Diabetes In Youth Study Research Articles

The association of low-density lipoprotein cholesterol with elevated arterial stiffness in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth study.

Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors. We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors. At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D. Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.

Progression to hypertension in youth and young adults with type 1 or type 2 diabetes: The SEARCH for Diabetes in Youth Study.

Central obesity may contribute to the development of hypertension in youths with diabetes. The SEARCH for Diabetes in Youth Study followed 1518 youths with type 1 diabetes (T1D) and 177 with type 2 diabetes (T2D) diagnosed when <20 years of age for incident hypertension. Incident hypertension was defined as blood pressure ≥95th percentile (or ≥130/80 mm Hg) or reporting antihypertensive therapy among those without hypertension at baseline. Poisson regression models were stratified by diabetes type and included demographic and clinical factors, clinical site, and waist‐to‐height ratio (WHtR). Youths with T2D were more likely to develop hypertension than those with T1D (35.6% vs 14.8%, P < .0001). For each 0.01 unit of annual increase in WHtR, adjusted relative risk for hypertension was 1.53 (95% CI 1.36‐1.73) and 1.20 (95% CI 1.00‐1.43) for youths with T1D and T2D, respectively. Effective strategies targeted toward reducing central obesity may reduce hypertension among youths with diabetes.

Trends in Incidence of Type 1 and Type 2 Diabetes Among Youths - Selected Counties and Indian Reservations, United States, 2002-2015.

Diabetes is one of the most common chronic diseases among persons aged <20 years (1). Onset of diabetes in childhood and adolescence is associated with numerous complications, including diabetic kidney disease, retinopathy, and peripheral neuropathy, and has a substantial impact on public health resources (2,3). From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). To assess recent trends in incidence of diabetes in youths (defined for this report as persons aged <20 years), researchers analyzed 2002-2015 data from the SEARCH for Diabetes in Youth Study (SEARCH), a U.S. population-based registry study with clinical sites located in five states. The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. Among all youths, the incidence of type 1 diabetes increased from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change [APC]=1.9%). Among persons aged 10-19 years, type 2 diabetes incidence increased from 9.0 per 100,000 in 2002-2003 to 13.8 in 2014-2015 (APC=4.8%). For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.

Alcohol consumption patterns in young adults with type 1 diabetes: The SEARCH for diabetes in youth study

AimsThe objective of this study is to describe alcohol consumption behaviors of young adults with T1D and to examine associations between alcohol consumption and diabetes-related clinical markers. MethodsData from 602 SEARCH for Diabetes in Youth Study participants age ≥ 18 yrs. with T1D were collected from 12/2011 to 6/2015 (50% female, mean age 21.3(SD 2.4), 22% race/ethnic minority). Participants were characterized as alcohol non-drinkers (n = 269), drinkers but non-binge drinkers (n = 167), or binge drinkers (n = 166) based on reported consumption in the past 30 days. Analyses were conducted using one-way ANOVAs, chi-square tests, and logistic regression modeling to examine associations between drinking and clinical markers. ResultsFifty-five percent of participants reported alcohol consumption; 27.6% of participants reported binge drinking. After adjusting for demographic characteristics, neither binge drinking nor non-binge drinking were associated with HbA1c or severe hypoglycemic events relative to non-drinkers. Binge drinking was associated with higher HDL (p = 0.008), lower systolic blood pressure (p = 0.011), and a lower waist:height ratio compared to non-drinkers (p = 0.013). ConclusionsYoung adults with T1D in the SEARCH cohort reported similar alcohol use but higher rates of binge drinking compared to the general United States population and previously reported rates in adults with T1D.

Association of metformin and statin medications with surrogate measures of cardiovascular disease in youth with type 1 diabetes: the SEARCH for diabetes in youth study.

