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BACKGOUNDThe HEALTHY primary prevention trial developed an integrated multi-component intervention program to moderate risk factors for type 2 diabetes in middle schools. The nutrition component aimed to improve the quality of foods and beverages served to students. Changes in the School Breakfast Program (SBP), National School Lunch Program (NSLP), and a la carte venues are compared to the experience of control schools.METHODSThe intervention was implemented in 21 middle schools from winter 2007 through spring 2009 (following a cohort of students from sixth through eighth grades); 21 schools acted as observed controls. The nutrition component targeted school food service environmental change. Data identifying foods and nutrients served (selected by students for consumption) were collected over a 20-day period at baseline and end of study. Analysis compared end of study values for intervention versus control schools.RESULTSIntervention schools more successfully limited dessert and snack food portion size in NSLP and a la carte and lowered fat content of foods served. Servings of high fiber grain-based foods and/or legumes were improved in SBP but not NSLP. Intervention and control schools eliminated >1% fat milk and sugar added beverages in SBP, but intervention schools were more successful in NSLP and a la carte.CONCLUSIONThe HEALTHY program demonstrated significant changes in the nutritional quality of foods and beverages served in the SBP, NSLP, and a la carte venues, as part of an effort to decrease childhood obesity and support beneficial effects in some secondary HEALTHY study outcomes.

Context: Prenatal exposures, including undernutrition, overnutrition, and parental diabetes, are recognized risk factors for future cardiometabolic disease. There are currently no data on effects of parental diabetes on disease progression or complications in youth-onset type 2 diabetes (T2D). Objective: We analyzed effects of parental diabetes history on glycemic outcomes, β-cell function, and complications in a US cohort of youth on set T2D. Methods: Participants (N =699) aged 10 to 17 years with T2D were enrolled at 15 US centers and followed for up to 12 years as part of the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) and TODAY2 follow-up studies. Information about diabetes diagnosis in biological mothers was available for 621 participants (never=301; before or during pregnancy=218; after pregnancy= 102) and in biological fathers for 519 (no diabetes=352; paternal diabetes=167). Results: Maternal, but not paternal, diabetes was associated with loss of glycemic control over time, defined as glycated hemoglobin A1c greater than or equal to 8% for more than 6 months (P=.001). Similarly, maternal, but not paternal, diabetes was associated with increased risk of glomerular hyperfiltration (P=.01) and low heart rate variability (P=.006) after 12 years of follow-up. Effects were largely independent of age, sex, race/ethnicity, and household income. Maternal diabetes during vs after pregnancy had similar effects on outcomes. Conclusion: Maternal diabetes, regardless of whether diagnosed during vs after pregnancy, is associated with worse glycemic control, glomerular hyperfiltration, and reduced heart rate variability in youth with T2D in TODAY. The strong associations of diabetes outcomes with maternal diabetes suggest a possible role for in utero programming. [ABSTRACT FROM AUTHOR]

Objective: We examined predictors of early and late loss of glycemic control in individuals with youth-onset type 2 diabetes, as well as predictors of short-term deterioration in youth from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods: Demographic, physical, and biochemical measures at baseline and 48 months, and change over time, were examined in 584 participants separated into those with loss of glycemic control (sustained HbA1c ≥ 8%) before 48 months or at 48 months or later, and those who remained in control until the end of the study (median 6.8 years). Univariate and multivariate models, and receiver operating characteristic curve analyses were performed. Results: Approximately 45% of youth remained in control at 48 months; of these, 30% subsequently lost glycemic control prior to the end of follow-up. Predictors of early loss of glycemic control included baseline HbA1c, C-peptide index, oral disposition index, proinsulin, and proinsulin to insulin ratio. Predictors of late loss included baseline measures of insulin secretion and change in HbA1c and insulin processing at 48 months. A baseline HbA1c cutoff of ≥ 6.2% was optimally predictive of loss of glycemic control at any time, while an absolute rise in HbA1c > 0.5% related to loss of glycemic control within 3 to 6 months. Conclusion: This analysis demonstrates that youth with type 2 diabetes at risk for loss of glycemic control, including impending rapid deterioration, can be identified using available clinical measures, allowing for closer monitoring of at-risk youth, and facilitating the design of research on better therapeutic options. [ABSTRACT FROM AUTHOR]

