Barbara Linder

The Burden of Diabetes Mellitus Among US Youth: Prevalence Estimates From the SEARCH for Diabetes in Youth Study

OBJECTIVE. Our goal was to estimate the prevalence of diabetes mellitus in youth <20 years of age in 2001 in the United States, according to age, gender, race/ethnicity, and diabetes type. METHODS. The SEARCH for Diabetes in Youth Study is a 6-center observational study conducting population-based ascertainment of physician-diagnosed diabetes in youth. Census-based denominators for 4 geographically based centers and enrollment data for 2 health plan-based centers were used to calculate prevalence. Age-, gender-, and racial/ethnic group-specific prevalence rates were multiplied by US population counts to estimate the total number of US youth with diabetes. RESULTS. We identified 6379 US youth with diabetes in 2001, in a population of ∼3.5 million. Crude prevalence was estimated as 1.82 cases per 1000 youth, being much lower for youth 0 to 9 years of age (0.79 cases per 1000 youth) than for those 10 to 19 years of age (2.80 cases per 1000 youth). Non-Hispanic white youth had the highest prevalence (1.06 cases per 1000 youth) in the younger group. Among 10- to 19-year-old youth, black youth (3.22 cases per 1000 youth) and non-Hispanic white youth (3.18 cases per 1000 youth) had the highest rates, followed by American Indian youth (2.28 cases per 1000 youth), Hispanic youth (2.18 cases per 1000 youth), and Asian/Pacific Islander youth (1.34 cases per 1000 youth). Among younger children, type 1 diabetes accounted for ≥80% of diabetes; among older youth, the proportion of type 2 diabetes ranged from 6% (0.19 cases per 1000 youth for non-Hispanic white youth) to 76% (1.74 cases per 1000 youth for American Indian youth). We estimated that 154369 youth had physician-diagnosed diabetes in 2001 in the United States. CONCLUSIONS. The overall prevalence estimate for diabetes in children and adolescents was ∼0.18%. Type 2 diabetes was found in all racial/ethnic groups but generally was less common than type 1, except in American Indian youth.

A clinical trial to maintain glycemic control in youth with type 2 diabetes.

BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes. METHODS Eligible patients 10 to 17 years of age were treated with metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin. RESULTS Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P=0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants. CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.).

The SEARCH for Diabetes in Youth study: rationale, findings, and future directions.

The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort 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 persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.

Characteristics of Adolescents and Youth with Recent-Onset Type 2 Diabetes: The TODAY Cohort at Baseline

CONTEXT The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort represents the largest and best-characterized national sample of American youth with recent-onset type 2 diabetes. OBJECTIVE The objective of the study was to describe the baseline characteristics of participants in the TODAY randomized clinical trial. DESIGN Participants were recruited over 4 yr at 15 clinical centers in the United States (n = 704) and enrolled, randomized, treated, and followed up 2-6 yr. SETTING The study was conducted at pediatric diabetes care clinics and practices. PARTICIPANTS Eligible participants were aged 10-17 yr inclusive, diagnosed with type 2 diabetes for less than 2 yr and had a body mass index at the 85th percentile or greater. INTERVENTIONS After baseline data collection, participants were randomized to one of the following groups: 1) metformin alone, 2) metformin plus rosiglitazone, or 3) metformin plus a lifestyle program of weight management. MAIN OUTCOME MEASURES Baseline data presented include demographics, clinical/medical history, biochemical measurements, and clinical and biochemical abnormalities. RESULTS At baseline the cohort included the following: 64.9% were female; mean age was 14.0 yr; mean diabetes duration was 7.8 months; mean body mass index Z-score was 2.15; 89.4% had a family history of diabetes; 41.1% were Hispanic, 31.5% were non-Hispanic black; 38.8% were living with both biological parents; 41.5% had a household annual income of less than

Prevalence of Cardiovascular Disease Risk Factors in U.S. Children and Adolescents With Diabetes The SEARCH for Diabetes in Youth Study

25,000; 26.3% had a highest education level of parent/guardian less than a high school degree; 26.3% had a blood pressure at the 90th percentile or greater; 13.6% had a blood pressure at the 95th percentile or greater; 13.0% had microalbuminuria; 79.8% had a low high-density lipoprotein level; and 10.2% had high triglycerides. CONCLUSIONS The TODAY cohort is predominantly from racial/ethnic minority groups, with low socioeconomic status and a family history of diabetes. Clinical and biochemical abnormalities and comorbidities are prevalent within 2 yr of diagnosis. These findings contribute greatly to our understanding of American youth with type 2 diabetes.

CORTISOL PRODUCTION RATE IN CHILDHOOD AND ADOLESCENCE

OBJECTIVE—The purpose of this study was to determine the prevalence and correlates of selected cardiovascular disease (CVD) risk factors among youth aged <20 years with diabetes. RESEARCH DESIGN AND METHODS—The analysis included 1,083 girls and 1,013 boys examined as part of the SEARCH for Diabetes in Youth study, a multicenter, population-based study of youth 0–19 years of age with diabetes. Diabetes type was determined by a biochemical algorithm based on diabetes antibodies and fasting C-peptide level. CVD risk factors were defined as follows: HDL cholesterol <40 mg/dl; age- and sex-specific waist circumference >90th percentile; systolic or diastolic blood pressure >90th percentile for age, sex, and height or taking medication for high blood pressure; and triglycerides >110 mg/dl. RESULTS—The prevalence of having at least two CVD risk factors was 21%. The prevalence was 7% among children aged 3–9 years and 25% in youth aged 10–19 years (P < 0.0001), 23% among girls and 19% in boys (P = 0.04), 68% in American Indians, 37% in Asian/Pacific Islanders, 32% in African Americans, 35% in Hispanics, and 16% in non-Hispanic whites (P < 0.0001). At least two CVD risk factors were present in 92% of youth with type 2 and 14% of those with type 1A diabetes (P < 0.0001). In multivariate analyses, age, race/ethnicity, and diabetes type were independently associated with the odds of having at least two CVD risk factors (P < 0.0001). CONCLUSIONS—Many youth with diabetes have multiple CVD risk factors. Recommendations for weight, lipid, and blood pressure control in youth with diabetes need to be followed to prevent or delay the development of CVD as these youngsters mature.