PurposeYouth with type 1 diabetes mellitus (T1DM) are at risk of cardiovascular disease (CVD). We evaluated if metformin or statin use was associated with surrogate measures of improved CVD.MethodsWe included participants from the SEARCH observational study. Participants treated with insulin plus metformin (n=42) or insulin plus statin (n=39) were matched with 84 and 78 participants, respectively, treated with insulin alone. Measures of arterial stiffness obtained were pulse wave velocity (PWV), augmentation index (AI75), and heart rate variability as standard deviation of the normal-to-normal interval (SDNN) and root mean square differences of successive NN intervals (RMSSD).ResultsCVD measures were not significantly different among participants on insulin plus metformin versus those on insulin alone: PWV (5.9±1.0 m/sec vs. 5.8±1.5 m/sec, P=0.730), AI75 (1.8 [-6.0 to 8.0] vs. -2.4 [-10.7 to 3.8], P=0.157), SDNN (52.4 [36.8–71.1] m/sec vs. 51.8 [40.1–74.9] m/sec, P=0.592), and RMSSD (43.2 [29.4–67.6] vs. 47.4 [28.0–76.3], P=0.952). CVD measures were not different for statin users versus nonusers: PWV (5.7±0.8 m/sec vs. 5.9 ±1.1 m/sec, P=0.184), AI75 ( -4.0 [-9.5 to 1.7] vs. -6.7 [-11.3 to 5.7], P=0.998), SDNN (54.6 [43.5–77.2] m/sec vs. 63.1 [44.2–86.6] m/sec, P=0.369), and RMSSD (49.5 [31.2–74.8] vs. 59.2 [38.3–86.3], P=0.430).ConclusionsWe found no associations of statin or metformin use with surrogate measures of CVD. Future prospective pediatric clinical trials could address this issue.

Changes in diabetes medication regimens and glycemic control in adolescents and young adults with youth-onset type 2 diabetes: The SEARCH for diabetes in youth study

Changes in diabetes medication regimens and glycemic control in adolescents and young adults with youth-onset type 2 diabetes: The SEARCH for diabetes in youth study

Body Mass Index Z-Score Modifies the Association between Added Sugar Intake and Arterial Stiffness in Youth with Type 1 Diabetes: The Search Nutrition Ancillary Study.

The relationship between added sugar and arterial stiffness in youth with type 1 diabetes (T1D) has not been well-described. We used data from the SEARCH for Diabetes in Youth Study (SEARCH), an ongoing observational cohort study, to determine the association between added sugar and arterial stiffness in individuals diagnosed with T1D <20 years of age (n = 1539; mean diabetes duration of 7.9 ± 1.9 years). Added sugar intake was assessed by a food frequency questionnaire, and arterial stiffness measures included pulse wave velocity (PWV) and augmentation index. Separate multivariate linear regression models were used to evaluate the association between added sugar and arterial stiffness. Separate interaction terms were included to test for effect modification by body mass index (BMI) z-score and physical activity (PA). Overall, there was no association between added sugar and arterial stiffness (P > 0.05); however, the association between added sugar and arterial stiffness differed by BMI z-score (P for interaction = 0.003). For participants with lower BMI z-scores, added sugar intake was positively associated with PWV trunk measurements, whereas there was no association for those who had a higher BMI z-score. PA did not significantly modify the association between added sugar and arterial stiffness. Further research is needed to determine the longitudinal relationship and to confirm that obesity differentially affects this association.

Increasing burden of type 2 diabetes in Navajo youth: The SEARCH for diabetes in youth study.

