Search

Few studies have explored durability of insulin pump use, and none have explored the link between depression and pump discontinuation. To examine the relationship between depressive symptoms [measured by the Children's Depression Inventory (CDI)], method of insulin delivery, and hemoglobin A1c (A1c), mixed models were used with data from 150 adolescents with type 1 diabetes (T1D) and visits every 6 months for 2 years. Of the 63% who used a pump, compared with multiple daily injections (MDI) at baseline, there were higher proportions who were non-minorities, had caregivers with a college degree, private insurance, and two caregivers in the home (p ≤ 0.01). After adjusting for time, sex, age, T1D duration, frequency of blood glucose monitoring, ethnicity, insurance, and caregiver number and education, baseline pump use was associated with -0.79% lower mean A1c [95% confidence interval (CI): -1.48, -0.096; p = 0.03]. For those using a pump at baseline, but switching to MDI during the study (n = 9), mean A1c was 1.38% higher (95% CI: 0.68, 2.08; p < 0.001) than that for those who did not switch method of delivery. A 10-point increase in CDI was associated with a 0.39% increase in A1c (95% CI: 0.16, 0.61; p = 0.001), independent of pump use. Regarding the temporal relationship between CDI score and changing method of insulin delivery, prior higher CDI score was associated with switching from pump to MDI (odds ratio = 1.21; 95% CI: 1.05, 1.39; p = 0.007). Clinicians should be aware of the associations between depressive symptoms, change in insulin delivery method, and the effect on glycemic control.

OBJECTIVE: To examine the association between diabetes stigma, socioeconomic status, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of AYAs from the SEARCH for Diabetes in Youth study who completed a survey on diabetes-related stigma, generating a total diabetes stigma score. Using multivariable modeling, stratified by diabetes type, we examined the relationship of diabetes stigma with variables of interest. RESULTS: Of the 1,608 AYAs who completed the diabetes-related stigma survey, 78% had type 1 diabetes, and the mean age was 21.7 years. Higher diabetes stigma scores were associated with food insecurity (P = 0.001), disordered eating (P < 0.0001), depressive symptoms (P < 0.0001), and decreased health-related (P < 0.0001) and diabetes-specific quality of life (P < 0.0001). CONCLUSIONS: Diabetes stigma is associated with food insecurity, disordered eating, and lower psychosocial well-being. [ABSTRACT FROM AUTHOR]

Objective. We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D). Design. In this cross-sectional study, age-adjusted scores for composite fluid cognition, and sub-domain scores for receptive language and inhibitory control and attention, were stratified by diabetes type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure the composite fluid cognition score. The NIHT-CB Picture Vocabulary Test was used to assess the crystallized cognition score, and rapid identification of congruent versus noncongruent items was used to assess inhibitory control and attention score. Setting. The SEARCH for Diabetes in Youth study is representative of five U.S. states. Participants. Included 1,574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% were non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c). Results. Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite fluid cognition score (β = −2.5, 95% confidence interval (CI) = −4.8, −0.1) and a lower crystallized cognition score (β = −3.4, CI = −5.6, −1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D, effect modification by glycemic levels was found in the association between FI and composite fluid cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p = 0.0531). Conclusions. Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors. [ABSTRACT FROM AUTHOR]

Aims. Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study, we aimed to assess the frequency of CD and the potential for undiagnosed CD among youth with childhood onset type 1 diabetes. In addition, we assessed the burden of cardiovascular risk factors and diabetes-associated complications in youth with type 1 diabetes by CD status and IgA tissue transglutaminase autoantibody (tTGA) levels. Methods. 2,444 youths with type 1 diabetes completed a CD questionnaire and underwent tTGA testing. Integrating the celiac disease questionnaire and tTGA results for this cross-sectional analysis, participants were categorized as follows: (1) reported CD; (2) seropositive for CD (no reported CD and seropositive tTGA); and (3) type 1 diabetes only (comparison group: no reported CD and seronegative tTGA). Subanalyses were performed on those with no reported CD and tTGA ≥10x ULN, designated potentially undiagnosed CD. Cardiovascular risk factors and diabetes-associated complications were evaluated by CD status and tTGA levels utilizing a Poisson model to estimate relative risk. Results. Reported CD in youths with type 1 diabetes was 7%. Seropositivity for tTGA with no reported CD was present in 4%, and 1.2% had potentially undiagnosed CD. Youths with potentially undiagnosed CD had a 2.69x higher risk of diabetic retinopathy than comparison group. In addition, CD with tTGA <0.05 (controlled CD) was associated with lower HbA1c. Conclusions. Undiagnosed CD is likely present in youths with type 1 diabetes and potentially undiagnosed CD is associated with a higher risk of diabetic retinopathy. These findings indicate the importance of routine screening for CD in type 1 diabetes in youths. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adults with diabetes are at risk for cardiovascular (CV) events, possibly due to increased arterial stiffness (AS) and cardiac autonomic neuropathy (CAN). We sought to determine whether 1) AS is associated with cardiac target organ damage in young adults with youth-onset diabetes, 2) whether CAN is associated with AS, as one possible etiology for increased AS in this cohort, and 3) whether these relationships differ by type of diabetes. RESEARCH DESIGN AND METHODS: Participants from the SEARCH for Diabetes in Youth Study (type 1 diabetes [T1D], n = 222; type 2 diabetes [T2D], n = 177; mean age 23 years) had clinical, echocardiographic, AS, and CAN assessed. Linear regression was performed to determine whether AS was associated with cardiac changes and CAN and whether relationships differed by diabetes type. RESULTS: AS was significantly associated with cardiac structure (left ventricular mass index, P < 0.0001), systolic function (ejection fraction, P = 0.03) and diastolic function (transmitral peak early [E]/atrial [A] wave velocities ratio, P = 0.008; early [e′]/atrial [a′] waves, P = 0.02) after adjustments for CV risk factors. The association between AS and CAN was not significant when other important covariates were added. These relationships were mostly similar in both T1D and T2D. CONCLUSIONS: AS is associated with cardiac changes in young adults with diabetes. CAN-induced AS does not appear to be an etiology for cardiac abnormalities in this cohort. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between diabetes stigma and HbA1c, treatment plan and acute and chronic complications in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: The SEARCH for Diabetes in Youth study is a multicenter cohort study that collected questionnaire, laboratory, and physical examination data about AYAs with diabetes diagnosed in childhood. A five-question survey assessed frequency of perceived diabetes-related stigma, generating a total diabetes stigma score. We used multivariable linear modeling, stratified by diabetes type, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic characteristics, clinic site, diabetes duration, health insurance, treatment plan, and HbA1c. RESULTS: Of 1,608 respondents, 78% had type 1 diabetes, 56% were female, and 48% were non-Hispanic White. The mean (SD) age at study visit was 21.7 (5.1) years (range, 10–24.9). The mean (SD) HbA1c was 9.2% (2.3%; 77 mmol/mol [2.0 mmol/mol]). Higher diabetes stigma scores were associated with female sex and higher HbA1c (P < 0.01) for all participants. No significant association between diabetes stigma score and technology use was observed. In participants with type 2 diabetes, higher diabetes stigma scores were associated with insulin use (P = 0.04). Independent of HbA1c, higher diabetes stigma scores were associated with some acute complications for AYAs with type 1 diabetes and some chronic complications for AYAs with type 1 or type 2 diabetes. CONCLUSIONS: Diabetes stigma in AYAs is associated with worse diabetes outcomes and is important to address when providing comprehensive diabetes care. [ABSTRACT FROM AUTHOR]

