Continuous Glucose Monitoring in Older Adults: What We Know and What We Have Yet to Learn.

OBJECTIVE: To assess the growing use of continuous glucose monitoring (CGM) systems by older adults and explore additional areas integration that could benefit adults with frailty. BACKGROUND: The use of CGM devices has expanded rapidly in the last decade. This has been supported by substantial data showing significant benefit in glycemic metrics: hemoglobin A1c improvements, less hypoglycemia, and improved quality of life. However, sub-populations, such as older persons, exist where available data are limited. Furthermore, frail older adults represent a heterogeneous population with their own unique challenges to the management of diabetes. This group has some of the poorest outcomes related to the sequela of diabetes. For example, hypoglycemia resulting in significant morbidity and mortality is more frequent in older person with diabetes than in younger persons with diabetes. METHOD: We present a concise literature review on CGM use in the older adult as well as expand upon glycemic and nonglycemic benefits of CGM for patients, caregivers, and providers. Retrospective analysis of inpatient glycemic data of 16,935 older adults with Type 2 diabetes mellitus at Atrium Health Wake Forest Baptist indicated those with fraility managed with insulin or sulfonylurea had the highest rates of delirium (4.8%), hypoglycemia (3.5%), cardiovascular complications (20.2%) and ED visits/hospitalizatoins (49%). In addition, we address special consideration of specific situations including inpatient, palliative and long term care settings. CONCLUSION: This review article summarizes the available data for CGM use in older adults, discusses the benefits and obstacles with CGM use in this population, and identifies areas of future research needed for improved delivery of care to older persons with diabetes.

Neural correlates of automatic emotion regulation and their association with suicidal ideation in adolescents during the first 90-days of residential care.

BACKGROUND: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI. METHODS: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. Daily reports of SI were collected during the participants' first 90-days in residential care. Participants were presented with a task-fMRI measure of emotion regulation - the Affective Number Stroop task shortly after recruitment. Participants were divided into two groups matched for age, sex and IQ based on whether they demonstrated SI. RESULTS: Participants who demonstrated SI showed increased recruitment of regions including dorsomedial prefrontal cortex/supplemental motor area and parietal cortex during task (congruent and incongruent) relative to view trials in the context of emotional relative to neutral distracters. CONCLUSIONS: Participants with SI showed increased recruitment of regions implicated in executive control during the performance of a task indexing automatic emotion regulation. Such data might suggest a relative inefficiency in the recruitment of these regions in individuals with SI.

Primary Adrenal Insufficiency due to Cryptococcus With Persistent Adrenal Enlargement and Insufficiency.

Background/Objective: Infiltrative fungal infections are an unusual cause of primary adrenal insufficiency (AI). Our objective is to present a long-term follow-up of a patient with AI due to cryptococcal adrenalitis. Case Report: A 47-year-old woman presented in January 2004, with 50-lb weight loss, nausea, emesis, and headache with diplopia. During the 6 months prior to her presentation the patient had multiple admissions for evaluation of recurrent nausea and emesis. Prior to the most recent of these admissions, the patient developed a headache; evaluation of her cerebrospinal fluid revealed the presence of Cryptococcus, and she was treated with a 2-week course of amphotericin B. Physical examination demonstrated a temperature of 101.1 °F, heart rate of 110 bpm, and blood pressure of 94/65 mm Hg. She appeared ill and was underweight with dry mucous membranes and photophobia. Laboratory tests revealed random cortisol of 0.5 µg per dL. CT imaging showed bilateral adrenal gland enlargement and fine needle aspiration of the adrenal gland revealed encapsulated budding yeast. Stress dose intravenous glucocorticoids were administered and switched to oral hydrocortisone and fludrocortisone because the patient clinically improved with a second course of amphotericin B. Further evaluation in 2017 revealed persistently enlarged adrenal glands, positive cryptococcus antigen, and low IgG levels. Discussion: Our literature review noted few publications of AI caused by disseminated cryptococcus with no long-term follow-up of these cases beyond a 1- to 4-year time frame. Conclusion: Patients with AI due to disseminated fungal infection need long-term follow-up to assess for resolution of adrenal enlargement and evaluation of immunocompromised status.

Precision nephrotoxicity testing using 3D in vitro models.

Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.

Thyroglobulin Cutoff Values for Detecting Excellent Response to Therapy in Patients With Differentiated Thyroid Cancer.

