Correlation Between the Glycemia Risk Index and Longitudinal Hemoglobin A1c in Children and Young Adults With Type 1 Diabetes.

BACKGROUND: The glycemia risk index (GRI) is a composite metric developed and used to estimate quality of glycemia in adults with diabetes who use continuous glucose monitor (CGM) devices. In a cohort of youth with type 1 diabetes (T1D), we examined the utility of the GRI for evaluating quality of glycemia between clinic visits by analyzing correlations between the GRI and longitudinal glycated hemoglobin A1c (HbA1c) measures. METHOD: Using electronic health records and CGM data, we conducted a retrospective cohort study to analyze the relationship between the GRI and longitudinal HbA1c measures in youth (T1D duration ≥1 year; ≥50% CGM wear time) receiving care from a Midwest pediatric diabetes clinic network (March 2016 to May 2022). Furthermore, we analyzed correlations between HbA1c and the GRI high and low components, which reflect time spent with high/very high and low/very low glucose, respectively. RESULTS: In this cohort of 719 youth (aged = 2.5-18.0 years [median = 13.4; interquartile range [IQR] = 5.2]; 50.5% male; 83.7% non-Hispanic White; 68.0% commercial insurance), baseline GRI scores positively correlated with HbA1c measures at baseline and 3, 6, 9, and 12 months later (r = 0.68, 0.65, 0.60, 0.57, and 0.52, respectively). At all time points, strong positive correlations existed between HbA1c and time spent in hyperglycemia. Substantially weaker, negative correlations existed between HbA1c and time spent in hypoglycemia. CONCLUSIONS: In youth with T1D, the GRI may be useful for evaluating quality of glycemia between scheduled clinic visits. Additional CGM-derived metrics are needed to quantify risk for hypoglycemia in this population.

The Glycemia Risk Index Predicts Performance of Diabetes Self-Management Habits in Youth With Type 1 Diabetes Mellitus.

BACKGROUND: The Glycemia Risk Index (GRI) was developed in adults with diabetes and is a validated metric of quality of glycemia. Little is known about the relationship between GRI and type 1 diabetes (T1D) self-management habits, a validated assessment of youths' engagement in habits associated with glycemic outcomes. METHOD: We retrospectively examined the relationship between GRI and T1D self-management habits in youth with T1D who received care from a Midwest pediatric diabetes clinic network. The GRI was calculated using seven days of continuous glucose monitor (CGM) data, and T1D self-management habits were assessed ±seven days from the GRI score. A mixed-effects Poisson regression model was used to evaluate the total number of habits youth engaged in with GRI, glycated hemoglobin A1c (HbA1c), age, race, ethnicity, and insurance type as fixed effects and participant ID as a random effect to account for multiple clinic visits per individual. RESULTS: The cohort included 1182 youth aged 2.5 to 18.0 years (mean = 13.8, SD = 3.5) comprising 50.8% male, 84.6% non-Hispanic White, and 64.8% commercial insurance users across a total of 6029 clinic visits. Glycemia Risk Index scores decreased as total number of habits performed increased, suggesting youth who performed more self-management habits achieved a higher quality of glycemia. CONCLUSIONS: In youth using CGMs, GRI may serve as an easily obtainable metric to help identify youth with above target glycemia, and engagement/disengagement in the T1D self-management habits may inform clinicians with suitable interventions for improving glycemic outcomes.

Effects of methylphenidate on impulsive choice and delay aversion in Lewis rats.

Attention-deficit/hyperactivity disorder (ADHD), a common behavioral disorder in children and young adults, is characterized by symptoms of impulsivity, inattention, and hyperactivity. The purpose of this study was to evaluate the Lewis rat strain as a model of ADHD by testing their impulsive choices. Lewis rats were compared to their source strain, the Wistar rat, on an impulsive choice task. Rats completed the tasks on and off methylphenidate, a commonly prescribed medication for ADHD. Off methylphenidate, Lewis rats made more impulsive choices than Wistar rats. Analyses of acquisition of choice behavior suggested that both strains were able to discriminate reward sizes, but Lewis rats still chose the smaller-sooner option more than the larger-later (LL) option when the delays to reward were the same. This may be due to an aversion to the LL lever, which was associated with the longest delays to reward. Higher doses of methylphenidate increased LL choices in Lewis rats but decreased LL choices in Wistar rats. Altogether, these results suggest Lewis rats may be a viable model for ADHD in individuals whose symptoms are characterized by impulsive choices.

Effects of the estrous cycle on impulsive choice and interval timing in female rats.

Research in humans and animals shows differences in impulsive choice, which is a failure to wait for larger, delayed rewards, when comparing males and females. It is possible that fluctuations in sex hormones (estradiol and progesterone) across the reproductive cycle contribute to sex differences in impulsive choice. The current study delivered an impulsive choice task with peak interval trials to female rats while estrous cycles, the rodent reproductive cycle, were tracked over the course of the task. Female rats were more sensitive to changes in delay in the proestrus phase of the estrous cycle and made more larger-later choices when in estrus, particularly when the delay to the smaller reward was short. Estradiol increases dramatically during proestrus while progesterone peaks during estrus, suggesting that estradiol and progesterone may affect impulsive choice through mechanisms such as delay discounting, delay aversion, and/or timing processes. Analyses of timing of the choice task delays showed inconsistent effects of the estrous cycle across delays, suggesting that reward-timing interactions may have complicated how hormone fluctuations affected interval timing. Further research is needed to determine the mechanism underlying increased larger-later choices during the estrus phase, increased delay sensitivity during the proestrus phase, and variability in interval timing across delays and estrous cycle stages.

