Glycemic Variability Is Associated with Markers of Vascular Stress in Adolescents

Dasari, Paul S.; Gandomani, Benjamin S.; Teague, April M.; Pitale, Ameya; Otto, Michael; Short, Kevin R.

doi:10.1016/j.jpeds.2016.01.065

Cited by 21 publications

(21 citation statements)

References 45 publications

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“…Improved HbA 1c with an HCL system was also reported by Thabit et al, 18 who performed a study of long enough duration to obtain HbA 1c levels, and by Kovatchev et al 14 who performed a 6-month closed-loop control study in a limited number of individuals with a low baseline HbA 1c of 7.2% that was 7.0% at study end. As reported in two other closed-loop studies, 6,17 we also showed that HCL control reduced glycemic variability, which may have important implications for oxidative stress 27 and long-term diabetes-related complications. 28 Based on the data presented, the HCL system could be a transformative therapeutic option for insulin-treated patients.…”

Section: Discussionsupporting

confidence: 86%

Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes

Garg

Weinzimer

Tamborlane

et al. 2017

Diabetes Technology & Therapeutics

525

360

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Background: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated.Methods: Adolescents (n = 30, ages 14–21 years) and adults (n = 94, ages 22–75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase.Results: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%–88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%–92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P < 0.001) and from 7.3% ± 0.9% to 6.8% ± 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71–180 mg/dL) sensor glucose (SG) values increased from 60.4% ± 10.9% to 67.2% ± 8.2% (P < 0.001) in adolescents and from 68.8% ± 11.9% to 73.8% ± 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT® blood glucose values was 67.4% ± 27.7% compared to SG values of 72.0% ± 11.6% for adolescents and 74.2% ± 17.5% compared to 76.9% ± 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort.Conclusions: HCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA1c, hyperglycemia and hypoglycemia, compared to baseline. Trial Registration: identifier: NCT02463097.

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Section: Discussionsupporting

confidence: 86%

Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes

Garg

Weinzimer

Tamborlane

et al. 2017

Diabetes Technology & Therapeutics

525

360

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“…In addition, recent studies indicate that greater oxidative stress is associated with higher MAGE measured by CGM and induced glycemic fluctuations, both hyperglycemic and hypoglycemic spikes, trigger production of reactive oxygen species, proinflammatory cytokines, and epigenetic changes damaging to endothelial cells . One small study in youth with T2D (n = 12) found an association between MAGE and oxidative stress markers, supporting the proposed contributions of glycemic variability and risk for future cardiovascular disease . It has been argued that, because GA and 1,5AG can identify glycemic fluctuations before noticeable changes in HbA1c occur, they may be better than HbA1c for identifying patients who could benefit from more aggressive treatment to reduce glycemic variability.…”

Section: Discussionmentioning

confidence: 92%

Alternate glycemic markers reflect glycemic variability in continuous glucose monitoring in youth with prediabetes and type 2 diabetes

et al. 2016

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Objective To determine whether the alternate glycemic markers, fructosamine (FA), glycated albumin (GA), and 1,5-anhydroglucitol (1,5AG), predict glycemic variability captured by continuous glucose monitoring (CGM) in obese youth with prediabetes and type 2 diabetes (T2D). Study Design Youth with BMI ≥85th%ile, 10-18 years, had collection of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), FA, GA, and 1,5AG and 72 hours of CGM. Participants with HbA1c ≥5.7% were included. Relationships between glycemic markers and CGM variables were determined with Spearman correlation coefficients. Linear models were used to examine the association between alternate markers and CGM measures of glycemic variability – standard deviation (SD) and mean amplitude of glycemic excursions (MAGE) – after controlling for HbA1c. Results Total n=56; Median (25th%ile,75th%ile) age=14.3 yrs (12.5, 15.9), 32% male, 64% Hispanic, 20% black, 13% white, HbA1c=5.9% (5.8, 6.3), FA=211mmol/L (200, 226), GA=12% (11%, 12%), and 1,5AG=22mcg/ml (19,26). HbA1c correlated with average sensor glucose, AUC, SD, MAGE, and %time>140mg/dl. FA and GA correlated with average and peak sensor glucose, %time>140mg/dl and >200mg/dl, and MAGE. GA also correlated with SD and AUC180. 1,5AG correlated with peak glucose, AUC180, SD, and MAGE. After adjusting for HbA1c, all 3 markers independently predicted MAGE; FA and GA independently predicted SD. Conclusions Alternate glycemic markers predict glycemic variability as measured by CGM in youth with prediabetes and T2D. After adjusting for HbA1c, these alternate markers continued to predict components of glycemic variability detected by CGM.

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“…We measured spexin in adolescents, 13 to 21 years old, who completed two separate protocols in our laboratory, the details of which have been recently published . In the first protocol, there were 12 participants classified as healthy and normal weight (NW), 10 classified as obese with normal glucose tolerance (Ob), and 12 classified as obese with type 2 diabetes mellitus (T2DM) . From the second protocol, we used data and samples from 10 of the 11 healthy control participants, all of whom were classified as healthy and normal weight .…”

Section: Methodsmentioning

confidence: 99%

“…We made an exception for metformin, used by 9 of the 12 T2DM participants, because it is the most common treatment approach for youth with T2DM. None of the participants with T2DM used exogenous insulin …”

Section: Methodsmentioning

confidence: 99%

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Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents

et al. 2017

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Spexin is a novel peptide that has been reported to be down regulated in obese adults and children and in normoglycemic adults following glucose ingestion. Spexin may therefore have a role in metabolic regulation. The purpose of the current study was to determine the effect of obesity and type 2 diabetes (T2DM), and the effect of glucose ingestion on circulating spexin concentration in adolescents. Boys and girls (mean age 16 years old) classified as healthy normal weight (NW, n = 22), obese (Ob, n = 10), or obese with T2DM (n = 12) completed measurements of body composition, blood pressure, cardiorespiratory fitness, and blood concentrations of glucose, insulin, and lipids. The median fasting serum spexin concentration did not differ between groups (NW: 0.35; Ob: 0.38, T2DM: 0.34 ng/mL, respectively). In 10 NW participants who completed a standard oral glucose tolerance test, spexin concentration was unchanged at 30 and 120 minutes relative to the fasting baseline. Finally, spexin was not significantly correlated with any of the body composition, fitness, or blood biochemical measurements. These data do not support the proposed role of spexin as a metabolic regulator or biomarker of glucose control in adolescents.

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Glycemic Variability Is Associated with Markers of Vascular Stress in Adolescents

Cited by 21 publications

References 45 publications

Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes

Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes

Alternate glycemic markers reflect glycemic variability in continuous glucose monitoring in youth with prediabetes and type 2 diabetes

Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents

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