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OBJECTIVE - Youth with diabetes are at increased risk for depression. The objectives of this study were to provide preliminary evidence that this at-risk status for depression is associated with metabolic and inflammatory markers and to inform future, more

BACKGROUND/OBJECTIVES: This study aimed to determine the association between a Mediterranean diet and glycemic control and other cardiovascular risk factors among youth with type I diabetes (TID). SUBJECTS/METHODS: Incident TID cases aged < 20 years at diagnosis between 2002 and 2005 were included. Participants were seen at baseline (N = 793), 1-year (N = 512) and 5-year follow-up visits (N = 501). Mediterranean diet score was assessed using a modified KIDMED index (mKIDMED). Multivariate linear regression and longitudinal mixed model were applied to determine the association between mKIDMED score and log-HbA1c, lipids, blood pressure (BP) and obesity. RESULTS: In cross-sectional analyses using baseline data, for individuals with the hemoglobin A1c (HbA1c) of 7.5%, a two-point higher mKIDMED score (1 s.d.) was associated with 0.15% lower HbA1c (P = 0.02). A two-point higher mKIDMED score was associated with 4.0 mg/dl lower total cholesterol (TC) (P =0.006), 3.4 mg/dl lower low-density lipoprotein cholesterol (LDL-C) (P = 0.004), 3.9 mg/dl lower non-high-density lipoprotein cholesterol (non-HDL-C) (P = 0.004) and 0.07 lower LDL-C/HDL-C ratio (P = 0.02). Using longitudinal data, a two-point increase in mKIDMED score was associated with 0.01% lower log-HbA1c (P = 0.07), 1.8 mg/dl lower TC (P =0.05), 1.6 mg/dl lower LDL-C (P = 0.03) and 1.8 mg/dl lower non-HDL-C (P = 0.03) than would otherwise have been expected. HbA1c mediated ~ 20% of the association for lipids in both cross-sectional and longitudinal models. An unexpected positive association between mKIDMED score and systolic BP was found among non-Hispanic white youth in cross-sectional analyses (P = 0.009). Mediterranean diet was not associated with obesity. CONCLUSIONS: Mediterranean diet may improve glycemic control and cardiovascular health in TID youth. European Journal of Clinical Nutrition (2016) 70, 802-807; doi: 10.1038/ejcn.2016.8; published online 24 February 2016, INTRODUCTION Type I diabetes (TID) is associated with 2-4 fold-increased risk in cardiovascular mortality and morbidity. (1,2) Poor glycemic control is commonly seen in youth with TID, (3) contributing further [...]

BACKGROUND/OBJECTIVES: Youth with type 1 diabetes (T1DM) are at substantially increased risk for adverse vascular outcomes, but little is known about the influence of dietary behavior on cardiovascular disease (CVD) risk profile. We aimed to identify dietary intake patterns associated with CVD risk factors and evaluate their impact on arterial stiffness (AS) measures collected thereafter in a cohort of youth with T1DM. SUBJECTS/METHODS: Baseline diet data from a food frequency questionnaire and CVD risk factors (triglycerides, low density lipoprotein-cholesterol, systolic blood pressure, hemoglobin A1c, C-reactive protein and waist circumference) were available for 1153 youth aged [greater than or equal to] 10 years with T1DM from the SEARCH for Diabetes in Youth Study. A dietary intake pattern was identified using 33 food groups as predictors and six CVD risk factors as responses in reduced rank regression (RRR) analysis. Associations of this RRR-derived dietary pattern with AS measures (augmentation index (AIx75), n = 229; pulse wave velocity, n = 237; and brachial distensibility, n = 228) were then assessed using linear regression. RESULTS: The RRR-derived pattern was characterized by high intakes of sugar-sweetened beverages (SSB) and diet soda, eggs, potatoes and high-fat meats and low intakes of sweets/desserts and low-fat dairy; major contributors were SSB and diet soda. This pattern captured the largest variability in adverse CVD risk profile and was subsequently associated with AIx75 (β = 0.47; P < 0.01). The mean difference in AIx75 concentration between the highest and the lowest dietary pattern quartiles was 4.3% in fully adjusted model. CONCLUSIONS: Intervention strategies to reduce consumption of unhealthy foods and beverages among youth with T1DM may significantly improve CVD risk profile and ultimately reduce the risk for AS. European Journal of Clinical Nutrition (2014) 68, 1327-1333; doi: 10.1038/ejcn.2014.96; published online 28 May 2014, INTRODUCTION Type 1 diabetes (T1DM) is one of the leading chronic diseases in childhood. According to the SEARCH for Diabetes in Youth Study, approximately 15 000 cases of T1DM are [...]

