Dyslipidemia In Youth Research Articles

Algorithms for Treating Dyslipidemia in Youth.

The goal of this article is to review algorithms for treating dyslipidemia in youth, discuss pitfalls, propose enhanced algorithms to address pitfalls, and consider future directions. The presence of modifiable and non-modifiable cardiovascular disease (CVD) risk factors during childhood is associated with CVD-related events in adulthood. Recent data has shown that childhood initiation of statin therapy in youth < 18years of age with familial hypercholesterolemia reduces the risk of adult CVD. However, pediatric dyslipidemia remains undertreated in part due to a lack of primary health care providers with adequate understanding of screening guidelines and pediatric lipidologists with experience in treatment and follow-up of this unique population. Management algorithms have been published by the National Heart, Lung, and Blood Institute and American Heart Association as tools to empower clinicians to manage dyslipidemia. We propose enhanced algorithms, which incorporate recently approved pharmacotherapy to address the management gaps. Future algorithms based upon clinical risk scores may enhance treatment and improve outcomes. Algorithms for dyslipidemia management which target youth < 18years of age are tools which empower clinicians to manage dyslipidemia in this unique population. Enhanced algorithms may help address pitfalls. We acknowledge the need for further risk assessment tools in pediatrics for tailored dyslipidemia management.

Epidemic trends of dyslipidemia in young adults: a real-world study including more than 20,000 samples

BackgroundThere is an urgent need to learn more about the epidemiological features of dyslipidemia in youth to address the high burden of cardiovascular disease.MethodsThis experiment was an observational, cross-sectional study. The samples were collected from 22,379 college students at Xinjiang Medical University.ResultThe overall prevalence of dyslipidemia was 13.17%, which was significantly higher in men (23%) than in women (7.2%), p < 0.01. Similarly, the prevalence rate of obesity in men (11.4%) was significantly higher than that in women (3.4%). The composition of blood lipids, such as triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), began to increase gradually from the age of 22 and showed a sharp increase after the age of 30; however, a reverse trend was present in high density lipoprotein cholesterol (HDL-C). In terms of the proportion of dyslipidemia in both men and women, low HDL-C accounted for the largest proportion (74%), followed by elevated TGs (14.5%). The overall distribution of rates of dyslipidemia and excess weight showed a U-shaped trend with increasing age, with the lowest rates seen in the 20–24 age group.ConclusionOur study sheds light on the epidemiological features of dyslipidemia in young adults and enriches the limited data available on dyslipidemia, providing a reference for the close monitoring and control of risk factors to reduce the occurrence and progression of atherosclerotic cardiovascular disease events.

Factors Associated With the Development of Dyslipidemia Among Pediatric Patients With Diabetes: A Single-centre–based Study

ObjectivesThe prevalence of pediatric diabetes is increasing. Dyslipidemia is an important modifiable cardiovascular disease risk factor often present in children with diabetes. In this study, we evaluated the adherence to Diabetes Canada 2018 lipid screening guidelines in a pediatric diabetes program to determine the prevalence of dyslipidemia in youth with diabetes and to identify risk factors related to dyslipidemia. MethodsThis retrospective chart review included patients at McMaster Children’s Hospital with diabetes (types 1 and 2), who were at least 12 years of age as of January 1, 2019. Extracted data included age, sex, family history of diabetes or dyslipidemia, date of diagnosis, body mass index, glycemia monitoring system used, lipid profile, glycated hemoglobin (A1C), and thyroid-stimulating hormone values at the time the lipid profile was measured. Statistical methods included descriptive statistics and logistic regression modelling. ResultsOf the 305 patients included, 61% had a lipid profile measured according to guidelines, 29% had lipid screening completed outside of the recommended window, and 10% had no lipid profile on record. Among screened patients, 45% had dyslipidemia, most commonly hypertriglyceridemia (35%). Dyslipidemia was highest amongst those with type 2 diabetes, obesity, older age, short duration of diabetes, higher A1C, and those who used capillary blood glucose for monitoring (p<0.05). ConclusionsA high proportion of patients were screened for dyslipidemia, but many outside the recommended window. Dyslipidemia is highly prevalent in this patient population and was associated with the presence of obesity, but 44% of patients without obesity also had dyslipidemia.

Diet Quality and Cardiometabolic Risk Factors in Adolescents with Down Syndrome.

