Comparing the activPAL software's Primary Time in Bed Algorithm against Self-Report and van der Berg's Algorithm.

The purpose of this study was to compare activPAL algorithm-estimated values for time in bed (TIB), wake time (WT) and bedtime (BT) against self-report and an algorithm developed by van der Berg and colleagues. Secondary analyses of baseline data from the Community Activity for Prevention Study (CAPS) were used in which adults ≥ 18 years wore the activPAL for seven days. Mixed-effects models compared differences between TIB, WT, and BT for all three methods. Bland-Altman plots examined agreement and the two-one-sided test examined equivalence. activPAL was not equivalent to self-report or van der Berg in estimating TIB, but was equivalent to self-report for estimating BT, and was equivalent to van der Berg for estimating WT. The activPAL algorithm requires adjustments before researchers can use it to estimate TIB. However, researchers can use activPAL's option to manually enter self-reported BT and WT to estimate TIB and better understand 24-hour movement patterns.

CAPS on the move: Crafting an approach to recruitment for a randomized controlled trial of community gardening.

OBJECTIVE: To describe and evaluate recruitment approaches for a randomized controlled trial (RCT) of community gardening in Denver, Colorado. (ClinicalTrials.gov: NCT03089177). METHODS: We used community and staff feedback to adapt our recruitment approach from year 1 to year 2 of a multi-year RCT to address health behaviors related to cancer prevention. In year 2, we added a full-time recruitment coordinator, designed and implemented a tracking spreadsheet, and engaged advisory committee members, local garden leaders, and health partners in planning and outreach. Screening and consent rates, staff time and costs for years 1 and 2 are compared. RESULTS: In year 1, recruitment methods yielded 136 initial contacts, 106 screenings and 64 consented participants. In year 2, enhanced staffing and outreach yielded 257 initial contacts, 193 screenings, and 123 consented participants. Personal referrals, health fairs, NextDoor, and fliers yielded the highest percentage of consented participants. School and community meetings yielded the lowest yield for potential participants. Spanish-speaking participants were mostly recruited by direct methods. Compared to year 1 recruitment, which required 707 h of staff time and cost $14,446, year 2 recruitment required 1224 h of staff time and cost $22,992. Average cost for retained participants was $226 (year 1) and $186 (year 2). DISCUSSION: Those planning pragmatic clinical trials with recruitment in multi-ethnic communities can use the results from this study to understand the efficacy of techniques, and to budget costs for recruitment. While our culturally-tailored recruitment methods cost more, they provided more effective and efficient ways to reach recruitment goals.

Rationale and design for the community activation for prevention study (CAPs): A randomized controlled trial of community gardening.

BACKGROUND: Engaging in health-promoting behaviors (e.g., healthy fruit- and vegetable-rich diet, physical activity) and living in supportive social and built environments are consistently and significantly associated with reductions in cancer, heart disease, diabetes, and other chronic diseases. Interventions to change diet and physical activity behaviors should aim to educate individuals, change the environments in which people live, work and recreate, improve access, availability, and affordability of healthy foods, and create safe places the facilitate active lifestyles. This trial will assess whether community gardening increases fruit and vegetable consumption and physical activity, improves social support and mental health, and reduces age-associated weight gain and sedentary time among a multi-ethnic, mixed-income population. METHODS/DESIGN: A randomized controlled trial of community gardening began in Denver, Colorado in January 2017. Over 3 years, we will recruit 312 consenting participants on Denver Urban Gardens' waitlists and randomize them to garden or remain on the waitlist. At baseline (pre-gardening), harvest time, and post-intervention, study participants will complete three 24-hour dietary recalls, a 7-day activity monitoring period using accelerometry, a health interview and physical anthropometry. DISCUSSION: This project addresses health-promoting behaviors among a multi-ethnic, mixed-income adult population in a large metropolitan area. If successful, this trial will provide evidence that community gardening supports and sustains healthy and active lifestyles, which can reduce risk of cancer and other chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03089177: Registered on 03/17/17.

Exploring residual risk for diabetes and microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS).

