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Abstract Context Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking. Objective To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor. Design Multicenter, prospective study. Setting Twelve centers within the T1D Exchange Clinic Network. Patients or Participants Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index. Intervention Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days. Main Outcome Measures CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. Results A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d). Conclusion By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies. This study provides normative sensor glucose data in a healthy, nondiabetic population of children and adults.

OBJECTIVE:--The most promising β-cell replacement therapy for children with type 1 diabetes is a closed-loop artificial pancreas incorporating continuous glucose sensors and insulin pumps. The Medtronic MiniMed external physiological insulin delivery (ePID) system combines an external pump and sensor with a variable insulin infusion rate algorithm designed to emulate the physiological characteristics of the β-cell. However, delays in insulin absorption associated with the subcutaneous route of delivery inevitably lead to large postprandial glucose excursions. RESEARCH DESIGN AND METHODS--We studied the feasibility of the Medtronic ePID system in youth with type 1 diabetes and hypothesized that small manual premeal \"priming\" boluses would reduce postprandial excursions during closed-loop control. Seventeen adolescents (aged 15.9 ± 1.6 years; A1C 7.1 ± 0.8%) underwent 34 h of closed-loop control; 8 with full closed-loop (FCL) control and 9 with hybrid closed-loop (HCL) control (premeal priming bolus). RESULTS:--Mean glucose levels were 135 ± 45 mg/dl in the HCL group versus 141 ± 55 mg/dl in the FCL group (P = 0.09); daytime glucose levels averaged 149 ± 47 mg/dl in the HCL group versus 159 ± 59 mg/dl in the FCL group (P = 0.03). Peak postprandial glucose levels averaged 194 ± 47 mg/dl in the HCL group versus 226 ± 51 mg/dl in the FCL group (P = 0.04). Nighttime control was similar in both groups (111 ± 27 vs. 112 ± 28 mg/dl). CONCLUSIONS:--Closed-loop glucose control using an external sensor and insulin pump provides a means to achieve near-normal glucose concentrations in youth with type 1 diabetes during the overnight period. The addition of small manual priming bolus doses of insulin, given 15 min before meals, improves postprandial glycemic excursions.

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

The prevalence and magnitude of childhood obesity are increasing dramatically. These investigators examined the effect of the degree of obesity on the prevalence of the metabolic syndrome and the relation of the syndrome to insulin resistance and C-reactive protein and adiponectin levels in a large multiracial, multiethnic cohort of children and adolescents. The relation of the syndrome to insulin resistance and C-reactive protein and adiponectin levels. In 1988, Reaven and colleagues 1 described “the metabolic syndrome” as a link between insulin resistance and hypertension, dyslipidemia, type 2 diabetes, and other metabolic abnormalities associated with an increased risk of atherosclerotic cardiovascular disease 2 in adults. Recent studies suggest that the metabolic syndrome may originate in utero. 2 , 3 Obesity, which is the most common cause of insulin resistance in children, 4 is also associated with dyslipidemia, 5 type 2 diabetes, 6 and long-term vascular complications. 7 – 9 In a sample of adolescents in the United States who were included in the third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and . . .

The aim of this study was to examine differences between adolescents and adults in persistence of the benefits of intensive therapy 10 years after completion of the Diabetes Control and Complications Trial (DCCT). During the Epidemiology of Diabetes Interventions and Complications (EDIC) study, progression of retinopathy from DCCT closeout to EDIC year 10 was evaluated in 1,055 adults and 156 adolescents. During 10 years of follow-up, HbA(1c) (A1C) was similar between original intensive (INT) and conventional (CON) groups and between former adolescents and adults. At EDIC year 10, adults in the former INT group continued to show slower progression of diabetic retinopathy than those in the CON group (adjusted hazard reduction 56%, P < 0.0001), whereas in adolescents this beneficial effect had disappeared (32%, P = 0.13). Seventy-nine percent of observed differences in the prolonged treatment effect between adults and adolescents at year 10 were explained by differences in mean A1C during DCCT between adolescents and adults (8.9 vs. 8.1%), particularly between INT adolescents and adults (8.1 vs. 7.2%). Prior glycemic control during DCCT is vital for the persistence of the beneficial effects of INT therapy 10 years later. Lowering A1C to as close to normal as safely possible without severe hypoglycemia and starting as early as possible should be attempted for all subjects with type 1 diabetes. These results underscore the importance of maintaining A1C at target values for as long as possible because the benefits of former INT treatment wane over time if A1C levels rise.

Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood. Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of \"no-go > go\" were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct \"go\" trials; r = -0.36, 95% CI -0.53 to -0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < -0.29, 95% CIs -0.47 to -0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = -0.22, 95% CI -0.41 to -0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI -0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown. These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.

