Two-step recruitment process optimizes retention in FLEX clinical trial.

INTRODUCTION: The Flexible Lifestyle Empowering Change Study (FLEX) is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management and improve glycemic control for adolescents with type 1 diabetes mellitus. A two-step recruitment process was used to optimize study retention by facilitating informed decision-making regarding participation. METHODS: Those who expressed interest at first contact were given more detailed study information followed by telephone calls to the adolescents and their parents to answer questions and explore potential barriers to participation before making a decision regarding study enrollment. RESULTS: Of 694 eligible adolescents who were invited to participate, 397 (57.2%) expressed interest when initially contacted (Step 1). Upon completion of the follow-up telephone calls (Step 2), 276 (39.8%) still agreed to participate; and 258 (37.2%) enrolled and completed a baseline visit with a parent/guardian. Completion rates for measurement visits remained high throughout the study, with an end-of-study retention rate of 93.4%; and only 12 (4.7%) families withdrew from the study. CONCLUSION: The two-step recruitment process encourages potential participants to thoughtfully evaluate their willingness to participate, as well as their ability to make a commitment to the full completion of study requirements. When demonstrating the efficacy of a randomized controlled trial, it may be preferable to accept lower recruitment rates in order to optimize retention rates. The additional time and effort required to implement this two-step process is worthwhile. With a high retention rate, we can be more confident that the outcomes of the randomized controlled trial actually reflect the impact of the intervention.

Dietary quality and markers of inflammation: No association in youth with type 1 diabetes.

BACKGROUND: Systemic inflammation is a key process underlying cardiovascular disease (CVD) development, and CVD risk is significantly elevated in persons with type 1 diabetes (T1D). Youth with T1D exhibit increased levels of inflammation. Studies in persons without diabetes suggest that dietary quality influences inflammation, yet little is known about dietary influences on inflammation in youth with T1D. METHODS: This study evaluated the association of four distinct dietary quality indices (Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index 2010 (HEI2010), modified KIDMED and Total Antioxidant Capacity (TAC)) with biomarkers of inflammation (C-reactive protein (CRP), fibrinogen and interleukin-6 (IL-6)) in a sample of 2520 youth with T1D participating in the SEARCH for Diabetes in Youth Study. RESULTS: Average diet quality was moderate to poor, with mean scores of 43 (DASH, range 0-80), 55 (HEI2010, range 0-100), 3.7 (mKIDMED, range 3-12) and 7237 (TAC). None of the four diet quality scores was associated with the selected biomarkers of inflammation in any analyses. Evaluation of a non-linear relationship or interactions with BMI or levels of glycemic control did not alter the findings. Replication of analyses using longitudinal data yielded consistent findings with our cross-sectional results. CONCLUSIONS: Biomarkers of inflammation in youth with T1D may not be directly influenced by dietary intake, at least at the levels of dietary quality observed here. More work is needed to understand what physiologic mechanisms specific to persons with T1D might inhibit the generally beneficial influence of high dietary quality on systemic inflammation observed in populations without diabetes.

Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study.

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.

Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study.

PURPOSE: The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment. METHODS: Using the SEARCH for Diabetes in Youth registry, we examined whether time from diabetes diagnosis to case registration differed by diabetes type, patient demographics, and the type of provider reporting the case to the study. Plots for time from diagnosis to registration were developed, and differences by key variables were examined using the log-rank test. RESULTS: Compared with time to registration for type 1 cases, it took 2.6 (95% confidence interval [CI], 2.5-2.6) times longer to register 50% of type 2 diabetes cases, and 2.3 (95% CI, 2.0-2.5) times longer to register 90% of type 2 cases. For type 1 diabetes cases, a longer time to registration was associated with older age, minority race/ethnicity, and cases, where the referring provider was not an endocrinologist. For type 2 diabetes cases, older age, non-Hispanic white race/ethnicity, and cases reported by providers other than an endocrinologist took longer to identify and register. CONCLUSIONS: These findings highlight the need for continued childhood diabetes surveillance to identify future trends and influences on changes in prevalence and incidence.

Trends in incidence of type 1 diabetes among non-Hispanic white youth in the U.S., 2002-2009.

The SEARCH for Diabetes in Youth Study prospectively identified youth aged <20 years with physician-diagnosed diabetes. Annual type 1 diabetes (T1D) incidence per 100,000 person-years (95% CI) overall, by age-group, and by sex were calculated for at-risk non-Hispanic white (NHW) youth from 2002 through 2009. Joinpoint and Poisson regression models were used to test for temporal trends. The age- and sex-adjusted incidence of T1D increased from 24.4/100,000 (95% CI 23.9-24.8) in 2002 to 27.4/100,000 (26.9-27.9) in 2009 (P for trend = 0.0008). The relative annual increase in T1D incidence was 2.72% (1.18-4.28) per year; 2.84% (1.12-4.58) per year for males and 2.57% (0.68-4.51) per year for females. After adjustment for sex, significant increases were found for youth aged 5-9 years (P = 0.0023), 10-14 years (P = 0.0008), and 15-19 years (P = 0.004) but not among 0-4-year-olds (P = 0.1862). Mean age at diagnosis did not change. The SEARCH study demonstrated a significant increase in the incidence of T1D among NHW youth from 2002 through 2009 overall and in all but the youngest age-group. Continued surveillance of T1D in U.S. youth to identify future trends in T1D incidence and to plan for health care delivery is warranted.

Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study.

OBJECTIVE: To estimate temporal changes in the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 or type 2 diabetes in youth and to explore factors associated with its occurrence. METHODS: Five centers identified incident cases of diabetes among youth aged 0 to 19 years starting in 2002. DKA presence was defined as a bicarbonate level <15 mmol/L and/or a pH <7.25 (venous) or <7.30 (arterial or capillary) or mention of DKA in the medical records. We assessed trends in the prevalence of DKA over 3 time periods (2002-2003, 2004-2005, and 2008-2010). Logistic regression was used to determine factors associated with DKA. RESULTS: In youth with type 1 diabetes (n = 5615), the prevalence of DKA was high and stable over time (30.2% in 2002-2003, 29.1% in 2004-2005, and 31.1% in 2008-2010; P for trend = .42). Higher prevalence was associated with younger age at diagnosis (P < .0001), minority race/ethnicity (P = .019), income (P = .019), and lack of private health insurance (P = 008). Among youth with type 2 diabetes (n = 1425), DKA prevalence decreased from 11.7% in 2002-2003 to 5.7% in 2008-2010 (P for trend = .005). Higher prevalence was associated with younger age at diagnosis (P = .001), minority race/ethnicity (P = .013), and male gender (P = .001). CONCLUSIONS: The frequency of DKA in youth with type 1 diabetes, although stable, remains high, indicating a persistent need for increased awareness of signs and symptoms of diabetes and better access to health care. In youth with type 2 diabetes, DKA at onset is less common and is decreasing over time.

Longitudinal associations between sex, diabetes self-care, and health-related quality of life among youth with type 1 or type 2 diabetes mellitus.

OBJECTIVE: To examine the longitudinal associations between sex, diabetes self-care, and the health-related quality of life (HRQL) of children and adolescents with type 1 or type 2 diabetes. STUDY DESIGN: The sample included 910 participants with type 1 and 241 participants with type 2, ages 10-22 years at baseline, from the SEARCH for Diabetes in Youth Study, a longitudinal observational study. The primary outcome measure was the Pediatric Quality of Life Inventory. Repeated measures, mixed-model regression analysis was conducted with the use of data from baseline and at least one follow-up assessment, spanning approximately 4 years. RESULTS: HRQL was greater among those with type 1 versus type 2 diabetes. Among participants with type 1, greater (better) Pediatric Quality of Life Inventory total scores over time were related to greater parent education (P = .0007), lower glycated hemoglobin values (P < .0001), and greater physical activity during the past 7 days (P = .0001). There was a significant interaction between sex and age (P < .0001); girls' HRQL remained stable or decreased over time, whereas males' HRQL increased. For participants with type 2 diabetes, there was no significant interaction by age and sex, but lower total HRQL was related to being female (P = .011) and greater body mass index z-scores (P = .014). CONCLUSIONS: HRQL in this cohort varied by diabetes type. The interaction between sex and age for type 1 participants, coupled with poorer HRQL among female than male participants with type 2 diabetes, suggests the impacts of diabetes on HRQL differ by sex and should be considered in clinical management. Encouraging physical activity and weight control continue to be important in improving HRQL.