Lower birth weight is associated with an increased occurrence of type 2 diabetes in later life. Whether this relationship is explained by environmental or genetic factors is unknown. We have examined the potential for genetic influences by determining whether parental diabetes is associated with lower birth weight in 1,608 children of known birth weight and gestational age born between 1941 and 1993 in the Gila River Indian Community in Arizona. The previously described relationships of maternal diabetes to increased birth weight and offspring diabetes were observed. In contrast to this we have determined novel relationships between low birth weight and paternal diabetes. The offspring of diabetic fathers were, on average, 78 g lighter than the offspring of nondiabetic fathers. For fathers, lower birth weight in their offspring was associated with an increased risk of later diabetes, i.e., fathers of offspring in the lowest quintile of birth weight, who were not diabetic at the time of birth of their child, had a 1.8-fold increased risk of developing diabetes later in life (95% CI 1.2-2.7; P = 0.004). For children, lower birth weight predicted diabetes in the offspring if paternal but not maternal diabetes was present, but it was not associated with higher plasma glucose if neither parent had diabetes. We conclude that the risk of diabetes associated with low birth weight is strongly related to the development of paternal diabetes, suggesting a genetic link between lower birth weight and later diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study compared heart rate variability (HRV) parameters in youth with and without type 1 diabetes and explored potential contributors of altered HRV.Research Design and Methods: HRV parameters were measured among 354 youth with type 1 diabetes (mean age 18.8 years, diabetes duration 9.8 years, and mean A1C 8.9%) and 176 youth without diabetes (mean age 19.2 years) participating in the SEARCH CVD study. Multiple linear regression was used to assess the relationship between diabetes status and HRV parameters, adjusting for covariates.Results: Compared with control subjects, youth with type 1 diabetes had reduced overall HRV (10.09 ms lower SD of NN intervals [SDNN]) and markers of parasympathetic loss (13.5 ms reduced root mean square successive difference of NN intervals [RMSSD] and 5.2 normalized units (n.u.) reduced high frequency [HF] power) with sympathetic override (5.2 n.u. increased low frequency [LF] power), independent of demographic, anthropometric, and traditional cardiovascular risk factors. Older age, female sex, higher LDL cholesterol and triglyceride levels, and presence of microalbuminuria were independently associated with lower HRV but did not account for the observed differences between youth with and without diabetes. Youth with type 1 diabetes and A1C levels ≥7.5% had significantly worse HRV parameters than control subjects; however, in youth with optimal glycemic control (A1C <7.5%), HRV parameters did not differ significantly from control subjects.Conclusions: Youth with type 1 diabetes have signs of early cardiac autonomic neuropathy: reduced overall HRV and parasympathetic loss with sympathetic override. The main driver of these subclinical abnormalities appears to be hyperglycemia. [ABSTRACT FROM AUTHOR]

Objective: To examine the patterns and associations of insulin regimens and change in regimens with clinical outcomes in a diverse population of children with recently diagnosed type 1 diabetes.Research Design and Methods: The study sample consisted of youth with type 1 diabetes who completed a baseline SEARCH for Diabetes in Youth study visit after being newly diagnosed and at least one follow-up visit. Demographic, diabetes self-management, physical, and laboratory measures were collected at study visits. Insulin regimens and change in regimen compared with the initial visit were categorized as more intensive (MI), no change (NC), or less intensive (LI). We examined relationships between insulin regimens, change in regimen, and outcomes including A1C and fasting C-peptide.Results: Of the 1,606 participants with a mean follow-up of 36 months, 51.7% changed to an MI regimen, 44.7% had NC, and 3.6% changed to an LI regimen. Participants who were younger, non-Hispanic white, and from families of higher income and parental education and who had private health insurance were more likely to be in MI or NC groups. Those in MI and NC groups had lower baseline A1C (P = 0.028) and smaller increase in A1C over time than LI (P < 0.01). Younger age, continuous subcutaneous insulin pump therapy, and change to MI were associated with higher probability of achieving target A1C levels.Conclusions: Insulin regimens were intensified over time in over half of participants but varied by sociodemographic domains. As more intensive regimens were associated with better outcomes, early intensification of management may improve outcomes in all children with diabetes. Although intensification of insulin regimen is preferred, choice of insulin regimen must be individualized based on the child and family's ability to comply with the prescribed plan. [ABSTRACT FROM AUTHOR]