SEARCH has recently reported that both prevalence and incidence of youth onset type 2 diabetes (YT2D) increased among most US race/ethnic groups in the early 2000s. This study reports on the incidence (2002-2013) and prevalence (2001, 2009) of YT2D in the Navajo Nation among youth age < 20 years from 2001 to 2013. SEARCH sought to identify prevalent YT2D cases in 2001 (N = 75) and 2009 (N = 70) and all incident YT2D cases in three periods: 2002 to 2005 (N = 53), 2006 to 2009 (N = 68), and 2010 2013 (N = 90) in Navajo Nation. Denominators were based on the active Indian Health Service user population for eligible health care facilities. Prevalence (per 100 000) and period-specific incidence rates (per 100 000 person-years) were computed for youth aged 10 to 19 years. Changes in prevalence were tested with a two-sided skew-corrected inverted score test, while changes in incidence were tested with Poisson regression. YT2D prevalence was high but stable in 2001 and 2009, overall [146.6 (116.8, 184.0) vs 141.5 (112.0, 178.8), P = .65) and in all subgroups. In contrast, incidence rates increased particularly between the second and third periods overall and in most subgroups by age and by sex. These data confirm the high burden of YT2D among Navajo youth and suggest an increasing risk in more recent years. However, recent improvements in obesity reduction in this population demonstrate optimism for potential reductions in YT2D in Navajo Nation.

Estimating prevalence of type I and type II diabetes using incidence rates: the SEARCH for diabetes in youth study

PurposeMost surveillance efforts in childhood diabetes have focused on incidence, whereas prevalence is rarely reported. This study aimed to assess whether a mathematical illness-death model accurately estimated future prevalence from baseline prevalence and incidence rates in children. MethodsSEARCH for Diabetes in Youth is an ongoing population-based surveillance study of prevalence and incidence of diabetes and its complications among youth in the United States. We used age-, sex-, and race/ethnicity-specific SEARCH estimates of the prevalence of type I and type II diabetes in 2001 and incidence from 2002 to 2008. These data were used in a partial differential equation to estimate prevalence in 2009 with 95% bootstrap confidence intervals. Model-based prevalence was compared with the observed prevalence in 2009. ResultsMost confidence intervals for the difference between estimated and observed prevalence included zero, indicating no evidence for a difference between the two methods. The width of confidence intervals indicated high precision for the estimated prevalence when considering all races/ethnicities. In strata with few cases, precision was reduced. ConclusionsFuture prevalence of type I and type II diabetes in youth may be accurately estimated from baseline prevalence and incidence. Diabetes surveillance could benefit from potential cost savings of this method.

Socio-economic, demographic, and clinical correlates of poor glycaemic control within insulin regimens among children with Type 1 diabetes: the SEARCH for Diabetes in Youth Study.

To examine the distribution and association of sociodemographic, adherence, and barriers-to-care factors in relation to glycaemic control within insulin regimens in US children with Type 1 diabetes in the SEARCH for Diabetes in Youth Study. Self- or parent-reported data from 1095 children with Type 1 diabetes aged 10-17 years were collected on insulin regimen, sociodemographics, diabetes self-management, diabetes-related family conflict and barriers to care. Multivariable logistic regression analysis identified poor glycaemic control correlates within each insulin regimen. Participants included 694 children on insulin pump therapy, 188 receiving basal-bolus injections, and 213 on a mixed insulin regimen. Of these, 28.5%, 45.2% and 51.2%, respectively, had poor glycaemic control [HbA1c ≥ 80 mmol/mol (9.5%)]. Family conflict between parent and child regarding diabetes management was the only factor significantly associated with poor glycaemic control in all insulin regimens (insulin pump, P≤ 0.0001; basal-bolus injections, P=0.0002; mixed insulin regimen, P=0.0103). For children on insulin pump, poor control was significantly associated with non-white race (P=0.0008), living in multiple households (P=0.0331), having Medicaid insurance (P=0.0090), and decreased insulin adherence (P<0.0001). For children on a mixed insulin regimen, living in multiple households (P=0.0256) and not spending enough time with healthcare provider (P=0.0058) correlated with poor control. A high percentage of US children with Type 1 diabetes had poor glycaemic control, especially those not using an insulin pump. Early identification of children with risk factors associated with poor glycaemic control within insulin regimens and addressing diabetes-related family conflict may allow interventions to improve diabetes management.

1675-P: Does Intensification of Insulin Therapy Lead to Increased Body Fat among Youth and Young Adults with Type 1 Diabetes (T1D)?

