Blue Circle Health: A Novel Patient-Centered Model of Health Care Delivery for Low-Income Patients With Type 1 Diabetes.

Analog insulins, insulin pumps, and continuous glucose monitors (CGM) have revolutionized type 1 diabetes (T1D) treatment over the last 50 years. Nevertheless, less than 20% of patients in the United States reach guideline-based HbA1c targets. The dysfunctional delivery of U.S. health care has further worsened glycemic outcomes among structurally disadvantaged groups such as non-Hispanic Black and low-income populations. Administrative complexities resulting from mixed insurance coverage and delivery systems, incongruity between effective policies and reimbursement, structural racism, and implicit biases have led to high diabetes care-related costs, provider scarcity and burnout, and patient diabetes distress. The Extension for Community Healthcare Outcomes (ECHO) Diabetes tele-education outreach model was created to increase self-efficacy among primary care providers through a combination of weekly didactic sessions led by a team of diabetes experts and access to community-based peer coaches. As an evolution of ECHO Diabetes, Blue Circle Health has been established as a philanthropically funded health care delivery system, using a whole-person, individualized approach to T1D care for adults living in underserved communities. The program will provide direct-to-patient telehealth services, including diabetes education, management, and related psychological care regardless of ability to pay. Community-based diabetes support coaches will serve as the primary point of contact, or guide on the "Blue Circle Health Member Journey." Access to needed insulins, supplies, and CGMs will be provided at no cost to the individual. Through a continuous learning and improvement model, a person-centered, equitable, accessible, and effective health care delivery model will be built for people living with T1D.

Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas.

Type 1 diabetes has historically been described as an endocrine (ß-cell) specific autoimmune disease. However, a substantial reduction (20-50%) in pancreas organ size and subclinical to symptomatic exocrine pancreatic insufficiency are present at diagnosis and may begin even prior to the development of islet autoimmunity. The mechanisms of exocrine loss in type 1 diabetes are not well understood, but leading hypotheses include developmental defects, ß-cell loss resulting in exocrine atrophy, or autoimmune or inflammatory destruction of exocrine cells. Inflammatory changes including acute and chronic pancreatitis, exocrine T cell infiltration and classical complement activation, and serum exocrine autoantibodies within type 1 diabetes individuals suggest that an autoimmune or inflammatory process may contribute to exocrine pancreatic dysfunction. Exocrine pancreas atrophy primarily occurs prior to the onset of clinical disease. Indeed, recent work implicates exocrine-specific alterations in gene and protein expression as key in type 1 diabetes development. Measures of exocrine size and function could be useful additions in the prediction of disease onset and in identifying potential therapeutic responders to disease therapies, however, this is an underdeveloped area of research. Additionally, exocrine pancreatic insufficiency is underdiagnosed in individuals with type 1 diabetes and individualized treatment protocols are lacking. Much work remains to be done in this area, but we can definitively say that type 1 diabetes is a disorder of both the exocrine and endocrine pancreas likely from the start.

Thyroid Storm Caused by Hyperemesis Gravidarum.

Background: Transient thyrotoxicosis has been documented in the setting of hyperemesis gravidarum (HG) with elevated human chorionic gonadotropin (hCG) levels. Thyroid storm in pregnancy is rarer and typically associated with autoimmune hyperthyroidism. We described thyroid storm in a primigravid 18-year-old patient due to hCG level elevation secondary to HG, which resolved in the second trimester of pregnancy. Case Report: Our patient presented with vomiting, hyperthyroidism, and cardiac and renal dysfunction at 16 weeks' gestation. She was clinically found to have a thyroid storm, with undetectable thyroid-stimulating hormone (TSH) and a free thyroxine level of >6.99 ng/dL. The hCG level was elevated at 246 030 mIU/L (9040-56 451 mIU/L). She was treated with methimazole, saturated solution potassium iodide, and propranolol. Because thyroid autoantibodies were absent, thyroid ultrasound yielded normal results, and thyroid function testing results rapidly improved as the hCG level decreased, the medications were tapered and ultimately discontinued by day 10 of hospitalization. The thyroid function remained normal after discharge. Discussion: Because hCG and TSH have identical alfa subunits and similar beta subunits, hCG can bind to the TSH receptor and stimulate thyroxine production. The hCG level peaks at around 8-14 weeks of gestation, correlating with decreased TSH levels in this same time frame. This case emphasizes the relevant physiology and importance of timely and thorough evaluation to determine the appropriate management, prognosis, and follow-up for patients with thyroid storm in the setting of HG. Conclusion: Although transient thyrotoxicosis is documented in patients with HG, thyroid storm is rare, and our case illustrates a severe example of these comorbidities.

Challenges and Opportunities in Using Telehealth for Diabetes Care.

The ongoing coronavirus pandemic led to a rapid and dramatic increase in the use of telehealth for diabetes care. In the wake of this transition, we examine new opportunities and ongoing challenges for using telehealth within diabetes management, based on data and experiences from the pre-pandemic and pandemic time frames.

Characterising the age-dependent effects of risk factors on type 1 diabetes progression.