OBJECTIVE:--Type 2 diabetes in obese youth is an emerging problem. The metabolic and anthropometric predictors of change in glucose tolerance status in obese youth are unknown. RESEARCH DESIGN AND METHODS--A total of 117 obese children and adolescents were studied by performing an oral glucose tolerance test (OGTT) at baseline and after [approximately]2 years. Data from both OGTTs and changes in weight were examined to identify youth at highest risk for developing diabetes and the factors that have the strongest impact on glucose tolerance. RESULTS:--Eighty-four subjects had normal glucose tolerance (NGT) and 33 impaired glucose tolerance (IGT) at baseline. Eight subjects (all of whom had IGT at baseline) developed type 2 diabetes, whereas 15 subjects with IGT reverted to NGT. In this cohort, severe obesity, impaired glucose tolerance, and African-American background emerged as the best predictors of developing type 2 diabetes, whereas fasting glucose, insulin, and C-peptide were nonpredictive. Changes in insulin sensitivity, strongly related to weight change, had a significant impact on the 2-h glucose level on the follow-up study. CONCLUSIONS:--Severely obese children and adolescents with IGT, particularly of African-American descent, are at very high risk for developing type 2 diabetes over a short period of time. Parameters derived from an OGTT and not fasting samples can serve as predictors of changes in glucose tolerance.

A Randomized, Prospective Trial Comparing the Efficacy of Continuous Subcutaneous Insulin Infusion With Multiple Daily Injections Using Insulin Glargine Elizabeth A. Doyle (Boland) , MSN APRN, CDE , Stuart A. Weinzimer , MD , Amy T. Steffen , BS , Jo Ann H. Ahern , MSN APRN, CDE , Miranda Vincent , MSN APRN, CDE and William V. Tamborlane , MD From the Department of Pediatrics and the Children’s Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut Address correspondence and reprint requests to Elizabeth Doyle, MSN APRN, CDE, Yale Diabetes Research Program, 2 Church St. South, Suite 312, New Haven, CT 06519. E-mail: elizabeth.doyle{at}yale.edu Abstract OBJECTIVE —The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA 1c levels in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS —Thirty-two youth with type 1 diabetes (age 8–21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA 1c . HbA 1c , total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy. RESULTS —While there was no significant change in the glargine group (HbA 1c 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA 1c levels, from 8.1 to 7.2% after 16 weeks of therapy ( P < 0.02 vs. baseline and <0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P < 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group ( P < 0.01). CONCLUSIONS —Lower HbA 1c and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes. CSII, continuous subcutaneous insulin infusion DQOL-Y, Diabetes Quality of Life-Youth MDI, multiple daily injection TDD, total daily insulin dose Footnotes E.A.D.(B.), J.A.H.A., and M.V. have received consulting fees and honoraria for speaking engagements from Medtronic MiniMed and have received consulting fees from Deltec Cozmo. J.A.H.A. has also served on the advisory board for Deltec Cozmo. W.V.T. has received consulting fees, grant support, and honoraria from Medtronic MiniMed, Aventis Pharmaceuticals, and Novo Nordisk and has served on advisory boards for Medtronic MiniMed and Aventis Pharmaceuticals. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted April 15, 2004. Received January 8, 2004. DIABETES CARE

This trial assessed the efficacy and safety of liraglutide as compared with placebo, added to metformin (with or without basal insulin treatment), in children and adolescents with type 2 diabetes. The addition of liraglutide was efficacious and relatively safe in improving glycemic control over 52 weeks.

Impaired glucose tolerance is common among obese adolescents, but the changes in insulin sensitivity and secretion that lead to this prediabetic state are unknown. We investigated whether altered partitioning of myocellular and abdominal fat relates to abnormalities in glucose homoeostasis in obese adolescents with prediabetes. We studied 14 obese children with impaired glucose tolerance and 14 with normal glucose tolerance, of similar ages, sex distribution, and degree of obesity. Insulin sensitivity and secretion were assessed by the euglycaemichyperinsulinaemic clamp and the hyperglycaemic clamp. Intramyocellular lipid was assessed by proton nuclear magnetic resonance spectroscopy and abdominal fat distribution by magnetic resonance imaging. Peripheral glucose disposal was significantly lower in individuals with impaired than in those with normal glucose tolerance (mean 35·4 [SE 4·0] vs 60·6 [7·2] moles per kg lean body mass per min; p=0·023) owing to a reduction in non-oxidative glucose disposal metabolism (storage). Individuals with impaired glucose tolerance had higher intramyocellular lipid content (3·04 [0·43] vs 1·99 [0·19]%, p=0·03), lower abdominal subcutaneous fat (460 [47] vs 626 [39] cm 2, p=0·04), and slightly higher visceral fat than the controls (70 [11] vs 47 [6] cm 2, p=0·065), resulting in a higher ratio of visceral to subcutaneous fat (0·15 [0·02] vs 0·07 [0·01], p=0·002). Intramyocellular and visceral lipid contents were inversely related to the glucose disposal and non-oxidative glucose metabolism and positively related to the 2 h plasma glucose concentration. In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance.