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

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.).

Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study.

AIMS/HYPOTHESIS: Maternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. METHODS: The HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75 g OGTT at ~28 weeks gestation 10-14 years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including: (1) being overweight/obese according to sex- and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA1c values during pregnancy. RESULTS: Fully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA1c measures, ORs for each child adiposity outcome were in the range of 1.05-1.16 for maternal fasting glucose, 1.11-1.19 for 1 h glucose, 1.09-1.21 for 2 h glucose and 1.12-1.21 for HbA1c. Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls. CONCLUSIONS/INTERPRETATION: Exposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.

Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.

PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).MethodsSequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial. Associations between having a monogenic diabetes variant and clinical characteristics and time to treatment failure were analyzed.ResultsMore than 4% (22/488) had genetic variants causing monogenic diabetes (seven GCK, seven HNF4A, five HNF1A, two INS, and one KLF11). Patients with monogenic diabetes had a statistically, but not clinically, significant lower body mass index (BMI) z-score, lower fasting insulin, and higher fasting glucose. Most (6/7) patients with HNF4A variants rapidly failed TODAY treatment across study arms (hazard ratio = 5.03, P = 0.0002), while none with GCK variants failed treatment.ConclusionThe finding of 4.5% of patients with monogenic diabetes in an overweight/obese cohort of children and adolescents with T2D suggests that monogenic diabetes diagnosis should be considered in children and adolescents without diabetes-associated autoantibodies and maintained C-peptide, regardless of BMI, as it may direct appropriate clinical management.

Cardiovascular autonomic neuropathy in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Cohort 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.

Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism and Childhood Adiposity.

Importance: The sequelae of gestational diabetes (GD) by contemporary criteria that diagnose approximately twice as many women as previously used criteria are unclear. Objective: To examine associations of GD with maternal glucose metabolism and childhood adiposity 10 to 14 years' postpartum. Design, Setting, and Participants: The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study established associations of glucose levels during pregnancy with perinatal outcomes and the follow-up study evaluated the long-term outcomes (4697 mothers and 4832 children; study visits occurred between February 13, 2013, and December 13, 2016). Exposures: Gestational diabetes was defined post hoc using criteria from the International Association of Diabetes and Pregnancy Study Groups consisting of 1 or more of the following 75-g oral glucose tolerance test results (fasting plasma glucose ≥92 mg/dL; 1-hour plasma glucose level ≥180 mg/dL; 2-hour plasma glucose level ≥153 mg/dL). Main Outcomes and Measures: Primary maternal outcome: a disorder of glucose metabolism (composite of type 2 diabetes or prediabetes). Primary outcome for children: being overweight or obese; secondary outcomes: obesity, body fat percentage, waist circumference, and sum of skinfolds (>85th percentile for latter 3 outcomes). Results: The analytic cohort included 4697 mothers (mean [SD] age, 41.7 [5.7] years) and 4832 children (mean [SD] age, 11.4 [1.2] years; 51.0% male). The median duration of follow-up was 11.4 years. The criteria for GD were met by 14.3% (672/4697) of mothers overall and by 14.1% (683/4832) of mothers of participating children. Among mothers with GD, 52.2% (346/663) developed a disorder of glucose metabolism vs 20.1% (791/3946) of mothers without GD (odds ratio [OR], 3.44 [95% CI, 2.85 to 4.14]; risk difference [RD], 25.7% [95% CI, 21.7% to 29.7%]). Among children of mothers with GD, 39.5% (269/681) were overweight or obese and 19.1% (130/681) were obese vs 28.6% (1172/4094) and 9.9% (405/4094), respectively, for children of mothers without GD. Adjusted for maternal body mass index during pregnancy, the OR was 1.21 (95% CI, 1.00 to 1.46) for children who were overweight or obese and the RD was 3.7% (95% CI, -0.16% to 7.5%); the OR was 1.58 (95% CI, 1.24 to 2.01) for children who were obese and the RD was 5.0% (95% CI, 2.0% to 8.0%); the OR was 1.35 (95% CI, 1.08 to 1.68) for body fat percentage and the RD was 4.2% (95% CI, 0.9% to 7.4%); the OR was 1.34 (95% CI, 1.08 to 1.67) for waist circumference and the RD was 4.1% (95% CI, 0.8% to 7.3%); and the OR was 1.57 (95% CI, 1.27 to 1.95) for sum of skinfolds and the RD was 6.5% (95% CI, 3.1% to 9.9%). Conclusions and Relevance: Among women with GD identified by contemporary criteria compared with those without it, GD was significantly associated with a higher maternal risk for a disorder of glucose metabolism during long-term follow-up after pregnancy. Among children of mothers with GD vs those without it, the difference in childhood overweight or obesity defined by body mass index cutoffs was not statistically significant; however, additional measures of childhood adiposity may be relevant in interpreting the study findings.

Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood.

Importance: The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown. Objective: To determine the prevalence of and risk factors for complications related to type 1 diabetes vs type 2 diabetes among teenagers and young adults who had been diagnosed with diabetes during childhood and adolescence. Design, Setting, and Participants: Observational study from 2002 to 2015 in 5 US locations, including 2018 participants with type 1 and type 2 diabetes diagnosed at younger than 20 years, with single outcome measures between 2011 and 2015. Exposures: Type 1 and type 2 diabetes and established risk factors (hemoglobin A1c level, body mass index, waist-height ratio, and mean arterial blood pressure). Main Outcomes and Measures: Diabetic kidney disease, retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension. Results: Of 2018 participants, 1746 had type 1 diabetes (mean age, 17.9 years [SD, 4.1]; 1327 non-Hispanic white [76.0%]; 867 female patients [49.7%]), and 272 had type 2 (mean age, 22.1 years [SD, 3.5]; 72 non-Hispanic white [26.5%]; 181 female patients [66.5%]). Mean diabetes duration was 7.9 years (both groups). Patients with type 2 diabetes vs those with type 1 had higher age-adjusted prevalence of diabetic kidney disease (19.9% vs 5.8%; absolute difference [AD], 14.0%; 95% CI, 9.1%-19.9%; P < .001), retinopathy (9.1% vs 5.6%; AD, 3.5%; 95% CI, 0.4%-7.7%; P = .02), peripheral neuropathy (17.7% vs 8.5%; AD, 9.2%; 95% CI, 4.8%-14.4%; P < .001), arterial stiffness (47.4% vs 11.6%; AD, 35.9%; 95% CI, 29%-42.9%; P < .001), and hypertension (21.6% vs 10.1%; AD, 11.5%; 95% CI, 6.8%-16.9%; P < .001), but not cardiovascular autonomic neuropathy (15.7% vs 14.4%; AD, 1.2%; 95% CI, -3.1% to 6.5; P = .62). After adjustment for established risk factors measured over time, participants with type 2 diabetes vs those with type 1 had significantly higher odds of diabetic kidney disease (odds ratio [OR], 2.58; 95% CI, 1.39-4.81; P=.003), retinopathy (OR, 2.24; 95% CI, 1.11-4.50; P = .02), and peripheral neuropathy (OR, 2.52; 95% CI, 1.43-4.43; P = .001), but no significant difference in the odds of arterial stiffness (OR, 1.07; 95% CI, 0.63-1.84; P = .80) and hypertension (OR, 0.85; 95% CI, 0.50-1.45; P = .55). Conclusions and Relevance: Among teenagers and young adults who had been diagnosed with diabetes during childhood or adolescence, the prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1, but frequent in both groups. These findings support early monitoring of youth with diabetes for development of complications.

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 Cooperative Health Research in South Tyrol (CHRIS) study: rationale, objectives, and preliminary results.

The Cooperative Health Research In South Tyrol (CHRIS) study is a population-based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment.

Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009.

