Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

The Maintain High Blood Glucose subscale of the child hypoglycemia fear survey: proposed preliminary cut points for screening youth with type 1 diabetes.

OBJECTIVE: To improve the clinical utility of the Maintain High Blood Glucose subscale of the Hypoglycemia Fear Surveys (HFS) by identifying clinically meaningful cut points associated with glycemic outcomes. METHODS: Youth (N = 994; 13.96 ± 2.3 years) with type 1 diabetes and their caregivers (N = 1,111; 72% female) completed the Child or Parent version of the HFS. Modal Score Distribution, Standard Deviation Criterion, and Elevated Item Criterion approaches were used to identify proposed preliminary cut points for the Maintain High Blood Glucose subscale. The association between proposed preliminary cut points was examined with youth glycemic outcomes. RESULTS: A cut point of ≥7 for the Maintain High Blood Glucose subscale on the Child HFS was associated with a greater percentage of blood glucose readings >180 mg/dl (p < .01), higher mean blood glucose (p < .001), and a higher hemoglobin A1c (p < .05). In subsequent multiple regression analyses, controlling for other factors associated with glycemia, the significant association between scores above ≥7 and higher mean blood glucose and higher hemoglobin A1c remained. A clinically useful cut point was not identified for caregivers. However, elevated youth scores on the Maintain High Blood Glucose subscale were positively associated with elevated caregiver scores (phi = .171, p < .001). CONCLUSIONS: The proposed preliminary cut point for the Maintain High Blood Glucose subscale will aid the type 1 diabetes care team in identifying youth whose behaviors may be contributing to their suboptimal glycemia.

Body mass index moderates the association between diabetes distress and objective self-management behaviours in adolescents with type 1 diabetes and elevated A1Cs.

OBJECTIVE: To examine the cross-sectional associations between diabetes distress, BMI (zBMI; BMI z-score), objectively measured mean daily blood glucose readings and insulin boluses administered, and A1C in adolescents with type 1 diabetes (T1D) using insulin pumps. METHODS: T1D self-management behaviour data were downloaded from adolescents' (N = 79) devices and mean daily frequency of blood glucose readings and insulin boluses were calculated. Diabetes distress was measured (Problem Areas in Diabetes-Teen questionnaire [PAID-T]), A1C collected, and zBMI calculated from height and weight. Three multiple linear regressions were performed with blood glucose readings, insulin boluses, and A1C as the three dependent variables and covariates (age, T1D duration), zBMI, diabetes distress, and the diabetes distress x zBMI interaction as independent variables. RESULTS: Participants (55.7% female) were 14.9 ± 1.9 years old with T1D for 6.6 ± 3.4 years. zBMI moderated the relationship between diabetes distress and mean daily insulin boluses administered (b = -0.02, p = 0.02); those with higher zBMI and higher diabetes distress administered fewer daily insulin boluses. zBMI was not a moderator of the association between diabetes distress and blood glucose readings (b = -0.01, p = 0.29) or A1C (b = 0.002, p = 0.81). CONCLUSIONS: Using objective behavioural data is useful for identifying how adolescent diabetes distress and zBMI affect daily bolusing behaviour amongst adolescent insulin pump users. Although distinct interventions exist to improve T1D self-management or diabetes distress, none addresses them together while considering zBMI. Decreasing diabetes distress could be especially important for youth with high zBMI.

Anxiety and Risk Perception in Parents of Children Identified by Population Screening as High Risk for Type 1 Diabetes.