Context: Serum thyroglobulin (Tg) is a biochemical marker for detecting persistent or recurrent differentiated thyroid carcinoma (DTC) post-thyroidectomy. Tg can indicate DTC before structural disease (SD) is visible with imaging procedures. Objective: This work aimed to evaluate the clinical performance of the Elecsys® Tg II assay at a Tg cutoff of 0.2 ng/mL for ruling out SD in adults with DTC after total/near-total thyroidectomy, with or without radioiodine ablation (RAI). Methods: Patients were enrolled into 2 cohorts: longitudinal (Tg assessed every 6 months over 2 years under thyroid-stimulating hormone [TSH] suppression therapy following thyroidectomy with or without RAI) and cross-sectional with confirmed SD (Tg assessed once >12 weeks after thyroidectomy). Analyses were performed for both cohorts combined and in the longitudinal cohort. Results: The study included 530 clinically evaluable samples, the majority (n = 424 samples) from patients who had not received RAI treatment. Following correction for SD prevalence (4.97% in the longitudinal cohort), an Elecsys Tg II cutoff of 0.2 ng/mL ruled out SD with a negative predictive value of 99.9% (95% CI, 99.5%-100%). The assay had excellent sensitivity (98.5%-100%) and acceptable specificity (53.4%-53.5%) for detecting SD (Tg ≥ 0.2 ng/mL) for both cohorts combined and in the longitudinal cohort, with similar findings in RAI-treated and non-RAI-treated subgroups. Conclusion: In this cohort of DTC patients post-thyroidectomy, a Tg cutoff of 0.2 ng/mL was highly effective for ruling out the presence of SD under TSH-suppressed conditions, including in patients who had not received RAI treatment.

Family history of substance use disorder and parental impulsivity are differentially associated with neural responses during risky decision-making.

Background: Risky decision-making is associated with the development of substance use behaviors during adolescence. Although prior work has investigated risky decision-making in adolescents at familial high risk for developing substance use disorders (SUDs), little research has controlled for the presence of co-morbid externalizing disorders (EDs). Additionally, few studies have investigated the role of parental impulsivity in offspring neurobiology associated with risky decision-making. Methods: One-hundred twenty-five children (28 healthy controls, 47 psychiatric controls with EDs without a familial history of SUD, and 50 high-risk children with co-morbid EDs with a familial history of SUD) participated in the Balloon Analog Risk Task while undergoing functional magnetic resonance imaging. Impulsivity for parents and children was measured using the UPPS-P Impulsive Behavior Scale. Results: We found that individuals in the psychiatric control group showed greater activation, as chances of balloon explosion increased, while making choices, relative to the healthy control and high-risk groups in the rostral anterior cingulate cortex (rACC) and lateral orbitofrontal cortex (lOFC). We also found a positive association between greater activation and parental impulsivity in these regions. However, within rACC, this relationship was moderated by group, such that there was a positive relationship between activation and parental impulsivity in the HC group, but an inverse relationship in the HR group. Conclusions: These findings suggest that there are key differences in the neurobiology underlying risky decision-making in individuals with EDs with and without a familial history of SUD. The current findings build on existing models of neurobiological factors influencing addiction risk by integrating parental factors. This work paves the way for more precise risk models in which to test preventive interventions.

A Consensus Statement for Continuous Glucose Monitoring Metrics for Inpatient Clinical Trials.

Diabetes Technology Society organized an expert consensus panel to develop metrics for research in the use of continuous glucose monitors (CGMs) in a hospital setting. The experts met virtually in small groups both before and after an April 13, 2023 virtual meeting of the entire panel. The goal of the panel was to develop consensus definitions in anticipation of greater use of CGMs in hospital settings in the future. Establishment of consensus definitions of inpatient analytical metrics will be easier to compare outcomes between studies. Panelists defined terms related to 10 dimensions of measurements related to the use of CGMs including (1) hospital hypoglycemia, (2) hospital hyperglycemia, (3) hospital time in range, (4) hospital glycemic variability, (5) hospital glycemia risk index, (6) accuracy of CGM devices and reference methods for CGMs in the hospital, (7) meaningful time blocks for hospital glycemic goals, (8) hospital CGM data sufficiency, (9) using CGM data for insulin dosing, and (10) miscellaneous factors. The panelists voted on 51 proposed recommendations. Based on the panel vote, 51 recommendations were classified as either strong (43) or mild (8). Additional research is needed on CGM performance in the hospital. This consensus report is intended to support that type of research intended to improve outcomes for hospitalized people with diabetes.

Latent profiles of substance use, early life stress, and attention/externalizing problems and their association with neural correlates of reinforcement learning in adolescents.

BACKGROUND: Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other. METHODS: In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13-18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations. RESULTS: In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons). CONCLUSIONS: Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.

Feasibility of intraoperative continuous glucose monitoring: An observational study in general surgery patients.

BACKGROUND: Perioperative hyperglycemia is associated with adverse outcomes in surgical patients, and major societies recommend intraoperative monitoring and treatment targeting glucose <180-200 mg/dL. However, compliance with these recommendations is poor, in part due to fear of unrecognized hypoglycemia. Continuous Glucose Monitors (CGMs) measure interstitial glucose with a subcutaneous electrode and can display the results on a receiver or smartphone. Historically CGMs have not been utilized for surgical patients. We investigated the use of CGM in the perioperative setting compared to current standard practices. METHOD: This study evaluated the use of Abbott Freestyle Libre 2.0 and/or Dexcom G6 CGMs in a prospective cohort of 94 participants with diabetes mellitus undergoing surgery of ≥3 h duration. CGMs were placed preoperatively and compared to point of care (POC) BG checks obtained by capillary samples analyzed with a NOVA glucometer. Frequency of intraoperative blood glucose measurement was at the discretion of the anesthesia care team, with a recommendation of once per hour targeting BG of 140-180 mg/dL. Of those consented, 18 were excluded due to lost sensor data, surgery cancellation, or rescheduling to a satellite campus resulting in 76 enrolled subjects. There were zero occurrences of failure with sensor application. Paired POC BG and contemporaneous CGM readings were compared with Pearson product-moment correlation coefficients, and Bland-Altman plots. RESULTS: Data for use of CGM in perioperative period was analyzed for 50 participants with Freestyle Libre 2.0, 20 participants with Dexcom G6, and 6 participants with both devices worn simultaneously. Lost sensor data occurred in 3 participants (15%) wearing Dexcom G6, 10 participants wearing Freestyle Libre 2.0 (20%) and 2 of the participants wearing both devices simultaneously. The overall agreement of the two CGM's utilized had a Pearson correlation coefficient of 0.731 in combined groups with 0.573 in Dexcom arm evaluating 84 matched pairs and 0.771 in Libre arm with 239 matched pairs. Modified Bland-Altman plot of the difference of CGM and POC BG indicated for the overall dataset a bias of -18.27 (SD 32.10). CONCLUSIONS: Both Dexcom G6 and Freestyle Libre 2.0 CGMs were able to be utilized and functioned well if no sensor error occurred at time of initial warmup. CGM provided more glycemic data and further characterized glycemic trends more than individual BG readings. Required time of CGM warm up was a barrier for intraoperative use as well as unexplained sensor failure. CGMs had a fixed warm of time, 1 h for Libre 2.0 and 2 h for Dexcom G6 CGM, before glycemic data obtainable. Sensor application issues did not occur. It is anticipated that this technology could be used to improve glycemic control in the perioperative setting. Additional studies are needed to evaluate use intraoperatively and assess further if any interference from electrocautery or grounding devices may contribute to initial sensor failure. It may be beneficial in future studies to place CGM during preoperative clinic evaluation the week prior to surgery. Use of CGMs in these settings is feasible and warrants further evaluation of this technology on perioperative glycemic management.

Efficacy of Control-IQ Technology in a General Endocrine Clinic.

OBJECTIVE: Recent advances in technology have allowed for the expanded use of hybrid closed-loop insulin pump therapy and automated insulin delivery systems for the management of diabetes mellitus. We assessed the outcomes of introducing Tandem t:slim X2 with the Control-IQ technology in a general endocrine clinic. METHODS: Data from 66 adults with type 1 (n = 61) and type 2 (n = 5) diabetes mellitus were aggregated for analysis. Patients were either transitioned from traditional insulin pump therapy or multiple daily injection therapy to Tandem t:slim X2 with the Control-IQ technology from January 2020 to June 2021. The assessed clinical end points included changes in time below range, time above range, and time in target range. Changes in hemoglobin A1C before and after Control-IQ technology implementation were noted. The primary outcome was a change in time in target range with the Control-IQ technology. RESULTS: There was a significant increase in time in target range when comparing pre- and post-Control-IQ technology (49.5% vs 63.3%, P < .0003) values. There was a reduction in time above range (46.8% vs 34.9%, P < .0013), a decrease in time below range (4.0% vs 1.7%, P = .017), and a decrease in hemoglobin A1C after transitioning to the Control-IQ technology (7.7% [61 mmol/mol] vs 7.1% [54 mmol/mol], P < .017). The patient dropout rate was low (7%). CONCLUSION: The Control-IQ technology system was effective in reducing hyperglycemia while increasing time in target range and decreasing hypoglycemia. This technology is a useful and effective addition to the growing number of automated insulin delivery systems. The clinical outcomes mirror the results found in the key adult pivotal trials.

