As incidence of youth onset T1D and T2D is increasing and associated with earlier vascular complications and mortality, it is important to analyze dyslipidemia prevalence and associations with CVD risk factors between T2D and T1D in the diverse pediatric population. Our study represents retrospective data from a single large diabetes care center with an ethnically diverse population, which showed a high percentage of youth with LDL-C not at goal (< 100 mg/dL/ < 2.6 mmol/L): 32.7% (556/1701) with T1D and 47.7% (142/298) with T2D. Of those that likely met criteria to start statin therapy (LDL > 130 mg/dL/3.4 mmol/L), there were 9% (153/1701) with T1D and 16.4% (49/298) with T2D. These numbers slightly underestimate the total population with dyslipidemia at our institution as we excluded those that were already started on statin treatment, and for those whom LDL-C could not be calculated due to elevated TG. However, this prevalence of dyslipidemia in our patient population is lower than we hypothesized but overall comparable to, if not slightly less, than other population studies. In the SEARCH for Diabetes in Youth population, a national multicenter study in the United States evaluating children and young adults with diabetes, it was reported in 2006 that 47% of patients with T1D above age 10 years had LDL > 100 mg/dL (> 2.6 mmol/L), with 15% > 130 mg/dL (> 3.4 mmol/L), and 57% of those with T2D had LDL > 100 mg/dL (> 2.6 mmol/L), with 24% with LDL > 130 mg/dL (> 3.4 mmol/L) [24]. Since then other studies worldwide have shown varying high prevalence of dyslipidemia in the pediatric diabetes population. In 2008, a single center in the UK showed that 38% of children with T1D had LDL > 100 mg/dL (> 2.6 mmol/L), and 10.8% with LDL > 130 mg/dL (> 3.4 mmol/L) [25]. More recently, in 2015 another study at a center in Brazil, showed high LDL > 100 mg/dL in 44% of T1D (age 5–31 years of age), and a study from a center in Turkey in 2017 showed 21% with high LDL > 130 mg/dL (> 3.4 mmol/l) [26]. For type 2 diabetes in youth, a single center in California, USA in 2008, showed that 39.4% of youth with T2D had LDL > 130 mg/dL (> 3.4 mmol/L). In 2017, a study from India showed prevalence of high LDL-C > 100 mg/dL (> 2.6 mmol/L) was 64.5% in youth with T2D [27]. One possibility of our prevalence of dyslipidemia being slightly lower than expected, is the increased attention lately to the high rates of dyslipidemia in pediatric patients with diabetes. Also our screening rate was surprisingly high, > 98%, which leads to early detection and hopefully early discussions about dyslipidemia management. Despite these, the prevalence of dyslipidemia in our diabetes population is still high, which shows the need for improved management of dyslipidemia in pediatric patients with diabetes.
Our study population is an ethnically diverse population with high Hispanic prevalence (57.8% of T2D and 22.9% of T1D), higher than that of the national multicenter SEARCH for Diabetes in Youth population (27.6% of T2D and 13.0% of the T1D), or of the NHANES (National Health and Nutrition Examination Survey) adolescent populations [12, 28]. Racial disparities have been reported in both T1D and T2D where minorities compared to Non-Hispanic White tend to have increased CVD risk factors including dyslipidemia, however the relationship and mechanism is unclear and complicated [7, 29, 30]. Our study population with a high Hispanic proportion, showed a high prevalence of dyslipidemia, emphasizing the importance of screening and treating dyslipidemia in these youth.
On further analysis of our study population, higher LDL-C and/or lower HDL-C were independently associated with older age, Hispanic ethnicity, female sex, overweight and obesity, longer diabetes duration, higher HbA1C, and T2D. We chose these risk factors to analyze as they have been associated with dyslipidemia [5, 7, 25, 31,32,33,34,35,36], and to evaluate if they were also significantly associated in our population. The role of sex in dyslipidemia in those with T1D or T2D is varied, where generally sex is not associated with increased CV risk factors in those with diabetes [7], though another study showed that females had higher LDL-C and higher TC [5], while another study showed that males were associated with higher odds of progression of HDL-C [31]. Higher BMI is associated with dyslipidemia in many studies and our study was concordant with this [32,33,34]. Worsening glycemic control has been associated independently with dyslipidemia in multiple studies [25, 31, 32, 34,35,36]. Higher duration of diabetes is also typically associated with worsening dyslipidemia [25]. It is interesting that in our study, worsening glycemic control and longer duration of diabetes were associated with increased HDL-C concentrations. One possibility for this association is lower HDL-C was associated with T2D, and T2D was associated with lower duration of diabetes and lower HbA1C in our population. We did try to evaluate these factors separately in T1D and T2D. In T1D, higher HbA1C was again associated with HDL-C, however duration of diabetes was not significant. In T2D, both factors were not significant, likely due to not enough of a sample size (data not shown).
We then adjusted for the significant risk factors, to evaluate whether higher LDL-C and lower HDL-C would be still be associated with specifically T2D versus T1D, as the prevalence of T2D is increasing in pediatrics, and known to be associated with earlier microvascular and macrovascular complication [10, 11]. In our population, after adjusting for age, sex, race/ethnicity, obesity, diabetes duration, and HbA1C, both higher LDL-C and lower HDL-C concentrations were associated T2D than T1D. We found that the type of diabetes, specifically T2D, is associated with higher LDL-C and lower HDL-C even after accounting for the major risk factors that contribute to CVD. Additionally, for patients with LDL-C not at goal, presence of other CVD risk factors of obesity and low HDL-C were associated with T2D than T1D. Our analysis is concordant with recent findings from the national multicenter SEARCH for Diabetes in Youth population, where the prevalence of > 2 CVD risk factors among youth with T2D was 8–10 times as high as youth with T1D [12]. These are consistent with studies showing youth onset T2D is associated with earlier complications than youth onset T1D or adults with T2D [9,10,11, 37]. It has been suggested that there are differences in the pathophysiology of dyslipidemia in T2D vs T1D, however this mechanism has not yet been elucidated [38]. Thus, we need to be vigilant with dyslipidemia management in youth onset diabetes, especially T2D.
At our institution, lipid screening was at the discretion of the individual providers, and not based on standardized institutional protocols for screening and ongoing management. This led to limitations of lipid concentrations that were both fasting and non-fasting, leading to a small percentage of LDL-C concentrations that were unable to be calculated due to high triglycerides. Another limitation is that there were high rates of unreported tobacco status. Other cardiovascular risk factors including family history of cardiovascular disease, hypertension, diet history, and exercise were other factors unable to be obtained due to limitations with the electronic health registry. In addition, our results may not be generalizable to the whole population as we present a retrospective chart review of our single tertiary diabetes care center with a high Hispanic population. Also, these findings do not necessarily predict CVD outcomes as we focused on the associations with lipid abnormalities and diabetes. Of note, the pediatric guidelines are extrapolated from adult data, thus in general more long term studies are needed to know the exact long term outcomes of improved dyslipidemia control in pediatric patients with diabetes. Despite the limitations, we had a large diverse population with T1D and T2D for analysis.