To assess changes in diabetes autoantibodies (DAs) over time in children and young adults with diabetes and determine whether observed changes were associated with demographic characteristics, clinical parameters and diabetes complications. Participants had DAs measured at baseline (10.3 ± 7.1 months after diabetes diagnosis) and at 12, 24 months and ≥5 years after the baseline measurement. At the ≥5‐year follow‐up, the presence of diabetes complications was assessed. We examined the associations between change in number of positive DAs and changes in individual DA status with the participants' characteristics and clinical parameters over time. Out of 4179 participants, 62% had longitudinal DA data and 51% had complications and longitudinal DA data. In participants with ≥1 baseline positive DA (n = 1699), 83.4% remained positive after 7.3 ± 2.3 years duration of diabetes. Decrease in number of positive DAs was associated with longer diabetes duration (p = 0.003 for 1 baseline positive DA; p < 0.001 for 2 baseline positive DAs) and younger age at diagnosis (p < 0.001 for 2 baseline positive DAs). No associations were found between change in number of positive DAs in participants with ≥1 baseline positive DA (n = 1391) and HbA1c, insulin dose, acute, or chronic complications after 7.7 ± 1.9 years duration of diabetes. DA status likely remains stable in the first 7 years after diabetes diagnosis. Younger age at diabetes diagnosis and longer duration were associated with less persistence of DAs. Measuring DAs after initial presentation may aid in diabetes classification but not likely in predicting the clinical course. [ABSTRACT FROM AUTHOR]

Objective: We compared arterial stiffness and heart rate variability (HRV) over time by diabetes type and determined the risk factors associated with worsening arterial stiffness and HRV in young adults with youth-onset diabetes.Research Design and Methods: Arterial stiffness (pulse wave velocity, augmentation index) and six indices of heart rate variability were measured twice, 4.5 years apart, among participants with either youth-onset type 1 or type 2 diabetes in the SEARCH for Diabetes in Youth study. Multivariable linear regression models were used to assess risk factors associated with arterial stiffness and HRV at follow-up.Results: Of 1,159 participants studied, 949 had type 1 diabetes (mean age 17.1 ± 4.7 years, 60.3% non-Hispanic White, 55% female) and 210 had type 2 diabetes (mean age 22.1 ± 3.5 years, 23.8% non-Hispanic White, 71% female) at initial assessment when diabetes duration was 7.9 years (both groups). Participants with type 2 versus type 1 diabetes had greater arterial stiffness and more abnormalities in HRV at initial and follow-up assessment and a greater change over time (all P < 0.05). Risk factors associated with worse arterial stiffness and HRV at follow-up in both types of diabetes included higher blood pressure, hemoglobin A1c, waist circumference, and triglycerides over time and longer diabetes duration.Conclusions: Arterial stiffness and HRV worsened over time with greater changes among participants with type 2 versus type 1 diabetes and among those with features of the metabolic syndrome. The risk factor profile documents potentially modifiable pathways to prevent or limit cardiovascular complications in young adults with youth-onset diabetes. [ABSTRACT FROM AUTHOR]

Objective: Genetic risk scores (GRS) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S.Research Design and Methods: We generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRS in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA+/-) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other).Results: T1D and T2D GRS were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA+/IS group and lowest in the DAA-/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA+/IR and DAA-/IS individuals had a greater probability of T1D than T2D. In DAA- individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency.Conclusions: Diabetes type-specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA- children. [ABSTRACT FROM AUTHOR]

Aims. To explore how changes in insulin regimen are associated with estimated adiposity over time among youths and young adults with type 1 diabetes and whether any associations differ according to sex. Materials and Methods. Longitudinal data were analyzed from youths and young adults with type 1 diabetes in the SEARCH for Diabetes in Youth study. Participants were classified according to insulin regimen categorized as exclusive pump ("pump only"), exclusive injections ("injections only"), injection-pump transition ("injections-pump"), or pump-injection transition ("pump-injections") for each follow-up visit completed. Estimated body fat percentage (eBFP) was calculated using validated equations. Sex-specific, linear mixed effects models examined the relationship between the insulin regimen group and change in eBFP during follow-up, adjusted for baseline eBFP, baseline insulin regimen, time-varying insulin dose, sociodemographic factors, and baseline HbA1c (≥9.0% vs. <9.0%). Results. The final sample included 284 females and 304 males, of whom 80% were non-Hispanic white with mean diagnosis age of 12.7 ± 2.4 years. In fully adjusted models for females, exclusive pump use over the study duration was associated with significantly greater increases in eBFP compared to exclusive use of injections (difference in rate of change = 0.023 % increase per month, 95 % CI = 0.01 , 0.04). Injection-to-pump transitions and pump-to-injection transitions were also associated with greater increases in eBFP compared to exclusive use of injections (difference in rate of change = 0.02 % , 95 % CI = 0.004 , 0.03, and 0.02%; 95 % CI = 0.0001 , 0.04, respectively). There was no relationship between the insulin regimen and eBFP among males. Conclusions. Among females with type 1 diabetes, exclusive and partial pump use may have the unintended consequence of increasing adiposity over time compared to exclusive use of injections, independent of insulin dose. [ABSTRACT FROM AUTHOR]