AIM: Approximately half of the participants in the Diabetes Prevention Outcomes Study (DPPOS) had diabetes after 15 years of follow-up, whereas nearly all the others remained with pre-diabetes. We examined whether formerly unexplored factors in the DPPOS coexisted with known risk factors that posed additional risk for, or protection from, diabetes as well as microvascular disease. METHODS: Cox proportional hazard models were used to examine predictors of diabetes. Sequential modelling procedures considered known and formerly unexplored factors. We also constructed models to determine whether the same unexplored factors that associated with progression to diabetes also predicted the prevalence of microvascular disease. Hazard ratios (HR) are per standard deviation change in the variable. RESULTS: In models adjusted for demographics and known diabetes risk factors, two formerly unknown factors were associated with risk for both diabetes and microvascular disease: number of medications taken (HR = 1.07, 95% confidence intervals (95% CI) 1.03 to 1.12 for diabetes; odds ratio (OR) = 1.10, 95% CI 1.04 to 1.16 for microvascular disease) and variability in HbA1c (HR = 1.02, 95% CI 1.01 to 1.03 for diabetes; OR = 1.06, 95% CI 1.04 to 1.09 for microvascular disease per sd). Total comorbidities increased risk for diabetes (HR = 1.10, 95% CI 1.04 to 1.16), whereas higher systolic (OR = 1.22, 95% CI 1.13 to 1.31) and diastolic (OR = 1.14, 95% CI 1.05 to 1.22) blood pressure, as well as the use of anti-hypertensives (OR = 1.41, 95% CI 1.23 to 1.62), increased risk of microvascular disease. CONCLUSIONS: Several formerly unexplored factors in the DPPOS predicted additional risk for diabetes and/or microvascular disease - particularly hypertension and the use of anti-hypertensive medications - helping to explain some of the residual disease risk in participants of the DPPOS.

Transitions in pregnancy planning in women recruited for a large prospective cohort study.

STUDY QUESTION: Do the rates at which women transition among different intensities of pregnancy planning vary with age, marital status and race/ethnicity? SUMMARY ANSWER: Rates of transition from low or moderate pregnancy probability groups (PPGs) to higher PPGs vary by age, marital status and race/ethnicity. WHAT IS KNOWN ALREADY: The design of prospective studies of the effects of pre- and peri-conception exposures on fecundity, pregnancy and children's health is challenging because at any specific time only a small percentage of reproductive age women is attempting to conceive. To our knowledge, there has been no population-based, prospective study that repeatedly assessed pregnancy planning, which included women who were not already planning pregnancy at enrollment and whose ages spanned the female reproductive age range. STUDY DESIGN, SIZE, DURATION: A longitudinal study was carried out that repeatedly assessed pregnancy probability in 12 916 women for up to 21 months from January 2009 to September 2010. PARTICIPANTS/MATERIALS, SETTING, METHOD: We analyzed data from the National Children's Study Vanguard Study, a pilot study for a large-scale epidemiological birth cohort study of children and their parents. During the Vanguard Study, investigators followed population-based samples of reproductive age women in each of seven geographically dispersed and diverse study locations over time to identify when they sought to become pregnant, providing a unique opportunity to prospectively assess changes in pregnancy planning in a large sample of US women. At study entry and each follow-up contact, which occurred at 1, 3 or 6 month intervals depending on PPG, a questionnaire was used to assess behavior dimensions of pregnancy planning to assign women to low, moderate, high non-tryer and high tryer PPGs. MAIN RESULTS AND THE ROLE OF CHANCE: Crude rates of pregnancy increased with higher assigned PPG, validating the utility of the instrument. The initial PPG and probabilities of transitioning from low or moderate PPG to higher PPG or pregnancy varied with age, marital status and race/ethnicity. Women aged 25 to <35 years had shorter times to transition to higher PPGs or to pregnant compared with women <25 years. Women who were not currently married had longer times to transition from any initial PPG to pregnant, high tryer or high non-tryer status than currently married women. Non-Hispanic Black (NHB) and Hispanic women had shorter time to transition from low or moderate to high non-tryer than non-Hispanic White (NHW) women. NHB women also had shorter time to transition from low to high tryer than NHW women. High tryers are more likely to be aged 25 to <30 years, to be married, and to be Hispanic, NHB or other race/ethnicity than women in the low PPG. LIMITATIONS, REASONS FOR CAUTION: Loss to follow-up varied by age, marital status and race/ethnicity. Although weights were not developed for the Vanguard study, the self-weighting design minimizes the bias of unweighted analysis. Nonetheless, the SEs for some estimates may be under-estimated. WIDER IMPLICATIONS OF THE FINDINGS: Our results show that demographic characteristics are strong predictors of women's behaviors toward pregnancy. The results further show that frequent follow-up assessments of pregnancy planning behavior in large numbers of women are required to recruit an unbiased sample of preconception women. These findings will be useful to investigators designing prospective studies of fecundability, pregnancy outcomes and children's health. STUDY FUNDING/COMPETING INTERESTS: National Institutes of Health (contracts N01-HD53414, N01-HD63416, N01-HD53410, N01-HD53415, N01-HD53396, N01-HD53413 and N01-HD-53411; grant R21 ES016846) and by the University of California Irvine Center for Occupational and Environmental Health. No competing interests. TRIAL REGISTRATION NUMBER: None.

