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Context Prenatal exposures, including undernutrition, overnutrition, and parental diabetes, are recognized risk factors for future cardiometabolic disease. There are currently no data on effects of parental diabetes on disease progression or complications in youth-onset type 2 diabetes (T2D). Objective We analyzed effects of parental diabetes history on glycemic outcomes, β-cell function, and complications in a US cohort of youth-onset T2D. Methods Participants (N = 699) aged 10 to 17 years with T2D were enrolled at 15 US centers and followed for up to 12 years as part of the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) and TODAY2 follow-up studies. Information about diabetes diagnosis in biological mothers was available for 621 participants (never = 301; before or during pregnancy = 218; after pregnancy = 102) and in biological fathers for 519 (no diabetes = 352; paternal diabetes = 167). Results Maternal, but not paternal, diabetes was associated with loss of glycemic control over time, defined as glycated hemoglobin A1c greater than or equal to 8% for more than 6 months (P = .001). Similarly, maternal, but not paternal, diabetes was associated with increased risk of glomerular hyperfiltration (P = .01) and low heart rate variability (P = .006) after 12 years of follow-up. Effects were largely independent of age, sex, race/ethnicity, and household income. Maternal diabetes during vs after pregnancy had similar effects on outcomes. Conclusion Maternal diabetes, regardless of whether diagnosed during vs after pregnancy, is associated with worse glycemic control, glomerular hyperfiltration, and reduced heart rate variability in youth with T2D in TODAY. The strong associations of diabetes outcomes with maternal diabetes suggest a possible role for in utero programming.

OBJECTIVETo assess the prevalence of high diabetes distress and associated factors in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY2) study cohort of young adults with youth-onset type 2 diabetes.RESEARCH DESIGN AND METHODSParticipants completed the Diabetes Distress Scale (DDS) at end-of-study visits. Factors examined for association with high distress were demographic (sex, race/ethnicity, age, education, income), medical (HbA1c, BMI, complications), psychological (depressive and anxiety symptoms), and social (number in household, offspring, health care coverage, established with diabetes care provider). Univariate logistic regression identified factors associated with high distress that were controlled for in multivariate logistic regressions.RESULTSOf 438 participants, 66% were female (mean age 26.8 years, 18% non-Hispanic White, 37% non-Hispanic Black, 38% Hispanic). High distress (DDS ≥2) was reported by 105 (24%) participants. Subscales identified 40% with high regimen distress and 29.7% with high emotional burden. A greater percentage of those with high distress were female (P = 0.002), diagnosed with hypertension (P = 0.037) and retinopathy (P = 0.005), treated with insulin, had higher HbA1c, and had moderate to severe depressive and anxiety symptoms (all P < 0.001). In multivariate analyses, female sex (P < 0.001), HbA1c (P < 0.001), anxiety symptoms (P = 0.036), and lack of health care coverage (P = 0.019) were associated with high distress, after controlling for potential confounders. Moderate to severe depressive symptoms were associated with high regimen distress (P = 0.018) and emotional burden (P < 0.001); insulin treatment was associated with high emotional burden (P = 0.027).CONCLUSIONSFuture research should identify modifiable factors associated with high diabetes distress in young adults with youth-onset type 2 diabetes that may inform distress interventions with this medically vulnerable group.

Objectives: To assess prevalence of high diabetes distress and associated factors in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort of young adults with youth-onset type 2 diabetes. Methods: Participants completed the Diabetes Distress Scale (DDS) at end-of-study visits. Factors examined for association with high distress were demographic (gender, race/ethnicity, age, education, income), medical (HbA1c, BMI, complications), psychological (depressive and anxiety symptoms), and social (number in household, have offspring, healthcare coverage, established with diabetes care provider). Univariate logistic regressions identified factors associated with high distress that were controlled for in multivariate logistic regressions. Results: Of 438 participants, 66% were female, mean age=26.8 years, 18% non-Hispanic white, 37% non-Hispanic Black, 38% Hispanic. High distress (DDS ≥2) was reported by 105 (24%) participants. Subscales identified 40% with high “Regimen Distress,” 29.7% with high “Emotional Burden.” A greater percentage of those with high distress were female (p=0.002), diagnosed with hypertension (p=0.037) and retinopathy (p=0.005), insulin treated, had higher HbA1c, and moderate-to-severe depressive and anxiety symptoms (all p’s In multivariate analyses, female gender, HbA1c (p Conclusion: Future research should identify modifiable factors associated with high diabetes distress in those with youth-onset type 2 diabetes that may inform distress interventions with this medically vulnerable group.