Generalizability of time-based interventions: Effects of choice procedure and smaller-sooner delay.

Interventions exposing rats to delayed-reward contingencies attenuate suboptimal impulsive choices, a preference for a smaller-sooner (SS) over a larger-later (LL) reward. Interventions may potentially improve delay-tolerance, timing of delays, and/or discrimination of reward magnitudes. Generalization from the intervention to impulsive choice under different procedures can provide insights into the processes that underlie the intervention effects. Experiment 1 tested intervention effects on systematic-delay (SYS) and adjusting-delay (ADJ) procedures, predicting that intervention effects would be more effective on the SYS procedure with predictable delays. The ADJ procedure did not benefit significantly from intervention, but the SYS procedure, unexpectedly, showed greater impulsive choices following intervention. Experiment 2 tested whether short (5 s) SS intervention delays may have promoted greater impulsivity in the SYS impulsive choice procedure in Experiment 1. Short SS delays in choice and intervention procedures increased impulsive choices in comparison to longer (10 s) delays. Incongruent SS delays in the intervention/choice procedures resulted in negative intervention effects. The results suggest that short SS delays are detrimental to self-control and that specific temporal information generalizes from the intervention to the SYS choice task, but not the ADJ choice task.

Hazard function effects on promoting self-control in variable interval time-based interventions in rats.

The present experiments investigated properties of time-based interventions used to increase self-control. Rats received impulsive-choice assessments before and after interventions that consisted of different distributions of delays to reinforcement. In Experiment 1, rats received an intervention with an increasing hazard function where delays were more evenly distributed, a decreasing hazard function where delays were mostly short, or a constant hazard function where delays were exponentially distributed. Surprisingly, rats that received the decreasing hazard function made the most self-controlled choices. Response rates during intervention trials showed that rats anticipated reinforcement based on the shape of the distributions they received. In Experiment 2, rats received an intervention with a decreasing hazard function with a steep slope or a shallow slope. Both time-based interventions increased self-control and produced similar response-rate patterns, indicating that the slope of the decreasing hazard function may not play a strong role in intervention efficacy. While this research aligns with previous literature showing that time-based interventions improved self-control, exposure to short delays produced the biggest improvements. Ultimately, exposure to short delays may increase the subjective value of the larger-later choice while occasional long delays may promote the ability to wait, which may have important implications for translational applications.

A time-based intervention to treat impulsivity in male and female rats.

Time-based interventions have emerged as promising treatments for disorders associated with impulsivity. These interventions can be implemented to test their efficacy in preventing or treating impulsive choice in animal models of diseases related to impulsivity such as drug abuse. Impulsive choice is typically defined as choosing a smaller-sooner (SS) reward over a larger-later (LL) reward when the LL is relatively more optimal. Previous research has shown that these interventions promote LL choices in males and females, but sex differences have not been assessed. Because sex differences can complicate the application of therapies, it is critical to compare the effects of the intervention in males and females. The intervention group received exposure to 10-s and 30-s interval schedules, and the control rats received no delay to reward. Different impulsive choice tasks were used to assess the intervention efficacy across the two experiments. Following the intervention, reductions in impulsive choice were found in male and female rats, but the degree of improvement was inconsistent across sex and task. Bayesian analyses that combined the results revealed robust evidence of an overall intervention effect with the intervention group showing greater self-control, but there was no evidence for the intervention affecting males and females differently. Taken together, these results suggest that time-based interventions are effective tools to treat impulsivity in both males and females and offer promising translational capability to humans.

Cognitive and behavioral training interventions to promote self-control.

This review article discusses various cognitive and behavioral interventions that have been developed with the goal of promoting self-controlled responding. Self-control can exert a significant impact on human health and impulsive behaviors are associated with a wide range of diseases and disorders, leading to the suggestion that impulsivity is a trans-disease process. The self-control interventions include effort exposure, reward discrimination, reward bundling, interval schedules of reinforcement, impulse control training, and mindfulness training. Most of the interventions have been consistently shown to increase self-control, except for mindfulness training. Some of the successful interventions are long-lasting, whereas others may be transient. Most interventions are domain-specific, targeting specific cognitive and behavioral processes that relate to self-control rather than targeting overall self-control. For example, effort exposure appears to primarily increase effort tolerance, which in turn can improve self-control. Similarly, interval schedules primarily target interval timing, which promotes self-controlled responses. A diagram outlining a proposed set of intervention effects on self-control is introduced to motivate further research in this area. The diagram suggests that the individual target processes of the interventions may potentially summate to produce general self-control, or perhaps even produce synergistic effects. In addition, it is suggested that developing a self-control profile may be advantageous for aligning specific interventions to mitigate specific deficits. Overall, the results indicate that interventions are a promising avenue for promoting self-control and may help to contribute to changing health outcomes associated with a wide variety of diseases and disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).