Intensive insulin therapy may have the unintended consequence of increased adiposity, contributing to the high prevalence of overweight and obesity in people with T1D. We examined the longitudinal association of insulin intensification with estimated body fat percentage (eBFP) among 746 individuals with T1D (age 10-21 years at initial visit) in the SEARCH for Diabetes in Youth study. eBFP was calculated using validated, published sex and race/ethnic specific formulae incorporating age and anthropometrics. Insulin intensification was defined as more intense, less intense or no change, in which “more intense” was an increased number of injections or addition of long-acting insulin, or a change from injections to an insulin pump. Sex-specific, linear mixed effects models used continuous eBFP at each available visit (baseline, and 1-4 follow-up visits; median T1D duration at the last visit, 8 years). Interaction terms between time and insulin intensification relative to change in eBFP tested the study hypothesis. Mean diagnosis age was 12.7 years ± 2.5, 47% were female, 80% non-Hispanic white. At baseline, mean BMIz score was 0.51 ± 0.93, with 32% overweight or with obesity. Although BMIz and weight status did not differ by sex, eBFP was significantly higher in females compared to males (32.4% ± 5.3 and 25.3% ± 5.9 respectively; p&amp;lt;0.0001). After adjustment for age at diagnosis, study site, and sociodemographic factors, there was a statistically significant increase in eBFP over time for females (4.8% over the median duration of 8 years) and a statistically significant decrease for males (1.6% over the median duration of 8 years). For females, this increase was 2.2% greater over the median duration of 8 years for more intense compared to less intense therapy (p=0.0009). Rates of change in eBFP did not depend on insulin intensification for males (p=0.09). Further work may determine metabolic and behavioral drivers of this unintended increase in eBFP, particularly among females with T1D. Disclosure E. Mayer-Davis: None. B.A. Reboussin: None. C. Pihoker: None. A.R. Kahkoska: None. D. Dabelea: None. L.M. Dolan: None. E.T. Jensen: None. D. Igudesman: None. J.M. Lawrence: None. S. Saydah: None. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Beta Bionics, MannKind Corporation, Novo Nordisk Inc., Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Other Relationship; Self; Dexcom, Inc. Funding Centers for Disease Control and Prevention; National Institutes of Health

82-OR: A T1D Genetic Risk Score Combined with Clinical Features and Autoantibodies Enables Accurate Diabetes Classification in a Racial/Ethnically Diverse Population: The Search for Diabetes in Youth Study

Accurate classification of diabetes type guides correct treatment. We recently showed a type 1 diabetes (T1D) genetic risk score (GRS-1), combined with clinical features and biomarkers discriminates between T1D and type 2 (T2D) and MODY in European adults. We aimed to test the ability of an improved 67 SNP T1D score (GRS-2) to discriminate T1D in an ethnically diverse U.S. pediatric population. We included 1818 SEARCH Study participants who had a C-peptide at a median (IQR) of 8 (6-9) years post diagnosis. T1D was defined based on severe insulin deficiency (fasting C-peptide &amp;lt;0.25 ng/ml) at follow-up. We generated genetic risk scores from SNP data, and assessed discriminative power of the T1D GRS-2 using the area under the receiver operating curve (AUC) in the three largest ethnic groups in SEARCH: white (n=1101, 95% T1D), black (n=228, 59% T1D) and Hispanic (n=257, 77% T1D). We then assessed the discriminative power of GRSs combined with autoantibody and clinical data. The T1D GRS-2 was discriminative of T1D across all three ethnic groups AUC (95% CI) for GRS-1 vs. GRS-2 was 0.88 (0.84, 0.93) vs. 0.88 (0.83, 0.92) in white, 0.82 (0.77, 0.87) vs. 0.87 (0.83, 0.92) in blacks, and 0.87 (0.82, 0.92) vs. 0.9 (0.86, 0.95) in Hispanics). Combined risk scores were most accurate at classifying T1D. AUC for different scores were: 0.93 (0.91, 0.95) for type assigned by provider at diagnosis, 0.95 (0.93, 0.96) for age and BMI, 0.95 (0.94, 0.97) for GAD/IA-2/ZNT8 autoantibodies, and 0.99 (0.99, 1.00) for a combined approach using autoantibodies, GRS-2 and clinical features. These results were similar across all race/ethnic groups. A new T1D GRS-2 is discriminative of T1D in a racial/ethnically diverse pediatric population. Using GRS2 in a combined model of clinical features, autoantibodies and genetics offers near perfect classification of T1D and could be used to accurately classify diabetes type. Disclosure R.A. Oram: Other Relationship; Self; Randox Laboratories Ltd. S.A. Sharp: None. C. Pihoker: None. L.A. Ferrat: None. G. Imperatore: None. S. Saydah: None. A.H. Williams: None. L.E. Wagenknecht: None. J.M. Lawrence: None. M.N. Weedon: None. R. Dagostino: Consultant; Self; Acelity, Amgen Inc. W. Hagopian: Research Support; Self; Novo Nordisk A/S. J. Divers: None. D. Dabelea: None. Funding National Institutes of Health (UC4DK108173)