Objective: To estimate difference in population-level glycemic control and the emergence of diabetes complications given a theoretical scenario in which non-White youth and young adults (YYA) with type 1 diabetes (T1D) receive and follow an equivalent distribution of diabetes treatment regimens as non-Hispanic White YYA.Research Design and Methods: Longitudinal data from YYA diagnosed 2002-2005 in the SEARCH for Diabetes in Youth Study were analyzed. Based on self-reported race/ethnicity, YYA were classified as non-White race or Hispanic ethnicity (non-White subgroup) versus non-Hispanic White race (White subgroup). In the White versus non-White subgroups, the propensity score models estimated treatment regimens, including patterns of insulin modality, self-monitored glucose frequency, and continuous glucose monitoring use. An analysis based on policy evaluation techniques in reinforcement learning estimated the effect of each treatment regimen on mean hemoglobin A1c (HbA1c) and the prevalence of diabetes complications for non-White YYA.Results: The study included 978 YYA. The sample was 47.5% female and 77.5% non-Hispanic White, with a mean age of 12.8 ± 2.4 years at diagnosis. The estimated population mean of longitudinal average HbA1c over visits was 9.2% and 8.2% for the non-White and White subgroup, respectively (difference of 0.9%). Within the non-White subgroup, mean HbA1c across visits was estimated to decrease by 0.33% (95% CI -0.45, -0.21) if these YYA received the distribution of diabetes treatment regimens of the White subgroup, explaining ∼35% of the estimated difference between the two subgroups. The non-White subgroup was also estimated to have a lower risk of developing diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy with the White youth treatment regimen distribution (P < 0.05), although the low proportion of YYA who developed complications limited statistical power for risk estimations.Conclusions: Mathematically modeling an equalized distribution of T1D self-management tools and technology accounted for part of but not all disparities in glycemic control between non-White and White YYA, underscoring the complexity of race and ethnicity-based health inequity. [ABSTRACT FROM AUTHOR]

Aims: To compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function. Methods: In a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function. Results: Of 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p < 0.05). Abnormal diastolic function, quantified using healthy controls, was pronounced in both groups but greater in those with T2D than T1D (T2D: 57.7% vs T1D: 47.2%, respectively), p < 0.05. Risk factors associated with worse diastolic function included older age at diabetes diagnosis, female sex, higher BP, heart rate and HbA1c and longer diabetes duration. Conclusions: LV structure and diastolic function is worse in individuals with T2D compared to T1D. However, abnormal diastolic function in seen in both groups compared to published values from age similar healthy controls. [ABSTRACT FROM AUTHOR]

SEARCH for Diabetes in Youth (SEARCH) was initiated in 2000 as a multicenter study to address major gaps in the understanding of childhood diabetes in the United States. An active registry of youth diagnosed with diabetes at age <20 years since 2002 assessed prevalence, annual incidence, and trends by age, race/ethnicity, sex, and diabetes type. An observational cohort nested within the population‐based registry was established to assess the natural history and risk factors for acute and chronic diabetes‐related complications, as well as the quality of care and quality of life of children and adolescents with diabetes from diagnosis into young adulthood. SEARCH findings have contributed to a better understanding of the complex and heterogeneous nature of youth‐onset diabetes. Continued surveillance of the burden and risk of type 1 and type 2 diabetes is important to track and monitor incidence and prevalence within the population. SEARCH reported evidence of early diabetes complications highlighting that continuing the long‐term follow‐up of youth with diabetes is necessary to further our understanding of its natural history and to develop the most appropriate approaches to primary, secondary, and tertiary prevention of diabetes and its complications. This review summarizes two decades of research and suggests avenues for further work. [ABSTRACT FROM AUTHOR]

Objective: We previously reported a high (˜30%) but stable prevalence of diabetic ketoacidosis (DKA) at youth-onset diagnosis of type 1 diabetes (2002 and 2010). Given the changing demographics of youth-onset type 1 diabetes, we sought to evaluate temporal trends in the prevalence of DKA at diagnosis of type 1 diabetes from 2010 to 2016 among youth <20 years of age and evaluate whether any change observed was associated with changes in sociodemographic distribution of those recently diagnosed.Research Design and Methods: We calculated prevalence of DKA within 1 month of type 1 diabetes diagnosis by year and evaluated trends over time (2010-2016) (n = 7,612 incident diabetes cases; mean [SD] age 10.1 [4.5] at diagnosis). To assess whether trends observed were attributable to the changing distribution of sociodemographic factors among youth with incident type 1 diabetes, we estimated an adjusted relative risk (RR) of DKA in relation to calendar year, adjusting for age, sex, race/ethnicity, income, education, health insurance status, language, season of diagnosis, and SEARCH for Diabetes in Youth Study site.Results: DKA prevalence increased from 35.3% (95% CI 32.2, 38.4) in 2010 to 40.6% (95% CI 37.8, 43.4) in 2016 (Ptrend = 0.01). Adjustment for sociodemographic factors did not substantively change the observed trends. We observed a 2% annual increase in prevalence of DKA at or near diagnosis of type 1 diabetes (crude RR 1.02 [95% CI 1.01, 1.04] and adjusted RR 1.02 [95% CI 1.01, 1.04]; P = 0.01 for both).Conclusions: Prevalence of DKA at or near type 1 diabetes diagnosis has increased from 2010 to 2016, following the high but stable prevalence observed from 2002 to 2010. This increase does not seem to be attributable to the changes in distribution of sociodemographic factors over time. [ABSTRACT FROM AUTHOR]

Background: There is significant global variation in the prevalence of diabetic ketoacidosis (DKA) at diagnosis among youth with type 1 diabetes (T1D). However, data for youth with type 2 diabetes (T2D) are limited, even in developed countries. We compared the prevalence of DKA at diagnosis among individuals with T1D and T2D from the SEARCH for Diabetes in Youth (SEARCH) and the Registry of Youth Onset Diabetes in India (YDR) registries. Methods: We harmonized the SEARCH and YDR registries to the structure and terminology in the Observational Medical Outcome Partnership Common Data Model. Data used were from youth with T1D and T2D diagnosed before 20 years and newly diagnosed between 2006 and 2012 in YDR and 2009 and 2012 in SEARCH. Results: There were 5366 US youth (4078 with T1D, 1288 with T2D) and 2335 Indian youth (2108 with T1D, 227 with T2D). More than one third of T1D youth enrolled in SEARCH had DKA at diagnosis which was significantly higher than in YDR (35.3% vs 28.7%, P <.0001). The burden of DKA in youth with T1D was significantly higher among younger age groups; this relationship was similar across registries (P =.4). The prevalence of DKA among T2D in SEARCH and YDR were 5.5% and 6.6% respectively (P =.4). Conclusions: There is significant burden of DKA at diagnosis with T1D among youth from United States and India, especially among the younger age groups. The reasons for this high prevalence are largely unknown but are critical to developing interventions to prevent DKA at diagnosis. [ABSTRACT FROM AUTHOR]

