Dana Dabelea

Low Plasma Adiponectin Levels Predict Progression of Coronary Artery Calcification

Background—Circulating adiponectin levels are lower in men than in women and lower in advanced coronary artery disease, obesity, and type 2 but not type 1 diabetes. However, it is not known whether low adiponectin levels predict development of atherosclerosis independently of other cardiovascular risk factors. Methods and Results—Progression of coronary artery calcification (CAC) over an average of 2.6 years (range, 1.6 to 3.3) was assessed in a cohort of patients with type 1 diabetes and nondiabetic subjects 19 to 59 years of age. In this nested case-control substudy, plasma adiponectin levels were measured in 101 cases with significant CAC progression and in 205 controls. Controls were oversampled on the basis of age, gender, diabetes status, and presence of baseline CAC. In conditional logistic regression adjusted for baseline CAC volume and other significant predictors of CAC progression, adiponectin levels were inversely related to progression of CAC in diabetic (OR, 0.47; 95% CI, 0.24 to 0.94) and nondiabetic (OR, 0.15; 95% CI, 0.05 to 0.40 for a doubling in adiponectin levels) subjects. Adjustment for additional cardiovascular risk factors did not change this association. In conditional logistic regression models by quartiles of plasma adiponectin levels, the probability value for trend was statistically significant for all participants (P<0.001) and nondiabetic participants (P<0.001) and was borderline for type 1 diabetics (P=0.08). Conclusions—Low plasma adiponectin levels are associated with progression of CAC in type 1 diabetic and nondiabetic subjects independently of other cardiovascular risk factors.

Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study.

Liu LL, Lawrence JM, Davis C, Liese AD, Pettitt DJ, Pihoker C, Dabelea D, Hamman R, Waitzfelder B, Kahn HS. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth Study.

Presence of Diabetic Ketoacidosis at Diagnosis of Diabetes Mellitus in Youth: The Search for Diabetes in Youth Study

OBJECTIVE. The purpose of this work was to determine the prevalence and predictors of diabetic ketoacidosis at the diagnosis of diabetes in a large sample of youth from the US population. PATIENTS AND METHODS. The Search for Diabetes in Youth Study, a multicenter, population-based registry of diabetes with diagnosis before 20 years of age, identified 3666 patients with new onset of diabetes in the study areas in 2002–2004. Medical charts were reviewed in 2824 (77%) of the patients in a standard manner to abstract the results of laboratory tests and to ascertain diabetic ketoacidosis at the time of diagnosis. Diabetic ketoacidosis was defined by blood bicarbonate <15 mmol/L and/or venous pH < 7.25 (arterial/capillary pH < 7.30), International Classification of Diseases, Ninth Revision, code 250.1, or listing of diabetic ketoacidosis in the medical chart. RESULTS. More than half (54%) of the patients were hospitalized at diagnosis, including 93% of those with diabetic ketoacidosis and 41% without diabetic ketoacidosis. The prevalence of diabetic ketoacidosis at the diagnosis was 25.5%. The prevalence decreased with age from 37.3% in children aged 0 to 4 years to 14.7% in those aged 15 to 19 years. Diabetic ketoacidosis prevalence was significantly higher in patients with type 1 (29.4%) rather than in those with type 2 diabetes (9.7%). After adjusting for the effects of center, age, gender, race or ethnicity, diabetes type, and family history of diabetes, diabetic ketoacidosis at diagnosis was associated with lower family income, less desirable health insurance coverage, and lower parental education. CONCLUSION. At the time of diagnosis, 1 in 4 youth presents with diabetic ketoacidosis. Those with diabetic ketoacidosis were more likely to be hospitalized. Diabetic ketoacidosis was a presenting feature of <10% of youth with type 2. Young and poor children are disproportionately affected.

Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort

Aims/hypothesisThe aim of the study was to examine the association of existing diabetes (i.e. already diagnosed prior to pregnancy), gestational diabetes and glycosuria (both diagnosed and ascertained during pregnancy) with birthweight and future offspring BMI, waist circumference and fat mass (assessed by dual x-ray emission absorptiometry).MethodsA prospective pregnancy/birth cohort study was performed using data from the Avon Longitudinal Study of Parents and Children.ResultsAmong 10,591 mother–offspring pairs included in analyses with birth size, women with existing diabetes (nu2009=u200940), those diagnosed with gestational diabetes (nu2009=u200953) and those with at least two episodes of ++ glycosuria (nu2009=u2009372) had greater mean birthweight and odds for macrosomia (birthweightu2009>u20094,000xa0g) than women with none of these. Adjusted odds ratios for macrosomia were 3.56 (95%u2009CI 1.53–8.28), 5.50 (95%u2009CI 1.18–10.30) and 1.58 (95%u2009CI 1.18–2.12) for existing diabetes, gestational diabetes and glycosuria, respectively. Among 6,842 mother–offspring pairs with anthropometric measurements at age 9–11xa0years, maternal gestational diabetes and glycosuria (but not existing diabetes) were associated with increased offspring odds of general or central overweight/obesity. For gestational diabetes, these associations attenuated towards the null with adjustment for maternal prepregnancy BMI, but independent associations remained for glycosuria. The adjusted odds ratio for general overweight/obesity when comparing women with at least two episodes of ++ glycosuria with those with no evidence of diabetes or glycosuria was 1.35 (95%u2009CI 1.00–1.82) and that for central obesity (top 10% waist circumference vs all others) was 1.31 (95%u2009CI 1.00–1.72).Conclusions/interpretationThese results provide some evidence for a long-term effect of maternal glycaemia in pregnancy on offspring obesity risk.