Objective: Elevated serum uric acid (SUA) is increasingly recognized as a risk factor for kidney disease in adults with diabetes, but data in youth are limited. We hypothesized that elevated SUA predicts development of elevated urinary albumin excretion (UAE) and hypertension over time in teens with type 2 diabetes (T2D).Research Design and Methods: Serum creatinine, cystatin C, SUA, and the urine albumin-to-creatinine ratio (UACR) were assessed in 539 obese youth, ages 12-17 years, with T2D duration <2 years at baseline in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and cystatin C. Hypertension was defined as systolic or diastolic blood pressure ≥130/80 mmHg and elevated UAE as UACR ≥30 mg/g. Cox proportional hazards models evaluated the relationship between SUA and outcome variables longitudinally over an average follow-up of 5.7 years, adjusting for age, sex, race/ethnicity, BMI, HbA1c, eGFR, ACE inhibitor/angiotensin receptor blocker use, and TODAY treatment group assignment.Results: At baseline, hyperuricemia (≥6.8 mg/dL) was present in 25.6% of participants, hypertension in 18.7%, and elevated UAE in 6.1%. During follow-up of up to 7 years, hypertension developed in 37.4% and UAE in 18.0%. Higher baseline SUA increased the risk of incident hypertension (hazard ratio [HR] 1.19, 95% CI 1.03-1.38, per 1 mg/dL increase in SUA) and elevated UAE (HR 1.24, 95% CI 1.03-1.48) in adjusted models.Conclusions: Hyperuricemia was common in youth with T2D. Higher baseline SUA independently increased the risk for onset of hypertension and elevated UAE. Research is needed to determine whether SUA-lowering therapies can impede development of diabetic kidney disease and hypertension in T2D youth. [ABSTRACT FROM AUTHOR]

Objective: Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function.Research Design and Methods: OGTTs (n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (△C30/△G30), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups.Results: At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) (P < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity.Conclusions: In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To characterize middle-school students from the HEALTHY study with glycemic abnormalities, specifically high-risk hemoglobin A1c (A1C) (hrA1C; A1C = 5.7-6.4%) and impaired fasting glucose (IFG; fasting plasma glucose [FPG] = 100-125 mg/dL). RESEARCH DESIGN AND METHODS--History was collected by self-report, physical measurement was collected by trained study staff, and fasting blood was drawn by trained phlebotomists and analyzed centrally. RESULTS--At baseline, among 3,980 sixth graders, 128 (3.2%) had hrA1C and 635 (16.0%) had IFG. Compared with A1C <5.7%, hrA1C was associated with non-Hispanic black race/ ethnicity, family history of diabetes, and higher measurements of BMI, waist circumference, and fasting insulin. Compared with FPG <100 mg/dL, IFG was associated with Hispanic ethnicity; increased BMI, waist circumference, and fasting insulin; higher frequency of high blood pressure; and higher mean triglycerides. Two years later, children with hrA1C persisted as hrA1C in 59.4%, and one child (0.8%) developed A1C ≥6.5%; children with IFG persisted with IFG in 46.9%, and seven children (1.1%) developed FPG ≥126 mg/dL. Those with hrA1C compared with IFG had a higher BMI in sixth grade, which persisted to eighth grade. CONCLUSIONS--In the HEALTHY study cohort, hrA1C and IFG define different groups of youth with differentially increased diabetes risk markers. IFG is approximately fivefold more common, but hrA1C is more persistent over time. Optimal screening strategies for diabetes in youth remain unresolved. [ABSTRACT FROM AUTHOR]

The article assesses the phenotypic expression of sarcoidosis among affected African-American siblings. Ocular involvement among the siblings has been found. Concordance in pulmonary function change over time is weak. There is a minimal concordance of clinical outcomes of sarcoidosis in the siblings.