OBJECTIVE: To assess anxiety and risk perception among parents whose children screened positive for islet autoantibodies, indicating elevated risk for type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The Autoimmunity Screening for Kids (ASK) study identified 319 children age 1 to 17 years at risk for T1D via screening for islet autoantibodies; 280 children with confirmed islet autoantibodies and their caregivers enrolled in a follow-up education and monitoring program to prevent diabetic ketoacidosis at diagnosis. Parents completed questionnaires at each monitoring visit, including a 6-item version of the State Anxiety Inventory (SAI), to assess anxiety about their child developing T1D, and a single question to assess risk perception. RESULTS: At the first ASK follow-up monitoring visit, mean parental anxiety was elevated above the clinical cutoff of 40 (SAI 46.1 ± 11.2). At the second follow-up monitoring visit (i.e., visit 2), mean anxiety remained elevated but started to trend down. Approximately half (48.9%) of parents reported their child was at increased risk for T1D at the initial follow-up monitoring visit (visit 1). Parents of children with more than one islet autoantibody and a first-degree relative with T1D were more likely to report their child was at increased risk. CONCLUSIONS: Most parents of autoantibody-positive children have high anxiety about their child developing T1D. Information about the risk of developing T1D is difficult to convey, as evidenced by the wide range of risk perception reported in this sample.

Historical Insights and Current Perspectives on the Diagnosis and Management of Presymptomatic Type 1 Diabetes.

Objective: The article provides practical guidance for (1) interpreting and confirming islet autoantibody screening results for type 1 diabetes (T1D) and (2) follow-up of individuals with early stages of T1D with the goal of ensuring medical safety and providing patients and their families with an assessment of risk for progression to a clinical diagnosis of T1D. Research Design and Methods: We used an explicit a priori methodology to identify areas of agreement and disagreement in how to manage patients with early T1D. We used a modified Delphi method, which is a systematic, iterative approach to identifying consensus. We developed a list of topic questions, ranked them by importance, and developed consensus statements based on available evidence and expert opinion around each of the 30 topic questions consistently ranked as being most important. Results: Consensus statements for screening and monitoring are supported with figures proposing an algorithm for confirmation of T1D diagnosis and management of early T1D until clinical diagnosis. Conclusions: Disseminating and increasing knowledge related to how to interpret T1D screening tests, confirm early T1D diagnosis and monitor for medical safety and clinical disease risk prediction is critically important as there are currently no clinical recommendations. Published guidance will promote better management of T1D screening-detected individuals.

A randomized controlled clinical trial to improve health outcomes in youth with type 1 diabetes: Study design and baseline characteristics.

Most adolescents with T1D do not meet glycemic recommendations or consistently perform the required self-management behaviors to prevent acute- and long-term deleterious health outcomes. In addition, most youth with T1D do not have access to behavioral health services to address T1D management barriers. Thus, delivering behavioral interventions during routine medical appointments may hold promise for improving T1D outcomes in adolescents. The overall objective of this study was to examine the effect of behavioral interventions, either a Personalized T1D Self-Management Behaviors Feedback Report or Problem-Solving Skills, delivered by a T1D behavioral health provider and a T1D medical provider during a joint, fully integrated appointment to improve health outcomes in youth with T1D. This paper describes the study rationale, design, and baseline characteristics for the 109 adolescent-caregiver dyads who participated. Primary and secondary outcomes include hemoglobin A1c (A1C), T1D self-management behaviors, and biological indicators of complications.

Bring Blood Glucose Down! An intervention to reduce fear of hypoglycemia in caregivers of adolescents with type 1 diabetes: Study design and participant characteristics.

Fear of hypoglycemia (FOH) is anxiety or extreme worry about having a low blood glucose and its consequences. FOH is common in individuals with type 1 diabetes (T1D) of all ages, as well as their caregivers, and can lead to inappropriate T1D self-management and suboptimal health outcomes. Despite its prevalence and serious health consequences, there has been very little attention focused on developing interventions to reduce FOH and its associated maladaptive T1D management behaviors. The primary aim of the present study, Bring BG Down!, was to implement a pilot intervention targeting FOH in mothers of adolescents with T1D. Exploratory aims included determining if the intervention had an impact on the adolescent's FOH, glycemia, as well as other generalized anxiety symptoms or symptoms of obsessive-compulsive disorder in both the mother and adolescent. Caregiver participants and their adolescents with T1D were randomized to either the Bring BG Down! group or the Control group. Individuals in the Bring BG Down! group participated in intervention sessions for 6 months via telehealth and they completed questionnaires, whereas those in the Control group only completed questionnaires. Follow-up occurred at 7-months and 10-months. The purpose of this paper is to describe the Bring BG Down! study design and rationale, and participant characteristics at the start of the study.