IMPORTANCE: Despite concern about an "epidemic," there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups. OBJECTIVE: To estimate changes in the prevalence of type 1 and type 2 diabetes in US youth, by sex, age, and race/ethnicity between 2001 and 2009. DESIGN, SETTING, AND PARTICIPANTS: Case patients were ascertained in 4 geographic areas and 1 managed health care plan. The study population was determined by the 2001 and 2009 bridged-race intercensal population estimates for geographic sites and membership counts for the health plan. MAIN OUTCOMES AND MEASURES: Prevalence (per 1000) of physician-diagnosed type 1 diabetes in youth aged 0 through 19 years and type 2 diabetes in youth aged 10 through 19 years. RESULTS: In 2001, 4958 of 3.3 million youth were diagnosed with type 1 diabetes for a prevalence of 1.48 per 1000 (95% CI, 1.44-1.52). In 2009, 6666 of 3.4 million youth were diagnosed with type 1 diabetes for a prevalence of 1.93 per 1000 (95% CI, 1.88-1.97). In 2009, the highest prevalence of type 1 diabetes was 2.55 per 1000 among white youth (95% CI, 2.48-2.62) and the lowest was 0.35 per 1000 in American Indian youth (95% CI, 0.26-0.47) and type 1 diabetes increased between 2001 and 2009 in all sex, age, and race/ethnic subgroups except for those with the lowest prevalence (age 0-4 years and American Indians). Adjusted for completeness of ascertainment, there was a 21.1% (95% CI, 15.6%-27.0%) increase in type 1 diabetes over 8 years. In 2001, 588 of 1.7 million youth were diagnosed with type 2 diabetes for a prevalence of 0.34 per 1000 (95% CI, 0.31-0.37). In 2009, 819 of 1.8 million were diagnosed with type 2 diabetes for a prevalence of 0.46 per 1000 (95% CI, 0.43-0.49). In 2009, the prevalence of type 2 diabetes was 1.20 per 1000 among American Indian youth (95% CI, 0.96-1.51); 1.06 per 1000 among black youth (95% CI, 0.93-1.22); 0.79 per 1000 among Hispanic youth (95% CI, 0.70-0.88); and 0.17 per 1000 among white youth (95% CI, 0.15-0.20). Significant increases occurred between 2001 and 2009 in both sexes, all age-groups, and in white, Hispanic, and black youth, with no significant changes for Asian Pacific Islanders and American Indians. Adjusted for completeness of ascertainment, there was a 30.5% (95% CI, 17.3%-45.1%) overall increase in type 2 diabetes. CONCLUSIONS AND RELEVANCE: Between 2001 and 2009 in 5 areas of the United States, the prevalence of both type 1 and type 2 diabetes among children and adolescents increased. Further studies are required to determine the causes of these increases.

A school-based intervention for diabetes risk reduction.

BACKGROUND: We examined the effects of a multicomponent, school-based program addressing risk factors for diabetes among children whose race or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes. METHODS: Using a cluster design, we randomly assigned 42 schools to either a multicomponent school-based intervention (21 schools) or assessment only (control, 21 schools). A total of 4603 students participated (mean [+/- SD] age, 11.3 [+/- 0.6 years; 54.2% Hispanic and 18.0% black; 52.7% girls). At the beginning of 6th grade and the end of 8th grade, students underwent measurements of body-mass index (BMI), waist circumference, and fasting glucose and insulin levels. RESULTS: There was a decrease in the primary outcome--the combined prevalence of overweight and obesity--in both the intervention and control schools, with no significant difference between the school groups. The intervention schools had greater reductions in the secondary outcomes of BMI z score, percentage of students with waist circumference at or above the 90th percentile, fasting insulin levels (P=0.04 for all comparisons), and prevalence of obesity (P=0.05). Similar findings were observed among students who were at or above the 85th percentile for BMI at baseline. Less than 3% of the students who were screened had an adverse event; the proportions were nearly equivalent in the intervention and control schools. CONCLUSIONS: Our comprehensive school-based program did not result in greater decreases in the combined prevalence of overweight and obesity than those that occurred in control schools. However, the intervention did result in significantly greater reductions in various indexes of adiposity. These changes may reduce the risk of childhood-onset type 2 diabetes. (Funded by the National Institutes of Health and the American Diabetes Association; ClinicalTrials.gov number, NCT00458029.)

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Improve Diabetes Treatment and Reduce Complications.

The Treatment and Complications subcommittee of the National Clinical Care Commission focused on factors likely to improve the delivery of high-quality care to all people with diabetes. The gap between available resources and the needs of people living with diabetes adversely impacts both treatment and outcomes. The Commission's recommendations are designed to bridge this gap. At the patient level, the Commission recommends reducing barriers and streamlining administrative processes to improve access to diabetes self-management training, diabetes devices, virtual care, and insulin. At the practice level, we recommend enhancing programs that support team-based care and developing capacity to support technology-enabled mentoring interventions. At the health system level, we recommend that the Department of Health and Human Services routinely assess the needs of the health care workforce and ensure funding of training programs directed to meet those needs. At the health policy level, we recommend establishing a process to identify and ensure pre-deductible insurance coverage for high-value diabetes treatments and services and developing a quality measure that reduces risk of hypoglycemia and enhances patient safety. We also identified several areas that need additional research, such as studying the barriers to uptake of diabetes self-management education and support, exploring methods to implement team-based care, and evaluating the importance of digital connectivity as a social determinant of health. The Commission strongly encourages Congress, the Department of Health and Human Services, and other federal departments and agencies to take swift action to implement these recommendations to improve health outcomes and quality of life among people living with diabetes.

The National Clinical Care Commission Report to Congress: Recommendations to Better Leverage Federal Policies and Programs to Prevent and Control Diabetes.

The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non-health-related federal agencies. It held 12 public meetings, solicited public comments, met with numerous interested parties and key informants, and performed comprehensive literature reviews. The final report, transmitted to Congress in January 2022, contained 39 specific recommendations, including 3 foundational recommendations that addressed the necessity of an all-of-government approach to diabetes, health equity, and access to health care. At the general population level, the NCCC recommended that the federal government adopt a health-in-all-policies approach so that the activities of non-health-related federal agencies that address agriculture, food, housing, transportation, commerce, and the environment be coordinated with those of health-related federal agencies to affirmatively address the social and environmental conditions that contribute to diabetes and its complications. For individuals at risk for type 2 diabetes, including those with prediabetes, the NCCC recommended that federal policies and programs be strengthened to increase awareness of prediabetes and the availability of, referral to, and insurance coverage for intensive lifestyle interventions for diabetes prevention and that data be assembled to seek approval of metformin for diabetes prevention. For people with diabetes and its complications, the NCCC recommended that barriers to proven effective treatments for diabetes and its complications be removed, the size and competence of the workforce to treat diabetes and its complications be increased, and new payment models be implemented to support access to lifesaving medications and proven effective treatments for diabetes and its complications. The NCCC also outlined an ambitious research agenda. The NCCC strongly encourages the public to support these recommendations and Congress to take swift action.

HEALTHY study rationale, design and methods: moderating risk of type 2 diabetes in multi-ethnic middle school students.

The HEALTHY primary prevention trial was designed and implemented in response to the growing numbers of children and adolescents being diagnosed with type 2 diabetes. The objective was to moderate risk factors for type 2 diabetes. Modifiable risk factors measured were indicators of adiposity and glycemic dysregulation: body mass index > or =85th percentile, fasting glucose > or =5.55 mmol l(-1) (100 mg per 100 ml) and fasting insulin > or =180 pmol l(-1) (30 microU ml(-1)). A series of pilot studies established the feasibility of performing data collection procedures and tested the development of an intervention consisting of four integrated components: (1) changes in the quantity and nutritional quality of food and beverage offerings throughout the total school food environment; (2) physical education class lesson plans and accompanying equipment to increase both participation and number of minutes spent in moderate-to-vigorous physical activity; (3) brief classroom activities and family outreach vehicles to increase knowledge, enhance decision-making skills and support and reinforce youth in accomplishing goals; and (4) communications and social marketing strategies to enhance and promote changes through messages, images, events and activities. Expert study staff provided training, assistance, materials and guidance for school faculty and staff to implement the intervention components. A cohort of students were enrolled in sixth grade and followed to end of eighth grade. They attended a health screening data collection at baseline and end of study that involved measurement of height, weight, blood pressure, waist circumference and a fasting blood draw. Height and weight were also collected at the end of the seventh grade. The study was conducted in 42 middle schools, six at each of seven locations across the country, with 21 schools randomized to receive the intervention and 21 to act as controls (data collection activities only). Middle school was the unit of sample size and power computation, randomization, intervention and primary analysis.

Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism.

OBJECTIVE: Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS: HAPO Follow-up Study (FUS) included 4,160 children ages 10-14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks of gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index. RESULTS: For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78-1.52) for IFG and 1.96 (1.41-2.73) for IGT. GDM was positively associated with child's 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference -76.3 [95% CI -130.3 to -22.4] and -0.12 [-0.17 to -0.064]), respectively, but not insulinogenic index. CONCLUSIONS: Offspring exposed to untreated GDM in utero are insulin resistant with limited ß-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT.

Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism.

OBJECTIVE: This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS: HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10-14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT. RESULTS: Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased. CONCLUSIONS: Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.

Prevalence of gestational diabetes and subsequent Type 2 diabetes among U.S. women.