Prevalence of diabetes in U.S. youth in 2009: the SEARCH for diabetes in youth study.

OBJECTIVE: To estimate the prevalence of diabetes in U.S. youth aged <20 years in 2009 and to estimate the total number of youth with diabetes in the U.S. by age, race/ethnicity, and diabetes type. RESEARCH DESIGN AND METHODS: To address one of its primary aims, the SEARCH for Diabetes in Youth Study identified youth aged <20 years on 31 December 2009 with physician-diagnosed diabetes in selected areas of Colorado, Ohio, South Carolina, and Washington, among health plan members of Kaiser Permanente Southern California and among American Indians living on reservations in Arizona and New Mexico. Diabetes was classified as type 1, type 2, or other. Race/ethnicity was by self-report. RESULTS: From a population of 3,458,974 youth aged <20 years, 7,695 youth with diabetes were identified (2.22/1,000): 6,668 with type 1 diabetes (1.93/1,000), 837 with type 2 diabetes (0.24/1,000), and 190 (0.05/1,000) with other diabetes types. Prevalence increased with age, was slightly higher in females than males, and was most prevalent in non-Hispanic White and least prevalent in Asian/Pacific Islanders, with Native American and black youth having the highest prevalence of type 2 diabetes. An estimated 191,986 U.S. youth aged <20 years have diabetes; 166,984 type 1 diabetes, 20,262 type 2 diabetes, and 4,740 other types. CONCLUSIONS: Diabetes, one of the leading chronic diseases in childhood, affects >190,000 (1 of 433) youth aged <20 years in the U.S., with racial and ethnic disparities seen in diabetes prevalence, overall and by diabetes type.

Peripheral neuropathy in adolescents and young adults with type 1 and type 2 diabetes from the SEARCH for Diabetes in Youth follow-up cohort: a pilot study.

OBJECTIVE: To estimate the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in a pilot study among youth participating in the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS: DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI) (examination for foot abnormalities, distal vibration perception, and ankle reflexes). An MNSI exam (MNSIE) score >2 is diagnostic for DPN. RESULTS: The MNSIE was completed in 399 subjects, including 329 youth with type 1 diabetes (mean age 15.7 ± 4.3 years, duration 6.2 ± 0.9 years) and 70 with type 2 diabetes (mean age 21.6 ± 4.1 years, duration 7.6 ± 1.8 years). Glycated hemoglobin (A1C) was similar in both groups (8.8 ± 1.8% for type 1 vs. 8.5 ± 2.9% for type 2). The prevalence of DPN was significantly higher in youth with type 2 compared with those with type 1 diabetes (25.7 vs. 8.2%; P < 0.0001). In unadjusted analyses, diabetes type, older age, longer duration of diabetes, increased waist circumference, elevated blood pressure, lower HDL cholesterol, and presence of microalbuminuria (urinary albumin-to-creatinine ratio >30 mg/g) were associated with DPN. The association between diabetes type and DPN remained significant after adjustment for age and sex (odds ratio 2.29 [95% CI 1.05-5.02], P = 0.03). CONCLUSIONS: DPN prevalence among youth with type 2 diabetes approached rates reported in adult populations with diabetes. Our findings suggest not only that youth with diabetes are at risk for DPN but also that many already show measurable signs of DPN.

Prevalence of asthma and its association with glycemic control among youth with diabetes.

OBJECTIVE: To estimate the prevalence of asthma among youth with types 1 and 2 diabetes and examine associations between asthma and glycemic control. METHODS: This was a cross-sectional analysis of data from the SEARCH for Diabetes in Youth study, which included youth diagnosed with type 1 (n = 1683) and type 2 (n = 311) diabetes from 2002 through 2005. Asthma status and medications were ascertained from medical records and self-administered questionnaires, and glycemic control was assessed from hemoglobin A1c measured at the study visit. RESULTS: Prevalence of asthma among all youth with diabetes was 10.9% (95% confidence interval [CI]: 9.6%-12.3%). The prevalence was 10.0% (95% CI: 8.6%-11.4%) among youth with type 1 and 16.1% (95% CI: 12.0%-20.2%) among youth with type 2 diabetes and differed according to race/ethnicity. Among youth with type 1 diabetes, those with asthma had higher mean A1c levels than those without asthma, after adjustment for age, gender, race/ethnicity, and BMI (7.77% vs 7.49%; P = .034). Youth with asthma were more likely to have poor glycemic control, particularly those with type 1 diabetes whose asthma was not treated with pharmacotherapy, although this association was attenuated by adjustment for race/ethnicity. CONCLUSIONS: Prevalence of asthma may be elevated among youth with diabetes relative to the general US population. Among youth with type 1 diabetes, asthma is associated with poor glycemic control, especially if asthma is untreated. Specific asthma medications may decrease systemic inflammation, which underlies the complex relationship between pulmonary function, BMI, and glycemic control among youth with diabetes.