Trends in prevalence of cardiovascular risk factors from 2002 to 2012 among youth early in the course of type 1 and type 2 diabetes. The SEARCH for Diabetes in Youth Study.

Given diabetes is an important risk factor for cardiovascular disease (CVD), we examined temporal trends in CVD risk factors by comparing youth recently diagnosed with type 1 diabetes (T1D) and type 2 diabetes (T2D) from 2002 through 2012. The SEARCH for Diabetes in Youth Study identified youth with diagnosed T1D (n = 3954) and T2D (n = 706) from 2002 to 2012. CVD risk factors were defined using the modified Adult Treatment Panel III criteria for metabolic syndrome: (a) hypertension; (b) high-density lipoprotein cholesterol ≤40 mg/dL; (c) triglycerides ≥110 mg/dL; and (d) waist circumference (WC) >90th percentile. Prevalence of CVD risk factors, stratified by diagnosis year and diabetes type, was reported. Univariate and multivariate logistic models and Poisson regression were fit to estimate the prevalence trends for CVD risk factors individually and in clusters (≥2 risk factors). The prevalence of ≥2 CVD risk factors was higher in youth with T2D than with T1D at each incident year, but the prevalence of ≥2 risk factors did not change across diagnosis years among T1D or T2D participants. The number of CVD risk factors did not change significantly in T1D participants, but increased at an annual rate of 1.38% in T2D participants. The prevalence of hypertension decreased in T1D participants, and high WC increased in T2D participants. The increase in number of CVD risk factors including large WC among youth with T2D suggests a need for early intervention to address these CVD risk factors. Further study is needed to examine longitudinal associations between diabetes and CVD.

Disordered Eating Behaviors in Youth and Young Adults With Type 1 or Type 2 Diabetes Receiving Insulin Therapy: The SEARCH for Diabetes in Youth Study.

This study examines the prevalence of disordered eating behaviors (DEB) and its associations with glycemic control, insulin sensitivity (IS), and psychosocial functioning in a large, diverse cohort of youth and young adults with type 1 or type 2 diabetes. In the SEARCH for Diabetes in Youth study, 2,156 youth and young adults with type 1 diabetes (mean ± SD age 17.7 ± 4.3 years; 50.0% female) and 149 youth and young adults with type 2 diabetes (age 21.8 years ± 3.5; 64.4% female) who were receiving insulin therapy completed the Diabetes Eating Problem Survey-Revised (DEPS-R), a self-reported measure for identifying disordered eating. DEB were defined as a DEPS-R score ≥20. Demographic characteristics, clinical measures, and health behaviors of participants with DEB and those without DEB were compared by using t tests. DEB were observed in 21.2% of participants with type 1 diabetes and 50.3% of participants with type 2 diabetes. Participants encountered challenges in maintaining a healthy weight while controlling their diabetes. For both types of diabetes, individuals with DEB had a significantly higher BMI z score, lower insulin sensitivity, more depressive symptoms, and poorer quality of life than those without DEB. Diabetic ketoacidosis episodes occurred more frequently in youth with type 1 diabetes with DEB compared to those without DEB. These findings highlight that DEB are prevalent among youth and young adults with type 1 and type 2 diabetes and who are receiving insulin therapy, and DEB are associated with poorer clinical outcomes and psychosocial well-being. Heightened awareness and early interventions are needed to address DEB for this at-risk population, as are longitudinal studies evaluating the course of DEB and diabetes outcomes.

