Effects of moderate-to-vigorous intensity physical activity on overnight and next-day hypoglycemia in active adolescents with type 1 diabetes

OBJECTIVE: Physical activity (PA) provides many benefits to adolescents with type 1 diabetes; however, these individuals tend to have lower fitness and PA levels than their disease-free counterparts. The purpose of this study was to examine the acute temporal associations between moderate-to-vigorous intensity PA (MVPA) and hypoglycemia (continuous glucose monitor [CGM] reading ≤70 mg/dL). RESEARCH DESIGN AND METHODS: Nineteen participants (53% females) 14-20 years old with type 1 diabetes were recruited. Participant fitness was evaluated via indirect calorimetry using a maximal exercise test; body composition was measured using air displacement plethysmography. An accelerometer was worn continuously (3-5 days) and acceleration data used to estimate MVPA (minutes per day). Blood glucose values were simultaneously tracked using CGM. Controlling for sex, percent body fat (¿), fitness, and concurrent MVPA, the likelihood of nighttime and next-day hypoglycemia due to MVPA was examined using logistic regression. RESULTS: Participants were of average fitness (females: 43.9 mL/kg/min; males: 49.8 mL/kg/min) and adiposity (females: 26.2%; males: 19.2%); 63.2% met the U.S. federal guideline of accumulating 60 min/day of MVPA. Hypoglycemia was 31% more likely in those who accumulated 30 min/day more MVPA in the previous afternoon than those with less (95% CI 1.05-1.63; P = 0.017). CONCLUSIONS: The results suggest that participating in afternoon MVPA increases the risk of overnight and next-day hypoglycemia, independent of sex, ¿, fitness, and concurrent MVPA. While promoting PA as a healthy behavior, it is important to educate adolescents with type 1 diabetes on prevention of hypoglycemia following PA

Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes

Context: Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown. Objective: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes. Design: Double-blind, placebo-controlled clinical trial. Setting: Multi-center at eight sites of the T1D Exchange Clinic Network. Participants: A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled. Intervention: Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment. Main outcome measures: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis. Results: Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population. Conclusions: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes

Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122422/1/pedi12295_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122422/2/pedi12295.pd

A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System to Manage Children and Adolescents With Diabetes

After assessing previously published methods, we developed a practical approach to adjusting insulin doses using rtCGM trend arrows in pediatric patients with diabetes

An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.

BackgroundType 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.MethodsWe conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals.ResultsA total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed.ConclusionsTeplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.)

Targeting effector memory T cells with alefacept in new onset type 1 diabetes: 12 month results from the T1DAL study

Background Type 1 diabetes (T1D) results from autoimmune targeting of the pancreatic beta cells, likely mediated by effector memory T cells (Tems). CD2, a T cell surface protein highly expressed on Tems, is targeted by the fusion protein alefacept, depleting Tems and central memory T cells (Tcms). We hypothesized that alefacept would arrest autoimmunity and preserve residual beta cells in newly diagnosed T1D. Methods The T1DAL study is a phase II, double-blind, placebo-controlled trial that randomised T1D patients 12-35 years old within 100 days of diagnosis, 33 to alefacept (two 12-week courses of 15 mg IM per week, separated by a 12-week pause) and 16 to placebo, at 14 US sites. The primary endpoint was the change from baseline in mean 2-hour C-peptide area under the curve (AUC) at 12 months. This trial is registered with ClinicalTrials.gov, number NCT00965458. Findings The mean 2-hour C-peptide AUC at 12 months increased by 0.015 nmol/L (95% CI -0.080 to 0.110 nmol/L) in the alefacept group and decreased by 0.115 nmol/L (95% CI -0.278 to 0.047) in the placebo group, which was not significant (p=0.065). However, key secondary endpoints were met: the mean 4-hour C-peptide AUC was significantly higher (p=0.019), and daily insulin use and the rate of hypoglycemic events were significantly lower (p=0.02 and p<0.001, respectively) at 12 months in the alefacept vs. placebo groups. Safety and tolerability were comparable between groups. There was targeted depletion of Tems and Tcms, with sparing of naïve and regulatory T cells (Tregs). Interpretation At 12 months, alefacept preserved the 4-hour C-peptide AUC, lowered insulin use, and reduced hypoglycemic events, suggesting a signal of efficacy. Depletion of memory T cells with sparing of Tregs may be a useful strategy to preserve beta cell function in new-onset T1D

Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients

BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D

Effects of Moderate-to-Vigorous Intensity Physical Activity on Overnight and Next-Day Hypoglycemia in Active Adolescents With Type 1 Diabetes

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.OBJECTIVE: Physical activity (PA) provides many benefits to adolescents with type 1 diabetes; however, these individuals tend to have lower fitness and PA levels than their disease-free counterparts. The purpose of this study was to examine the acute temporal associations between moderate-to-vigorous intensity PA (MVPA) and hypoglycemia (continuous glucose monitor [CGM] reading ≤70 mg/dL). RESEARCH DESIGN AND METHODS: Nineteen participants (53% females) 14-20 years old with type 1 diabetes were recruited. Participant fitness was evaluated via indirect calorimetry using a maximal exercise test; body composition was measured using air displacement plethysmography. An accelerometer was worn continuously (3-5 days) and acceleration data used to estimate MVPA (minutes per day). Blood glucose values were simultaneously tracked using CGM. Controlling for sex, percent body fat (%BF), fitness, and concurrent MVPA, the likelihood of nighttime and next-day hypoglycemia due to MVPA was examined using logistic regression. RESULTS: Participants were of average fitness (females: 43.9 mL/kg/min; males: 49.8 mL/kg/min) and adiposity (females: 26.2%; males: 19.2%); 63.2% met the U.S. federal guideline of accumulating 60 min/day of MVPA. Hypoglycemia was 31% more likely in those who accumulated 30 min/day more MVPA in the previous afternoon than those with less (95% CI 1.05-1.63; P = 0.017). CONCLUSIONS: The results suggest that participating in afternoon MVPA increases the risk of overnight and next-day hypoglycemia, independent of sex, %BF, fitness, and concurrent MVPA. While promoting PA as a healthy behavior, it is important to educate adolescents with type 1 diabetes on prevention of hypoglycemia following PA