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Abstract Background Young children who are overweight are at increased risk of becoming obese and developing type 2 diabetes and cardiovascular disease later in life. Therefore, early intervention is critical. This paper describes the rationale, design, methodology, and sample characteristics of a 5-year cluster randomized controlled trial being conducted in eight elementary schools in rural North Carolina, United States. Methods/Design The first aim of the trial is to examine the effects of a two-phased intervention on weight status, adiposity, nutrition and exercise health behaviors, and self-efficacy in overweight or obese 2nd, 3 rd, and 4th grade children and their overweight or obese parents. The primary outcome in children is stabilization of BMI percentile trajectory from baseline to 18 months. The primary outcome in parents is a decrease in BMI from baseline to 18 months. Secondary outcomes for both children and parents include adiposity, nutrition and exercise health behaviors, and self-efficacy from baseline to 18 months. A secondary aim of the trial is to examine in the experimental group, the relationships between parents and children's changes in weight status, adiposity, nutrition and exercise health behaviors, and self-efficacy. An exploratory aim is to determine whether African American, Hispanic, and non-Hispanic white children and parents in the experimental group benefit differently from the intervention in weight status, adiposity, health behaviors, and self-efficacy. A total of 358 African American, non-Hispanic white, and bilingual Hispanic children with a BMI ≥ 85th percentile and 358 parents with a BMI ≥ 25 kg/m2 have been inducted over 3 1/2 years and randomized by cohort to either an experimental or a wait-listed control group. The experimental group receives a 12-week intensive intervention of nutrition and exercise education, coping skills training and exercise (Phase I), 9 months of continued monthly contact (Phase II) and then 6 months (follow-up) on their own. Safety endpoints include adverse event reporting. Intention-to-treat analysis will be applied to all data. Discussion Findings from this trial may lead to an effective intervention to assist children and parents to work together to improve nutrition and exercise patterns by making small lifestyle pattern changes. Trial registration NCT01378806.

Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 ± 2 µM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 µM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium mitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group (n = 17 subjects), plasma vitamin C (22 ± 3 µM), fasting glucose (159 ± 12 mg/dl), insulin (19 ± 7 µU/ml), and SIclamp [2.06 ± 0.29 × 10-4 dl·kg-1·min-1/(µU/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 ± 2 µM) increased to 48 ± 6 µM (P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 µM). No significant changes in fasting glucose (156 ± 11 mg/dl), insulin (14 ± 2 µU/ml), SIclamp [2.71 ± 0.46 × 10-4 dl·kg-1· min-1/(µU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

After a constant insulin infusion is initiated, determination of steady-state conditions for glucose infusion rates (GIR) typically requires >or=3 h. The glucose infusion follows a simple time-dependent rise, reaching a plateau at steady state. We hypothesized that nonlinear fitting of abbreviated data sets consisting of only the early portion of the clamp study can provide accurate estimates of steady-state GIR. Data sets from two independent laboratories were used to develop and validate this approach. Accuracy of the predicted steady-state GDR was assessed using regression analysis and Altman-Bland plots, and precision was compared by applying a calibration model. In the development data set (n = 88 glucose clamp studies), fitting the full data set with a simple monoexponential model predicted reference GDR values with good accuracy (difference between the 2 methods -0.37 mg x kg(-1) x min(-1)) and precision [root mean square error (RMSE) = 1.11], validating the modeling procedure. Fitting data from the first 180 or 120 min predicted final GDRs with comparable accuracy but with progressively reduced precision [fitGDR-180 RMSE = 1.27 (P = NS vs. fitGDR-full); fitGDR-120 RMSE = 1.56 (P < 0.001)]. Similar results were obtained with the validation data set (n = 183 glucose clamp studies), confirming the generalizability of this approach. The modeling approach also derives kinetic parameters that are not available from standard approaches to clamp data analysis. We conclude that fitting a monoexponential curve to abbreviated clamp data produces steady-state GDR values that accurately predict the GDR values obtained from the full data sets, albeit with reduced precision. This approach may help reduce the resources required for undertaking clamp studies.

Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 +/- 2 microM) levels. Thirty-two diabetic subjects with low plasma vitamin C (<40 microM) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group (n = 17 subjects), plasma vitamin C (22 +/- 3 microM), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 microU/ml), and SI(Clamp) [2.06 +/- 0.29 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 +/- 2 microM) increased to 48 +/- 6 microM (P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (>80 microM). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 microU/ml), SI(Clamp) [2.71 +/- 0.46 x 10(-4) dl x kg(-1) x min(-1)/(microU/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes.