Elizabeth J. Mayer-Davis

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.)

Prevalence, Characteristics and Clinical Diagnosis of Maturity Onset Diabetes of the Young Due to Mutations in HNF1A, HNF4A, and Glucokinase: Results From the SEARCH for Diabetes in Youth

AIMSnOur study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify youth with maturity-onset diabetes of the young (MODY).nnnMETHODSnThe SEARCH for Diabetes in Youth study is a US multicenter, population-based study of youth with diabetes diagnosed at age younger than 20 years. We sequenced genomic DNA for mutations in the HNF1A, HNF4A, and glucokinase genes in 586 participants enrolled in SEARCH between 2001 and 2006. Selection criteria included diabetes autoantibody negativity and fasting C-peptide levels of 0.8 ng/mL or greater.nnnRESULTSnWe identified a mutation in one of three MODY genes in 47 participants, or 8.0% of the tested sample, for a prevalence of at least 1.2% in the pediatric diabetes population. Of these, only 3 had a clinical diagnosis of MODY, and the majority was treated with insulin. Compared with the MODY-negative group, MODY-positive participants had lower FCP levels (2.2 ± 1.4 vs 3.2 ± 2.1 ng/mL, P < .01) and fewer type 2 diabetes-like metabolic features. Parental history of diabetes did not significantly differ between the 2 groups.nnnCONCLUSIONS/INTERPRETATIONnIn this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.

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%; Pu2009<u2009.001), retinopathy (9.1% vs 5.6%; AD, 3.5%; 95% CI, 0.4%-7.7%; Pu2009=u2009.02), peripheral neuropathy (17.7% vs 8.5%; AD, 9.2%; 95% CI, 4.8%-14.4%; Pu2009<u2009.001), arterial stiffness (47.4% vs 11.6%; AD, 35.9%; 95% CI, 29%-42.9%; Pu2009<u2009.001), and hypertension (21.6% vs 10.1%; AD, 11.5%; 95% CI, 6.8%-16.9%; Pu2009<u2009.001), but not cardiovascular autonomic neuropathy (15.7% vs 14.4%; AD, 1.2%; 95% CI, –3.1% to 6.5; Pu2009=u2009.62). 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; Pu2009=u2009.02), and peripheral neuropathy (OR, 2.52; 95% CI, 1.43-4.43; Pu2009=u2009.001), but no significant difference in the odds of arterial stiffness (OR, 1.07; 95% CI, 0.63-1.84; Pu2009=u2009.80) and hypertension (OR, 0.85; 95% CI, 0.50-1.45; Pu2009=u2009.55). 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.

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.

Insulin regimens and clinical outcomes in a type 1 diabetes cohort: the SEARCH for Diabetes in Youth study.

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.

Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study

Aims/hypothesisFew studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study.MethodsParticipants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20xa0years, who were followed from a median of 8xa0months post diagnosis, for approximately 30xa0months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models.ResultsAmong DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA1c and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month).Conclusions/interpretationSEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.

Use of administrative and electronic health record data for development of automated algorithms for childhood diabetes case ascertainment and type classification: the SEARCH for Diabetes in Youth Study

The performance of automated algorithms for childhood diabetes case ascertainment and type classification may differ by demographic characteristics.

Predictors of Sustained Reduction in Energy and Fat Intake in the Diabetes Prevention Program Outcomes Study Intensive Lifestyle Intervention

BACKGROUNDnFew lifestyle intervention studies examine long-term sustainability of dietary changes.nnnOBJECTIVEnTo describe sustainability of dietary changes over 9 years in the Diabetes Prevention Program and its outcomes study, the Diabetes Prevention Program Outcomes Study, among participants receiving the intensive lifestyle intervention.nnnDESIGNnOne thousand seventy-nine participants were enrolled in the intensive lifestyle intervention arm of the Diabetes Prevention Program; 910 continued participation in the Diabetes Prevention Program Outcomes Study. Fat and energy intake derived from food frequency questionnaires at baseline and post-randomization Years 1 and 9 were examined. Parsimonious models determined whether baseline characteristics and intensive lifestyle intervention session participation predicted sustainability.nnnRESULTSnSelf-reported energy intake was reduced from a median of 1,876 kcal/day (interquartile range [IQR]=1,452 to 2,549 kcal/day) at baseline to 1,520 kcal/day (IQR=1,192 to 1,986 kcal/day) at Year 1, and 1,560 kcal/day (IQR=1,223 to 2,026 kcal/day) at Year 9. Dietary fat was reduced from a median of 70.4 g (IQR=49.3 to 102.5 g) to 45 g (IQR=32.2 to 63.8 g) at Year 1 and increased to 61.0 g (IQR=44.6 to 82.7 g) at Year 9. Percent energy from fat was reduced from a median of 34.4% (IQR=29.6% to 38.5%) to 27.1% (IQR=23.1% to 31.5%) at Year 1 but increased to 35.3% (IQR=29.7% to 40.2%) at Year 9. Lower baseline energy intake and Year 1 dietary reduction predicted lower energy and fat gram intake at Year 9. Higher leisure physical activity predicted lower fat gram intake but not energy intake.nnnCONCLUSIONSnIntensive lifestyle intervention can result in reductions in total energy intake for up to 9 years. Initial success in achieving reductions in fat and energy intake and success in attaining activity goals appear to predict long-term success at maintaining changes.

Long-term changes in dietary and food intake behaviour in the Diabetes Prevention Program Outcomes Study

To compare change in dietary intake, with an emphasis on food groups and food intake behaviour, over time across treatment arms in a diabetes prevention trial and to assess the differences in dietary intake among demographic groups within treatment arms.

Albuminuria according to status of autoimmunity and insulin sensitivity among youth with type 1 and type 2 diabetes.

OBJECTIVE To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes. RESEARCH DESIGN AND METHODS SEARCH is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA+/insulin-sensitive (IS) (n = 1,351); DAA+/insulin-resistant (IR) (n = 438); DAA−/IR (n = 379); and DAA−/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR. RESULTS Adjusted UACR means across the four groups were as follows: DAA+/IS = 154 μg/mg; DAA+/IR = 137 μg/mg; DAA−/IR = 257 μg/mg; and DAA−/IS = 131 μg/mg (P < 0.005). Only DAA−/IR was significantly different. We performed post hoc multivariable regression analysis restricted to the two IR groups to explore the contribution of DAA status and insulin sensitivity (continuous) to the difference in UACR between the IR groups. Only insulin sensitivity was significantly associated with UACR (β = −0.54; P < 0.0001). CONCLUSIONS In youth with diabetes, the DAA−/IR group had a greater UACR than all other groups, possibly because of the greater magnitude of insulin resistance. Further exploration of the relationships between severity of insulin resistance, autoimmunity, and albuminuria in youth with diabetes is warranted.