Aim: 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. Method: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: There is limited information regarding the potential effect macronutrients have on postprandial glycemic variability in young children with type 1 diabetes (T1D). To date, studies examining nutrition and glycemic outcomes either assess these factors at a single timepoint, or aggregate large datasets for group level analyses. This study examined how inter- and intraindividual fluctuations in carbohydrate, fat, and protein intake impact glycemic variability in the postprandial period for young children with T1D.Methods: Thirty-nine young children, aged 2-6 years, wore a continuous glucose monitor for 72 hr, while their parents completed detailed diet records of all food intake. The analyses tested three multilevel models to examine intra- and interindividual differences between food intake and postprandial glycemic variability.Results: The results suggest carbohydrate intake, relates to greater postprandial glycemic variability. In contrast, the results reveal the inverse effect for protein, suggesting a tendency for young children who ate more protein at some meals to have lower postprandial glycemic variability, with the exception of lunch. There was no effect for fat on postprandial glycemic variability.Conclusion: These results suggest protein consumption may be an important consideration when aiming for optimal glycemic levels for some meals. When counseling parents of young children with T1D on common behaviors underlying glycemic excursion, pediatric psychologists may consider discussing the nutritional make up of children's meals. Further, the results demonstrate retaining longitudinal data at the person level, versus aggregating individual data for group level analyses, may offer new information regarding macronutrient intake and glycemic outcomes. [ABSTRACT FROM AUTHOR]

To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes. The objective of the study was to compare plasma levels of campesterol and β-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes. Serum samples were obtained from adolescent subjects with type 1 diabetes (n = 175, mean age 15.2 years, mean duration of diabetes 8.2 years) and without diabetes (n = 74, mean age 15.4 years). Campesterol, β-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables. Campesterol and β-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure. Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed. • Cholesterol absorption markers are increased in type 1 diabetes. • Cholesterol synthesis markers are decreased in type 1 diabetes. • Cholesterol absorption markers correlate with HbA1c in type 1 diabetes. • Cholesterol synthesis markers correlate with BMI, TG, and BP in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Youth 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. Methods: We 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). Results: CVD 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). Conclusion: We found no associations of statin or metformin use with surrogate measures of CVD. Future prospective pediatric clinical trials could address this issue. [ABSTRACT FROM AUTHOR]

The article reports on the diabetes-related out of pocket expenses (OOPEs) for families of adolescents and young adults with type 1 diabetes from the SEARCH for Diabetes in Youth (SEARCH) study and their association with demographic, socioeconomic, clinical, and health care characteristics. Topics discussed include adjusted association of OOPEs presented as an OOPE rate relative to the reference group, finding on most adolescents and youth with type 1 diabetes, and limitations of the study.

Objective: To estimate the prevalence of and risk factors for cardiovascular autonomic neuropathy (CAN) in adolescents and young adults with type 1 and type 2 diabetes enrolled in the SEARCH for Diabetes in Youth Study. Methods: The study included 1646 subjects with type 1 diabetes (age 18 ± 4 years, diabetes duration 8 ± 2 years, HbA1c 9.1 ± 1.9%, 76% non‐Hispanic Whites) and 252 with type 2 diabetes (age 22 ± 4 years, diabetes duration 8 ± 2 years, HbA1c 9.2 ± 3.0%, 45% non‐Hispanic Blacks). Cross‐sectional and longitudinal risk factors were assessed at baseline and follow‐up visits. Area under the curve (AUC) was used to assess the longitudinal glycemic exposure and cardiovascular risk factors. CAN was assessed by time and frequency domain indices of heart rate variability (HRV). CAN was defined as the presence of ≥3 of 5 abnormal HRV indices. Results: The prevalence of CAN was 12% in adolescents and young adults with type 1 diabetes and 17% in those with type 2 diabetes. Poor long‐term glycemic control (AUC HbA1c), high blood pressure, and elevated triglyceride levels were correlates of CAN in subjects with type 1 diabetes. In those with type 2 diabetes, CAN was associated with elevated triglycerides and increased urinary albumin excretion. Conclusions: The prevalence of CAN in this multiethnic cohort of adolescents and young adults with type 1 and type 2 diabetes are comparable to those reported in adults with diabetes. Suboptimal glycemic control and elevated triglycerides were the modifiable risk factors associated with CAN. [ABSTRACT FROM AUTHOR]

Objective: We assessed the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the SEARCH for Diabetes in Youth (SEARCH) study.Research Design and Methods: The Michigan Neuropathy Screening Instrument (MNSI) was used to assess DPN in 1,734 youth with T1D (mean ± SD age 18 ± 4 years, T1D duration 7.2 ± 1.2 years, and HbA1c 9.1 ± 1.9%) and 258 youth with T2D (age 22 ± 3.5 years, T2D duration 7.9 ± 2 years, and HbA1c 9.4 ± 2.3%) who were enrolled in the SEARCH study and had ≥5 years of diabetes duration. DPN was defined as an MNSI exam score of >2. Glycemic control over time was estimated as area under the curve for HbA1c.Results: The prevalence of DPN was 7% in youth with T1D and 22% in youth with T2D. Risk factors for DPN in youth with T1D were older age, longer diabetes duration, smoking, increased diastolic blood pressure, obesity, increased LDL cholesterol and triglycerides, and lower HDL cholesterol (HDL-c). In youth with T2D, risk factors were older age, male sex, longer diabetes duration, smoking, and lower HDL-c. Glycemic control over time was worse among those with DPN compared with those without for youth with T1D (odds ratio 1.53 [95% CI 1.24; 1.88]) but not for youth with T2D (1.05 [0.7; 1.56]).Conclusions: The high rates of DPN among youth with diabetes are a cause of concern and suggest a need for early screening and better risk factor management. Interventions in youth that address poor glycemic control and dyslipidemia may prevent or delay debilitating neuropathic complications. [ABSTRACT FROM AUTHOR]

Aims: We compared cystatin C in youth with versus without diabetes and determined factors associated with cystatin C in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D).Methods: Youth (ages 12-19years) without diabetes (N=544) were ascertained from the NHANES Study 2000-2002 and those with T1D (N=977) and T2D (N=168) from the SEARCH for Diabetes in Youth Study. Adjusted means of cystatin C concentrations were compared amongst the 3 groups. Next, we performed multivariable analyses within the T1D and T2D SEARCH samples to determine the association between cystatin C and race, sex, age, diabetes duration, HbA1c, fasting glucose, and BMI.Results: Adjusted cystatin C concentrations were statistically higher in NHANES (0.85mg/L) than in either the T1D (0.75mg/L) or T2D (0.70mg/L) SEARCH groups (P<0.0001). Fasting glucose was inversely related to cystatin C only in T1D (P<0.001) and BMI positively associated only in T2D (P<0.01) while HbA1c was inversely associated in both groups.Conclusions: Cystatin C concentrations are statistically higher in youth without diabetes compared to T1D or T2D, however the clinical relevance of this difference is quite small, especially in T1D. In youth with diabetes, cystatin C varies with BMI and acute and chronic glycemic control, however their effects may be different according to diabetes type. [ABSTRACT FROM AUTHOR]