Evaluating instrumental learning and striatal-cortical functional connectivity in adolescent alcohol and cannabis use.

Adolescence is a vulnerable time for the acquisition of substance use disorders, potentially relating to ongoing development of neural circuits supporting instrumental learning. Striatal-cortical circuits undergo dynamic changes during instrumental learning and are implicated in contemporary addiction theory. Human studies have not yet investigated these dynamic changes in relation to adolescent substance use. Here, functional magnetic resonance imaging was used while 135 adolescents without (AUD-CUDLow ) and with significant alcohol (AUDHigh ) or cannabis use disorder symptoms (CUDHigh ) performed an instrumental learning task. We assessed how cumulative experience with instrumental cues altered cue selection preferences and functional connectivity strength between reward-sensitive striatal and cortical regions. Adolescents in AUDHigh and CUDHigh groups were slower in learning to select optimal instrumental cues relative to AUD-CUDLow adolescents. The relatively fast learning observed for AUD-CUDLow adolescents coincided with stronger functional connectivity between striatal and frontoparietal regions during early relative to later periods of task experience, whereas the slower learning for the CUDHigh group coincided with the opposite pattern. The AUDHigh group not only exhibited slower learning but also produced more instrumental choice errors relative to AUD-CUDLow adolescents. For the AUDHigh group, Bayesian analyses evidenced moderate support for no experience-related changes in striatal-frontoparietal connectivity strength during the task. Findings suggest that adolescent cannabis use is related to slowed instrumental learning and delays in peak functional connectivity strength between the striatal-frontoparietal regions that support this learning, whereas adolescent alcohol use may be more closely linked to broader impairments in instrumental learning and a general depression of the neural circuits supporting it.

Reliability of Inpatient CGM: Comparison to Standard of Care.

BACKGROUND: Optimal inpatient glycemic management targets a blood glucose (BG) of 140-180 mg/dL and is an important safety measure for hospitalized patients with hyperglycemia. Traditional barriers to appropriate insulin administration include incorrect timing of prandial insulin administration, failure to administer basal insulin to persons with insulin deficiency/type 1 diabetes mellitus (DM), and inaccurate insulin dosing or timing resulting in hypoglycemia. Given the ongoing rapid assimilation of technology to manage our patients with DM, we investigated the use of continuous glucose monitoring (CGM) in the inpatient setting as a potential solution to traditional barriers to optimal hyperglycemia management for inpatient care. In this study, we evaluated the efficacy of use of inpatient CGM for insulin dosing in comparison with current standard of care and whether CGM could aid in minimizing hypoglycemic events. METHODS: This study evaluated the use of Abbott professional (blinded) Freestyle Libre CGMs in participants treated with basal bolus insulin administered with subcutaneous insulin (basal bolus therapy [BBT]: n = 20) or on intravenous insulin (IVI) infusions (n =16) compared with standard point of care (POC) BG measurements. All participants on IVI were admitted with a diagnosis of diabetic ketoacidosis (DKA). The CGM data was not available in real time. Sensors were removed at the time of discharge and data uploaded to Libre View. Continuous BG data were aggregated for each subject and matched to POC BG or lab chemistry values within five minutes. The POC BG results were assessed for comparability (CGM vs standard BG testing). Data were further analyzed for clinical decision-making for correction insulin. RESULTS: The overall mean absolute relative difference including both IVI and BBT groups was 22.3% (SD, 9.0), with a median of 20.0%. By group, the IVI arm mean was 19.6% (SD, 9.4), with a median of 16.0%; for BBT, the arm mean was 24.6% (SD, 8.1), with a median 23.4%. Using the Wilcoxon two-sample test, the means were not different (P = .10), whereas the medians were (P = .015). The CGM consistently reported lower glucose values than POC BG in the majority of paired values (BBT arm mean difference = 44.8 mg/dL, IVI mean difference = 19.7 mg/dL). Glucose results were in agreement for the group 83% of the time with Bland-Altman Plot of Difference versus the mean of all glucometric data. Analysis of correction dose insulin using either CGM or POC BG values resulted in a negligible difference in calculated insulin dose recommended in those receiving subcutaneous insulin. Corrective doses were based on weight and insulin sensitivity (type 1 vs type 2 DM). Participants initially on IVI were included in a data set of BBT once IVI therapy ceased and basal bolus insulin regimen was started. The data of all basal bolus therapy participants with 1142 paired values of CGM versus POC glucose were used. The dosing difference was less for CGM than POC BG in the majority of paired values, and there was an absolute difference in dose of insulin of only 1.34 units. In the IVI group with 300 paired values of CGM versus POC glucose, there was an absolute difference in dose of insulin of only 0.74 units. About a third of the patients studied in the BBT arm experienced a hypoglycemic event with POC BG <70 mg/dL. If used in real time, CGM would have identified a hypoglycemic event for our patients on average 3 hours and 34 minutes before it was detected by standard POC BG. Two participants incurred severe nocturnal hypoglycemia during the study with POC BG <54 mg/dL with hypoglycemia detected on CGM up to 3 hours and 42 minutes before POC testing. CONCLUSIONS: These results suggest that the use of inpatient CGM arrives at similar correction insulin dosing. The routine use of CGM for inpatients would consistently underestimate the BG compared with POC BG and could aid in minimizing and predicting hypoglycemia in the hospital setting. Our data support that the model of adoption of real-time inpatient CGM technology is anticipated to have significant impact in the clinical setting in efforts to maintain adequate glycemic control targeting BG 140-180 mg/dL while minimizing the frequency of hypoglycemic events.