Psychometric Properties of the Hypoglycemia Fear Survey in a Clinical Sample of Adolescents with Type 1 Diabetes and Their Caregivers.

OBJECTIVE: A previously published exploratory factor analysis suggested that the Hypoglycemia Fear Survey-Child and Parent Versions, is comprised of three subscales: Maintain High Blood Glucose, Helplessness/Worry About Low Blood Glucose, and Worry About Negative Social Consequences. The primary aim of this study was to confirm this three-factor model with a clinical population of adolescents with type 1 diabetes (T1D) and their caregivers. METHODS: Participants included N = 1,035 youth ages 10-17.99 years with T1D, and their female (N = 835) and/or male (N = 326) caregivers who completed the Hypoglycemia Fear Survey independently during a routine medical appointment. We conducted confirmatory factor analysis and examined reliability of the Hypoglycemia Fear Survey and its associations with demographics and clinical outcomes (e.g., mean blood glucose, glycemic control). RESULTS: Confirmatory factor analysis supported the three-factor model in youth and female and male caregivers. The internal consistencies for Maintain High Blood Glucose, Helplessness/Worry About Low Blood Glucose, and Worry About Negative Social Consequences were acceptable. The majority of demographic and clinical outcome variables correlated as hypothesized with the three subscales. CONCLUSIONS: Using a large clinical sample of adolescents with T1D and their caretakers, we confirmed the three-factor model for the Hypoglycemia Fear Survey, which is sufficiently reliable to be used in a clinical setting. Important areas of future research include examining moderators for the effect of fear of hypoglycemia on clinical outcomes, and possible inclusion of items related to modern diabetes devices.

Pump It Up! A randomized clinical trial to optimize insulin pump self-management behaviors in adolescents with type 1 diabetes.

Individuals with type 1 diabetes (T1D) must engage in a variety of complex and burdensome self-management behaviors daily to maintain near normal blood glucose levels and prevent complications. There is a need for interventions to improve use of sophisticated diabetes technologies, such as insulin pumps, during adolescence - a very high-risk developmental period for individuals with T1D. All diabetes devices, including insulin pumps, store large amounts of behavioral data that can be downloaded and analyzed to evaluate adherence to recommended T1D self-management behaviors. The overall objective of the present study, Pump it Up!, was to use objectively downloaded insulin pump data to inform and test two interventions to optimize insulin pump use in adolescents with T1D and their caregivers. Multiphase Optimization Strategy (MOST) was used to achieve the overall goal of this study - to separately test the main effect of the Pump It Up! Personalized T1D Self-Management Behaviors Feedback Report and the main effect of Pump It Up! Problem-Solving Skills intervention to improve T1D self-management behaviors using a 2 × 2 factorial design. The purpose of this paper is to describe the Pump It Up! study design and rationale, and participant baseline characteristics. Longitudinal data analyses will be conducted, and moderating effects of psychosocial factors will be examined in relation to primary (insulin pump self-management behaviors) and secondary (A1C) outcomes.

Suicide Risk Assessment in Youth and Young Adults With Type 1 Diabetes.

OBJECTIVE: To describe sociodemographic and clinical characteristics of youth and young adults with type 1 diabetes who endorsed suicidal ideations as part of routine depression screening and the results of their suicide risk assessments. RESEARCH DESIGN AND METHODS: The Patient Health Questionnaire-9 was used to assess depressive symptoms and suicide/death ideation in 550 youth and young adults with type 1 diabetes ages 10-24 years. Only individuals who endorsed suicidal/death ideations (n = 49) completed a standardized suicide risk assessment protocol and safety planning. RESULTS: Nine percent of individuals endorsed suicidal/death ideation and of those, 83.4% reported clinically elevated depressive symptoms; 16% made a previous suicide attempt. No youth (n = 39) or young adults (n = 11) disclosed current plans or preparations for suicide, but five who expressed suicidal ideation acknowledged the lethality of insulin for an attempt. Three previously used insulin to attempt suicide. The overwhelming majority of individuals were classified as being low risk for future suicide attempt/completion. None were hospitalized as a part of the suicide risk assessment, and no suicide completions have occurred. CONCLUSIONS: The findings of this study provide initial insight into the behaviors and cognitions of youth and young adults with type 1 diabetes who experience suicidal and death ideations. Comprehensive suicide risk assessment and safety planning are feasible during routine type 1 diabetes clinic appointments.

