Type 1 Diabetes Exchange Registry Research Articles

50-OR: Validation of Fear of Hypoglycemia Screener: Results from the T1D Exchange Registry

Objective: To examine reliability and validity of a newly developed fear of hypoglycemia (FoH) screener as a practical and actionable tool for in-clinic use in adults with type 1 diabetes (T1D), in accordance with ADA’s position on psychosocial care. Methods: In this validation study, adults with T1D were recruited from the T1D Exchange Registry to complete a draft screener online; potential items were previously identified from literature review, and interviews with health care professionals (HCPs) and people with T1D. Standard psychometric analyses assessed reliability and validity of the screener. The final FoH screener comprised 9 items assessing 2 domains - “worry” (6 items) and “behavior” (3 items). Results: The final sample comprised 592 adults with T1D (age 43.1 ± 15.3 years; duration of T1D 24.1 ± 15 years, 66.7% females, 91.6% White, 5.2% Hispanic, self-reported HbA1c 7.1% ± 1.2%). Approximately 30% of participants reported severe hypoglycemia in the past 12 months; 33.4% reported impaired awareness of hypoglycemia. The FoH screener showed internal consistency (Cronbach’s α=0.88) and was highly correlated (r=0.71-0.75) with the Hypoglycemia Fear Survey (“worry” and “behavior” subscales and total scores), confirming reliability. Construct validity of the FoH screener was demonstrated with significant correlations with depression (r=0.44), anxiety (r=0.47), Diabetes Distress Subscales (powerlessness, management distress, hypoglycemia distress) (r=0.49-0.66); These correlations are considered moderate. Additionally, multivariable regression analysis showed that higher FoH screener scores were significantly associated with higher HbA1c (regression coefficient, β=0.04) and multi-morbidities (β=0.03). Conclusions: This 9-item FoH screener demonstrated good reliability and validity. Further research is planned to assess clinical usability to help appropriately identify patients and assist effective HCP-patient conversations around FoH. Disclosure J. Liu: None. J. Poon: Employee; Self; Eli Lilly and Company. J. Bispham: None. M. Perez-nieves: Employee; Self; Eli Lilly and Company. A. Hughes: None. K. S. M. Chapman: None. B. Mitchell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. F. J. Snoek: Advisory Panel; Self; Abbott Diabetes, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Novo Nordisk, Sanofi. L. Fisher: Consultant; Self; Ascensia Diabetes Care, Lilly Diabetes, Speaker’s Bureau; Self; Dexcom, Inc. Funding Eli Lilly and Company

Does Type 1 Diabetes Affect Male Infertility: Type 1 Diabetes Exchange Registry-Based Analysis

 Introduction: The prevalence of type 1 diabetes (T1D) has been increasing over the last few decades and is commonly believed to negatively impact male fertility. We aimed to estimate the prevalence of infertility among men with T1D and to characterize potential clinical predictors for male infertility among men with T1D. Methods: We used data collected from the T1D Exchange Registry from 2012 to 2017. Men with T1D completed an infertility questionnaire indicating whether they had ever had problems conceiving a child or had ever received abnormal results from infertility testing. Collected data included age at questionnaire, age at diagnosis of T1D, duration of T1D, race/ethnicity, insurance status, education level, annual household income, hemoglobin A1c (HbA1c), low density lipoprotein (LDL), diabetic retinopathy, micro/macroalbuminuria, and renal failure. Results: The survey was completed by 2171 registry members, 33 (1.5%) of whom reported male infertility. Mean age at questionnaire was 38 and 56 years in the fertile and infertile groups, respectively (P < 0.001). There was no statistically significant difference in the mean age at T1D diagnosis (16 and 27 years), mean duration of T1D at questionnaire (22 and 30 years), white non-Hispanic ethnicity (1906/2138, 89% versus 30/33, 91%), private insurance (1509/2138, 79% versus 30/33, 91%), and annual household income in US dollars ≥ $100,000 (757/2138, 45% versus 16/33, 55%) in the fertile and infertile men, respectively. On multivariate analysis, for each year of advancing age, men were 5% more likely to experience infertility. Age at questionnaire was the only significant predictor of infertility (OR 1.05; 95%CI 1.03 to 1.08). Age at T1D diagnosis (OR 1.01; 95%CI 0.99 to 1.04), duration of T1D (OR 0.99; 95%CI 0.96 to 1.01), mean HbA1C (OR 1.03; 95%CI 0.77 to 1.37), diabetic retinopathy (OR 1.04; 95%CI 0.50 to 2.15), and mean LDL (OR 1.01; 95%CI 0.99 to 1.02) failed to independently predict infertility; however, presence of renal failure (OR 3.38; 95%CI 0.94 to 12.13) and micro/macroalbuminuria (OR 1.27; 95%CI 0.42 to 3.82) trended toward increased odds of infertility. Conclusions: This study highlights the prevalence of male infertility among men with T1D. Beyond age, there were no independent clinical predictors for male infertility among men with T1D; however, men with clinical evidence of diabetes-associated renal compromise trended toward greater odds of infertility. Further studies of fertility in this growing, at-risk population are warranted.