Dysfunction in differential reward-punishment responsiveness in conduct disorder relates to severity of callous-unemotional traits but not irritability.

BACKGROUND: Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD. METHODS: The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment. RESULTS: Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices. CONCLUSIONS: The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Editorial: The Epidemiology and Cognitive Characteristics of Attention-Deficit/Hyperactivity Disorder Depend on How Strictly the Disorder Is Defined.

In this month's issue of the Journal, Cordova et al.1 advance knowledge in our field by leveraging the Adolescent Brain Cognitive Development (ABCD) Study dataset to characterize the prevalence and comorbidities of attention-deficit/hyperactivity disorder (ADHD) in a large community sample. The ABCD dataset2 is useful because it is one of the largest samples of its kind (N = 11,878) and includes data from multiple measures and from multiple informants. This allows for sophisticated latent variable approaches to define ADHD from both a categorical and a dimensional perspective. Latent variables are variables that are not directly observed but are detected via measurement of other directly observed variables and statistical modeling.3.

Telehealth Technologies and Their Benefits to People With Diabetes.

This article reviews the current diabetes technology landscape and how recent advancements are being used to help overcome barriers in the management of diabetes. The authors offer case examples of how digital tools and platforms can facilitate diabetes care via telehealth and remote patient monitoring for individuals in special populations. They also provide tips to ensure success in implementing diabetes technology to provide the best possible care for people with diabetes in outpatient settings.

Real-World Efficacy of the Hybrid Closed-Loop System.

BACKGROUND: Hybrid closed-loop (HCL) insulin pump therapy (Medtronic 670G) is an emerging technology that is growing in use worldwide. Initial clinical trials demonstrated the effectiveness of HCL in reducing hypoglycemia and improving glucose control; however, these subjects were intensely monitored and supervised. There has been concern regarding the ability of patients to remain in auto mode. We aimed to assess HCL when used in a typical outpatient endocrine clinic. METHODS: We initially analyzed data from 80 individuals with type 1 diabetes managed in an endocrine clinic by a single certified diabetes educator (CDE). We then included our other providers and had 230 subjects by the end of the study. Patients were either transitioned from traditional insulin pump or multiple daily insulin injection therapy (MDI) to HCL. Patients initiated to HCL pump therapy from July 2017 through February 2020 were studied. Endpoints of change in time in hypoglycemic/hyperglycemic range and time in target range were analyzed. The primary outcome was a change in percent time in the target range during manual mode compared with auto mode. RESULTS: There was an 18.2% increase in average time in target range when comparing manual mode to auto mode (59.3% vs 70.1%, P < .0001). Average time in hyperglycemic range was significantly reduced by 26.7% (39.0% vs 28.6%, P < .0001) but without increasing average time in hypoglycemic range (1.7% vs 1.3%, P = 0.95). CONCLUSIONS: HCL was effective in reducing hyperglycemia and increasing time in the target range but did not increase hypoglycemia. These data suggest HCL will improve the metrics of glucose control.