Factors Associated with Self-Injurious Behaviors in Children with Autism Spectrum Disorder: Findings from Two Large National Samples.

In this study, we explored potential associations among self-injurious behaviors (SIB) and a diverse group of protective and risk factors in children with autism spectrum disorder from two databases: Autism and Developmental Disabilities Monitoring (ADDM) Network and the Autism Speaks-Autism Treatment Network (AS-ATN). The presence of SIB was determined from children's records in ADDM and a parent questionnaire in AS-ATN. We used multiple imputation to account for missing data and a non-linear mixed model with site as a random effect to test for associations. Despite differences between the two databases, similar associations were found; SIB were associated with developmental, behavioral, and somatic factors. Implications of these findings are discussed in relation to possible etiology, future longitudinal studies, and clinical practice.

Leptin levels at birth and infant growth: the EPOCH study.

OBJECTIVE: To examine the association of cord blood leptin with body mass index (BMI) growth velocity from birth to 12 months of age among infants exposed and not exposed to over-nutrition in utero (defined as maternal overweight/obesity or presence of gestational diabetes). METHODS: 185 infants enrolled in the Exploring Perinatal Outcomes among Children study (76 exposed and 109 not exposed) had leptin and insulin measured in cord blood. Longitudinal weight and length measures in the first 12 months of life (average 4 per participant) obtained from medical records were used to compute BMI growth rates. Mixed models were used to examine associations of cord blood leptin with growth. RESULTS: Compared with unexposed infants, those exposed had significantly higher cord blood insulin (8.64 v. 6.97 uU/ml, P<0.01) and leptin levels (8.89 v. 5.92 ng/ml, P=0.05) as well as increased birth weights (3438.04 v. 3306.89 g, P=0.04). There was an inverse relationship between cord leptin levels and BMI growth from birth to 12 months of age (P=0.005); however, exposure to over-nutrition in utero did not significantly modify this association (P=0.59). CONCLUSION: We provide support of a possible operational feedback mechanism by which lower cord blood leptin levels are associated with faster infant growth in the first year of life. Our data do not tend to support the hypothesis that this mechanism is altered in infants exposed to over-nutrition in utero; however our sample is too small to provide sufficient evidence. Larger epidemiological studies are needed to elucidate the mechanisms responsible for increased propensity for obesity in exposed offspring.

Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program.

AIMS: To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program. METHODS: A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes. RESULTS: The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA(1c), estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56-1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%). CONCLUSIONS: These data suggest that 'diabetes autoimmunity', as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes.

Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Is low birth weight associated with adiposity in contemporary U.S. youth? The Exploring Perinatal Outcomes among Children (EPOCH) Study.