Objective: Understanding the risk factors associated with progression and regression of dyslipidemia in youth with type 1 diabetes may guide treatments.Research Design and Methods: We 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).Results: Non-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.Conclusions: A1C and WHtR are modifiable risk factors associated with change in dyslipidemia over time in youth with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Youth with type 1 diabetes have worse cardiovascular (CV) risk factors and higher carotid intima-media thickness (IMT) than their peers without diabetes. Whether the burden of CV risk factors over time is associated with carotid IMT at follow-up in youth with type 1 diabetes is not known.Research Design and Methods: Two hundred ninety-eight youth with type 1 diabetes (mean age 13.3 ± 2.9 years, 87.6% non-Hispanic white, 53.7% male) had two study visits 5 years apart. CV risk factors, including BMI, lipids, blood pressure, hemoglobin A(1c), and smoking status, were assessed at both visits, and carotid IMT was measured at follow-up using B-mode ultrasonography. Linear regression models with an area under the curve measurement that incorporated the baseline and follow-up CV risk factors were used to evaluate the relationship with carotid IMT at follow-up.Results: All CV risk factors worsened significantly over time (except LDL cholesterol) (P < 0.05). From baseline to follow-up, the number of abnormal CV risk factors also increased (P < 0.05). Predictors of carotid IMT were older age, male sex, and higher BMI z score area under the curve (all P < 0.05).Conclusions: The CV risk factor burden increases over time in youth with type 1 diabetes. BMI z score was the only modifiable CV risk factor that predicted carotid IMT. This study highlights the critical need to better understand the risk factors that influence carotid IMT early in the course of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background Microvascular dysfunction is a key event in the development of atherosclerosis, which predates the clinical manifestations of vascular disease including stroke and myocardial infarction. Dysfunction of the microvasculature can be measured as a decreased microperfusion in response to heat. Objective We sought to evaluate the microvasculature using heat among adolescents and young adults with type 1 diabetes (T1D) compared to healthy non-diabetic controls. We hypothesized that youth with T1D would have impaired microvascular function measured as decreased perfusion. Methods We studied 181 adolescents and young adults with T1D and 96 age-, race-, and sex-matched healthy controls (mean age 19 yr). Patients were seen at an in-person study visit where demographics, anthropometrics, and laboratory data was obtained. Skin microvascular perfusion was measured on the volvar surface of the right forearm using a standard laser flow Doppler. Measurements were taken at baseline and after heating to 44° C. Results Youth with T1D had decreased microvascular perfusion as measured by lower percent change of perfusion units (1870 ± 945 vs. 2539 ± 1255, p < 0.01) and percent change in area under the curve (1870 ± 945 vs. 2539 ± 1255, p < 0.01) compared to controls. Glycosylated hemoglobin A1c (HbA1c) was found to be an independent determinant of microvascular function (p < 0.05). Conclusions Adolescents and young adults with T1D have evidence of microvascular dysfunction that can be detected using heat, a non-invasive physiologic stimulus. HbA1c appears to play an independent role in determining microvascular perfusion suggesting tight glycemic control is probably important for the development of vascular disease. [ABSTRACT FROM AUTHOR]

Background Arterial stiffness is a useful parameter to predict future cardiovascular disease. Objective We sought to compare arterial stiffness in adolescents and young adults with and without type 1 diabetes (T1D) and explore the risk factors associated with the differences observed. Subjects and methods Carotid-femoral pulse wave velocity ( PWV), augmentation index ( AI75), and brachial distensibility ( BrachD) were measured in 402 adolescents and young adults with T1D (age 18.8 ± 3.3 yr, T1D duration 9.8 ± 3.8 yr) and 206 non-diabetic controls that were frequency-matched by age, sex, and race/ethnicity in a cross-sectional study. General linear models were used to explore variables associated with an increase in arterial stiffness after adjustment for demographic and metabolic covariates. Results T1D status was associated with a higher PWV (5.9 ± 0.05 vs. 5.7 ± 0.1 m/s), AI75 (1.3 ± 0.6 vs. −1.9 ± 0.7%), and lower BrachD (6.2 ± 0.1 vs. 6.5 ± 0.1%Δ/ mmHg), all p < 0.05. In multivariate models, age, sex, race, adiposity, blood pressure, lipids, and the presence of microalbuminuria were found to be independent correlates of increased arterial stiffness. After adjustment for these risk factors, T1D status was still significantly associated with arterial stiffness (p < 0.05). Conclusions Peripheral and central subclinical vascular changes are present in adolescents and young adults with T1D compared to controls. Increased cardiovascular risk factors alone do not explain the observed differences in arterial stiffness among cases and controls. Identifying other risk factors associated with increased arterial stiffness in youth with T1D is critical to prevent future vascular complications. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10 −8 ). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D. [ABSTRACT FROM AUTHOR]

Objective 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. Study Design 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). Results 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. Conclusions Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D. [ABSTRACT FROM AUTHOR]

Objective In their Strategic Impact Goal Statement, the American Heart Association focused on primordial prevention of cardiovascular risk factors by defining metrics for ideal cardiovascular health ( ICH). The prevalence of ICH among youth with type 1 diabetes is unknown. Youth with type 1 diabetes face an increased risk of cardiovascular disease ( CVD) as they age. The purpose of this report was to examine the prevalence of ICH in a population of youth with type 1 diabetes and to examine the association of ICH with measures of cardiovascular structure and function. Research design and methods This report is based on SEARCH CVD an ancillary study to the SEARCH for Diabetes in Youth. A total of 190 adolescents with type 1 diabetes had complete data on all of the ICH metrics at baseline and had measures of arterial stiffness [pulse wave velocity ( PWV), brachial distensibility ( BrachD), and augmentation index ( AIx)] and carotid intima-media thickness completed at a follow-up visit [on average 5 yr after baseline (interquartile range 4-5)]. Results No subjects met the ICH criteria for all 7 metrics. Meeting an increasing number of ICH metrics was significantly associated with lower arterial stiffness [lower PWV of the trunk (β = −0.02 ±0.01; p = 0.004) and AIx (β = −2.2 ±0.66; p = 0.001), and increased BrachD (β = 0.14 ±0.07; p = 0.04)]. Conclusions Increasing number of ICH metrics was significantly associated with decreased arterial stiffness, but prevalence of ICH in this population was low. Youth with type 1 diabetes could benefit from improvements in their cardiovascular health. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with type 1 diabetes (T1D) and its role in maintaining plasma cholesterol levels. The variables considered include correlations between PCSK9 and age, body mass index (BMI), insulin level, blood glucose and pressure, triglycerides and cholesterol. The effect of PCSK9 in male and female patients is discussed.