The CGM Experience of Minority Adults With Type 1 Diabetes in the South Bronx

Objective: To describe the state of type 1 diabetes (T1D) in minority adults in the South Bronx, and their experience with continuous glucose monitoring (CGM). Introduction: In a recent analysis of data from the Type 1 Diabetes Exchange Registry, one notable finding was the difference in metabolic control and use of diabetes technology in patients of different socioeconomic status and racial/ethnic backgrounds. With limited data available on Hispanic and Black patients, we sought to examine the use of and experience with continuous glucose monitoring (CGM) in our hospital system, which primarily serves a low-income, minority population in the South Bronx. Methods: 68 adults with T1D who attended the Endocrinology clinic at our hospital from 2017 to 2019 were identified. Patients were contacted by telephone to complete a questionnaire regarding CGM use and satisfaction. A retrospective chart review was conducted to obtain additional demographic and clinical information. Results: Out of 68 patients with T1D in the hospital database who were contacted, 47 patients completed the questionnaire. The age range was 23 to 63 years. 42.6% were male. 59.6% were Hispanic, 19.1% Black/African American (AA), 4.3% Caucasian, and 17% not specified. 87.2% had public insurance. Overall, 48.9% of patients were actively using CGM, 19.1% had discontinued use of CGM, and 31.9% had never used CGM. In Hispanic patients using CGM, mean HbA1C was 8.2% compared to 10.1% in Hispanic non-users. In Black/AA patients using CGM, mean HbA1C was 9.2% compared to 9.9% in Black/AA non-users. Hospitalizations for acute diabetes complications were lower in CGM users (4.3%) compared to non-CGM users (16.7%). Among active CGM users, 74% rated their satisfaction as “extremely satisfied” or “very satisfied.” Perceived benefits included the prevention of hypoglycemia and awareness of inappropriate food intake. Discussion: Our study population, mainly comprised of Hispanic and Black T1D adults, showed a higher CGM utilization rate than previously reported. After stratification by socioeconomic status, CGM utilization was reported to be as low as 16% in Hispanic and 10% in Black patients with household income <$50,000/year in the T1D Exchange Registry. By comparison, 49% of our studied population possessing similar demographics was actively using CGM. This study demonstrated that CGM acceptance was high in this largely minority, low-income population in the South Bronx, and was associated with lower A1C levels, high degree of patient satisfaction and reduction in diabetes-related hospitalizations. However, glycemic control remained suboptimal overall despite CGM access. Additional strategies to optimize the utility of CGM are needed to improve clinical outcomes such as HbA1C levels in minority T1D patients.

1405-P: HbA1c Trajectories across Early Adulthood in the T1D Exchange Registry

Glycemic control in adolescents with type 1 diabetes (T1D) is poor; however, it typically improves during early adulthood. Factors related to improvement of glycemic control are unclear. A total of 1,775 participants aged 18-30 years at enrollment in the T1D Exchange Registry followed for an average of 6 years were included in this analysis. Latent class trajectory modeling was used to determine sub-groups following a similar HbA1c trajectory over time. Five distinct trajectories of HbA1c classes were identified: Groups 1 and 2 had low or moderate HbA1c with a gradual decline with age, Group 3 had high HbA1c and remained stable, and Groups 4 and 5 had very high HbA1c with rapid or gradual decline (Figure). Compared with Group 3, Groups 1 and 2 were more likely to be male (P = 0.01), white non-Hispanic (P = 0.02), non-smokers (P = 0.001), check glucose more frequently (P &amp;lt; 0.001), and have higher education (P &amp;lt; 0.001), lower BMI (P = 0.01), and lower daily insulin dose (P &amp;lt; 0.001); if female, those in Group 1 were more likely to have a pregnancy during the time observed (P = 0.04). Group 4 was more likely to increase number of SMBG checks (P = 0.02) and have BMI increase over time (P = 0.02) compared with Group 5. We determined 5 distinct patterns of glycemic control from young adulthood into adulthood. Further evaluation into the modifiable factors associated with a declining A1c trajectory would aid in the development of targeted interventions. Disclosure E. Toschi: None. R. Bailey: None. K. Miller: None. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2016PG-T1D053)