Transition From Pediatric to Adult Care for Youth Diagnosed With Type 1 Diabetes in Adolescence

OBJECTIVE: Youth with type 1 diabetes mellitus are at risk for poor glycemic control as they age into adulthood. The aim of this study was to describe sociodemographic and clinical correlates of poor glycemic control associated with the transfer of care from pediatric to adult diabetes providers among a cohort of youth with type 1 diabetes diagnosed in adolescence. METHODS: Analyses included 185 adolescent participants with recently diagnosed type 1 diabetes in the SEARCH for Diabetes in Youth Study with pediatric care at baseline who were age ≥18 years at follow-up. Demographic and clinical factors were measured by survey and laboratory results. Survival analysis was used to estimate the age of transition. Logistic regression analysis assessed the association of demographic and clinical factors with the transition of care and poor glycemic control at follow-up. RESULTS: Fifty-seven percent of participants had transitioned to adult diabetes care providers by the follow-up visit. The estimated median age of transition of care was 20.1 years (95% confidence interval 19.8–20.4). Older age, lower baseline glycosylated hemoglobin, and less parental education were independently associated with increased odds of transition. The odds of poor glycemic control at follow-up were 2.5 times higher for participants who transitioned to adult care compared with those who remained in pediatric care. CONCLUSIONS: Transferring from pediatric to adult care, experienced by more than half the sample, was associated with an increased risk of poor glycemic control at follow-up. These findings suggest that young adults need additional support when moving to adult care.

Measurement of abdominal fat by CT compared to waist circumference and BMI in explaining the presence of coronary calcium

OBJECTIVE: To evaluate the association between standard and computed tomography (CT)-based measures of obesity and subclinical atherosclerosis, defined as coronary artery calcium (CAC) by Electron Beam Computed Tomography (EBCT).DESIGN: Cross-sectional, observational study of anthropometric and CT obesity measures and presence of CAC.SUBJECTS: Participants were 383 men and 379 women, aged 20–58u2009y and asymptomatic for coronary artery disease (CAD).MEASUREMENTS: Intra-abdominal fat (IAF) and subcutaneous fat (SQF) were measured at the level of lumbar 2–3 and 4–5 spaces, using EBCT. Body mass index (BMI) was calculated from height and weight, and minimum waist circumference and maximum hip circumference were measured. CAC was measured by EBCT.RESULTS: In both men and women, BMI, waist circumference, IAF, and SQF were significantly related to CAC. However, BMI or waist circumference explained variation in the presence of CAC as well as IAF or SQF, univariately and after adjustment for additional cardiovascular risk factors.CONCLUSION: CT-based obesity exposure measures are not superior to BMI or waist circumference in association studies of subclinical CAD.

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

Background/Objectives:Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition.Methods:Our analysis was conducted using a prebirth observational cohort of 1079 mother–offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72u2009h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age.Results:Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (β=0.58, 95% confidence interval (CI) 0.07–1.1, P<0.05) and FM (β=20.74; 95% CI 1.49–40.0; P<0.05) but no difference in FFM.Conclusions:Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

The impact of lifestyle intervention on sedentary time in individuals at high risk of diabetes

AbstractAims/hypothesisThe Diabetes Prevention Program (DPP) lifestyle intervention successfully achieved its goal of increasing leisure physical activity levels. This current study examines whether the lifestyle intervention also changed time spent being sedentary and the impact of sedentary time on diabetes development in this cohort.Methods3,232 DPP participants provided baseline data. Sedentary behaviour was assessed via an interviewer-administered questionnaire and reported as time spent watching television specifically (or combined with sitting at work). Mean change in sedentary time was examined using repeated measures ANCOVA. The relationship between sedentary time and diabetes incidence was determined using Cox proportional hazards models.ResultsDuring the DPP follow-up (mean: 3.2xa0years), sedentary time declined more in the lifestyle than the metformin or placebo participants (pu2009<u20090.05). For the lifestyle group, the decrease in reported mean television watching time (22 [95% CI 26, 17] min/day) was greater than in the metformin or placebo groups (pu2009<u20090.001). Combining all participants together, there was a significantly increased risk of developing diabetes with increased television watching (3.4% per hour spent watching television), after controlling for age, sex, treatment arm and leisure physical activity (pu2009<u20090.01), which was attenuated when time-dependent weight was added to the model.Conclusions/interpretationIn the DPP, the lifestyle intervention was effective at reducing sedentary time, which was not a primary goal. In addition, in all treatment arms, individuals with lower levels of sedentary time had a lower risk of developing diabetes. Future lifestyle intervention programmes should emphasise reducing television watching and other sedentary behaviours in addition to increasing physical activity.n Trial registration: ClinicalTrials.gov NCT00004992

TCF7L2 Polymorphism, Weight Loss and Proinsulin: Insulin Ratio in the Diabetes Prevention Program

Aims TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. Methods We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (Nu200a=u200a2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. Results We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P<0.001), higher baseline proinsulin∶insulin ratio (p<0.0001) and increased proinsulin∶insulin ratio over a median of 2.5 years of follow-up (Pu200a=u200a0.003). Effects were comparable across treatment arms. Conclusions The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin∶insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.

Determinants of adiponectin levels in young people with Type 1 diabetes

Aimsu2003 To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non‐diabetic controls, and explore potential determinants for this difference.