Aims: Diabetes distress (DD) is associated with poor health outcomes. Little is known about level of DD in young adults (YAs) with youth-onset type 2 diabetes (T2D) or individual factors associated with DD. Aims were to assess level of DD, and factors associated with high DD, in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. Methods: YAs completed the Diabetes Distress Scale (DDS), PHQ-9 (depressive symptoms) and GAD7 (anxiety), at the end-of-study visit. Factors that may relate to DD were demographics (sex, race/ethnicity, age, education, income), medical history (HbA1c, BMI, complications), and social/economic factors (# persons in household, parent status, healthcare coverage, access to diabetes care provider). Univariate logistic regressions found factors associated with high DD. Multivariate regression controlled for sex, HbA1c, healthcare coverage, anxiety, depressive symptoms and retinopathy. Results: Of 457 YAs, mean age=26.7 yrs, 65% were female, 20% non-Hispanic white, 38% non-Hispanic Black, 20% Hispanic, 62% Conclusion: In young adults with youth-onset T2D, high DD was significantly more likely in females, and those with anxiety, high HbA1c, and without healthcare coverage. Disclosure P. M. Trief: None. M. S. Rayas: Research Support; Self; National Center for Advancing Translational Sciences. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. D. Uschner: None. M. Tung: None. L. Chao: None. R. M. Farrell: Stock/Shareholder; Self; Tandem Diabetes Care. J. Keady: None. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. M. D. Marcus: Advisory Panel; Self; Weight Watchers International, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61212, U01DK61230, U01DK61239, U01DK61242, U01DK61254)

Vision-threatening DR (vtDR) is commonly defined as moderate nonproliferative or more severe DR, or the presence of diabetic macular edema (DME). Modifiable risk factors of DR and vtDR are well-established in adults. This study identified risk factors associated with DR and vtDR in a large pediatric cohort with T1D. Medical chart review was performed of baseline visits of pediatric (≤21 yrs old) patients at an academic eye center from 2005-2020 to collect demographic characteristics, medical history and DR severity. Analyses were adjusted for correlation between eyes of the same person. In total, 1735 subjects (3454 eyes) were included with mean±SD age 15.4±4.6 years, T1D duration 7.1±5.3 years, T1D onset 8.3±5.4 years, and A1c 8.4±1.3; 50.7% were female, 30.7% were overweight/obese and 4.1% had elevated/high BP. Any DR was present in 8.5% and vtDR in 2.4% of eyes. Unadjusted analyses found DR presence associated with higher A1c (p Disclosure C. Jacoba: None. K. Sampani: None. C. Gilbert: None. P. S. Silva: Research Support; Self; Hillrom, Optomed, Optos plc. J. Keady: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. L. P. Aiello: Consultant; Self; KalVista Pharmaceuticals, Novo Nordisk, Regeneron Pharmaceuticals Inc., Stock/Shareholder; Self; KalVista Pharmaceuticals. J. Sun: Other Relationship; Self; Novo Nordisk, Roche Pharma, Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Optovue, Roche Pharma.

Background: Prenatal exposures, including parental nutrition and diabetes (DM) status, are increasingly viewed as risk factors for future cardiometabolic health. There are currently no data on effects of parental DM on disease progression or complications in youth-onset T2D. Aims: To analyze effects of parental history of DM on glycemic outcomes and complications in the TODAY study. Methods: Participants (n=699) aged 10-14 yr with newly diagnosed T2D were enrolled at 14 U.S. centers and followed for up to 15 yr. Subjects had negative islet autoantibodies and BMI >= 85th %. Information about DM diagnosis in mothers of participants was available for 621 participants [Never (MN) =301; During pregnancy (MD) =218; After pregnancy (MA)=102)] and in biological fathers in 519 (No DM=352; Paternal DM=167). Results: Maternal, but not paternal, DM was associated with accelerated loss of glycemic control, defined as HbA1c >8% for over 6 months (p < 0.0001). Participants whose mothers had diabetes had 60% higher risk of loss of glycemic control [MD vs. MN hazard ratio (HR): 1.58 (1.28, 1.95), p < 0.0001; MA vs. MN HR: 1.57 (1.20, 2.04), p = 0.0009]. Similarly, maternal, but not paternal, diabetes was associated with glomerular hyperfiltration [MD vs. MN HR: 1.58 (1.18-2.1), p = 0.0021; MA vs. MN HR: 1.56 (1.08, 2.24), p = 0.0170;], diabetic retinopathy (MD: 50.0%; MA: 59.7%; MN: 41.8%, p=0.0439), and pulse wave velocity indices reflecting heart rate variability, including SD of normal R-R interval [(SDNN), MD: 42 ± 26 ms; MA: 41 ± 26 ms; MN: 54 ± 31 ms; p = 0.0005] and proportion of successive NN intervals greater than 50 ms [(pNN50%), MD: 14.1 ± 19.4; MA: 16.2 ± 21.5; MN: 21.9 ± 23.5; p = 0.0069], after 10 to 15 yr of follow-up. Associations were maintained after adjusting for multiple confounders. Conclusions: Maternal, but not paternal, diabetes is associated with adverse diabetes outcomes and accelerated onset of complications in their offspring with T2D in TODAY. Disclosure E. M. Isganaitis: None. M. A. Van name: None. R. Shah: None. S. Chernausek: None. R. M. Farrell: Stock/Shareholder; Self; Tandem Diabetes Care. M. Geffner: Advisory Panel; Self; Daiichi Sankyo, Novo Nordisk, Pfizer Inc., Consultant; Self; Gilead Sciences, Inc., Other Relationship; Self; Ascendis Pharma A/S, McGraw-Hill, UpToDate, Research Support; Self; Novo Nordisk. J. Keady: None. M. M. Kelsey: Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. B. Tesfaldet: None. J. B. Tryggestad: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61212, U01DK61230, U01DK61239, U01DK61242, U01DK61254)

