Sarah D. Corathers

Joint Genetic Susceptibility to Type 1 Diabetes and Autoimmune Thyroiditis: from Epidemiology to Mechanisms

Type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) frequently occur together within families and in the same individual. The co-occurrence of T1D and AITD in the same patient is one of the variants of the autoimmune polyglandular syndrome type 3 [APS3 variant (APS3v)]. Epidemiological data point to a strong genetic influence on the shared susceptibility to T1D and AITD. Recently, significant progress has been made in our understanding of the genetic association between T1D and AITD. At least three genes have been confirmed as major joint susceptibility genes for T1D and AITD: human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22. Moreover, the first whole genome linkage study has been recently completed, and additional genes will soon be identified. Not unexpectedly, all the joint genes for T1D and AITD identified so far are involved in immune regulation, specifically in the presentation of antigenic peptides to T cells. One of the lessons learned from the analysis of the joint susceptibility genes for T1D and AITD is that subset analysis is a key to dissecting the etiology of complex diseases. One of the best demonstrations of the power of subset analysis is the CTLA-4 gene in T1D. Although CTLA-4 showed very weak association with T1D, when analyzed in the subset of patients with both T1D and AITD, the genetic effect of CTLA-4 was significantly stronger. Gene-gene and genetic-epigenetic interactions most likely play a role in the shared genetic susceptibility to T1D and AITD. Dissecting these mechanisms will lead to a better understanding of the etiology of T1D and AITD, as well as autoimmunity in general.

Transition From Pediatric to Adult Care for Youth Diagnosed With Type 1 Diabetes in Adolescence

OBJECTIVE: Youth with type 1 diabetes mellitus are at risk for poor glycemic control as they age into adulthood. The aim of this study was to describe sociodemographic and clinical correlates of poor glycemic control associated with the transfer of care from pediatric to adult diabetes providers among a cohort of youth with type 1 diabetes diagnosed in adolescence. METHODS: Analyses included 185 adolescent participants with recently diagnosed type 1 diabetes in the SEARCH for Diabetes in Youth Study with pediatric care at baseline who were age ≥18 years at follow-up. Demographic and clinical factors were measured by survey and laboratory results. Survival analysis was used to estimate the age of transition. Logistic regression analysis assessed the association of demographic and clinical factors with the transition of care and poor glycemic control at follow-up. RESULTS: Fifty-seven percent of participants had transitioned to adult diabetes care providers by the follow-up visit. The estimated median age of transition of care was 20.1 years (95% confidence interval 19.8–20.4). Older age, lower baseline glycosylated hemoglobin, and less parental education were independently associated with increased odds of transition. The odds of poor glycemic control at follow-up were 2.5 times higher for participants who transitioned to adult care compared with those who remained in pediatric care. CONCLUSIONS: Transferring from pediatric to adult care, experienced by more than half the sample, was associated with an increased risk of poor glycemic control at follow-up. These findings suggest that young adults need additional support when moving to adult care.

Improving Depression Screening for Adolescents With Type 1 Diabetes

OBJECTIVE: Depression is common among adolescents, but rates increase significantly in the presence of chronic health conditions. Outpatient screening for depression is recommended but rarely formally conducted due to barriers of implementation. METHODS: To provide a model for depression screening of youth with chronic health conditions, a standard process using a self-administered electronic version of the Children’s Depression Inventory (CDI) was developed. Quality improvement methodology and traditional analytic approaches were used to test the feasibility and outcomes of routine screening in patients 13 to 17 years of age with type 1 diabetes. RESULTS: Of the 528 eligible adolescents, 509 (96%) received at least 1 depression screen during the first year. The process was tested and refined in over 1200 patient encounters, which resulted in an increase in depression screening rates from <5% to a median of 85% over the initial 12 months. Both patients and staff reported acceptance of screening on qualitative surveys. Elevated CDI scores (≥16) were found in 8% of the sample; moderate scores (10–15) in 12% of the sample. Low risk scores were found in 80% of the sample. Higher CDI scores correlated with lower blood glucose monitoring frequency and higher hemoglobin A1c, confirming the link between more depression symptoms and poorer diabetes management and control. Suicidal ideation was endorsed in 7% of the population. CONCLUSIONS: Systematic depression screening in adolescents with type 1 diabetes can be reliably implemented with clinically significant results. A systematic approach, such as described in this study, can serve as a model for other chronic health conditions.

The role of hyperglycemia in acute illness: Supporting evidence and its limitations

Hyperglycemia is common in acutely ill hospitalized patients and has been linked to poor outcomes, independent of pre-existing diabetes. Correction of hyperglycemia has been shown to decrease morbidity and mortality; however, establishing evidence-based guidelines has been challenging because insulin intervention studies have varied in the questions they have addressed, glucose levels studied, feeding regimen, and quality of methodology. This article reviews the findings and limitations of recent intervention studies that have addressed treatment of inpatient hyperglycemia with intravenous insulin infusion therapy. Discussion of underlying causes of hospital-related hyperglycemia and mechanisms explaining the deleterious effects of hyperglycemia and improved outcomes with insulin intervention are described. Current guidelines from various professional organizations recommend treatment of inpatient hyperglycemia, although exact glycemic targets and identification of which patient subsets will receive greatest benefit from glucose lowering remain an area of ongoing research.