Little is known about the relationship between low birth weight (BW), as a marker of under-nutrition in utero, and childhood body mass index (BMI) and adiposity parameters, including skinfold thickness, abdominal subcutaneous (SAT) and visceral adipose tissues (VAT) and intramyocellular accumulation of lipids (IMCL). The EPOCH Study (Exploring Perinatal Outcomes among Children) explored the association between BW and markers of adiposity in contemporary, multi-ethnic children from Colorado. A total of 442 youth age 6-13 years (50% male, mean age 10.5 years) had anthropometric measurements, abdominal SAT and VAT measured by magnetic resonance imaging and IMCL deposition in the soleus muscle measured by nuclear magnetic resonance spectroscopy. BW and gestational age were ascertained from an electronic perinatal database. A weak positive association between BW and current BMI (P=0.05) was seen, independent of demographic, perinatal, socio-economic and current lifestyle factors. When adjusted for current BMI, every one standard deviation decrease in BW (~500 g), was associated with a 8.8 cm(2) increase in SAT, independent of potential confounders. In conclusion, in a contemporary cohort of youth, BW was positively, but weakly, associated with BMI and inversely, though weakly, associated with SAT, independent of current BMI. There were no significant associations between BW and waist circumference, skinfolds, VAT and IMCL. Our results provide some support to the hypothesis that under-nutrition in utero, as reflected by lower BW, is associated with lower overall childhood body size, but an increased propensity for abdominal adiposity, reflected in this young age-group, predominantly as subcutaneous fat.

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

AIMS/HYPOTHESIS: Few 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. METHODS: Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models. RESULTS: Among 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), HbA(1c) 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/INTERPRETATION: SEARCH 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.

The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH Study.

OBJECTIVE: To evaluate the influence of breast-feeding on the body mass index (BMI) growth trajectory from birth through 13 years of age among offspring of diabetic pregnancies (ODP) and offspring of non-diabetic pregnancies (ONDP) participating in the Exploring Perinatal Outcomes Among Children Study. SUBJECTS: There were 94 ODP and 399 ONDP who had multiple BMI measures obtained from birth throughout childhood. A measure of breast milk-months was derived from maternal self-report to categorize breast-feeding status as adequate (≥6 breast milk-months) or low (<6 breast milk-months). Mixed linear-effects models were constructed to assess the impact of breast-feeding on the BMI growth curves during infancy (birth to 27 months) and childhood (27 months to 13 years). RESULTS: ODP who were adequately breast-fed had a slower BMI growth trajectory during childhood (P=0.047) and slower period-specific growth velocity with significant differences between 4 and 6 years of age (P=0.03) and 6 to 9 years of age (P=0.01) compared with ODP with low breast-feeding. A similar pattern was seen in the ONDP, with adequate breast-feeding associated with lower average BMI in infancy (P=0.03) and childhood (P=0.0002) and a slower growth trajectory in childhood (P=0.0002). Slower period-specific growth velocity was seen among the ONDP associated with adequate breast-feeding with significant differences between 12-26 months (P=0.02), 4-6 years (P=0.03), 6-9 years (P=0.0001) and 9-13 years of age (P<0.0001). CONCLUSION: Our study provides novel evidence that breast-feeding is associated with long-term effects on childhood BMI growth that extend beyond infancy into early and late childhood. Importantly, these effects are also present in the high-risk offspring, exposed to overnutrition during pregnancy. Breast-feeding in the early postnatal period may represent a critical opportunity to reduce the risk of childhood obesity.

Association of insulin sensitivity to lipids across the lifespan in people with Type 1 diabetes.