Prevalence of Diabetes in U.S. Youth in 2009: The SEARCH for Diabetes in Youth Study

We studied the daily cortisol production rate in 33 normal children and adolescents, using a stable isotope-dilution technique employing high-performance liquid chromatography-mass spectrometry. Two indwelling intravenous catheters were inserted and tracer 9,12,12-2H3-cortisol (deuterated cortisol) was infused continuously for 30 hours. After 6 hours of tracer infusion to allow for equilibration, blood was obtained every 20 minutes for 24 hours. The mean (+/- SD) cortisol production rate was 9.5 +/- 2.5 mg/day (6.8 +/- 1.9 mg/m2/day). Cortisol production rate did not vary with sex or pubertal stage. These results suggest that the cortisol production rate in children and adolescents is significantly lower than previously estimated.

Diabetes in Non-Hispanic White Youth Prevalence, incidence, and clinical characteristics: 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.

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012.

OBJECTIVE—To investigate the incidence, prevalence, and clinical characteristics of diabetes among U.S. non-Hispanic white (NHW) youth. RESEARCH DESIGN AND METHODS—Data from the SEARCH for Diabetes in Youth Study (SEARCH study), a multicenter study of diabetes among youth aged 0–19 years, were examined. Incidence rates were calculated per 100,000 person-years across 4 incident years (2002–2005), and prevalence in 2001 was calculated per 1,000 youths. Information obtained by questionnaire, physical examination, and blood and urine collection was analyzed to describe the characteristics of youth who completed an in-person visit. RESULTS—The prevalence of type 1 diabetes (at ages 0–19 years) was 2.00/1,000, which was similar for male (2.02/1,000) and female (1.97/1,000) subjects. The incidence of type 1 diabetes was 23.6/100,000, slightly higher for male compared with female subjects (24.5 vs. 22.7 per 100,000, respectively, P = 0.04). Incidence rates of type 1 diabetes among youth aged 0–14 years in the SEARCH study are higher than all previously reported U.S. studies and many European studies. Few cases of type 2 diabetes in youth aged <10 years were found. The prevalence of type 2 diabetes (at ages 10–19 years) was 0.18/1,000, which is significantly higher for female compared with male subjects (0.22 vs. 0.15 per 1,000, P = 0.01). Incidence of type 2 diabetes was 3.7/100,000, with similar rates for female and male subjects (3.9 vs. 3.4 per 1,000, respectively, P = 0.3). High levels of abnormal cardiometabolic and behavioral risk factor profiles were common among youth with both type 1 and type 2 diabetes. For example, within each of four age-groups for youth with type 1 diabetes and two age-groups for youth with type 2 diabetes, >40% had elevated LDL cholesterol, and <3% of youth aged >10 years met current recommendations for intake of saturated fat. Among youth aged ≥15 years, 18% with type 1 and 26% with type 2 diabetes were current smokers. CONCLUSIONS—The SEARCH study is one of the most comprehensive studies of diabetes in NHW youth. The incidence of type 1 diabetes in NHW youth in the U.S. is one of the highest in the world. While type 2 diabetes is still relatively rare, rates are several-fold higher than those reported by European countries. We believe efforts directed at improving the cardiometabolic and behavioral risk factor profiles in this population are warranted.

Higher Prevalence of Elevated Albumin Excretion in Youth With Type 2 Than Type 1 Diabetes: The SEARCH for Diabetes in Youth Study

BACKGROUND Diagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001–2009 period, but data on recent incidence trends are lacking. METHODS We ascertained cases of type 1 and type 2 diabetes mellitus at five study centers in the United States. Denominators (4.9 million youths annually) were obtained from the U.S. Census or health‐plan member counts. After the calculation of annual incidence rates for the 2002–2012 period, we analyzed trends using generalized autoregressive moving‐average models with 2‐year moving averages. RESULTS A total of 11,245 youths with type 1 diabetes (0 to 19 years of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified. Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4% annually (from 19.5 cases per 100,000 youths per year in 2002–2003 to 21.7 cases per 100,000 youths per year in 2011–2012, P=0.03). In adjusted pairwise comparisons, the annual rate of increase was greater among Hispanics than among non‐Hispanic whites (4.2% vs. 1.2%, P<0.001). Overall unadjusted incidence rates of type 2 diabetes increased by 7.1% annually (from 9.0 cases per 100,000 youths per year in 2002–2003 to 12.5 cases per 100,000 youths per year in 2011–2012, P<0.001 for trend across race or ethnic group, sex, and age subgroups). Adjusted pairwise comparisons showed that the relative annual increase in the incidence of type 2 diabetes among non‐Hispanic whites (0.6%) was lower than that among non‐Hispanic blacks, Asians or Pacific Islanders, and Native Americans (P<0.05 for all comparisons) and that the annual rate of increase among Hispanics differed significantly from that among Native Americans (3.1% vs. 8.9%, P=0.01). After adjustment for age, sex, and race or ethnic group, the relative annual increase in the incidence of type 1 diabetes was 1.8% (P<0.001) and that of type 2 diabetes was 4.8% (P<0.001). CONCLUSIONS The incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002–2012 period, particularly among youths of minority racial and ethnic groups. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Centers for Disease Control and Prevention.)