AIMS: The true prevalence of gestational diabetes (GDM) in the United States is unknown. This study determined the prevalence of GDM and a subsequent diagnosis of diabetes in a nationally representative sample of U.S. women. METHODS: The crude and age-adjusted prevalence of GDM and subsequent diabetes were evaluated by sociodemographic and health-related characteristics among women age ≥20 years in the National Health and Nutrition Examination Surveys, 2007-2014 (N = 8185). Logistic regression analyzed independent factors associated with GDM and subsequent diabetes. RESULTS: The prevalence of GDM was 7.6%. Women who were Mexican American (vs. non-Hispanic white), had ≥4 live births (vs. 1), had a family history of diabetes, or were obese (vs. normal weight) had a higher age-standardized prevalence of GDM (each p < 0.04). Among women with a history of GDM, 19.7% had a subsequent diagnosis of diabetes; subsequent diabetes diagnosis was higher for those with health insurance, more time since GDM diagnosis, greater parity, family history of diabetes, and obesity, and lower for those with higher education and income (all p ≤ 0.005). By logistic regression, significant factors associated with GDM were age at first birth, parity, family history of diabetes, and obesity; significant factors for subsequent diabetes were older age, greater years since GDM diagnosis, less education, family history of diabetes, and obesity (each p < 0.01). CONCLUSIONS: The prevalence of GDM in the U.S. was 7.6%, with 19.7% of these women having a subsequent diabetes diagnosis. Women with a history of GDM, family history of diabetes, and obesity should be carefully monitored for dysglycemia.

Incidence of diabetes in youth in the United States.

CONTEXT: Data on the incidence of diabetes mellitus (DM) among US youth according to racial/ethnic background and DM type are limited. OBJECTIVE: To estimate DM incidence in youth aged younger than 20 years according to race/ethnicity and DM type. DESIGN, SETTING, AND PARTICIPANTS: A multiethnic, population-based study (The SEARCH for Diabetes in Youth Study) of 2435 youth with newly diagnosed, nonsecondary DM in 2002 and 2003, ascertained at 10 study locations in the United States, covering a population of more than 10 million person-years. MAIN OUTCOME MEASURE: Incidence rates by age group, sex, race/ethnicity, and DM type were calculated per 100,000 person-years at risk. Diabetes mellitus type (type 1/type 2) was based on health care professional assignment and, in a subset, further characterized with glutamic acid decarboxylase (GAD65) autoantibody and fasting C peptide measures. RESULTS: The incidence of DM (per 100,000 person-years) was 24.3 (95% confidence interval [CI], 23.3-25.3). Among children younger than 10 years, most had type 1 DM, regardless of race/ethnicity. The highest rates of type 1 DM were observed in non-Hispanic white youth (18.6, 28.1, and 32.9 for age groups 0-4, 5-9, and 10-14 years, respectively). Even among older youth (> or =10 years), type 1 DM was frequent among non-Hispanic white, Hispanic, and African American adolescents. Overall, type 2 DM was still relatively infrequent, but the highest rates (17.0 to 49.4 per 100,000 person-years) were documented among 15- to 19-year-old minority groups. CONCLUSIONS: Our data document the incidence rates of type 1 DM among youth of all racial/ethnic groups, with the highest rates in non-Hispanic white youth. Overall, type 2 DM is still relatively infrequent; however, the highest rates were observed among adolescent minority populations.

Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes.

OBJECTIVE: The "accelerator hypothesis" predicts that fatness is associated with an earlier age at onset of type 1 diabetes. We tested the hypothesis using data from the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS: Subjects were 449 youth aged <20 years at diagnosis who had positive results for diabetes antibodies measured 3-12 months after diagnosis (mean 7.6 months). The relationships between age at diagnosis and fatness were examined using BMI as measured at the SEARCH visit and reported birth weight, both expressed as SD scores (SDSs). RESULTS: Univariately, BMI SDS was not related to age at diagnosis. In multiple linear regression, adjusted for potential confounders, a significant interaction was found between BMI SDS and fasting C-peptide (FCP) on onset age (P < 0.0001). This interaction remained unchanged after additionally controlling for number and titers of diabetes antibodies. An inverse association between BMI and age at diagnosis was present only among subjects with FCP levels below the median (<0.5 ng/ml) (regression coefficient -7.9, P = 0.003). A decrease of 1 SDS in birth weight (639 g) was also associated with an approximately 5-month earlier age at diagnosis (P = 0.008), independent of sex, race/ethnicity, current BMI, FCP, and number of diabetes antibodies. CONCLUSIONS: Increasing BMI is associated with younger age at diagnosis of type 1 diabetes only among those U.S. youth with reduced beta-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.

Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes: the SEARCH for diabetes in youth study.

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 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.