Youth with Down syndrome (DS) have a high prevalence of obesity and dyslipidemia. Diet quality may influence cardiometabolic risk (CMR) in youth. The aim of this secondary analysis was to investigate the relationship between diet quality (Healthy Eating Index [HEI-2015]) with CMR factors in youth with DS compared with age, sex, race, ethnicity, and body mass index percentile matched, typically developing controls. Adolescents (aged 10 to 20 years) with DS and controls of comparable age, sex, race, ethnicity, and body mass index percentile were recruited from 2012 to 2017 for a cross-sectional study from two large children's hospitals (Children's Hospital of Philadelphia and the Children's National Health System in Washington, DC). CMRs in 143 adolescents with DS were compared with 100 controls. Exclusion criteria consisted of major organ-system illnesses. The average of three 24-hour dietary recalls was used to calculate the HEI-2015. Anthropometrics, blood pressure, and fasting labs were collected. Group differences were tested using Wilcoxon rank-sum tests. Relationships of CMR factors with HEI-2015 score within DS and controls were tested using linear regression models adjusted for sex, age, race, and body mass index z score. Compared with controls (n= 100, median age= 14.8 years [interquartile range= 12.2 to 17.3 years]; 41% male; 24% African American; 65% with body mass index ≥85th percentile), adolescents with DS (n= 143, median age= 14.7 years [interquartile range= 11.4 to 17.4 years]; 44% male; 18% African American; 62% with body mass index ≥85th percentile) had higher scores (more aligned with dietary recommendations) for total HEI-2015 (DS: 52.7 [interquartile range= 46.8 to 58.6] vs controls: 45.1 [interquartile range= 39.5 to 55.0]; P < 0.0001). Youth with DS also had higher HEI-2015 component scores for fruits, greens/beans, dairy, refined grains, and saturated fats, but lower whole grains and sodium scores. Within the group with DS, total HEI-2015 was not significantly associated with CMR measures. Whereas HEI-2015 in the DS group was negatively associated with fasting glucose levels, the difference did not meet the set level of statistical significance (-0.14, 95% CI -0.29 to 0.00; P= 0.053). Adolescents in both the control and DS groups reported low-quality diets, although the DS group had HEI-2015 scores more closely aligned with recommendations. In the DS group, diet quality was not significantly associated with CMR factors. Although further research is needed, these results suggest that dyslipidemia in youth with DS may not be related to dietary intake.

Metabolome Alterations Linking Sugar-Sweetened Beverage Intake with Dyslipidemia in Youth: The Exploring Perinatal Outcomes among CHildren (EPOCH) Study.

The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in childhood (median 10 yrs) and adolescence (median 16 yrs). We used a multi-step approach: first, mixed models were used to examine the associations of SSB intake in childhood with CM measures across childhood and adolescence, which revealed a positive association between SSB intake and fasting triglycerides (β (95% CI) for the highest vs. lowest SSB quartile: 8.1 (−0.9,17.0); p-trend = 0.057). Second, least absolute shrinkage and selection operator (LASSO) regression was used to select 180 metabolite features (out of 767 features assessed by untargeted metabolomics) that were associated with SSB intake in childhood. Finally, 13 of these SSB-associated metabolites (from step two) were also prospectively associated with triglycerides across follow-up (from step one) in the same direction as with SSB intake (Bonferroni-adj. p < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. In this diverse cohort, we identified a panel of lipid metabolites that may serve as intermediary biomarkers, linking SSB intake to dyslipidemia risk in youth.

Metabolome Alterations Linking Sugar Sweetened Beverages with Dyslipidemia in Youth: The Exploring Perinatal Outcomes Among Children Study