Objective: To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence.Research Design and Methods: We used Markov modeling framework to generate yearly forecasts of the number of individuals in each of three states (diabetes, no diabetes, and death). We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for Diabetes in Youth study and U.S. Census Bureau population demographic projections. Two scenarios were considered for T1DM and T2DM incidence: 1) constant incidence over time; 2) for T1DM yearly percentage increases of 3.5, 2.2, 1.8, and 2.1% by age-groups 0-4 years, 5-9 years, 10-14 years, and 15-19 years, respectively, and for T2DM a yearly 2.3% increase across all ages.Results: Under scenario 1, the projected number of youth with T1DM rises from 166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and 2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388 in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144% increase]), with the greatest increase in youth of minority racial/ethnic groups. The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in 2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase).Conclusions: A linear increase in diabetes incidence could result in a substantial increase in the number of youth with T1DM and T2DM over the next 40 years, especially those of minority race/ethnicity. [ABSTRACT FROM AUTHOR]

Objective: To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study.Research Design and Methods: SEARCH conducted a comprehensive assessment of 2,291 subjects aged <20 years with recently diagnosed diabetes. Using autoimmunity (at least one of two diabetes autoantibodies) and insulin sensitivity (equation validated against hyperinsulinemic-euglycemic clamps) as the main etiologic markers, we described four categories along a bidimensional spectrum: autoimmune plus insulin-sensitive (IS), autoimmune plus insulin-resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR. We then explored how characteristics, including genetic susceptibility to autoimmunity (HLA genotypes), insulin deficiency, and clinical factors varied across these four categories.Results: Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of diabetes autoantibodies and similar distribution of HLA risk genotypes to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing.Conclusions: The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing. [ABSTRACT FROM AUTHOR]

Objective: Arterial stiffness occurs early in the atherosclerotic process; however, few data are available concerning risk factors for arterial stiffness in youth with diabetes. We identified factors associated with arterial stiffness in youth with diabetes and assessed the effects of these factors on the relationship between arterial stiffness and diabetes type (type 1 vs. type 2).Research Design and Methods: A subset of patients from the SEARCH for Diabetes in Youth study with type 1 (n = 535) and type 2 diabetes (n = 60), aged 10-23 years (52% male; 82% non-Hispanic white; diabetes duration 65 +/- 49 months) had arterial stiffness, anthropometrics, blood pressure, fasting lipids, and A1C measured. Arterial stiffness was measured by brachial distensibility (brachD), pulse wave velocity (PWV), and augmentation index adjusted to heart rate of 75 beats/min (AI75).Results: Youth with type 2 diabetes had worse brachD (5.2 +/- 0.9 vs. 6.1 +/- 1.2%/mmHg), PWV (6.4 +/- 1.3 vs. 5.3 +/- 0.8 m/s), and AI75 (6.4 +/- 9.9 vs. 2.2 +/- 10.2%) than those with type 1 diabetes (P < 0.01 for each). These differences were largely mediated through increased central adiposity and higher blood pressure in youth with type 2 diabetes. We also found a pattern of association of arterial stiffness measures with waist circumference and blood pressure, independent of diabetes type.Conclusions: Youth with type 2 diabetes have worse arterial stiffness than similar youth with type 1 diabetes. Increased central adiposity and blood pressure are associated with measures of arterial stiffness, independent of diabetes type. Whether these findings indicate that youth with type 2 diabetes will be at higher risk for future complications requires longitudinal studies. [ABSTRACT FROM AUTHOR]