AIMS: Insulin resistance and dyslipidaemia both increase cardiovascular risk in Type 1 diabetes. However, little data exist on the associations of insulin resistance to lipids in Type 1 diabetes. Our objective was to explore the associations between insulin resistance (assessed by glucose infusion rate) and lipids in people with Type 1 diabetes and determine whether adiposity and/or average glycaemia influence these associations. METHODS: Hyperinsulinaemic-euglycaemic clamp studies were performed in 60 subjects with Type 1 diabetes aged 12-19 years (age 15±2 years, 57% female, duration of diabetes 6.3±3.8 years, HbA(1c) 8.6±1.5%, IFCC=70 mmol/mol) and 40 subjects with Type 1 diabetes aged 27-61 years (age 45±9 years, 53% female, duration of diabetes 23±8 years, HbA(1c) 7.5±0.9%, IFCC=58 mmol/mol). Multiple linear regression models were fit to examine the association between glucose infusion rate and fasting lipid levels with adjustment for possible confounders. RESULTS: Lower glucose infusion rate was significantly associated with lower levels of HDL cholesterol in youths with Type 1 diabetes and with higher levels of triglycerides and higher triglyceride/HDL ratio in both youths and adults. The magnitude of the associations between glucose infusion rate and lipid levels translate into interquartile differences of 0.098 mmol/l for HDL cholesterol, 0.17 mmol/l for triglycerides and 1.06 for triglycerides/HDL in the adolescents and 0.20 mmol/l for triglycerides and 1.01 for triglycerides/HDL in the adults. The associations were attenuated and no longer statistically significant by adjustment for adiposity among adults, while adjustment for HbA(1c) had a small effect in youths and adults. CONCLUSIONS: Lower insulin sensitivity is associated with a more atherogenic lipid profile in both youths and adults with Type 1 diabetes.

Association testing of TCF7L2 polymorphisms with type 2 diabetes in multi-ethnic youth.

AIM/HYPOTHESIS: Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been associated with type 2 diabetes in adults. However, it is not known whether TCF7L2 variation increases the risk of early onset type 2 diabetes. Using a case-control design, we examined whether the reported variants [rs12255372 (T/G) and rs7903146 (T/C)] are associated with type 2 diabetes in SEARCH for Diabetes in Youth study participants. METHODS: Variants were genotyped in 694 non-Hispanic white (NHW) youth (86 cases, mean age 15.5 years, mean BMI 34.8; and 608 controls, mean age 14.4 years, mean BMI 22.3) and 545 African-American (AA) youth (154 cases, mean age 15.9, mean BMI 37; and 391 controls, mean age 14.8, mean BMI 23.8). Logistic regression adjusted for age, sex, BMI and West African ancestry. RESULTS: The association of the risk T allele with case/control status was different in AA and NHW youth (p = 0.025). Among AA youth, each copy of the T allele (rs7903146) was associated with a 1.97-fold (1.37, 2.82) increased odds for type 2 diabetes (p < 0.0001), after adjustment for age, sex, BMI and African ancestry. No significant association was detected in NHW youth (adjusted OR, 1.14; 0.73, 1.79). CONCLUSION/INTERPRETATION: TCF7L2 variation is associated with an increased risk of early-onset type 2 diabetes among AA youth, and the association appears to be stronger in AA than NHW youth. This suggests potential different contributions of genetic and environmental factors to early-onset type 2 diabetes by race.

Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study.

AIMS/HYPOTHESIS: The ability to measure insulin sensitivity across the phenotypic spectrum of diabetes may contribute to a more accurate characterisation of diabetes type. Our goal was to develop and validate an insulin sensitivity (IS) score using the euglycaemic-hyperinsulinaemic clamp in a subset (n = 85) of 12- to 19-year-old youths with diabetes participating in the SEARCH study in Colorado, USA. METHODS: Youths with a diagnosis of type 1 (n = 60) or type 2 diabetes (n = 25) underwent a 3 h clamp to measure glucose disposal rate (GDR, mg kg⁻¹ min⁻¹). Demographic (age, sex, race), clinical (BMI, waist, Tanner stage) and metabolic characteristics (HbA1(c), lipids, blood pressure, urine albumin:creatinine) were used to estimate log(e)IS score via stepwise linear regression on a model-development set (n = 53). Estimated IS score was evaluated for reproducibility on two validation sets: youths with diabetes (n = 33) and healthy control youths (n = 22). RESULTS: The best model included waist, triacylglycerol (TG) and HbA1(c) levels (R² = 0.74). Diabetes type did not enter the model and there were no significant interactions between diabetes type and other predictors. Estimated IS score correlated well (r = 0.65, p < 0.0001; r = 0.62, p = 0.002) with GDR on the two validation sets. Based on this analysis, we propose the following formula to estimate insulin sensitivity in youths with diabetes: [Formula: see text]. CONCLUSIONS/INTERPRETATION: Insulin sensitivity can be estimated in adolescents with diabetes using routinely collected measures. This score can be applied to epidemiological studies of youths with diabetes to characterise relationships between dimensions of diabetes type.

Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study.

AIMS/HYPOTHESIS: To evaluate whether exposure to maternal gestational diabetes (GDM) is associated with adiposity and fat distribution in a multiethnic population of children. METHODS: Retrospective cohort study of 82 children exposed to maternal GDM and 379 unexposed youths 6-13 years of age with measured BMI, waist circumference, skinfold thickness, and visceral and subcutaneous abdominal fat. RESULTS: Exposure to maternal GDM was associated with higher BMI (p = 0.02), larger waist circumference (p = 0.004), more subcutaneous abdominal fat (p = 0.01) and increased subscapular to triceps skinfold thickness ratio (p = 0.01) in models adjusted for age, sex, race/ethnicity and Tanner stage. Adjustment for socioeconomic factors, birthweight and gestational age, maternal smoking during pregnancy and current diet and physical activity did not influence associations; however, adjustment for maternal pre-pregnancy BMI attenuated all associations. CONCLUSIONS/INTERPRETATION: Exposure to maternal GDM is associated with increased overall and abdominal adiposity, and a more central fat distribution pattern in 6- to 13-year-old youths from a multi-ethnic population, providing further support for the fetal overnutrition hypothesis.

Association of glycaemia with lipids in adults with type 1 diabetes: modification by dyslipidaemia medication.

AIMS/HYPOTHESIS: Hyperglycaemia and dyslipidaemia are common metabolic abnormalities in adults with type 1 diabetes and both increase cardiovascular disease (CVD) risk. The hypothesis of this study was that change in HbA(1c) over 6 years would be associated with change in fasting lipids in adults with type 1 diabetes. METHODS: The Coronary Artery Calcification in Type 1 Diabetes (CACTI) study examined 652 patients with type 1 diabetes (54% female); 559 and 543 had follow-up visits at 3 and 6 years. Baseline age (mean ± SD) was 37 ± 9 years, diabetes duration 23 ± 9 years, and HbA(1c) 8.0 ± 1.3%. Use of dyslipidaemia medication was 17%, 32%, and 46% at the three visits. Separate longitudinal mixed models were fitted to examine the relationship between change in HbA(1c) and change in fasting total cholesterol (TC), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), log triacylglycerols (TG), and non-HDL-cholesterol (non-HDL-c). Because of an interaction between dyslipidaemia medication use and association of HbA(1c) with lipids, results were stratified by dyslipidaemia medication use. RESULTS: Among patients not using dyslipidaemia medication, a higher HbA(1c) was associated with significantly worse levels of the lipids TC, LDL-c, TG and non-HDL-c (per 1% change in HbA1c, TC 0.101 mmol/l, 95% CI 0.050, 0.152; LDL-c 0.103 mmol/l, 95% CI 0.058, 0.148; TG 0.052 mmol/l, 95% CI 0.024, 0.081; and non-HDL-c 0.129 mmol/l, 95% CI 0.078, 0.180) but not HDL-c (-0.20 mmol/l, 95% CI -0.047, 0.007). The associations between HbA(1c) and any lipid outcome among those on dyslipidaemia medication were in the same direction, but attenuated compared with persons not on medication. CONCLUSIONS/INTERPRETATION: Change in HbA(1c) is significantly associated with change in fasting lipids, but dyslipidaemia medications may be required to optimise lipid and cardiovascular health.

Association of a common G6PC2 variant with fasting plasma glucose levels in non-diabetic individuals.

BACKGROUND/AIMS: Fasting plasma glucose (FPG) levels correlate with cardiovascular disease and mortality in both diabetic and non-diabetic subjects. G6PC2 encodes a pancreatic islet-specific glucose-6-phosphatase-related protein and G6pc2-null mice were reported to exhibit decreased blood glucose levels. Two recent genome-wide association studies have implicated a role for G6PC2 in regulation of FPGlevels in the general European population and reported the strongest association with the rs560887 SNP. The purpose of this study was to replicate this association in our independent epidemiological samples. METHODS: DNA samples from non-Hispanic white Americans (NHWs; n = 623), Hispanic Americans (n = 410) and black Africans (n = 787) were genotyped for rs560887 using TaqMan allelic discrimination. RESULTS: While no minor allele A of rs560887 was observed among blacks, its frequency was 33% in NHWs and 17.5% in Hispanics. The rs560887 minor allele was associated with reduced FPG levels in non-diabetic NHWs (p = 0.002 under an additive model). A similar trend of association was observed in non-diabetic Hispanics (p = 0.076 under a dominant model), which was more pronounced in normoglycemic subjects (p = 0.036). CONCLUSIONS: Our results independently confirm the robust association of G6PC2/rs560887 with FPG levels in non-diabetic NHWs. The observed evidence for association in Hispanics warrants further studies in larger samples.

Childhood growth and age at diagnosis with Type 1 diabetes in Colorado young people.

OBJECTIVE: Studies have suggested that the age at diagnosis of Type 1 diabetes (T1D) is decreasing over time. The overload hypothesis postulates that risk factors, such as accelerated growth, may be responsible for this decrease. We assessed changes in age, body mass index (BMI), weight and height at diagnosis with T1D in non-Hispanic white (NHW) and Hispanic (HISP) young people from Colorado, using data from the IDDM Registry and SEARCH Study. METHODS: In three time periods, 656 (1978-1983), 562 (1984-1988) and 712 (2002-2004) young people aged 2-17 years were newly diagnosed with T1D. Age, weight, height and presence of diabetic ketoacidosis (DKA) at diagnosis with T1D were obtained from medical records. Trends over the three time periods were assessed with regression analyses. RESULTS: Age at diagnosis decreased by 9.6 months over time (P = 0.0002). Mean BMI standard deviation score (SDS), weight SDS and height SDS increased over time (P < 0.0001), while prevalence of DKA decreased (P < 0.0001). Increasing height over time accounted for 15% (P = 0.04) of the decreasing age at diagnosis with T1D. CONCLUSIONS: Our study provides evidence that increased linear growth, but not increased BMI or weight over time, may account, at least in part, for the younger age at diagnosis of T1D in Colorado children. This finding supports the hypothesis that increasing environmental pressure resulting from changes in potentially preventable risk factors may accelerate the onset of T1D in children.

First versus repeat treatment with a lifestyle intervention program: attendance and weight loss outcomes.

OBJECTIVE: Following unblinding of the Diabetes Prevention Program (DPP) results, a 16-session lifestyle intervention program was offered to all study participants, including those who had initially been randomized to lifestyle treatment. This study compares the effects of the lifestyle program between participants who had previous exposure and those who had not. DESIGN: A 16-session behavioral intervention was conducted in groups at each of the 27 DPP sites during a transitional (bridge) period from the DPP trial to the DPP Outcomes Study (DPPOS). Session participation for this 6-month behavioral weight loss program was confirmed by originally randomized treatment groups. SUBJECTS AND MEASUREMENTS: Independently assessed weight measurements were available within a 7-month period before and after the program for 2808 ethnically diverse participants. RESULTS: Participants from the lifestyle group in the DPP were the least likely to attend a repeat offering of a 16-session behavioral weight loss program conducted in groups. Weight loss during the transitional lifestyle program was strongly related to the duration of attendance in the three groups that were participating in the program for the first time (metformin, placebo and troglitazone), but not related to amount of earlier weight loss. CONCLUSION: Individuals who were naive to the behavioral program lost a greater amount of weight and this was strongly related to their degree of participation. A second exposure to a behavioral weight loss program resulted in unsatisfactory low attendance rates and weight loss.