We compared 3-hr OGTT model-derived measures of insulin sensitivity and β-cell function after 12 mo treatment with placebo (PLAC), metformin (MET), liraglutide plus MET (L+M), 3 mo glargine followed by 9 mo MET (G/M) and gastric banding (GB) in adults with IGT or T2D in the Restoring Insulin Secretion (RISE) Study. Modeling parameters included insulin sensitivity (OGIS), insulin secretion rate (ISR) at reference glucose 6.5 mM (ISR@6.5), total integrated ISR (tISR), glucose sensitivity (GS: slope ISR vs. glucose concentration) and rate sensitivity (RS: ISR relative to glucose rate of change). Adjusted linear mixed models compared model parameters over time within and between each study arm. Results: Baseline model parameters did not differ by treatment arm. OGIS increased in all groups except PLAC. ISRs and GS increased in L+M but decreased or were unchanged in the other treatment arms. RS only increased in the G/M and GB arms. Treatment effects differed by arm. For L+M, GS and ISRs were increased vs. all other arms. For GB, RS was increased and tISR decreased vs. PLAC and GS was increased vs. MET. In summary, L+M augments insulin secretion and increases GS, while GB increases RS. Clinically, both L+M and GB appear to improve β-cell function at 12 mo and may benefit adults with IGT or recent-onset T2D while on treatment. Disclosure: K. Utzschneider: Other Relationship; Self; Medtronic. L. El Ghormli: None. S. Sam: None. D.A. Ehrmann: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. E. Barengolts: None. T.S. Hannon: None. M. Tripputi: None. S. Edelstein: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. T. Consortium: None. Funding: American Diabetes Association (1-14-RISE-01); National Institute of Diabetes and Digestive and Kidney Diseases [ABSTRACT FROM AUTHOR]

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p<0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p <0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p<0.005), but not IIn. Following intervention, the change in OGTT-GRC did not differ significantly between youth and adults (improvement: 14.5% vs. 18.0%, worsening 21.0% vs. 17.3%, no change 64.5% vs. 64.6% respectively). Moreover, there was no impact of M or G-M treatment on the change in OGTT-GRC from randomization to M12 in youth and adults. In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape. Disclosure: S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding: American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases [ABSTRACT FROM AUTHOR]

Purpose/Objectives: The purpose of this study is to report the impact of the three-year middle school-based HEALTHY study on intervention school vending machine offerings. There were two goals for the vending machines: serve only dessert/snack foods with 200 kilocalories or less per single serving package, and eliminate 100% fruit juice and beverages with added sugar. Methods: Six schools in each of seven cities (Houston, TX, San Antonio, TX, Irvine, CA, Portland, OR, Pittsburg, PA, Philadelphia, PA, and Chapel Hill, NC) were randomized into intervention (n=21 schools) or control (n=21 schools) groups, with three intervention and three control schools per city. All items in vending machine slots were tallied twice in the fall of 2006 for baseline data and twice at the end of the study, in 2009. The percentage of total slots for each food/beverage category was calculated and compared between intervention and control schools at the end of study, using the Pearson chi-square test statistic. Results: At baseline, 15 intervention and 15 control schools had beverage and/or snack vending machines, compared with 11 intervention and 11 control schools at the end of the study. At the end of study, all of the intervention schools with beverage vending machines, but only one out of the nine control schools, met the beverage goal. The snack goal was met by all of the intervention schools and only one of the four control schools with snack vending machines. Applications to Child Nutrition Professionals: The HEALTHY study’s vending machine beverage and snack goals were successfully achieved in intervention schools, reducing access to less healthy food items outside the school meals program. Although the effect of these changes on student diet, energy balance and growth is unknown, these results suggest that healthier options for snacks can successfully be offered in school vending machines. [ABSTRACT FROM AUTHOR]