Validity of ICD-10-CM codes for determination of diabetes type for persons with youth-onset type 1 and type 2 diabetes

ObjectiveDiagnosis codes might be used for diabetes surveillance if they accurately distinguish diabetes type. We assessed the validity of International Classification of Disease, 10th Revision, Clinical Modification (ICD-10-CM) codes to...

Relation of the degree of obesity in childhood to adipose tissue insulin resistance

AimsIn this study, we investigated whether adipose tissue insulin resistance (IR) is affected by the degree of obesity during the fasting and post-prandial state, independent of glucose tolerance among obese children and adolescents. We also tested whether systemic subclinical inflammation is associated with adipose tissue IR.MethodsSubjects were recruited to the Yale Pathophysiology of Type 2 Diabetes in Youth Study (NCT01967849). An oral glucose-tolerance test was performed to establish glucose-tolerance status and blood samples were drawn for measurement of free fatty acids (FFAs), to calculate the area under the curve (AUC) of FFA. Adipose tissue insulin resistance was calculated as the product of insulin and FFA concentrations.ResultsIn total, 671 children and adolescents (58.6% females) were included with a mean age of 13.3(2.7) years and BMI Z score of 2.45(0.31). The degree of obesity emerged as an independent predictor of both fasting and post-prandial adipose IR, p < 0.0001. Higher degree of obesity was associated with greater AUC FFA (lower suppression) compared to lower degree of obesity, p = 0.01. Furthermore, higher levels of IL-6 were positively associated with post-prandial adipose tissue IR, p = 0.02.ConclusionsThe degree of obesity in childhood and adolescence is strongly associated with adipose tissue IR independent of glucose tolerance. This is reflected not only in calculated indices of adipose IR but also in lower suppression of FFAs during the OGTT regardless of glucose tolerance or fasting adipose tissue IR. Furthermore, markers of subclinical inflammation such as IL-6 are associated with adipose tissue IR, independent of other factors.

Diabetic ketoacidosis at diagnosis of type 1 diabetes and glycemic control over time: The SEARCH for diabetes in youth study.

The diagnosis of type 1 diabetes (T1D) in youth is often associated with diabetic ketoacidosis (DKA). We aimed to evaluate if the presence of DKA at diagnosis of T1D is associated with less favorable hemoglobin A1c (HbA1c) trajectories over time. The SEARCH for Diabetes in Youth study of 1396 youth aged <20 years with newly diagnosed T1D were followed for up to 13 (median 8 [interquartile range or IQR 6-9]) years after diagnosis. Of these, 397 (28%) had DKA (bicarbonate level < 15 mmol/L and/or pH < 7.25 (venous) or < 7.30 (arterial or capillary) or mention of DKA in medical records) at diabetes onset. Longitudinal HbA1c levels were measured at each follow-up visit (average number of HbA1c measures 3.4). A linear piecewise mixed effects model was used to analyze the effect of DKA status at diagnosis of T1D on long-term glycemic control, adjusting for age at diagnosis, diabetes duration at baseline, sex, race/ethnicity, household income, health insurance status, time-varying insulin regimen and glucose self-monitoring, study site, and baseline fasting C-peptide level. At baseline, HbA1c levels were significantly higher in youth with T1D diagnosed in DKA vs those who were not (9.9% ± 1.5% vs 8.5% ± 1.4%, respectively). After the first year with diabetes, there was a significant difference in the rate of change in HbA1c levels by DKA status: HbA1c was 0.16% higher each year in youth with DKA compared to those without (interaction P-value<0.0001), after adjusting for aforementioned covariates. DKA at T1D diagnosis is associated with worsening glycemic control over time, independent of demographic, socioeconomic, and treatment-related factors and baseline fasting C-peptide.