Abstract: This study examined mealtime behaviors in families of young children with type 1 diabetes (T1DM) on intensive insulin therapy. Behaviors were compared to published data for children on conventional therapy and examined for correlations with glycemic control. Thirty-nine families participated and had at least three home meals videotaped while children wore a continuous glucose monitor. Videotaped meals were coded for parent, child, and child eating behaviors using a valid coding system. A group difference was found for child request for food only. There were also associations found between children's glycemic control and child play and away. However, no associations were found between parent and child behaviors within meals and children's corresponding post-prandial glycemic control. Results reinforce existing research indicating that mealtime behavior problems exist for families of young children even in the context of intensive therapy and that some child behaviors may relate to glycemic control. [Copyright &y& Elsevier]

OBJECTIVE--To establish minimal clinically important difference (MCID) scores representing the smallest detectable change in quality of life (QOL), using the Pediatric Quality of Life Inventory (PedsQL) Generic Core and Diabetes Module among youth with diabetes and their parents, and to identify demographic and clinical correlates of QOL change over 1 year. RESEARCH DESIGN AND METHODS--Participants in the SEARCH for Diabetes in Youth Study aged > 5 years and parents of youth aged < 18 years completed PedsQL surveys at their initial and 12-month study visits. MCIDs for each PedsQL module were calculated using one standard error of measurement. Demographic and clinical characteristics associated with QOL change were identified through multiple linear and logistic regression analyses. RESULTS--The sample comprised 5,004 youth (mean age, 12.5 ± 4.7 years; mean diabetes duration, 3.4 ± 3.7 years). Of 100 possible points, PedsQL total score MCIDs for youth with type 1 and type 2 diabetes, respectively, were Generic Core, 4.88, 6.27 (parent) and 4.72, 5.41 (youth); Diabetes Module, 4.54,6.06 (parent) and 5.27, 5.96 (youth). Among 1,402 youth with a follow-up visit, lower baseline QOL, male sex, private insurance, having type 1 diabetes, longer diabetes duration, and better glycemic control predicted improvements in youth- and parent-reported PedsQL total scores over 1 year. Clinically meaningful (Si MCID) improvements in total score for at least one PedsQL module were predicted by private insurance, lower BMI, and lower A1C at baseline. CONCLUSIONS--These diabetes-specific reference points to interpret clinically meaningful change in PedsQL scores can be used in clinical care and research for youth with type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims In young people with Type 1 diabetes, depressive symptoms and shared responsibility for management of diabetes impact upon diabetes management and control. However, the simultaneous effects of both depressive symptoms and parental involvement on diabetes self-care and glycaemic control have not been examined. Thus, the aim of the current study was to examine the relationships between parental involvement and adolescent depressive symptoms in predicting blood glucose monitoring and glycaemic control. Methods One hundred and fifty young people with Type 1 diabetes (mean age 15.3 years) and their parents completed responsibility sharing and depressive symptom assessments, meter assessment of blood glucose monitoring and HbA1c at baseline and then 6, 12 and 18 months. Results Parental involvement affected HbA1c through blood glucose monitoring only at low levels of adolescent depressive symptoms (score ≤ 6), which made up only 20% of the sample. In the presence of more depressive symptoms, parental involvement no longer was related to HbA1c through blood glucose monitoring. This was the relationship in the majority of the sample (80%). Conclusions While most young people in this sample are not showing evidence of high levels of depressive symptoms, even modest levels of distress interfere with parental involvement in diabetes management. By addressing adolescent depressive symptoms, interventions promoting parental involvement in these families may be more effective. [ABSTRACT FROM AUTHOR]

Objectives To examine human leukocyte antigen HLA DRB1-DQB1 haplotypes within a multi-ethnic cohort and assess their association with characteristics of diabetes onset. Methods The sample included 1662 participants from the SEARCH for Diabetes in Youth Study who tested positive for GADA and/or IA-2A autoantibodies. Blood drawn at the study visit was used to measure fasting C-peptide (FCP) and genotype HLA DRB1 and DQB1 loci. Diabetic ketoacidosis ( DKA) at diagnosis was determined from medical records. Multivariable linear and logistic regression models stratified by race/ethnicity were used to assess associations with DRB1-DQB1 haplotypes. Results The frequency of DRB1*03 susceptibility haplotypes ranged 27.5-28.9% in all racial/ethnic groups. The frequency of susceptibility DRB1*04- DQB1*0302 was higher in non-Hispanic White ( NHW; 34.1%) and Hispanic (38.9%) compared to non-Hispanic Black ( NHB; 20.8%) youth. Neutral and protective haplotypes were low frequency in all groups. DBR1*03 haplotypes were associated with younger age at diagnosis in NHW and positivity for multiple autoantibodies in Hispanics. DRB1*04- DQB1*0302 haplotypes were associated with multiple autoantibody positivity in NHW and Hispanics, and lower FCP and higher odds of DKA in Hispanics only. Although protective DRB1*04- DQB1*0301 haplotypes were associated with older age at diagnosis in NHW, they were also associated with multiple autoantibody positivity in these youth. Protective DRB1*13 haplotypes were associated with decreased odds of multiple autoantibody positivity in NHB youth. Conclusions The distribution of DRB1-DQB1 haplotypes and their association with onset-related characteristics of autoimmune diabetes varies across major racial/ethnic groups in the USA. This may contribute to variation in clinical presentation of autoimmune diabetes by race/ethnicity. [ABSTRACT FROM AUTHOR]

Abstract: Diet is an important component of diabetes treatment and integral to successful management. While intensive insulin therapy can allow patients to eat more freely, it is not known how the rapid uptake of intensive therapy in young children with type 1 diabetes has impacted their diet and if diet and healthful eating in young children correlates with mealtime behaviors and glycemic control. This study examined diet, mealtime behaviors, and glucose control in a sample of 39 young children on intensive therapy. This was a one-sample, cross-sectional study. Children had a mean age of 5.1±1.1 years. Children''s 3-day diet diaries were assessed using a deviation scale (measure of adherence) and a healthy eating index. Mealtime behaviors were assessed using the Behavioral Pediatric Feeding Assessment Scale. Children''s glucose control was measured using continuous glucose monitoring. Children''s mean carbohydrate intake was 72%±24% of the recommended levels based on their age, sex, size, and activity level, and children exceeded national guidelines for percentage of calories from fat and saturated fat. A more healthful diet correlated with fewer child mealtime behavior problems, but better dietary adherence correlated with more parent mealtime behavior problems. Even in the context of intensive management, diet can be problematic for young children with type 1 diabetes. Parent-reported problems with mealtime behaviors seem to correlate with healthy eating and dietary adherence. [Copyright &y& Elsevier]