AIMS/HYPOTHESIS: Age is known to be one of the most important stratifiers of disease progression in type 1 diabetes. However, what drives the difference in rate of progression between adults and children is poorly understood. Evidence suggests that many type 1 diabetes disease predictors do not have the same effect across the age spectrum. Without a comprehensive analysis describing the varying risk profiles of predictors over the age continuum, researchers and clinicians are susceptible to inappropriate assessment of risk when examining populations of differing ages. We aimed to systematically assess and characterise how the effect of key type 1 diabetes risk predictors changes with age. METHODS: Using longitudinal data from single- and multiple-autoantibody-positive at-risk individuals recruited between the ages of 1 and 45 years in TrialNet's Pathway to Prevention Study, we assessed and visually characterised the age-varying effect of key demographic, immune and metabolic predictors of type 1 diabetes by employing a flexible spline model. Two progression outcomes were defined: participants with single autoantibodies (n=4893) were analysed for progression to multiple autoantibodies or type 1 diabetes, and participants with multiple autoantibodies were analysed (n=3856) for progression to type 1 diabetes. RESULTS: Several predictors exhibited significant age-varying effects on disease progression. Amongst single-autoantibody participants, HLA-DR3 (p=0.007), GAD65 autoantibody positivity (p=0.008), elevated BMI (p=0.007) and HOMA-IR (p=0.002) showed a significant increase in effect on disease progression with increasing age. Insulin autoantibody positivity had a diminishing effect with older age in single-autoantibody-positive participants (p<0.001). Amongst multiple-autoantibody-positive participants, male sex (p=0.002) was associated with an increase in risk for progression, and HLA DR3/4 (p=0.05) showed a decreased effect on disease progression with older age. In both single- and multiple-autoantibody-positive individuals, significant changes in HR with age were seen for multiple measures of islet function. Risk estimation using prediction risk score Index60 was found to be better at a younger age for both single- and multiple-autoantibody-positive individuals (p=0.007 and p<0.001, respectively). No age-varying effect was seen for prediction risk score DPTRS (p=0.861 and p=0.178, respectively). Multivariable analyses suggested that incorporating the age-varying effect of the individual components of these validated risk scores has the potential to enhance the risk estimate. CONCLUSIONS/INTERPRETATION: Analysing the age-varying effect of disease predictors improves understanding and prediction of type 1 diabetes disease progression, and should be leveraged to refine prediction models and guide mechanistic studies.

Substance Use Affects Type 1 Diabetes Pancreas Pathology: Implications for Future Studies.

Access to human pancreas samples from organ donors has greatly advanced our understanding of type 1 diabetes pathogenesis; however, previous studies have shown that donors have a high rate of substance use, and its impact on pancreatic histopathology in this disease is not well described. One-hundred-thirty-one type 1 diabetes and 111 control organ donor pancreata from persons 12-89 years of age (mean 29.8 ± 15.5 years) within the Network for Pancreatic Organ donors with Diabetes (nPOD) were examined for insulin positivity, insulitis, amyloid staining, acute and chronic pancreatitis, and chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis); findings were compared by history of substance use. A secondary analysis compared exocrine pancreatic histopathologic findings in type 1 diabetes versus control organ donors regardless of substance use history. We observed a high but congruent rate of substance use in type 1 diabetes and control organ donors (66.4% and 64% respectively). Among donors with type 1 diabetes (but not controls), islet amyloid (OR 9.96 [1.22, 81.29]) and acute pancreatitis (OR 3.2 [1.06, 9.63]) were more common in alcohol users while chronic exocrine changes (OR 8.86 [1.13, 69.31]) were more common in cocaine users. Substance use impacted the pancreata of donors with type 1 diabetes more than controls. Overall, despite similar rates of substance use, acute pancreatitis (15.3% versus 4.5%, p=0.0061), chronic pancreatitis (29.8% versus 9.9%, p=0.0001), and chronic exocrine changes (73.3% versus 36.9%, p<0.0001) were more common in type 1 diabetes donors than controls. Alcohol and/or cocaine use in type 1 diabetes organ donors increases exocrine pancreas pathology and islet amyloid deposition but does not affect insulitis or insulin positivity. Exocrine pathology in type 1 diabetes donors is common, and further study of the pathophysiology of these changes is needed.

Simple tests of cardiorespiratory fitness in a pediatric population.

A progressive, treadmill-based VO2max is the gold standard of cardiorespiratory fitness determination but is rarely used in pediatric clinics due to time requirements and cost. Simpler and shorter fitness tests such as the Squat Test or Step Test may be feasible and clinically useful alternatives. However, performance comparisons of these tests to treadmill VO2max tests are lacking. The primary aim of this cross-sectional study was to assess the correlation between Squat and Step Test scores and VO2max in a pediatric population. As secondary outcomes, we calculated correlations between Rated Perceived Exertion Scale (RPE) scores, NIH PROMIS Physical Activity scores, and BMI z-score with VO2max, and we also evaluated the ability of each fitness test to discriminate low and high-risk patients based on the FITNESSGram. Forty children aged 10-17 completed these simple cardiorespiratory fitness tests. Statistically significant correlations were observed between VO2max and the Step Test (r = -0.549) and Squat Test (r = -0.429) scores, as well as participant BMI z-score (r = -0.458). RPE and PROMIS scores were not observed to be correlated with VO2max. Area Under the Receiver Operator Curve was relatively high for BMI z-scores and the Step Test (AUC = 0.813, 0.713 respectively), and lower for the Squat Test (AUC = 0.610) in discriminating risk according to FITNESSGram Scores. In this sample, the Step Test performed best overall. These tests were safe, feasible, and may add great value in assessing cardiorespiratory fitness in a clinical setting.

Enhanced Understanding of the Natural History of Pre-Type 1 Diabetes: Fundamental to Prevention.

Due to well-designed studies of birth cohorts and at-risk individuals, our understanding of the natural history of pre- and early type 1 diabetes (T1D) has advanced considerably over the past decade. Genetic risk scores can predict with increasing precision and accuracy who is at risk for T1D, and early staging based upon islet autoantibody status allows for improved mechanistic and natural history studies as well as improved clinical trial design. A growing number of children are being diagnosed with islet autoimmunity prior to the onset of symptoms, and confusion remains surrounding their proper management. These patients should have access to appropriate counseling and should be referred to a center that can provide information regarding current prevention trials. In the future, a successful prevention strategy for T1D would justify population-based screening for all children.