Objective: Seasonal environment at birth may influence diabetes incidence in later life. We sought evidence for this effect in a large sample of diabetic youth residing in the U.S.Research Design and Methods: We compared the distribution of birth months within the SEARCH for Diabetes in Youth Study (SEARCH study) with the monthly distributions in U.S. births tabulated by race for years 1982-2005. SEARCH study participants (9,737 youth with type 1 diabetes and 1,749 with type 2 diabetes) were identified by six collaborating U.S. centers.Results: Among type 1 diabetic youth, the percentage of observed to expected births differed across the months (P = 0.0092; decreased in October-February and increased in March-July). Their smoothed birth-month estimates demonstrated a deficit in November-February births and an excess in April-July births (smoothed May versus January relative risk [RR] = 1.06 [95% CI 1.02-1.11]). Stratifications by sex or by three racial groups showed similar patterns relating type 1 diabetes to month of birth. Stratification by geographic regions showed a peak-to-nadir RR of 1.10 [1.04-1.16] in study regions from the northern latitudes (Colorado, western Washington State, and southern Ohio) but no birth-month effect (P > 0.9) in study regions from more southern locations. Among type 2 diabetic youth, associations with birth month were inconclusive.Conclusions: Spring births were associated with increased likelihood of type 1 diabetes but possibly not in all U.S. regions. Causal mechanisms may involve factors dependent on geographic latitude such as solar irradiance, but it is unknown whether they influence prenatal or early postnatal development. [ABSTRACT FROM AUTHOR]

Objective: To determine the extent of beta-cell function in youth with diabetes and GAD65 and/or IA2 autoantibodies.Research Design and Methods: Fasting C-peptide levels from 2,789 GAD65- and/or IA2 autoantibody-positive youth aged 1-23 years from the SEARCH for Diabetes in Youth study were used. Preserved beta-cell function was defined on the basis of cut points derived from the Diabetes Control and Complications Trial (DCCT) (fasting C-peptide > or =0.23 ng/ml) and from the U.S. adolescent population of the National Health and Nutrition Examination Survey (NHANES) 5th percentile for fasting C-peptide (> or =1.0 ng/ml). We compared the clinical characteristics between those with and without preserved beta-cell function.Results: Within the first year of diagnosis, 82.9% of youth had a fasting C-peptide > or =0.23 ng/ml and 31.2% had values > or =1.0 ng/ml. Among those with > or =5 years of diabetes duration, 10.7% had preserved beta-cell function based on the DCCT cutoff and 1.0% were above the 5th percentile of the NHANES population.Conclusions: Within the 1st year of diagnosis, four of five youth with autoantibody-positive diabetes have clinically significant amounts of residual beta-cell function and about one-third have fasting C-peptide levels above the 5th percentile of a healthy adolescent population. Even 5 years after diagnosis, 1 of 10 has fasting C-peptide above a clinically significant threshold. These findings have implications for clinical classification of youth with diabetes as well as clinical trials aimed to preserve beta-cell function after diabetes onset. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the lipid profile and the prevalence of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic control on the hypothesized altered lipid profile in youth with type 1 diabetes.Research Design and Methods: We conducted a cross-sectional analysis of 512 youth with type 1 diabetes (mean duration 4.22 years) and 188 healthy control subjects aged 10-22 years in Colorado and South Carolina. SEARCH for Diabetes in Youth (SEARCH) participants with type 1 diabetes and healthy control subjects recruited from primary care offices in the same geographic regions were invited to attend a research visit. Fasting lipid profiles were compared between youth with type 1 diabetes (stratified according to categories of optimal [A1C <7.5%] and suboptimal [A1C >or=7.5%] glycemic control) and healthy nondiabetic youth, using multiple linear and logistic regression.Results: Youth with type 1 diabetes and optimal A1C had lipid concentrations that were similar (total cholesterol, LDL cholesterol, and LDL particle size) or even less atherogenic (HDL cholesterol, non-HDL cholesterol, triglyceride, and triglyceride-to-HDL cholesterol ratio) than those observed in nondiabetic youth, whereas youth with suboptimal glycemic control had elevated standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL cholesterol). Youth with type 1 diabetes also had significantly elevated apolipoprotein B levels and more small, dense LDL particles than nondiabetic youth, regardless of glycemic control.Conclusions: Youth with type 1 diabetes have abnormal lipid levels and atherogenic changes in lipoprotein composition, even after a relatively short disease duration. As in adults, glycemic control is an important mediator of these abnormalities. [ABSTRACT FROM AUTHOR]