194-LB: T1D Exchange Registry: Current Data Insights and Future Impact

In a previous T1D Exchange led initiative, the T1D Exchange Clinic Registry encompassed 25,000 participants from 81 clinic sites across the U.S. who drove type 1 diabetes (T1D) research and produced real-world data on T1D. Upon the Clinic Registry’s closing, T1D Exchange launched the online T1D Exchange Registry in June of 2019 to lower barriers to research, increase participation, and strive to develop a more diverse population. The Registry is currently recruiting adults with T1D and parents/guardians of children who have T1D, living in the U.S. The Registry is a streamlined platform where participants enroll by completing screening questions, signing consent, and answering an initial questionnaire. Participants then complete an annual questionnaire to track health, disease management, and changes in outcomes over time. As of March 2020, there are over 5,300 participants enrolled in the Registry, with over 56% having completed their initial questionnaire. Currently, 10.9% of participants are between the ages of 1-17 years, 70.2% are between 18-55 years, and 18.9% are 56 years or above. This cohort represents a wide range of years since diagnosis, with 23.4% diagnosed within the past 5 years and 24.8% diagnosed more than 30 years ago. The majority identify as Caucasian (94.1%) and female (70.2%), with geographic representation from every U.S. state and territory. Among the pediatric cohort (&amp;lt;18 years), 24% reported A1C below 7.0%, whereas 36.1% of adults between 18-55 years reported A1C below 7.0%; 77.8% of adults 56 years or above reported A1C lower than 7.5%. The Registry cohort appears to be more technology-skilled than other T1D cohorts reported in the U.S., with 77.0% of participants currently using a CGM, and 67.2% using an insulin pump. Future projects for the Registry include analyzing longitudinal data, linking device data, sharing clinical trial opportunities, and providing additional research opportunities to participants. Disclosure K. LaFerriere: None. J. Liu: None. A. Hughes: None. W. Wolf: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2018PG-T1D074)

2016-P: Bariatric Surgery May Improve Glucose Control among Patients with Type 1 Diabetes

The prevalence of obesity in patients with type 1 diabetes (T1D) is increasing. Obesity and metabolic syndrome are risk factors which contribute to the development and progression of micro- and macrovascular complications. Several studies have shown the beneficial and durable effect of bariatric surgery in patients with type 2 diabetes, but data in patients with T1D are scarce. We evaluated the impact of bariatric surgery in adult T1D patients enrolled in the T1D Exchange Registry. Clinical characteristics, comorbidities, socioeconomic factors and laboratory data were obtained within 5 years before or after bariatric surgery. A linear mixed model was used to compare glycemic and clinical outcomes before and after surgery controlling for patient characteristics. Overall, data were available for 38 patients of which 34 were female, 31 were white non-Hispanic (2 missing race); age and T1D duration at time of surgery was 43±9 yrs and 22 ± 13 yrs. After bariatric surgery, patients had lower HbA1c (8.7±1.4 before vs. 8.1±1.3% after), BMI (37.3±10.2 vs. 33.0±7.2 kg/m2), and LDL level (88±27 vs. 79±19 mg/dL), but only BMI reached statistical significance (Table). Although limitations include a small number of subjects and lack of information on type of surgery, this is to date the largest sample size. Our results suggest evidence T1D bariatric surgery is associated with improvement in diabetes control, although more research is needed. Disclosure F. Vendrame: None. A. Casu: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Janssen Scientific Affairs, LLC., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2016PG-T1D053)

Diabetes Self-Management Decrements Mediate the Relation of Stressful Life Events and Hemoglobin A1c—Differences by Race/Ethnicity in Adolescents

PurposeThe aim of the study was to establish whether suboptimal self-management explains the relationship between stressful life events and hemoglobin A1c (HbA1c) in adolescents with type 1 diabetes and whether these relationships differ across race/ethnicity. MethodsParticipants were 6,368 adolescents enrolled in the U.S. T1D Exchange registry. The outcome, HbA1c, was chart-based; predictors and covariates were self-reported. Moderated mediation was tested using Mplus, adjusting for gender, age, insulin treatment modality, and socioeconomic status. ResultsHigher frequency of missed insulin doses and lower frequency of daily self-monitoring of blood glucose partially explained the relationship between past-year stressful life events and higher HbA1c. Mediation by self-monitoring of blood glucose was detected for those who identified as white non-Hispanic and Hispanic, but not for those who identified as African American. ConclusionsIn adolescents, there is some evidence for a behavioral mechanism in the stressor–HbA1c relationship. African American youth may be more resilient against some detrimental behavioral effects of stressors.

How Significant Is Severe Hypoglycemia in Older Adults With Diabetes?