Association of DASH diet with cardiovascular risk factors in youth with diabetes mellitus: the SEARCH for Diabetes in Youth study.

BACKGROUND: We have shown that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is related to blood pressure in youth with type 1 and type 2 diabetes mellitus. We explored the impact of the DASH diet on other cardiovascular disease risk factors. METHODS AND RESULTS: Between 2001 and 2005, data on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein particle density, apolipoprotein B, body mass index, waist circumference, and adipocytokines were ascertained in 2130 youth aged 10 to 22 years with physician-diagnosed diabetes mellitus. Dietary intake was assessed by food frequency questionnaire, categorized into the DASH food groups, and assigned an adherence score. Among youth with type 1 diabetes mellitus, higher adherence to the DASH diet was significantly and inversely associated with low-density lipoprotein/high-density lipoprotein ratio and A(1c) in multivariable-adjusted models. Youth in the highest adherence tertile had an estimated 0.07 lower low-density lipoprotein/high-density lipoprotein ratio and 0.2 lower A(1c) levels than those in the lowest tertile adjusted for confounders. No significant associations were observed with triglycerides, low-density lipoprotein particle density, adipocytokines, apolipoprotein B, body mass index Z score, or waist circumference. Among youth with type 2 diabetes mellitus, associations were observed with low-density lipoprotein particle density and body mass index Z score. CONCLUSIONS: The DASH dietary pattern may be beneficial in the prevention and management of cardiovascular disease risk in youth with diabetes mellitus.

Predictors of insulin regimens and impact on outcomes in youth with type 1 diabetes: the SEARCH for Diabetes in Youth study.

OBJECTIVES: To describe the insulin regimens used to treat type 1 diabetes mellitus (T1DM) in youth in the United States, to explore factors related to insulin regimen, and to describe the associations between insulin regimen and clinical outcomes, particularly glycemic control. STUDY DESIGN: A total of 2743 subjects participated in the SEARCH for Diabetes in Youth study, an observational population-based study of youth diagnosed with T1DM, conducted at 6 centers. Data collected during a study visit included clinical and sociodemographic information, body mass index, laboratory measures, and insulin regimen. RESULTS: Sociodemographic characteristics were associated with insulin regimen. Insulin pump therapy was more frequently used by older youth, females, non-Hispanic whites, and families with higher income and education (P = .02 for females, P < .001 for others). Insulin pump use was associated with the lowest hemoglobin A1C levels in all age groups. A1C levels were >7.5% in >70% of adolescents, regardless of regimen. CONCLUSIONS: Youth using insulin pumps had the lowest A1C; A1C was unacceptably high in adolescents. There is a need to more fully assess and understand factors associated with insulin regimens recommended by providers and the influence of race/ethnicity, education, and socioeconomic status on these treatment recommendations and to develop more effective treatment strategies, particularly for adolescents.

Association between the dietary approaches to hypertension diet and hypertension in youth with diabetes mellitus.