Abstract: Purpose: Deteriorating type 1 diabetes management and control are common among adolescents; however, clinical evidence suggests that individual trajectories can vary. The aim of this study was to examine patterns and predictors of blood glucose monitoring (BGM) frequency and glycemic control (hemoglobin A1c). Methods: Prospective data analysis spanning 18–24 months was conducted with 150 adolescent–parent pairs. Latent group-based trajectory modeling identified subgroups and determined medical, demographic, psychological, and family predictors of subgroup membership. Results: Three subgroups emerged, representing diabetes management and control that are “meeting treatment targets” (40%; A1c at baseline = 7.4%, BGM frequency at baseline = 4.8 checks/day) and two levels “not meeting targets”:“normatively similar” youth (40%; A1c = 9.2%, BGM frequency = 2.8 checks/day), and “high-risk” youth (20%; A1c = 11.2%, BGM frequency = 2.9 checks/day). Subgroup membership was maintained over 18–24 months. There was minimal change across time, although only one-third of adolescents met treatment targets. Older age, longer diabetes duration, ethnic minority status, unmarried caregiver status, insulin delivery via injections versus continuous subcutaneous insulin infusion, greater depressive symptoms, negative affect about BGM, and diabetes-specific family conflict each predicted membership in a subgroup with poorer diabetes management and control. Conclusions: Among the nearly two-thirds of adolescents with management and control that do not meet treatment targets, modifiable and nonmodifiable factors may signal the need for prevention or intervention. Demographic and medical factors may call for proactive efforts to prevent deterioration, and psychological symptoms and family conflict signal opportunities for clinical intervention to promote improved diabetes management and control in adolescence. [Copyright &y& Elsevier]

Objective To investigate the relation of changes in executive functioning to changes in diabetes self-management in a 2-year prospective study of a sample of youth aged 9–11 years at baseline (n = 239) with type 1 diabetes and their maternal caregivers. Research Design and Methods Youth and maternal caregivers completed the Diabetes Self-Management Profile (DSMP) at baseline, 12 months, and 24 months. Maternal caregivers completed the Behavioral Rating Inventory of Executive Functioning (BRIEF) at the same time points to assess global executive functioning, and the domains of behavioral regulation and metacognition. Results Youth reported self-management decreased over time (p < .01) while behavioral regulation (e.g., the child’s ability to shift cognitive set and moderate emotions and behaviors via emotional control) increased (p < .05). Changes in behavioral regulation significantly predicted rate of change in youth-reported self-management (p < .01). Global executive functioning and metacognition (e.g., the child’s ability to monitor, initiate, plan, organize, and sustain future-oriented problem solving and working memory) did not change over time and did not predict changes in self-management. Moreover, executive functioning and self-management did not predict changes in HbA1c. Conclusions Positive changes in behavioral regulation may enhance self-management of type 1 diabetes during the transition to adolescence. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that fetal exposure to a hyperglycemic intrauterine environment in women with type 1 diabetes is associated with asymmetrically distributed excessive fetal growth and imprinting consistent with adverse health issues later in life. Methods: We report findings from a feasibility study on 19 young adults, born to mothers with type 1 diabetes. Long-term follow-up of the offspring in young adulthood included: oral glucose tolerance test, body mass index (BMI), dual X-ray absorptiometry, and blood pressure (BP). We report z-BMI and z-BP to account for varying gender and age. Results: The young adults born to women with diabetes averaged 19.9 years at follow-up; 37% were female, and 21% African American. Maternal glycohemoglobin A1 concentration in the 2nd trimester was 9.2% for offspring born with asymmetric LGA and 7.5% for those born with symmetric LGA or AGA. There was significant correlation between maternal glucose control during pregnancy and fasting glucose, z-BMI and z-systolic BP in the young adults. Conclusion: The hyperglycemic intrauterine environment is associated with short-term morbidity, manifested as asymmetric LGA (the 'fat' baby). In addition, increasing level of maternal hyperglycemia during pregnancy is associated with increased adiposity and elevated fasting glucose in the young adult offspring. [ABSTRACT FROM AUTHOR]

Hood KK, Rausch JR, Dolan LM. Depressive symptoms predict change in glycemic control in adolescents with type 1 diabetes: rates, magnitude, and moderators of change. Objective: To determine whether depressive symptoms in adolescents with type 1 diabetes predict change in glycemic control over time. Research design and methods: A total of 145 adolescents (aged 13-18 yr) participated in two study visits (baseline and 6 months). They completed a measure of depressive symptoms (Children's Depression Inventory; CDI) and had their A1c values and adherence to blood glucose monitoring (BGM) documented. Results: Three variables predicted A1c change over 6 months: CDI change score (B = 0.11; p < 0.001), BGM frequency at baseline (B = −0.21; p = 0.03), and A1c at baseline (B = −0.23; p = 0.002). A three-way interaction among these variables was significant (p < 0.01) and showed that adolescents with high adherence to BGM who were achieving optimal glycemic control (≤7.5%) at baseline were resistant to increasing A1c values, even if depressive symptoms worsened. However, as adherence to BGM declines, there is a synergistic effect with depressive symptoms to accelerate the increase of A1c values over time, making it more difficult to bring A1c back to optimal levels. Conclusions: Results suggest that depressive symptoms are important predictors of A1c change by themselves as well as when considered with adherence to BGM. There is a need to screen for depressive symptoms and expand and develop prevention and intervention strategies in order to put adolescents with type 1 diabetes in the best position for optimal glycemic control. [ABSTRACT FROM AUTHOR]

Objective To analyze associations between factor scores for caregiver responsibility for direct and indirect diabetes management tasks with glycemic control and blood glucose monitoring (BGM) frequency. Methods Two hundred and sixty one adolescents with type 1 diabetes and their caregivers completed the Diabetes Family Responsibility Questionnaire (DFRQ). Data on diabetes management (e.g., BGM frequency) and glycemic control (e.g., A1c values) were obtained. Results Confirmatory factor analysis of the DFRQ revealed two factors—direct and indirect management tasks. Multivariate analyses demonstrated that adolescent perception of greater responsibility sharing with caregivers on direct management tasks was significantly associated with higher BGM frequency. Conclusions Adolescents who perceive greater caregiver responsibility, particularly around direct management tasks, engage in better diabetes management. Implications of these findings include designing interventions that encourage and sustain caregiver responsibility through adolescence and make explicit the contribution of caregivers. [ABSTRACT FROM PUBLISHER]