Severe hypoglycemia is a devastating event in the lives of people with diabetes treated with insulin and/or insulin secretogogues. Severe hypoglycemia is defined as an episode in which the person with diabetes requires the assistance of another to increase blood glucose, usually by administration of glucagon or contacting a medical professional. These occurrences are not rare. More than 10% of adult patients in the T1D Exchange registry reported at least one episode of severe hypoglycemia over the past 12 months (1). These events elicit profound fear in patients with diabetes. By depriving the brain of glucose, severe hypoglycemia acutely alters brain function, resulting in neuroglycopenic symptoms, seizures, or even death. The impact extends beyond the acute event. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that patients with type 2 diabetes who experience severe hypoglycemia were at higher risk for a major macrovascular event or death over the subsequent 12 months (2). As the population ages, there remains a critical need to understand the significance and impact of severe hypoglycemia in older patients with diabetes. In this issue of Diabetes Care , complementary articles provide new insights into the consequences of severe hypoglycemia in older adults. Lacy et al. (3) report that severe hypoglycemia is associated with reduced cognitive function in older adults with type 1 diabetes, and Standl et al. (4) confirm the bidirectional nature of the association between severe hypoglycemia and cardiovascular (CV) events in adults with type 2 diabetes. Both investigations …

Risk Factors for Cardiovascular Disease (CVD) in Adults with Type 1 Diabetes: Findings from Prospective Real-life T1D Exchange Registry.

Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. Observational study of CVD and CVD risk factors over a median of 5.3 years. The T1D Exchange clinic network. Adults (age ≥ 18 years) with type 1 diabetes and without known CVD diagnosed before or at enrollment. Associations between CVD risk factors and incident CVD were assessed by multivariable logistic regression. The study included 8,727 participants (53% female, 88% non-Hispanic white, median age 33 years [interquartile ratio {IQR} = 21, 48], type 1 diabetes duration 16 years [IQR = 9, 26]). At enrollment, median HbA1c was 7.6% (66 mmol/mol) (IQR = 6.9 [52], 8.6 [70]), 33% used a statin, and 37% used blood pressure medication. Over a mean follow-up of 4.6 years, 325 (3.7%) participants developed incident CVD. Ischemic heart disease was the most common CVD event. Increasing age, body mass index, HbA1c, presence of hypertension and dyslipidemia, increasing duration of diabetes, and diabetic nephropathy were associated with increased risk for CVD. There were no significant gender differences in CVD risk. HbA1c, hypertension, dyslipidemia and diabetic nephropathy are important risk factors for CVD in adults with type 1 diabetes. A longer follow-up is likely required to assess the impact of other traditional CVD risk factors on incident CVD in the current era.

Overweight and obese children with optimal control in the T1D Exchange Registry: How are they different from lean children with optimal control?

AimsIncreased adiposity is a risk factor for suboptimal diabetes control and cardiovascular disease (CVD) complications.Our goal was to identify modifiable behavioral characteristics of overweight and obese pediatric patients with type 1 diabetes mellitus (T1DM) who achieve optimal glycemic control and to evaluate their CVD risk compared to lean patients. Our hypothesis was that optimally controlled obese and overweight participants require more total daily insulin and are at higher CVD risk compared to optimally controlled lean participants. MethodsWe analyzed a cohort of 9263 participants with T1DM aged <21 years in the T1D Exchange Registry. Optimal diabetes control was defined as HbA1c ≤ 7.5% (58 mmol/mol). We compared factors that influence glycemic control in lean, overweight and obese participants with optimal vs. suboptimal control, using logistic regression. ResultsAge, race, overweight status, continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were important variables influencing glycemic control. In the optimally controlled cohort, 27% of participants were overweight or obese versus 30% in the suboptimally controlled cohort (P < 0.001). Overweight and obese participants with optimal control were not significantly different from lean participants in terms of CSII use, total daily insulin dosage per kg of bodyweight, glucose checks per day, boluses with bedtime snack, use of CGM, but had higher LDL cholesterol and triglycerides, and lower HDL cholesterol (P < 0.05). ConclusionsThere were no differences in modifiable behavioral characteristics between the obese, overweight and lean optimally controlled participants. However, predictors of cardiovascular disease were higher in the overweight and obese group.