Co-occurrence of early diabetes-related complications in adolescents and young adults with type 1 diabetes: an observational cohort study

One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication or comorbidity. We aimed to examine the prevalence and pattern of co-occurring complications in this population, as well as the related risk factors. This observational cohort study includes data from individuals diagnosed with type 1 diabetes before age 20 years who participated in the SEARCH for Diabetes in Youth Study across five sites in the USA. We assessed sociodemographic and metabolic risk factors at baseline and at follow-up, and diabetes complications at follow-up. A frequency analysis was done to examine the difference in observed versus expected prevalence (calculated using a contingency table assuming independence across cells) of co-occurring complications or comorbidities. A cluster analysis was done to identify unique clusters of participants based on demographic characteristics and metabolic risk factors. 1327 participants who completed the follow-up visit were included in the frequency analysis. The mean age was 10·1 (SD 3·9) years at the time of type 1 diabetes diagnosis and 18·0 (4·1) years at follow-up. At a mean diabetes duration of 7·8 [SD 1·9] years, co-occurrence of any two or more complications was observed in 78 (5·9%) participants, more frequently than expected by chance alone (58 [4·4%], p=0·015). Specifically, the complications that co-occurred more frequently than expected were retinopathy and diabetic kidney disease (11 [0·8%] vs three [0·2%]; p=0·0007), retinopathy and arterial stiffness (13 [1·0%] vs four [0·3%]; p=0·0016), and arterial stiffness and cardiovascular autonomic neuropathy (24 [1·8%] vs 13 [1·0%]; p=0·015). We identified four unique clusters characterised by progressively worsening metabolic risk factor profiles (longer duration of diabetes and higher glycated haemoglobin, non-HDL cholesterol, and waist-to-height ratio). The prevalence of at least two complications increased across the clusters (six [2·3%] of 261 in the low-risk cluster, 32 [6·3%] of 509 in the moderate-risk cluster, 28 [8%] of 348 in the high-risk cluster, and five [20·8%] of 24 in the highest-risk cluster). Compared with the low-risk and moderate-risk clusters, the high-risk and highest-risk clusters were characterised by a lower proportion of participants who were non-Hispanic white, and a higher proportion of participants who had a household income below US$50 000 and did not have private health insurance. Early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected. Identification of individuals with adverse risk factors could enable targeted behavioural or medical interventions that reduce the likelihood of early development of lifelong diabetes-related morbidity. US Centers for Disease Control and Prevention, US National Institutes of Health.

Short-Term Exposures to Traffic-Related Air Pollution and Pulse Wave Velocity in a Cohort of Children and Youth with Type 1 Diabetes