Aim: To explore associations between health-related quality of life (HRQOL) and comorbidities in youth with Type 2 diabetes. Patients & methods: Of 699 youth in the TODAY study, 685 (98%) had baseline HRQOL data, 649 (93%) at 6 months and 583 (83%) at 24 months. Comorbidities were defined by sustained abnormal values and treatment regimens. Results: At baseline, 22.2% of participants demonstrated impaired HRQOL. Only depressive symptoms distinguished those with versus without impaired HRQOL and were significantly related to later impaired HRQOL (p < 0.0001). A significant correspondence between impaired HRQOL and number of comorbidities (p = 0.0003) was noted, but was driven by the presence of depressive symptoms. Conclusion: Results emphasize the need for evaluation of depressive symptoms. Other comorbidities did not have a significant impact on HRQOL in this cohort.

Background: Glycemic control remains suboptimal in youth with type 1 diabetes. Retrospective continuous glucose monitoring (CGM) has demonstrated utility in fine-tuning diabetes management by detecting postprandial hyperglycemia and hypoglycemia. In this study, we explored the process of 3-day masked CGM use, subsequent treatment recommendations, and impact on A1c in a clinic-based sample of youth with type 1 diabetes. Methods: Over 2 years, 122 youth were referred for masked CGM. Patients/families completed a diary of blood glucose levels, insulin doses, food intake, and exercise during CGM use. A1c was assessed pre- and 2-3 months post-CGM. Treatment recommendations were formulated using data from CGM reports and diaries. Results: Mean age was 14.3 ± 3.9 years, diabetes duration was 7.5 ± 4.7 years, and A1c was 8.5 ± 1.1% (69 ± 12 mmol/mol); 61% were pump-treated. Patients received an average of 3.1 ± 1.1 treatment recommendations following review of the CGM report. Most (80%) received reinforcement of the importance of preprandial bolusing; 37% received a recommendation regarding advanced insulin management (use of combination boluses/attend to active insulin). Receipt of the latter recommendation was related to A1c improvement ≥0.5% (OR: 4.0, P < .001). Conclusions: Masked CGM offers opportunities to guide advanced insulin management (by injection or pump), which may yield A1c improvements in youth with type 1 diabetes.

The use of continuous glucose monitoring (CGM) in the pediatric population is not well characterized. We have evaluated the use of CGM over a 12-month interval in youth with type 1 diabetes (TID) and have provided a description of CGM use.Eighty subjects 8-17 years old with T1D and baseline hemoglobin A1c (HbA1c)or=7.0% used CGM as part of a 6-month randomized trial and subsequent 6-month extension study. Outcomes included frequency of CGM use, HbA1c levels, rate of severe hypoglycemia, and a CGM satisfaction scale.Seventy-six (95%) of 80 subjects were using CGM after 6 months (median use = 5.5 days/week) compared with 67 (84%) after 12 months (median use = 4.0 days/week). The 17 subjects using CGMor=6 days/week in month 12 had substantially greater improvement from baseline in HbA1c than did the 63 subjects using CGM6 days/week in month 12 (mean change - 0.8 +/- 0.6% vs. +0.1 +/- 0.7%, P0.001). They also reported greater satisfaction with use of CGM (P = 0.001). The incidence of severe hypoglycemic events was low during the 12 months of the study irrespective of the amount of CGM use.In youth with T1D, frequency of use decreases over time. Individuals who use CGM on a near-daily basis can have substantial improvement in glycemic control.