Autism spectrum disorder in children with Type 1 diabetes

Links between autism spectrum disorder (ASD) and autoimmune diseases, including Type 1 diabetes have been proposed. This study assessed the frequency of ASD in children with Type 1 diabetes in the T1D Exchange (T1DX) registry and the impact of ASD on characteristics of children with Type 1 diabetes. Analysis included 10032 participants aged <18 years (median Type 1 diabetes duration 6.5 years, 48% female, 77% non-Hispanic White). Diagnosis of ASD was defined as autism, Asperger's or pervasive developmental disorder. A diagnosis of ASD was recorded for 159 (1.58%) participants. Those with ASD were predominantly male (88% vs. 51% of those without ASD, P<0.001) and slightly older (median 14 vs. 13years, P=0.022). Occurrence of diabetic ketoacidosis at Type 1 diabetes diagnosis was similar (35% vs. 41%, P=0.161). Pump use was lower in those with ASD (51% vs. 63%, P=0.005) but continuous glucose monitor use was similar (24% vs. 27%, P=0.351). Median HbA1c was slightly lower in those with ASD [68 vs. 69 mmol/mol (8.4% vs. 8.5%), P=0.006]. This difference was more pronounced after adjusting for confounders. The frequency of ASD in the T1DX registry was similar to that in the general population. These data show that despite deficits in communication, occurrence of diabetic ketoacidosis was similar in youth with and without ASD. Pump use was less frequent in those with ASD, possibly due to sensory issues, although CGM use did not differ. The lower HbA1c may be due to a more regimented routine with ASD. Because comorbidities such as ASD complicate care of patients with Type 1 diabetes, further research is needed to support these children.

Biologic and social factors predict incident kidney disease in type 1 diabetes: Results from the T1D exchange clinic network

AimsDiabetic kidney disease (DKD) is a major complication of type 1 diabetes (T1D). To better understand the development of DKD in modern clinical practice, we evaluated risk factors in participants from the T1D Exchange Registry who completed 5-years of longitudinal follow-up. MethodsParticipants had T1D duration ≥ 1 year, age ≥ 10 years, eGFR ≥ 60 ml/min and no albuminuria at enrollment, and at least two serum creatinine and urine albumin measurements recorded during follow-up. Adverse kidney outcomes were defined as eGFR ≪ 60 ml/min and/or albuminuria (ALB) defined by as two consecutive albumin/creatinine ratios or two out of the past three measurements ≫ 30 μg/mg at any follow-up data collection. Associations of baseline characteristics with adverse kidney outcomes were assessed. ResultsAmong 3940 participants (mean age 41 ± 15 yrs, T1D duration 21 ± 13 yrs), 653 (16.6%) experienced an adverse kidney outcome: 268 (6.8%) experienced incident ALB only, 322 (8.2%) had eGFR decline to ≪60 ml/min without ALB, and 63 (1.6%) experienced eGFR ≪ 60 ml/min with ALB. In a multivariable analysis, higher HbA1c, higher SBP, lower DBP, older age and lower education level were associated with the development of adverse kidney outcomes (all p values ≤ 0.03). ConclusionsImproving modifiable risk factors, including glucose and blood pressure control, remain important to reduce the risk of DKD in T1D.

429-P: Therapeutic Inertia: Gap between Goals and Achievement between the T1DX and DPV Registries

Despite increased cardiovascular (CV) mortality in people with type 1 diabetes (T1D), treatment of CV risk factors may not be optimized. International registry comparisons highlight opportunities to improve clinical care and improve outcomes. We analyzed data from 28,494 patients from the German/Austrian DPV registry and 19,442 patients from the U.S. T1D Exchange (T1DX) Clinic registry with data between 01/2016 and 03/2018. Percent of patients by age category with HbA1c &amp;lt;7.5%, hypertension (HTN) and its treatment, dyslipidemia and its treatment, urine albumin to creatinine ratio &amp;gt;30 mg/g, BMI &amp;gt;30 kg/m2, and current smoking are reported. Logistic regression models by age group adjusted for sex and diabetes duration were used to calculate whether registry differences existed. The prevalence of obesity is lower in the DPV than the T1DX registry (Table). In those age &amp;lt;26 years more DPV than T1DX patients had A1c &amp;lt;7.5%. Hypertension was more prevalent in the DPV for those &amp;lt;26 years, but less prevalent for those &amp;gt;50 years. Dyslipidemia was more prevalent in DPV for those &amp;lt;50 years, but less for those &amp;lt;50 years. Elevated ACR and smoking are higher and HTN and dyslipidemia treatment are lower in the DPV than in the T1DX. Vascular disease remains the leading cause of morbidity and mortality in T1D. Comparison of risk factors and their treatment in these registries highlights opportunities to improve care and outcomes. Disclosure D.M. Maahs: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; Abbott, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. J. Hermann: None. N.C. Foster: None. W. Karges: None. K. Miller: None. A. Dost: None. R.S. Weinstock: Consultant; Self; Insulogic LLC. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Jaeb Center for Health Research, Kowa Pharmaceutical Europe Co. Ltd., Medtronic MiniMed, Inc., Oramed Pharmaceuticals. Other Relationship; Self; Unitio, Inc. M. Pavel: None. V.N. Shah: Advisory Panel; Self; Sanofi US. Consultant; Self; Dexcom, Inc. R.W. Holl: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust; German Center for Diabetes Research; German Diabetes Association; European Foundation for the Study of Diabetes; INNODIA