Consequences Matter: Compassion in Conservation Means Caring for Individuals, Populations and Species.

Human activity affecting the welfare of wild vertebrates, widely accepted to be sentient, and therefore deserving of moral concern, is widespread. A variety of motives lead to the killing of individual wild animals. These include to provide food, to protect stock and other human interests, and also for sport. The acceptability of such killing is widely believed to vary with the motive and method. Individual vertebrates are also killed by conservationists. Whether securing conservation goals is an adequate reason for such killing has recently been challenged. Conventional conservation practice has tended to prioritise ecological collectives, such as populations and species, when their interests conflict with those of individuals. Supporters of the 'Compassionate Conservation' movement argue both that conservationists have neglected animal welfare when such conflicts arise and that no killing for conservation is justified. We counter that conservationists increasingly seek to adhere to high standards of welfare, and that the extreme position advocated by some supporters of 'Compassionate Conservation', rooted in virtue ethics, would, if widely accepted, lead to considerable negative effects for conservation. Conservation practice cannot afford to neglect consequences. Moreover, the do-no-harm maxim does not always lead to better outcomes for animal welfare.

Glycobiology of Human Fungal Pathogens: New Avenues for Drug Development.

Invasive fungal infections (IFI) are an increasing threat to the developing world, with fungal spores being ubiquitous and inhaled every day. Some fungal species are commensal organisms that are part of the normal human microbiota, and, as such, do not pose a threat to the immune system. However, when the natural balance of this association is disturbed or the host's immune system is compromised, these fungal pathogens overtake the organism, and cause IFI. To understand the invasiveness of these pathogens and to address the growing problem of IFI, it is essential to identify the cellular processes of the invading organism and their virulence. In this review, we will discuss the prevalence and current options available to treat IFI, including recent reports of drug resistance. Nevertheless, the main focus of this review is to describe the glycobiology of human fungal pathogens and how various components of the fungal cell wall, particularly cell wall polysaccharides and glycoconjugates, are involved in fungal pathogenicity, their biosynthesis and how they can be potentially exploited to develop novel antifungal treatment options. We will specifically describe the nucleotide sugar transporters (NSTs) that are important in fungal survival and suggest that the inhibition of fungal NSTs may potentially be useful to prevent the establishment of fungal infections.

Graduated exposure to treat fear of hypoglycemia in a young adult with type 1 diabetes: A case study.

Hypoglycemia is a common and dangerous complication of type 1 diabetes (T1D). Although some worry about hypoglycemia is adaptive, some individuals develop severe and impairing anxiety symptoms about hypoglycemic episodes. This presentation, known as severe fear of hypoglycemia (FOH), is similar to a specific phobia, and becomes problematic when it interferes with one's quality of life or T1D management. Although FOH is common, there have not yet been any treatment studies to address severe and impairing levels of FOH in the T1D population. The purpose of the following case report is to: (a) describe the presentation of a severe case of FOH in a young adult with T1D; (b) demonstrate the effectiveness of graduated exposure therapy for treatment of severe FOH; and (c) provide implications for clinical practice. A previously developed conceptual model for FOH management guided treatment. Treatment using graduated exposure therapy for FOH resulted in reduced worry about low blood glucose (BG) and significant reduction in behaviors to maintain high BG levels. Assessment of FOH and the risk and benefits of using a continuous glucose monitor among individuals with T1D and their families are discussed.