal glycemic control have higher standard lipid levels and prevalence of lipid abnormalities (total cholesterol, LDL cholesterol, and non-HDL cholesterol) than nondiabetic youth. Moreover, youth with type 1 diabetes have significantly elevated apoB levels and more small, dense LDL particles than nondiabetic youth, regardless of glycemic control. We also found that the most frequent lipid abnormalities in youth with type 1 diabetes compared with nondiabetic control subjects are elevated apoB levels and an increased proportion with small, dense LDL particles.
Data on lipid and lipoprotein factors in youth with type 1 diabetes are scarce; studies are relatively small and often do not include a control group. Most data are based on adults with childhood-onset diabetes. Our observation that youth with type 1 diabetes and optimal glycemic control have a less atherogenic standard lipid profile, especially with respect to triglyceride and HDL cholesterol levels, agrees with previous data in adults (16
). In general, lipid concentrations were shown to be antiatherogenic in adults with type 1 diabetes who had optimal glycemic control or intensive insulin treatment (16
). However, the lack of abnormal lipid levels does not exclude the possibility of compositional changes that may be atherogenic, especially among those with poor glycemic control. James and Pometta (17
) found that in adults with poorly controlled type 1 diabetes, triglyceride-rich lipoprotein particles are increased; LDL subclass distribution shifts to relative excess of small, dense LDL; and LDL particles are more triglyceride rich compared with those of normal subjects. Under normal circumstances, triglyceride-rich particles are rapidly hydrolyzed by lipoprotein lipase. The enzyme is induced in adipose tissue by insulin, and thus, intensive insulin therapy is typically associated with a marked fall of triglyceride-rich particles (17
). This may be one explanation for lower triglyceride and higher HDL cholesterol concentrations in youth with type 1 diabetes versus healthy control subjects.
Our findings that youth with suboptimal glycemic control have increased concentrations and a higher prevalence of abnormal standard lipid levels, as well as more small, dense LDL particles and higher apoB levels, also agree with the previous literature in adults (18
). Similarly, among SEARCH youth with type 1 diabetes, total and LDL cholesterol, triglyceride, and non-HDL cholesterol levels (19
) and also dense LDL and apoB concentrations (14
) increased with increasing A1C.
The measurement of apoB and dense LDL in individuals with diabetes has been sparse, particularly in children and adolescents. The higher proportion of youth with type 1 diabetes with elevated apoB versus healthy control subjects can be explained by the increased concentration of triglyceride-rich apoB-containing lipoproteins and by the presence of dense LDL that is enriched in apoB relative to its cholesterol content. In our study, even youth with optimal A1C levels had elevated apoB and an increased proportion of small, dense LDL particles relative to those in nondiabetic control subjects, suggesting that even mild hyperglycemia may be associated with atherogenic compositional lipoprotein changes even if concentrations of standard lipid are unaffected.
Both apoB and small, dense LDL particles have been shown to be strong and independent predictors of CVD. ApoB has been shown to be a better predictor of incident CVD than LDL cholesterol and non-HDL cholesterol (20
). The dense LDL particle subclass is associated with increased risk of ischemic heart disease events (21
) and narrowing of an existing cardiac stenosis in adults (22
). Thus, elevated apoB and/or dense LDL particles in youth with type 1 diabetes may contribute substantially to increased cardiovascular morbidity and mortality in adulthood. Currently, the ADA guidelines for managing dyslipidemia in children and adolescents with diabetes advise optimizing glycemic control, improving diet, and keeping LDL cholesterol, HDL cholesterol, and triglycerides within specific targets (15
). Our data suggest that apoB and small, dense LDL particles may also represent important targets because they appear to be elevated even among patients with well-controlled type 1 diabetes and because CVD risk relates more closely to the level of apoB than to cholesterol indexes.
This study has several potential limitations. First, it is cross-sectional and thus is limited to describing observed associations. Half of the patients with type 1 diabetes in this study had a disease duration of <2 years, thus limiting the generalizability of our findings to the larger population of youth with type 1 diabetes. We had limited power to conduct race/ethnicity-specific analyses; however, similar patterns were noted across all racial/ethnic groups. Major strengths of our study include a relatively large sample of youth with type 1 diabetes, with a range of A1C levels, a detailed examination of lipid and lipoprotein profiles, and, importantly, a nondiabetic control group.
In summary, our study presents novel information on characteristics of dyslipidemia in youth with type 1 diabetes compared with nondiabetic control subjects. Youth with type 1 diabetes present with abnormal lipid levels and atherogenic changes in lipoprotein composition, even after a relatively short disease duration. As in adults, glycemic control seems to be an important mediator of these abnormalities. Further research is needed to fully understand the mechanisms by which type 1 diabetes contributes to altered lipid profiles and increased cardiovascular risk.