1688-P: Component Causes of HbA1c Trajectories among Adolescents/Young Adults with Type 1 Diabetes

We sought to examine trajectories in glycemic control across the transition from adolescence into early adulthood and identify component causes related to co-occurring psychosocial and behavioral changes. The cohort included 48,137 HbA1c values for 10,174 participants (ages 13-25) with T1D (49% female; 51% pump users) enrolled in the T1D Exchange registry. Multivariate mixed effects models were used to identify HbA1c trajectories; interactions between age and predictors were used to quantify how each predictor moderated trajectory shape. Mean HbA1c for the cohort was high (8.66), with only 14.0% meeting the adult target of &amp;lt;7.0%. Key indicators of self-management, including frequency of daily testing and testing before administering insulin, declined steadily into early adulthood while diabetes distress peaked in early 20s; in adjusted analyses, these strongly influenced the shape of HbA1c trajectories (see Figure) whereby increases in HbA1c were exacerbated with suboptimal self-management/distress. These psychosocial and self-management indicators were more influential than treatment regimen for predicting glycemic control. Late adolescence/early adulthood are periods of distinct vulnerability that warrant additional efforts to improve disease control via affecting self-management and distress. Disclosure L.E. Wisk: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1K01DK116932-01)

1681-P: Polyendocrinopathy in Type 1 Diabetes: A Transatlantic Comparison

Type 1 diabetes (T1D) is associated with additional autoimmune and endocrine disorders; however, their prevalences internationally are poorly understood. We analyzed 22,632 patients from the U.S. T1D Exchange (T1DX) registry (median age 18 years) and 38,470 patients from the German/Austrian DPV registry (median age 16 years) with T1D duration ≥1 year (median duration 10 and 6 years, respectively) with data between 01/2016 and 03/2018. Reported prevalences of thyroid disease, arthritis, Addison’s disease, and atrophic gastritis were compared using logistic regression models with registry, age group, and sex as covariates. Thyroid disease was more frequent in the T1DX, whereas arthritis was more frequent in the DPV. Prevalence increased with age in both registries. We found no significant differences between T1DX and DPV for Addison’s disease (Figure). Atrophic gastritis was rare in both registries (T1DX: n=3, DPV: n=21). After adjustment for age, thyroid disease was about twice as frequent in females compared with males (T1DX: 25 vs. 13%, DPV: 15 vs. 7%, both p&amp;lt;0.001). Likewise, arthritis was more frequent in females (T1DX: 0.23 vs. 0.16%, p=0.034; DPV: 1.45 vs. 0.88%, p&amp;lt;0.001), whereas Addison’s disease did not differ significantly by sex. Despite different prevalences, patterns of disease frequencies by age and sex were comparable in both registries. However, standardized clinical diagnoses are needed for valid comparisons between countries. Disclosure J. Hermann: None. K. Miller: None. G. Szinnai: None. N.C. Foster: None. T.M. Kapellen: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research &amp; Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. E. Fröhlich-Reiterer: None. J.B. McGill: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Dexcom, Inc., Medtronic, Novartis AG, Sanofi US. Speaker's Bureau; Self; Aegerion Pharmaceuticals, Dexcom, Inc., Janssen Pharmaceuticals, Inc., MannKind Corporation. R.W. Holl: None. D.M. Maahs: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; Abbott, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. Funding German Center for Diabetes Research; The Leona M. and Harry B. Helmsley Charitable Trust; German Center for Diabetes Research; German Diabetes Association; European Foundation for the Study of Diabetes; INNODIA

217-OR: Islet Transplantation vs. Standard of Care for Type 1 Diabetes Complicated by Severe Hypoglycemia from the Collaborative Islet Transplant Registry (CITR) and T1D Exchange (T1DX) Registry