Different forms of childhood maltreatment have different impacts on the neural systems involved in the representation of reinforcement value.

BACKGROUND: The current study aimed to address two gaps in the literature on child maltreatment, reinforcement processing and psychopathology. First, the extent to which compromised reinforcement processing might be particularly associated with either neglect or abuse. Second, the extent to which maltreatment-related compromised reinforcement processing might be associated with particular symptom sets (depression, conduct problems, anxiety) or symptomatology more generally. METHODS: A sample of adolescents (N = 142) aged between 14 and 18 years with varying levels of prior maltreatment participated in this fMRI study. They were scanned while performing a passive avoidance learning task, where the participant learns to respond to stimuli that engender reward and avoid responding to stimuli that engender punishment. Maltreatment (abuse and neglect) levels were assessed with the Childhood Trauma Questionnaire (CTQ). RESULTS: We found that: (i) level of neglect, but not abuse, was negatively associated with differential BOLD responses to reward-punishment within the striatum and medial frontal cortex; and (ii) differential reward-punishment responses within these neglect-associated regions were particularly negatively associated with level of conduct problems. CONCLUSION: Our findings demonstrate the adverse neurodevelopmental impact of childhood maltreatment, particularly neglect, on reinforcement processing. Moreover, they suggest a neurodevelopmental route by which neglect might increase the risk for conduct problems.

Altered amygdala-cortical connectivity in individuals with Cannabis use disorder.

BACKGROUND: Cannabis is one of the most commonly used substances in the United States. Prior literature using task-based functional magnetic resonance imaging (fMRI) has identified that individuals with Cannabis use disorder (CUD) show impairments in emotion processing circuitry. However, whether the functional networks involving these regions are also altered in CUD remains poorly understood. AIMS: Investigate changes in resting-state functional connectivity (rsFC) in regions related to emotional processing in CUD. METHODS: Sixty-two participants completed resting-state fMRI, including 21 with CUD, 20 with histories of illicit substance use but no current CUD diagnosis, and 21 with no history of illicit substance use. Whole-brain seed-based connectivity analyses were performed and one-way analyses of covariance (ANCOVAs) were conducted to detect group differences in the bilateral amygdalae, hippocampi, and the anterior and posterior cingulate cortices. RESULTS: The CUD group exhibited significant reductions in rsFC between the amygdala and the cuneus, paracentral lobule, and supplementary motor area, and between the cingulate cortices and the occipital and temporal lobes. There were no significant group differences in hippocampal functional connectivity. In addition, CUD symptom counts based on the Structured Clinical Interview for DSM-5 (SCID) and the Cannabis Use Disorders Identification Test (CUDIT) significantly correlated with multiple connectivity metrics. CONCLUSION: These data expand on emerging literature indicating that CUD is associated with dysfunction in the neural circuits underlying emotion processing. Dysfunction in emotion processing circuits may play a role in the behavioral impairments seen in emotion processing tasks in individuals with CUD, and the severity of CUD symptoms appears to be directly related to the degree of dysfunction in these circuits.

Oxytocin, PTSD, and sexual abuse are associated with attention network intrinsic functional connectivity.

Childhood maltreatment is linked to Posttraumatic Stress Disorder (PTSD) in adulthood. Neural attention network function contributes to resilience against PTSD following maltreatment; oxytocin administration alters functional connectivity differentially among resilient to PTSD groups. The present study examined intrinsic connectivity between ventral and dorsal neural attention networks (VAN and DAN) to clarify the nature of dysfunction versus resilience in the context of maltreatment-related PTSD, and to explore differential dysfunction related to varied aspects of maltreatment. Oxytocin administration was examined as a factor in these relationships. Resting-state functional connectivity data were collected from 39 adults with maltreatment histories, with and without PTSD, who were randomly assigned to receive oxytocin or placebo. We found that PTSD and sexual abuse (SA) were associated with reduced VAN-DAN connectivity. There were no significant effects with regard to physical abuse. Oxytocin was associated with greater VAN-DAN connectivity strength. These preliminary findings suggest dysfunction within attentional systems in PTSD, as well as following SA. Further, oxytocin may help ameliorate attentional neurocircuitry dysfunction in individuals with PTSD and those with maltreatment histories.