ObjectivesTo examine the intermediary metabolic alterations associated with sugar sweetened beverage (SSB) intake and cardiometabolic (CM) risk factors in a cohort of diverse youth.MethodsData were from 597 participants in the Colorado EPOCH Study who were followed in childhood (∼10 yrs) and adolescence (∼16 yrs). In childhood, SSB intake was assessed by Block Kids Questionnaire and untargeted metabolomics profiling was performed on serum. CM risk factors were assessed across childhood and adolescence by fasting blood draws [glucose, insulin resistance (homeostatic method), lipids]. A “meet in the middle” approach was employed to identify metabolites that mark the relationship between childhood SSB intake and CM risk: In Step 1, we used mixed models to test prospective associations of childhood SSB intake with CM markers across childhood/adolescence. In Step 2, we used least absolute shrinkage and selection operator (LASSO) regression with bootstrapping to identify metabolites associated with childhood SSB intake. Last, we used mixed models to test associations of SSB-associated metabolites (from step 2) with CM markers across childhood/adolescence (from step 1). All analyses were adjust for age, sex, and race/ethnicity.ResultsSSB intake in childhood was positively associated with triglycerides across childhood/adolescence [b (95% CI) for 4th vs. 1st SSB quartile: 8.1 (−0.9, 17.0); p-trend = 0.057]. Based on LASSO, 180 metabolites (out of 767) were associated with SSB intake in childhood based on selection in ³40% of bootstrap samples. Among these, 13 metabolites were also associated with triglycerides across childhood/adolescence in the same direction as with SSB intake (Bonferroni-adj. P < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids.ConclusionsIn this prospective multi-ethnic cohort, childhood SSB intake was associated with higher triglycerides, which may reflect sugar-induced disruptions in hepatic lipid metabolism. We also identified a panel of lipid metabolites that may serve as intermediary biomarkers linking SSBs to dyslipidemia, offering insights into potential causal mechanisms at play.Funding SourcesNational Institute of Diabetes, Digestive, and Kidney Disease (NIDDK); National Center for Advancing Translational Sciences (NCATS).

Dyslipidemia in youth: Epidemiology, pathophysiology, screening, management, and treatment: A review of the literature.

Atherosclerotic cardiovascular disease (ASCVD) is one of the major causes of death all over the world. Atherosclerosis is developed by atherogenic lipoproteins and inflammation. Thus, dyslipidemia (DLP) is a major risk factor for developing ASCVD. DLP is a condition characterised by unnaturally high levels of one or more lipid or lipoproteins in plasma. Although clinical manifestations of atherosclerosis are observed in middle age and above, atherosclerosis is a paediatric problem with a faster pathological procedure. Hence, increased awareness of the process of diagnosis, management, and treatment of children and adolescents with inherited or acquired DLPs among physicians and paediatricians is useful to prevent ASCVD in the future. The physicians and paediatricians must be aware of the current recommendations on DLP screening, pathophysiology, strategies for lifestyle modifications, pharmacotherapy, and guidelines for constant monitoring to better management of the disease. One of the most effective ways of managing DLP in childhood is to change lifestyle, in which parents have a critical role. In critical conditions, pharmacological interventions, along with changing lifestyle, may have significant effects on treating DLP. The aim of the present review was to investigate the epidemiology, pathophysiology, screening, management, and early treatment of DLP in youth. The data collected in this study increases our understanding of the importance of screening, management, and early treatment of DLP in order to prevent later risks and side effects that might even be life-threatening.

Genome-wide Association Study of Lipid Traits in Youth With Type 2 Diabetes.

ContextDyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood.ObjectiveTo evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study.Design, Participants, and Main Outcome MeasuresWe genotyped 206 928 variants and imputed 17 642 824 variants in 1076 youth (mean age 15.0 ± 2.48 years) with T2D from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) studies as part of the Progress in Diabetes Genetics in Youth (ProDiGY) consortium. We performed association testing for triglyceride and low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-c) concentrations adjusted for the genetic relationship matrix within each substudy followed by meta-analyses for each trait.ResultsWe identified a novel association between a deletion on chromosome 3 (3:67817380_AT/A_Deletion:RP11-81N13.1) and triglyceride levels at genome-wide level of significance (P = 2.3 × 10−8) with each risk allele increasing triglycerides by 20%. We also identified a genome-wide significant signal at rs247617 (P = 5.1 × 10−9) between HERFUD1 and CETP associated with HDL-c, with carriers of 1 copy of the risk allele having twice higher HDL-c.ConclusionsOur genetic analyses of lipid traits in youth with T2D have identified 1 novel and 1 previously known locus. Additional studies are needed to further characterize the genetic architecture of dyslipidemia in youth with T2D.