Late endocrine effects of childhood cancer

The cure rate for paediatric malignancies is increasing, and most patients who have cancer during childhood survive and enter adulthood. Surveillance for late endocrine effects after childhood cancer is required to ensure early diagnosis and treatment and to optimize physical, cognitive and psychosocial health. The degree of risk of endocrine deficiency is related to the childs sex and their age at the time the tumour is diagnosed, as well as to tumour location and characteristics and the therapies used (surgery, chemotherapy or radiation therapy). Potential endocrine problems can include growth hormone deficiency, hypothyroidism (primary or central), adrenocorticotropin deficiency, hyperprolactinaemia, precocious puberty, hypogonadism (primary or central), altered fertility and/or sexual function, low BMD, the metabolic syndrome and hypothalamic obesity. Optimal endocrine care for survivors of childhood cancer should be delivered in a multidisciplinary setting, providing continuity from acute cancer treatment to long-term follow-up of late endocrine effects throughout the lifespan. Endocrine therapies are important to improve long-term quality of life for survivors of childhood cancer.

Pediatricians and Screening for Obesity with Body Mass Index: Does Level of Training Matter?

Objectives. Pediatric obesity is increasing at epidemic rates in industrialized nations. It is recommended that pediatricians screen all children annually with the use of body mass index (BMI). However, it is unclear whether this recommendation is followed. This study sought to (1) determine the proportion of children screened for obesity with BMI, and (2) test whether attending physicians are more likely than resident physicians to document and plot BMI. Methods. We conducted a systematic review of medical records in an urban academic pediatric practice. Participants were children aged 5 to 11 years presenting for health care in 2004. We measured the proportion of subjects with documented and plotted BMI and compared results for attending and resident physicians. We used logistic regression analysis to determine factors associated with documentation of BMI. Results. Of 397 medical records reviewed, 59.7% contained the 2000 Centers for Disease Control and Prevention growth curve with BMI for age; 5.5% documented BMI, and 4.3% plotted BMI. Resident physicians were more likely to document (13.0% vs. 3.0%, p=0.0008) and plot (9.0% vs. 2.7%, p=0.0260) BMI compared with attending physicians. Children with a BMI ≥95% for age were more likely to have their BMI documented (odds ratio [OR] = 10.7, 95% confidence interval [CI] 3.7, 31.5) and plotted (OR=7.1, 95% CI 2.3, 21.6). Conclusion. We found the use of BMI to screen for childhood obesity very poor in this academic pediatric practice. Resident physicians were more likely to document and plot BMI than attending physicians.

Health Care Transition Preparation and Experiences in a U.S. National Sample of Young Adults With Type 1 Diabetes

OBJECTIVE Young adults with type 1 diabetes transitioning from pediatric to adult care are at risk for adverse outcomes. We developed a survey to evaluate transition experiences in two groups of young adults with type 1 diabetes, before (PEDS) and after (ADULT) transition to adult care. RESEARCH DESIGN AND METHODS We fielded an electronic survey to young adults (18 to <30 years) at 60 T1D Exchange Clinic Registry centers. RESULTS Surveys were completed by 602 young adults, 303 in the PEDS group (60% female, age 20 ± 2 years) and 299 in the ADULT group (62% female, age 24 ± 3 years). In the PEDS group, mean anticipated transition age was 22 ± 2 years; 64% remained in pediatric care because of emotional attachment to the provider. The ADULT group transitioned at age 19 ± 2 years, mainly after pediatric provider recommendation. More than 80% of respondents reported receiving counseling on type 1 diabetes self-management and screening tests from pediatric providers, but less than half (43% PEDS and 33% ADULT) reported discussing reproductive health. In the PEDS group, half had discussed transfer with pediatric providers. Of the ADULT participants, 63% received an adult provider referral, and 66% felt mostly/completely prepared to transition. ADULT participants with fewer pretransition pediatric visits or who felt unprepared for transition had increased odds of gaps >6 months between pediatric and adult care. Receipt of transition preparation counseling was not associated with self-reported hemoglobin A1c <7.0% in either group. CONCLUSIONS These results support the need for intensive efforts to integrate transition preparation counseling and care coordination into pediatric type 1 diabetes care.

Complications of Diabetes Therapy

Current strategies for the treatment of type 2 diabetes mellitus promote individualized plans to achieve target glucose levels on a patient-by-patient basis while minimizing treatment related risks. Maintaining glycemic control over time is a significant challenge because of the progressive nature of diabetes as a result of declining β-cell function. This article identifies complications of non-insulin treatments for diabetes. The major classes of medications are reviewed with special focus on target population, mechanism of action, effect on weight, cardiovascular outcomes and additional class-specific side effects including effects on bone. Effects on β-cell function are also highlighted.

Health-System-Based Interventions to Improve Care in Pediatric and Adolescent Type 1 Diabetes

Despite significant advances in pharmacology and technology, glycemic targets are difficult to achieve for patients with type 1 diabetes (T1D) and management remains burdensome for patients and their families. Quality improvement (QI) science offers a methodology to identify an aim, evaluate complex contributors to the goal, and test potential interventions to achieve outcomes of interest. Day-to-day management of diabetes is often an iterative process but interventions exist at all care levels: individual patient and family, clinic, and larger population and health system. This article reviews current literature and proposes novel QI interventions for enhancing health outcomes, with attention to essential determinants or drivers of improved glycemic control and patient experience for pediatric T1D in the context of the Chronic Care Model. In-depth consideration of key drivers of successful T1D care, including self-management and integration of technology, are explored, and examples of larger health systems with improved outcomes, including Learning Health Systems are highlighted.

Transfer from paediatric to adult care for young adults with Type 2 diabetes: the SEARCH for Diabetes in Youth Study

To describe factors associated with transfer from paediatric to adult care and poor glycaemic control among young adults with Type 2 diabetes, using the SEARCH for Diabetes in Youth study.