Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial.

INTRODUCTION: Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. METHODS: Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, β-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. RESULTS: Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. CONCLUSIONS: Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances. CLINICAL TRIALS NUMBER: NCT02204839, ClinicalTrials.gov

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

High-intensity interval exercise and glycemic control in adolescents with type one diabetes mellitus: a case study.

Current physical activity guidelines for youth with type 1 diabetes (T1D) are poorly supported by empirical evidence and the optimal dose of physical activity to improve glycemic control is unknown. This case report documents the effect of acute high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on 24-h glycemic control in three adolescents with T1D using continuous glucose monitoring. Results highlight varied individual response to exercise across the participants. In two participants both MIE and HIIE resulted in a drop in blood glucose during exercise (-38 to -42% for MIE and -21-46% in HIIE) and in one participant both MIE and HIIE resulted in increased blood glucose (+19% and + 36%, respectively). Over the 24-h period average blood glucose was lower for all participants in the HIIE condition, and for two for the MIE condition, compared to no exercise. All three participants reported HIIE to be more enjoyable than MIE These data show both HIIE and MIE have the potential to improve short-term glycemic control in youth with T1D but HIIE was more enjoyable. Future work with a larger sample size is required to explore the potential for HIIE to improve health markers in youth with T1D.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

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.)