1240-P: Dyslipidemia over Time in Youth with Type 2 Diabetes: The SEARCH for Diabetes in Youth Study

Limited information exists regarding the evolution of dyslipidemia in youth with type 2 diabetes (T2D). Understanding dyslipidemia risk factors may influence treatment. We studied 212 youth with T2D not on lipid lowering therapy (68% female, 43% non-Hispanic black, mean age 14.9±2.7y at baseline, mean follow-up 7.0±2.0y). Dyslipidemia was defined as HDL-C&amp;lt;35mg/dL, LDL-C&amp;gt;100mg/dL, or triglycerides (TG)&amp;gt;150mg/dL. Progression was defined as normal lipids at baseline, dyslipidemia at follow-up; regression as dyslipidemia at baseline, normal at follow-up; stable abnormal as dyslipidemia at both; stable normal as normal at both. Associations of A1c and abdominal adiposity (waist to height ratio, WHtR) over time (area under the curve, AUC) with progression and stable abnormal were examined and relative risks estimated. HDL-C progressed, regressed, was stable normal and stable abnormal in 12%, 11%, 62%, and 14%, respectively. Corresponding LDL-C values were 16%, 13%, 43% and 29%; TG were 17%, 11%, 56% and 16%. Each 1% increase in A1c AUC was associated with 13% higher risk of TG&amp;gt;150mg/dL and 22% higher risk of LDL-C&amp;gt;100mg/dL, after adjusting for WHtR (Table). There were no significant associations with WHtR. In youth with T2D, 33% and 45% had progression or stable dyslipidemia of TG and LDL-C, respectively. Higher A1c over time is associated with worse TG and LDL-C, highlighting the importance of glycemic control. Disclosure R.P. Brady: None. A.S. Shah: None. E.T. Jensen: None. J.M. Stafford: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. L.M. Dolan: None. L.M. Knight: None. G. Imperatore: None. C.B. Turley: None. A.D. Liese: None. E.M. Urbina: None. J.M. Lawrence: None. C. Pihoker: None. S.M. Marcovina: None. D. Dabelea: None. Funding Centers for Disease Control and Prevention (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); National Institutes of Health (1UC4DK108173)

Prevalence of, and biochemical and anthropometric risk factors for, dyslipidemia in children and adolescents aged 7 to 18 years in China: A cross-sectional study.

This study aimed to investigate the prevalence of dyslipidemia and its risk factors in children and adolescents aged 7 to 18 years in China. A cross-sectional study was conducted from November, 2013 to July, 2014. A total of 2283 children and adolescents from urban and rural areas in Hainan (South China) and Shaanxi Provinces (Northwest China) were selected using multi-stage stratified cluster sampling method. Each participant underwent anthropometric and serum biochemical tests which included serum lipids and hepatitis B virus surface antigen (HBsAg). The overall prevalence of high total cholesterol (TC), high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), hyperlipidemia and dyslipidemia were 6.5%, 7.5%, 5.2%, 9.1%, 14.3%, and 20.6%, respectively. After standardization by age, girls had higher prevalence of high TC (8.2%), high LDL-C (6.6%), and hyperlipidemia (16.4%), but lower prevalence of low HDL-C (8.21%) than boys (4.2%, 3.4%, 11.9%, and 11.3%, respectively). The risk of dyslipidemia increased with age (OR = 1.067, 95% CI: 1.030-1.106). Boys had a decreased risk of dyslipidemia (OR = 0.798, 95% CI: 0.640-0.994). The restricted cubic spline revealed a linear relationship between BMI and the risk of dyslipidemia (P < .001). Subjects who were HBsAg positive had higher risk of dyslipidemia (OR = 1.550, 95% CI: 1.050-2.287) compared with those who were HBsAg negative. Our study highlights the high prevalence of dyslipidemia in youth in China, and is the first study to reveal a positive association between positive status for HBsAg and abnormal lipid levels in children and adolescents.

177-OR: Genome-Wide Association Study of Lipid Traits in Youth with Type 2 Diabetes: The ProDiGY (Progress in Diabetes Genetics in Youth) Consortium

Type 2 diabetes (T2D) in youth is associated with a pro-atherogenic lipid profile characterized by high triglycerides (TG), high low-density lipoprotein cholesterol (LDL-c), and low high-density lipoprotein cholesterol (HDL-c). Genome wide association studies (GWAS) in adults have discovered more than 100 variants associated with lipid traits, but the association of genetic variants to dyslipidemia in youth with T2D remains unknown. Therefore, we genotyped 206,928 variants and imputed 17,642,824 variants in 1,076 youth with T2D from the Treatment Options for type 2 diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) as part of ProDiGY, a collaboration with type 2 diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES). Using a linear mixed model, we performed association testing for TG, LDL-c and HDL-c adjusted for age, sex, body mass index (BMI) Z-score, HbA1c, and genetic relationship matrix within each sub-study followed by meta-analyses for each lipid trait. We identified a novel variant between a deletion on chromosome 3 (3:67817380_AT/A_Deletion:RP11-81N13.1) that was associated with TG levels at genome wide level of significance (P-value=2.26×10-8, β=0.21±0.09). We also identified a genome-wide significant variant rs247617 (P-value=5.12×10-9, β=2.52±0.43) between HERFUD1 and CETP for association with HDL-c. This variant has been previously reported to be associated with HDL-c in adults in the Global Lipids Genetics Consortium (GLGC). We did not find any genome-wide significant variants in the LDL-c analysis. In summary, our genetic analyses of lipid traits in youth with T2D identified one novel and one previously known locus. Further multi-phenotype analysis may uncover additional loci associated with lipid traits in youth with T2D. Disclosure L. Chen: None. S. Srinivasan: None. N. Santoro: None. J. Todd: None. J. Divers: None. A.S. Shah: None. S. Gidding: Research Support; Self; Color Genomics. B.K. Burke: None. M.W. Haymond: Advisory Panel; Self; Daiichi Sankyo Company, Limited, Zealand Pharma A/S. Stock/Shareholder; Self; Xeris Pharmaceuticals, Inc. Other Relationship; Self; AstraZeneca. L. Lange: None. S.M. Marcovina: None. A. Chait: Consultant; Self; MedImmune. J. Flannick: Consultant; Self; Decibel Therapeutics. S. Caprio: None. J.C. Florez: None. Funding National Institutes of Health

Improving Long-Term Outcomes of Youth With Lipid Abnormalities-Expanding the Role of Pediatric Endocrinologists.

There is a disturbingly high prevalence of dyslipidemia in youth. Although pediatric endocrinologists are aware of the substantial cardiovascular (CV) risk associated with monogenic disorders of lipid and lipoprotein metabolism, relatively few recognize the CV disease (CVD)-related morbidity and premature mortality incurred by common endocrine disorders associated with dyslipidemia, such as diabetes mellitus, growth hormone deficiency, congenital adrenal hyperplasia, and hypopituitarism. In this article, we discuss the expanding role of pediatric endocrinologists in CV health and risk prevention. We reviewed available literature and summarized discussions with opinion leaders in pediatric endocrinology to accomplish the following: (i) provide an overview of this timely topic; (ii) identify opportunities for targeted education; and (iii) discuss ways of expanding clinical services to improve outcomes. In addition to well-known genetic disorders of lipid and lipoprotein metabolism, youth with common endocrine disorders, including type 1 and type 2 diabetes, would benefit from cholesterol screening and in some, early intervention, including use of lipid-lowering medications. Despite the growing need, the location and extent of services available to youth with dyslipidemia and the availability of providers with experience in treatment of dyslipidemia are largely unknown but likely inadequate to provide accessible, timely, and cost-effective intervention. With a new awareness of opportunities to prevent premature CVD in youth, including those with common endocrine disorders and CVD-related events during adulthood, there is an urgent need for additional clinical services and targeted education of current as well as future pediatric endocrinologists.

Predictors of Dyslipidemia Over Time in Youth With Type 1 Diabetes: For the SEARCH for Diabetes in Youth Study.

OBJECTIVEUnderstanding the risk factors associated with progression and regression of dyslipidemia in youth with type 1 diabetes may guide treatments.RESEARCH DESIGN AND METHODSWe studied 1,478 youth with type 1 diabetes (age 10.8 ± 3.9 years, 50% male, 77% non-Hispanic white, not on lipid-lowering medications) at baseline and at a mean follow-up of 7.1 ± 1.9 years in the SEARCH for Diabetes in Youth (SEARCH) study. Progression to dyslipidemia was defined as normal lipid concentrations at baseline and abnormal at follow-up (non–HDL-cholesterol [C] >130 mg/dL or HDL-C <35 mg/dL). Regression was defined as abnormal lipids at baseline and normal at follow-up. Multivariable logistic regression was used to evaluate factors associated with progression and regression compared with stable normal and stable abnormal, respectively. An area under the curve (AUC) variable was used for the time-varying covariates A1C and waist-to-height ratio (WHtR).RESULTSNon–HDL-C progressed, regressed, was stable normal, and stable abnormal in 19%, 5%, 69%, and 7% of youth with type 1 diabetes, respectively. Corresponding percentages for HDL-C were 3%, 3%, 94%, and 1%, respectively. Factors associated with non–HDL-C progression were higher A1C AUC and higher WHtR AUC in males. Non–HDL-C regression was associated with lower WHtR AUC, and HDL-C progression was associated with male sex and higher WHtR AUC. HDL-C regression was not modeled due to small numbers.CONCLUSIONSA1C and WHtR are modifiable risk factors associated with change in dyslipidemia over time in youth with type 1 diabetes.

Polycystic Ovary Syndrome and Increased Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis Levels Are Independent Predictors of Dyslipidemia in Youth

Background/Aims: Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) irrespective of age. Our aim was to investigate soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK), a cardiovascular risk marker in PCOS, and to determine if it is associated with dyslipidemia in youth. Methods: A prospective-observational study was carried out including 35 PCOS patients and 35 healthy controls. Serum sTWEAK levels were measured using commercially available kits. Multiple logistic regression analysis was then performed to verify the statistically significant differences in the possible predictors of dyslipidemia. Results: Serum sTWEAK levels and the percentage of women with dyslipidemia were significantly higher in the PCOS group (p = 0.024 and p < 0.001, respectively). Participants were further divided into 2 subgroups based on the presence of dyslipidemia. The percentage of women with PCOS was significantly higher in the dyslipidemic group when compared with controls; 70.7 vs. 20.7%, respectively (p < 0.001). Multiple logistic regression analysis revealed that both the presence of PCOS (OR 7.924, 95% CI 2.117-29.657, p = 0.002) and increased levels of sTWEAK (>693 pg/ml; OR 3.810, 95% CI 1.075-13.501, p = 0.038) were independently associated with dyslipidemia. Conclusions: Increased levels of both sTWEAK and PCOS were found to be independently associated with dyslipidemia in youth.

Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes.

Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D. We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c). We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz. Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D.

Dyslipidemia in Youth with Type 2 Diabetes (T2D)

Dyslipidemia in Youth with Type 2 Diabetes (T2D)

A longitudinal assessment of lipids in youth with type 1 diabetes

Type 1 diabetes and dyslipidemia are known risk factors for cardiovascular disease (CVD), but the relationship between lipid levels in youth with type 1 diabetes and future CVD remains unknown. To characterize lipid levels and CVD risk factors over time in youth with type 1 diabetes. The study included adolescents with type 1 diabetes (12-25 yr) with a minimum of 3-yr follow-up. A longitudinal prospective, observational study of 46 youth with type 1 diabetes was performed. Fasting lipid profiles, A1C, and body mass index (BMI) were measured every 6 months for at least 3 yr (median 4.2 yr). Low-density lipoprotein (LDL)-cholesterol, total cholesterol (TC), and triglycerides (TG) were divided into categorical variables. At baseline, median age was 14.3 yr, mean diabetes duration was 6.4 ± 3.8 yr, mean A1C was 8.1 ± 1.0%, and median BMI z-score was 0.92. Fifty percent of subjects had LDL levels ≤ 100 mg/dL (≤ 2.6 mmol/L) at study onset. After adjusting for confounding factors, increasing BMI z-score [β = 0.2, 95% confidence interval (CI ) = 0.03-0.38, p = 0.03] and increasing A1C (β = 0.18, 95% CI = 0.08-0.29, p = 0.001) were associated with increasing LDL category over time. Non-Hispanic ethnicity (β = 0.45, 95% CI = 0.12-0.79, p = 0.008) and family history of stroke (β = 0.38, 95% CI = 0.04-0.72, p = 0.03) were also associated with increasing LDL category. Age, diabetes duration, and tobacco exposure were not related to change in LDL. Increasing A1C was associated with increases in TG (β = 18.1, 95% CI = 2.3-33.9, p = 0.03), TC (β = 20.3, 95% CI = 9.0-31.5, p < 0.0001), and LDL (β = 13.4, 95% CI = 3.17- 23.6, p = 0.01). Glycemic control and BMI are modifiable risk factors for dyslipidemia in youth with type 1 diabetes.

Approach to Lipid Screening as a Risk Marker for Cardiovascular Disease in Pediatric Patients with Diabetes

Cardiovascular disease (CVD) is a well-known complication of diabetes mellitus (DM), and patients with DM are at an increased risk for early onset of CVD. Hyperglycemia is believed to be the primary mediator in premature development of atherosclerosis in patients with DM, but there are also derangements in cholesterol levels and inflammatory markers beyond the explanation of hyperglycemia. Although clinicians often screen for dyslipidemia as part of routine care for children and adolescents with DM, many do not feel comfortable treating this condition. Multiple guidelines exist to help clinicians with the prevention, screening, and treatment of CVD risk factors in pediatric patients with DM, but the guidelines do not always agree on screening intervals or medical treatment. Furthermore, the cost-effectiveness of medication use in this population has not been established. Research has advanced our understanding of the role of other biomarkers and radiologic studies of CVD risk, but these studies do not currently have a place in routine clinical practice. It is evident that the increased CVD risk in pediatric patients with DM is complex in origin and the optimal approach to managing dyslipidemia remains unclear. Therefore, an algorithm designed at the University of North Carolina (UNC), Division of Pediatric Endocrinology, is presented to help guide clinicians through screening and treatment of dyslipidemia in youth with DM.

Dose-response relationship between physical activity and dyslipidemia in youth

The minimal and optimal amount of physical activity associated with cardiovascular health benefits in young people is unknown. To determine the dose-response relationship between moderate-to-vigorous physical activity (MVPA) with high-risk low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride values in youth. The study sample consisted of 1235 adolescents (12 to 19 years of age) from the 20032004 and 20052006 cycles of the United States National Health and Nutrition Examination Survey. Objective measures of MVPA were obtained over seven days with accelerometers. LDL cholesterol, HDL cholesterol and triglycerides were measured from a fasting blood sample. High-risk values for these lipidslipoproteins were determined using age- and sex-specific thresholds. Logistic regression models were used to determine the dose-response relationships between MVPA and high-risk lipid levels. ORs for high-risk HDL cholesterol and triglyceride values decreased in a curvilinear manner with increasing minutes of MVPA. Compared with no MVPA (0 min), the ORs for high-risk HDL cholesterol values at 15 min, 30 min and 60 min per day of MVPA were 0.29 (95% CI 0.13 to 0.67), 0.24 (95% CI 0.10 to 0.64) and 0.21 (95% CI 0.07 to 0.61), respectively. The corresponding ORs for high-risk triglyceride values were 0.40 (95% CI 0.18 to 0.76), 0.22 (95% CI 0.06 to 0.66) and 0.10 (95% CI 0.01 to 0.51). There was no discernible dose-response relationship between MVPA and LDL cholesterol. Small amounts of MVPA were associated with a large reduction in the likelihood of having high-risk HDL cholesterol and triglyceride values in this representative sample of adolescents.

Inflammatory Markers Are Increased in Youth with Type 1 Diabetes: The SEARCH Case-Control Study

Increased inflammation may contribute to type 1 diabetes (T1D) complications. The objective of the study was to investigate the association of inflammation with obesity, hyperglycemia and dyslipidemia in youth with T1D. This was a cross-sectional study of youth with and without T1D. The study was conducted in Colorado and South Carolina. SEARCH Case-Control participants with T1D [n = 553, mean age 15 yr (range 10-22), median duration 2.7 yr] and without diabetes [n = 215, mean age 15 yr (range 10-22)]. This was an observational study. IL-6, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and leptin were measured. Inflammatory markers were evaluated by diabetes status, quartiles of glycated hemoglobin, and obesity using multiple linear regression analyses, adjusted for age, sex, study site, race/ethnicity, T1D duration, body mass index, and pubertal status. Compared with controls, youth with T1D had higher IL-6 and fibrinogen levels at all levels of glycemia and obesity, and hsCRP levels were significantly higher in youth with T1D in the top three quartiles of glycated hemoglobin (> or = 7.2%) and among normal-weight subjects. Leptin was lower in youth with poor glycemic control. Higher hsCRP and fibrinogen were correlated with higher total and LDL cholesterol, and apolipoprotein B in youth with T1D, whereas higher fibrinogen was correlated with higher LDL and apolipoprotein B in controls. T1D is characterized by excess inflammation, independent of adiposity and glycemic control. Even T1D youth in good glycemic control had higher levels of IL-6 and fibrinogen than controls. Elevated inflammatory markers were associated with an atherogenic lipid profile, which may contribute to accelerated atherosclerosis in youth with T1D.