Islet transplantation is an emerging treatment for T1D, in particular for those with long standing disease experiencing severe hypoglycemia events (SHE). A phase 3 trial of islet transplantation in T1D complicated by SHE demonstrated &amp;gt; 80% of islet recipients achieved HbA1c &amp;lt; 7.0% and absence of SHE at 1 year. To better understand the long-term benefit for glycemic control and risk of immunosuppression to kidney function associated with islet transplantation vs. standard of care, we selected patients from CITR with at least one SHE in the year prior to transplant, and compared them to patients from T1DX with at least one SHE in the prior year and followed over 5 years. The cohorts from CITR (n = 58) and T1DX (n = 213) were aged 42 ± 9 and 43 ± 17 with disease duration 29 ± 10 and 26 ± 15 years (P &amp;lt; 0.01) and experienced 5 ± 11 and 2 ± 1 SHE (P &amp;lt; 0.01) in the year prior to baseline with HbA1c 7.3 ± 1.0 vs. 7.8 ± 1.5 (P &amp;lt; 0.001). Mean HbA1c decreased to 6.3% vs. ranging 7.8-7.6% over 5 years (P &amp;lt; 0.001), and the % experiencing recurrent SHE was less in CITR than T1DX (P &amp;lt; 0.01), such that 78-77% vs. 23-28% met the primary endpoint of HbA1c &amp;lt; 7.0% and absence of SHE (P &amp;lt; 0.001). Insulin requirements were slightly less at baseline in CITR than T1DX (0.52 ± 0.14 vs. 0.64 ± 0.31 U/kg/d; P &amp;lt; 0.001), and decreased to 0.06-0.17 vs. remaining 0.66-0.56 U/kg/d over 5 years (P &amp;lt;0.001) with 80-48% insulin independent in CITR. GFR was 92 ± 17 and 90 ± 29 ml/min/1.73 m2 at baseline, and decreased to 83-78 vs. 87-81 ml/min/1.73 m2 over 5 years (P &amp;lt; 0.001). These data demonstrate long-term durability of islet transplantation to achieve near-normal glycemic control in the absence of SHE more often than that observed with standard of care delivered by specialized diabetes practice. Initial reduction in GFR observed during the first-year post-transplant may be attributable to the initiation of immunosuppression, but was not associated with further decline during 5 year follow-up. Disclosure M.R. Rickels: None. N.C. Foster: None. C.M. Ballou: None. B.J. Hering: Other Relationship; Self; Diabetes-Free, Inc. R. Alejandro: None. R. Beck: Other Relationship; Self; Abbott Laboratories, Ascensia Diabetes Care, Bigfoot Biomedical, Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Roche Diabetes Care, Tandem Diabetes Care. K. Miller: None. F.B. Barton: None. Funding National Institutes of Health; Leona M. and Harry B. Helmsley Charitable Trust

1355-P: HbA1c Trajectories from Time of Diagnosis in Youth with T1D

Most individuals with type 1 diabetes (T1D) do not achieve glycemic targets, particularly in youth. This analysis examined HbA1c trajectories of youth newly diagnosed with T1D. T1D Exchange registry participants &amp;lt;18 years with at least one HbA1c during the year of diagnosis and ≥3 duration-year aggregated HbA1c values over 10 years of follow-up were included. At diagnosis, the 4183 participants were 48% female, 81% Caucasian, age 6±4 years, and 77% privately insured. Suboptimal control was defined as HbA1c ≥9%. Group-based trajectory modelling was used to identify unique HbA1c trajectories over aggregated duration years. Five trajectories emerged (Figure). The majority of youth had stable trajectories within three distinct categories: those at (1) or above (3) glycemic target and those with suboptimal control (4). Two groups showed deterioration over time, one with suboptimal control from diagnosis (5) while the other had above target glycemia that worsened with time (2). Minority status was higher in groups with upward trend in HbA1c trajectory and suboptimal but stable control. Similar trends were seen for non-private insurance. Several distinct patterns of HbA1c progression exist in youth with T1D, partly dependent on HbA1c at diagnosis. Identifying characteristics of those with progressive deterioration in glycemic control and designing appropriate interventions for these groups is warranted. Disclosure J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Eli Lilly and Company, Insulet Corporation. Consultant; Self; Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi. Research Support; Self; Dexcom, Inc., Insulet Corporation. N.C. Foster: None. K. Bethin: Research Support; Self; Novo Nordisk Inc., Xeris Pharmaceuticals, Inc. L.A. Fox: None. L.D. Mastrandrea: Advisory Panel; Self; Pediatric Diabetes Consortium. Research Support; Self; AstraZeneca, JDRF, Novo Nordisk Inc., Sanofi-Aventis, T1D Exchange. Other Relationship; Self; Novo Nordisk Inc. B.M. Nathan: None. M.J. Redondo: None. J. Silverstein: None. J. Simmons: None. M.A. Clements: Advisory Panel; Self; Glooko, Inc. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Medtronic. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. K.M. Thrailkill: None. J.C. Wong: Advisory Panel; Self; Tidepool Project. Research Support; Self; Dexcom, Inc. J. Wood: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc.

Longitudinal Changes in Depression Symptoms and Glycemia in Adults With Type 1 Diabetes.