Background: Changes in vascular function may play a role in the association between short-term exposures to particulate matter (PM) air pollution and cardiovascular events. However, few studies have evaluated whether arterial stiffness increases in response to acute PM exposures, particularly among individuals who are at higher risk for developing cardiovascular disease (CVD), such as children and young adults with type 1 diabetes (T1D).Objectives: We examined the relationship of short-term exposures to PM2.5, elemental carbon (EC) and Atmospheric Dispersion Modeling System (ADMS)-Roads traffic-related PM near roadways with pulse wave velocity (PWV), a measure of arterial stiffness, using data from the SEARCH for Diabetes in Youth Study (SEARCH).Methods: PWV, lifestyle and demographic data were collected at a SEARCH study visit. Pollutant exposures were estimated using spatio-temporal models and assigned to the residential address of each participant for 7 days prior to the study visit. We estimated associations between different exposure windows (daily and weekly averages) of each air pollutant and PWV using separate generalized linear models adjusted for demographic and lifestyle variables.Results: Approximately 44% of the 352 participants were female and 86% were white, with a mean age of 14.6 years. In fully adjusted models, comparing the 25th and 75th percentiles of PM2.5 mass exposures on lag day 0 resulted in a 5.8% higher PWV (95% CI: 0.7%, 11.2%). No other significant associations were observed.Conclusions: In this population of youth with T1D, PWV was associated with PM2.5 mass on lag day 0. However, no associations were observed for acute exposures to other traffic-related air pollutants. In further analysis, we will examine the relationships of PM2.5 mass and traffic-related air pollutant exposures with additional measures of cardiovascular structure and function.

Association of Race and Ethnicity With Glycemic Control and Hemoglobin A1c Levels in Youth With Type 1 Diabetes

Health disparities in the clinical presentation and outcomes among youth with type 1 diabetes exist. Long-term glycemic control patterns in racially/ethnically diverse youth are not well described. To model common trajectories of hemoglobin A1c (HbA1c) among youth with type 1 diabetes and test how trajectory group membership varies by race/ethnicity. Longitudinal cohort study conducted in 5 US locations. The analysis included data from 1313 youths (aged <20 years) newly diagnosed in 2002 through 2005 with type 1 diabetes in the SEARCH for Diabetes in Youth study (mean [SD] age at diabetes onset, 8.9 [4.2] years) who had 3 or more HbA1c study measures during 6.1 to 13.3 years of follow-up. Data were analyzed in 2017. Self-reported race/ethnicity. Hemoglobin A1c trajectories identified through group-based trajectory modeling over a mean (SD) of 9.0 (1.4) years of diabetes duration. Multinomial models studied the association of race/ethnicity with HbA1c trajectory group membership, adjusting for demographic characteristics, clinical factors, and socioeconomic position. The final study sample of 1313 patients was 49.3% female (647 patients) with mean (SD) age 9.7 (4.3) years and mean (SD) disease duration of 9.2 (6.3) months at baseline. The racial/ethnic composition was 77.0% non-Hispanic white (1011 patients), 10.7% Hispanic (140 patients), 9.8% non-Hispanic black (128 patients), and 2.6% other race/ethnicity (34 patients). Three HbA1c trajectories were identified: group 1, low baseline and mild increases (50.7% [666 patients]); group 2, moderate baseline and moderate increases (41.7% [548 patients]); and group 3, moderate baseline and major increases (7.5% [99 patients]). Group 3 was composed of 47.5% nonwhite youths (47 patients). Non-Hispanic black youth had 7.98 higher unadjusted odds (95% CI, 4.42-14.38) than non-Hispanic white youth of being in the highest HbA1c trajectory group relative to the lowest HbA1c trajectory group; the association remained significant after full adjustment (adjusted odds ratio of non-Hispanic black race in group 3 vs group 1, 4.54; 95% CI, 2.08-9.89). Hispanic youth had 3.29 higher unadjusted odds (95% CI, 1.78-6.08) than non-Hispanic white youth of being in the highest HbA1c trajectory group relative to the lowest HbA1c trajectory group; the association remained significant after adjustment (adjusted odds ratio of Hispanic ethnicity in group 3 vs group 1, 2.24; 95% CI, 1.02-4.92). In stratified analyses, the adjusted odds of nonwhite membership in the highest HbA1c trajectory remained significant among male patients and youth diagnosed at age 9 years or younger, but not female patients and youth who were older than 9 years when they were diagnosed (P for interaction = .04 [sex] and .02 [age at diagnosis]). There are racial/ethnic differences in long-term glycemic control among youth with type 1 diabetes, particularly among nonwhite male patients and nonwhite youth diagnosed earlier in life.