Our long-term goal is to determine the utility of melatonin in prevention of hypertension in type 1 diabetes. We recently reported that 5 mg melatonin taken at bedtime increases the nocturnal drop of diastolic blood pressure (BP) in adolescents with type 1 diabetes. The present study tested the hypothesis that a higher dose of melatonin, 10 mg, lowers both systolic and diastolic BP in these patients. The design was an open-label trial of 10 mg melatonin taken at bedtime daily for 7 days. Nine normotensive adolescents with type 1 diabetes, 16.2 ± 0.3 yr old, and eight healthy controls, 16.6 ± 0.6 yr old participated. BP was measured every 20 min by ambulatory monitoring device for 24 hr before treatment onset and on the last treatment day; sleep was monitored by diary and wrist actigraphy. Outcome measures were BP during wake, sleep and over a 24-hr period. Sleep duration and number of awakenings were used as covariates. Significance for this pilot study was set at P < 0.10. In patients with diabetes the mean BP during sleep was lower on melatonin than before treatment: systolic 104.0 ± 2.4 and 108.4 ± 2.4 mmHg ( P = 0.085) and diastolic, 57.1 ± 1.9 and 59.3 ± 1.9 mmHg ( P = 0.079), respectively. In controls there was no significant effect of melatonin on BP. There was no significant effect of sleep duration or number of awakenings on the BP responses. We conclude that the present results justify phase III therapeutic trials to determine the utility of melatonin in prevention of hypertension and cardiovascular complications in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Cavallo A, Daniels SR, Dolan LM, Khoury JC, Bean JA. Blood pressure response to melatonin in type 1 diabetes. Diminished decline of blood pressure at night has been associated with increased risk of cardiovascular disease. Exogenous melatonin given to healthy normotensive adults reduces blood pressure. We hypothesized that melatonin increases the decline of blood pressure during sleep in normotensive adolescents with type 1 diabetes. Eleven normotensive normoalbuminuric patients with type 1 diabetes of 7.0 ± 3.5 yr duration and 10 healthy controls aged 14–18 yr participated in a randomized placebo-controlled double-blind crossover study of 5 mg melatonin for 1 wk, with a 1-wk washout. Blood pressure was measured every 20 min for 24 h by an ambulatory device on the day before and on the last day of each treatment. Sleep measures were recorded by a diary and a wrist activity meter. Blood pressure measures were grouped by 24 h, sleep, and wake periods. Statistical analysis used sleep duration, number of awakenings, and treatment sequence as covariates for the blood pressure comparisons by treatment. In the patients with type 1 diabetes, the decline in diastolic blood pressure during sleep was significantly greater on melatonin (17.8 ± 4.4 mmHg) than on placebo (16.0 ± 3.0 mmHg, p < 0.01). No significant drug effect was present in the controls. No significant side effects were noted. Melatonin amplifies the nocturnal decline in diastolic blood pressure in patients with type 1 diabetes. We propose that dose–response studies of short- and long-acting preparations of melatonin be conducted and that melatonin be considered in trials of prevention of hypertension in type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Type 1 diabetes mellitus causes increased carotid intima-media thickness (IMT) in adults. We evaluated IMT in young subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS--Participants with type 1 diabetes (N = 402) were matched to controls (N = 206) by age, sex, and race or ethnicity. Anthropometric and laboratory values, blood pressure, and IMT were measured. ANCOVA was used to assess differences controlling for demographic risk factors, cardiovascular risk factors, and HbA1c. RESULTS--Subjects were 18.±63.3 years old (50%male, 82.7% non-Hispanic white). Youth with type 1 diabetes had thicker bulb IMT, which remained signi cantly different after adjustment for demographics and cardiovascular risk factors. Age, sex, adiposity, and systolic blood pressure were consistent significant determinants of IMT. Adjustment for HbA1c eliminated the difference, suggesting the difference was attributable to poor glycemic control. CONCLUSIONS--Carotid IMT may be increased in youth with type 1 diabetes at high risk for cardiovascular disease. Better control of diabetesmay be essential in preventing progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

To determine contemporary incidence rates and risk factors for major adverse events in youth-onset T1D and T2D. Participant interviews were conducted once during in-person visits from 2018 to 2019 in SEARCH (T1D: N = 564; T2D: N = 149) and semi-annually from 2014 to 2020 in TODAY (T2D: N = 495). Outcomes were adjudicated using harmonized, predetermined, standardized criteria. Incidence rates (events per 10,000 person-years) among T1D participants were: 10.9 ophthalmologic; 0 kidney; 11.1 nerve, 3.1 cardiac; 3.1 peripheral vascular; 1.6 cerebrovascular; and 15.6 gastrointestinal events. Among T2D participants, rates were: 40.0 ophthalmologic; 6.2 kidney; 21.2 nerve; 21.2 cardiac; 10.0 peripheral vascular; 5.0 cerebrovascular and 42.8 gastrointestinal events. Despite similar mean diabetes duration, complications were higher in youth with T2D than T1D: 2.5-fold higher for microvascular, 4.0-fold higher for macrovascular, and 2.7-fold higher for gastrointestinal disease. Univariate logistic regression analyses in T1D associated age at diagnosis, female sex, HbA1c and mean arterial pressure (MAP) with microvascular events. In youth-onset T2D, composite microvascular events associated positively with MAP and negatively with BMI, however composite macrovascular events associated solely with MAP. In youth-onset diabetes, end-organ events were infrequent but did occur before 15 years diabetes duration. Rates were higher and had different risk factors in T2D versus T1D. [ABSTRACT FROM AUTHOR]

Aims: We examined the association between inflammation and progression of arterial stiffness in a population of youth with type 1 diabetes (T1D).Methods: A total of 287 youth with T1D (median age 13 years) from SEARCH CVD, an ancillary study to the SEARCH for Diabetes in Youth, were included. Markers of inflammation (CRP, IL-6, fibrinogen, leptin, and adiponectin) and measures of pulse wave velocity (PWV) of the arm (PWV-R), trunk (PWV-T), and lower extremity (PWV-LE) were measured at baseline. Measures of PWV were repeated approximately five years later.Results: PWV-R (0.50 m/s), PWV-T (0.65 m/s), and PWV-LE (1.0 m/s) significantly increased over the follow-up (p < 0.001 for each). A significant interaction was found between waist circumference and fibrinogen (p = 0.036) on the progression of PWV-T, suggesting that fibrinogen is more strongly associated with PWV progression in lean participants.Conclusions: Improved understanding of adiposity, inflammation, and functional changes in the vascular system in patients with T1D is crucial. [ABSTRACT FROM AUTHOR]