This study assessed longitudinal change in depression symptoms over ≥4 years in adults with type 1 diabetes and examined the association between change in depression symptom status and glycemia. Adults in the T1D Exchange registry with HbA1c and Patient Health Questionnaire (PHQ-8) at 1 year (baseline) and 5 years post-enrollment (follow-up; n = 2,744, mean age, 42 years; 57% female, 92% white; mean HbA1c, 7.6% [58 mmol/mol]) were included. Depression status was defined as Persistent Elevated Depression Symptoms (EDS) (EDS at baseline and follow-up), Resolved EDS (EDS at baseline, no EDS at follow-up), New Onset EDS (no EDS at baseline, EDS at follow-up), and Not Depressed (no EDS at baseline or follow-up). Overall, 131 (5%) had Persistent EDS, 122 (4%) had Resolved EDS, 168 (6%) had New Onset EDS, and 2,323 (85%) were Not Depressed. Of those with EDS (PHQ ≥ 10) at baseline, 53% had EDS at follow-up; of those not depressed at baseline, 7% had EDS at follow-up. An increase in PHQ-8 was associated with an increase in HbA1c (P < 0.001). Although HbA1c increased in all groups, the increase was less in the Resolved EDS and Not Depressed groups (P = 0.001). Persistent EDS and New Onset EDS groups were more likely to experience diabetic ketoacidosis (DKA) (P < 0.001). T1D Exchange registry data provide evidence for relationships over time between persistently, and newly developing EDSs and worsening glycemic control, and suggest relationships between depression symptoms and the occurrence of severe hypoglycemia and DKA. Successful treatment of depression symptoms may lead to better long-term diabetes outcomes.

SGLT Inhibitors for Type 1 Diabetes: Proceed With Extreme Caution.

Intensive insulin management is currently the only option for effective treatment of type 1 diabetes. Recent data from the T1D Exchange (T1DX) registry (1), which comprises leading U.S. diabetes treatment centers, show that despite the widespread availability of insulin analogs and increasing use of insulin pumps and continuous glucose monitoring systems, only about 20% of adult patients achieve the A1C target of <7% (53 mmol/mol) recommended by the American Diabetes Association (2). It is reasonable to assume that glycemic control of patients receiving care outside of major centers might be even worse. The T1DX registry has also shown that nearly 5% of adult participants experienced one or more episodes of diabetic ketoacidosis (DKA) within the past 12 months (3), and the Centers for Disease Control and Prevention recently reported a 6.3% annual increase in hospitalization rates for DKA from 2009 to 2014, with highest rates in persons aged <45 years (4). Moreover, the majority of patients are either overweight or obese, potentially increasing their risk of cardiovascular disease (1). There is clearly an unmet need for noninsulin adjunctive therapies that improve glycemic control without increasing the risk of hypoglycemia or contributing to weight gain, and it is noteworthy that among nearly 50,000 pediatric and adult participants in the T1DX registry in the U.S. and the Prospective Diabetes Follow-up (DPV) registry in Germany and Austria, two large consortia of diabetes centers, adjuvant medications are being used off-label by 5.4% of participants in T1DX and 1.6% in DPV (5). Sodium–glucose cotransporter 2 (SGLT2) inhibitors block the SGLT2 transporter in the proximal renal tubule resulting in glucosuria and natriuresis and are approved and indicated for type 2 diabetes. Dual SGLT1+2 inhibitors have the additional effect of inhibiting SGLT1 in the gastrointestinal tract, thereby delaying intestinal absorption of glucose and galactose. Owing to …

CGM Benefits and Burdens: Two Brief Measures of Continuous Glucose Monitoring.

Continuous glucose monitors (CGM) are underutilized by individuals with type 1 diabetes (T1D), particularly during the adolescent years. Little is known about perceptions of CGM benefit and burdens, and few tools exist to quantify this information. Two questionnaires were developed and validated-Benefit of CGM (BenCGM) and Burdens of CGM (BurCGM)-in a sample of adolescents ages 12-19 years involved in the T1D Exchange Registry. We chose to start the validation process with adolescents given their low CGM uptake and high risk for suboptimal glycemic outcomes. Exploratory and confirmatory factor analyses were conducted to confirm factor structure and select items. The resultant scales were tested for internal reliability and convergent/divergent validity with critical diabetes and quality of life outcomes: age, depression, diabetes distress, self-efficacy, technology attitudes, and diabetes technology attitudes. A total of 431 adolescents with T1D completed the questionnaires (51% female, mean age 16.3 ± 2.26, 83% white non-Hispanic, 70% having used CGM). Two single factor scales emerged, and scales were reduced to 8 items each. Those who perceived higher benefit of CGM exhibited lower diabetes distress, higher self-efficacy, and more positive attitudes toward technology. Those who perceived higher burden of CGM exhibited higher diabetes distress, lower self-efficacy, and less positive technology attitudes. The BenCGM and BurCGM questionnaires each comprise 8-items that demonstrate robust psychometric properties for use in adolescents with T1D, and can be used to develop targeted interventions to increase CGM wear to improve diabetes management.