Among youth with diabetes mellitus, elevated blood pressure represents one of the most common comorbidities. Hence, exploring dietary factors that may help prevent or control hypertension in this population is of paramount importance. We investigated whether adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with hypertension in youth with diabetes mellitus from the SEARCH for Diabetes in Youth Study. Between 2001 and 2005, 2830 youth aged 10 to 22 years (2440 with type 1 and 390 with type 2 diabetes mellitus) completed a study visit. For each of the 8 DASH food groups, a score of 10 was assigned when the DASH recommendation was met. Lower intakes were scored proportionately, and the 8 individual scores were summed. The association between the overall DASH score and hypertension was evaluated using multiple logistic regression. The crude prevalence of hypertension was 6.8% for youth with type 1 and 28.2% for youth with type 2 diabetes mellitus. In youth with type 1, a higher adherence to DASH was inversely related to hypertension, independent of demographic, clinical, and behavioral characteristics (tertile 2 versus 1: odds ratio: 0.7, 95% CI: 0.5 to 1.0; 3 versus 1: odds ratio: 0.6, 95% CI: 0.4 to 0.9; P(trend)=0.007). For type 2 diabetes mellitus, the DASH diet was not associated with hypertension (tertile 2 versus 1: odds ratio: 0.8, 95% CI: 0.5 to 1.4; 3 versus 1: odds ratio: 0.9, 95% CI: 0.5 to 1.5; P(trend)=0.6). Prospective observational studies or clinical trials are needed to investigate whether adherence to the DASH guidelines may help prevent hypertension in youth with type 1 diabetes mellitus. In type 2 diabetes mellitus, more research with a larger sample is necessary.

Health-related quality of life of children and adolescents with type 1 or type 2 diabetes mellitus: SEARCH for Diabetes in Youth Study.

OBJECTIVE: To examine the associations between demographic and diabetes management variables and the health-related quality of life (HRQOL) of youths with type 1 or type 2 diabetes mellitus (DM). DESIGN: Cross-sectional study. SETTINGS: Selected populations in Ohio, Washington, South Carolina, Colorado, Hawaii, and California; health service beneficiaries in 3 American Indian populations; and participants in the Pima Indian Study in Arizona. PARTICIPANTS: Two thousand four hundred forty-five participants aged 8 to 22 years in the SEARCH for Diabetes in Youth Study. MAIN OUTCOME MEASURE: Pediatric Quality of Life Inventory scores. RESULTS: Among youths with type 2 DM, HRQOL was lower compared with those with type 1. Among those with type 1 DM, worse HRQOL was associated with a primary insurance source of Medicaid or another government-funded insurance, use of insulin injections vs an insulin pump, a hemoglobin A(1c) value of at least 9%, and more comorbidities and diabetes complications. There was a significant age x sex interaction, such that, in older groups, HRQOL was lower for girls but higher for boys. For youths with type 2 DM, injecting insulin at least 3 times a day compared with using an oral or no diabetes medication was associated with better HRQOL, and having 2 or more emergency department visits in the past 6 months was associated with worse HRQOL. CONCLUSIONS: Youths with types 1 and 2 DM reported HRQOL differences by type of treatment and complications. The significant age x sex interaction suggests that interventions to improve HRQOL should consider gender differences in diabetes adjustment and management in different age groups.

Prevalence and correlates of depressed mood among youth with diabetes: the SEARCH for Diabetes in Youth study.

OBJECTIVE: The objective of this study was to determine if depressed mood among youth with diabetes was associated with type and duration of diabetes, mean glycosylated hemoglobin (HbA1c) level, and the frequency of diabetic ketoacidosis (DKA) and hypoglycemic episodes, hospitalizations, and emergency department (ED) visits. METHODS: A total of 2672 youth (aged 10-21 years) who had diabetes for a mean duration of 5 years completed a SEARCH study visit, in which their HbA1c was measured and information about their demographic characteristics, diabetes type and duration, and episodes of DKA, hypoglycemia, hospitalizations, and ED visits over the previous 6 months was collected. Their level of depressed mood was measured using the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Among these youth, 14% had mildly (CES-D 16-23) and 8.6% had moderately or severely (CES-D > or =24) depressed mood. Females had a higher mean CES-D score than males. After adjusting for demographic factors, and duration of diabetes, we found the prevalence of depressed mood to be higher among males with type 2 diabetes than those with type 1 diabetes and to be higher among females with comorbidities than those without comorbidities. Higher mean HbA1c and frequency of ED visits were associated with depressed mood. The prevalence of depressed mood among youth with diabetes was similar to that of published estimates of depressed mood among youth without diabetes. CONCLUSIONS: Physicians and other health care professionals should consider screening youth with diabetes for depressed mood in clinical settings, particularly youth with poor glycemic control, those with a history of frequent ED visits, males with type 2 diabetes, and females with comorbidities.