Objective: To compare cardiovascular disease (CVD) risk factors among recently diagnosed youth with type 2 diabetes and nondiabetic youth and investigate whether demographic, behavioral, or metabolic factors might account for observed differences.Research Design and Methods: Data from 106 type 2 diabetic and 189 nondiabetic multiethnic youth, aged 10-22 years, were analyzed. Prevalence of CVD risk factors were age and race/ethnicity adjusted using direct standardization. Multiple linear regression models were sequentially adjusted for demographic, behavioral (dietary saturated fat intake and physical activity), and metabolic (body adiposity and glycemia) factors to explore possible mechanisms associated with differences in CVD risk factors between the case and control groups.Results: Compared with control subjects, youth with type 2 diabetes had a higher prevalence of elevated blood pressure, obesity, large waist circumference, low HDL cholesterol, high triglycerides, and high albumin-to-creatinine ratio (P < 0.05 for each risk factor). Type 2 diabetic youth also had higher levels of apolipoprotein B, fibrinogen, interleukin (IL)-6, C-reactive protein, and leptin; lower adiponectin levels; and denser LDL particles (P < 0.05 for each risk factor). Adjustment for BMI, waist circumference, and A1C substantially attenuated differences in the CVD risk factors between the case/control groups, except for fibrinogen and IL-6, which remained significantly higher in type 2 diabetic youth.Conclusions: Compared with control youth, type 2 diabetic youth have a less favorable CVD risk factor profile. Adiposity and glycemia are important contributors to differences in CVD risk profiles among type 2 diabetic and control youth. Inflammatory and prothrombotic factors may also play an important role. [ABSTRACT FROM AUTHOR]

Objective: Limited data exist on the association between in utero exposure to maternal diabetes and obesity and type 2 diabetes in diverse youth. These associations were explored in African-American, Hispanic, and non-Hispanic white youth participating in the SEARCH Case-Control Study.Research Design and Methods: A total of 79 youth with type 2 diabetes and 190 nondiabetic control youth aged 10-22 years attended a research visit. In utero exposures to maternal diabetes and obesity were recalled by biological mothers.Results: Youth with type 2 diabetes were more likely to have been exposed to maternal diabetes or obesity in utero than were nondiabetic control youth (P < 0.0001 for each). After adjusting for offspring age, sex, and race/ethnicity, exposure to maternal diabetes (odds ratio [OR] 5.7 [95% CI 2.4-13.4]) and exposure to maternal obesity (2.8 [1.5-5.2]) were independently associated with type 2 diabetes. Adjustment for other perinatal and socioeconomic factors did not alter these associations. When offspring BMI was added, the OR for the association between in utero exposure to obesity and type 2 diabetes was attenuated toward the null (OR 1.1 [0.5-2.4]). Overall, 47.2% (95% CI 30.9-63.5) of type 2 diabetes in youth could be attributed to intrauterine exposure to maternal diabetes and obesity.Conclusions: Intrauterine exposures to maternal diabetes and obesity are strongly associated with type 2 diabetes in youth. Prevention efforts may need to target, in addition to childhood obesity, the increasing number of pregnancies complicated by obesity and diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate the prevalence of an elevated albumin-to-creatinine ratio (ACR) (> or = 30 microg/mg) among youth with type 1 or type 2 diabetes and to identify factors associated with elevated ACR and their effect on the relationship between elevated ACR and type of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional data were analyzed from 3,259 participants with onset of diabetes at < 20 years of age in the SEARCH for Diabetes in Youth, a multicenter observational study of diabetes in youth. Multiple logistic regression was used to explore determinants of elevated ACR and factors accounting for differences in this prevalence between type 2 and type 1 diabetes. RESULTS: The prevalence of elevated ACR was 9.2% in type 1 and 22.2% in type 2 diabetes (prevalence ratio 2.4 [95% CI 1.9-3.0]; P < 0.0001). In multiple logistic regression analysis, female sex, A1C and triglyceride values, hypertension, and type of diabetes (type 2 versus type 1) were significantly associated with elevated ACR. Adjustment for variables related to insulin resistance (obesity, hypertension, dyslipidemia, and inflammation) attenuated, but did not completely explain, the association of diabetes type with elevated ACR. CONCLUSIONS: Youth with type 2 diabetes have a higher prevalence of elevated ACR than youth with type 1 diabetes, in an association that apparently does not completely depend on age, duration of diabetes, race/ethnicity, sex, level of glycemic control, or features of insulin resistance. [ABSTRACT FROM AUTHOR]