Youth-onset Type Research Articles

Abstract 13940: Remnant Lipoprotein Particles and Cholesterol Contribute to Proatherogenic Phenotype and Subclinical Inflammation in Youth-Onset Type 2 Diabetes

Introduction: Youth-onset type 2 diabetes (YT2D) is a rapidly progressive disease characterized by severe insulin resistance (IR), elevated triglyceride concentrations, and low HDL-cholesterol (-C). However, the contribution of triglyceride-rich remnant lipoproteins (TRLp) and remnant-C to overall atherogenic risk in YT2D is unknown, especially in the absence of clinically relevant elevations in LDL-C. Hypothesis: We hypothesized that YT2D would have higher remnant TRLp, remnant-C, and greater subclinical inflammation and IR compared to healthy peers with obesity. Methods: We measured fasting lipoprotein particle size and number, GlycA (a composite marker of inflammation), and lipoprotein IR index (LPIR) using NMR LipoProfile® in 61 YT2D (age 17.2 ±2.9 y, mean±SD, BMI 39.1 ±8.4 kg/m2) and 25 healthy peers (age 17.9 ± 5.1 y, BMI 35.8 ±5.7 kg/m2). Remnant Lp (small TRLp plus very small TRLp) and remnant-C (total-C minus HDL-C minus LDL-C) were calculated and the relationship with GlycA and LPIR determined by spearman correlations. Results: YT2D had higher HemoglobinA1c (7.6 ± 2.0 vs 5.8 ± 0.8%), GlycA (427 [388, 474] vs 376 [332, 406] nmol/L, median[25th,75th]), LPIR (53.7 ± 23.6 vs 29.6 ± 16.5). YT2D had higher remnant TRLp and remnant-C (Figure 1) and a more proatherogenic lipid and lipoprotein profile: LDL-C: 89 ± 23 vs 74 ± 20 mg/dL; total LDLp: 1392 ±368 vs 1075 ±289 nmol/L; small LDLp: 890 ±450 vs 519 ±232 nmol/L, all P<0.01. LPIR was associated with remnant-C (r=0.6, P<0.001) but not with LDL-C (r=0.1, P=0.6). GlycA was associated with remnant-C, remnant TRLp, and small LDLp (all r≥0.3, P<0.01). Conclusion: The proatherogenic profile in YT2D is characterized by higher small LDLp, remnant TRLp, and remnant-C and is related to IR and subclinical inflammation compared to healthy peers with obesity. Future research is needed to determine whether reducing all proatherogenic lipoproteins and inflammation will reduce ASCVD risk.

THU141 Clinical Characteristics Of Korean Youth-onset Type 2 Diabetes Patients With Remission

Abstract Disclosure: S. Shin: None. H. Kim: None. S. Kim: None. J. Kim: None. Backgrounds: Improvement of beta cell function can occur in some patients with type 2 diabetes mellitus (T2DM). However, studies on remission of youth-onset T2DM with pharmacotherapy are sparse. We aimed to identify the clinical characteristics of pediatric patients experiencing remission. Methods: Medical records of pediatric patients with T2DM who were followed up for at least 1 year at Seoul National Bundang Hospital (2015-2022) were retrospectively reviewed. Remission of T2DM was defined as a return of HbA1c to <6.5% that persists for at least 3 months after discontinuation of glucose-lowering pharmacotherapy. Clinical characteristics between the remission and non-remission groups were compared at three time points (at diagnosis, 3 months after diagnosis, and remission). Results: Among 66 patients with T2DM (46 males, 69.7%), the mean age at diagnosis was 14.6±0.5 years, and the mean follow-up duration was 3.0±0.5 years. One (1.5%) patient underwent lifestyle modification only, 13 (19.7%) were treated with oral hypoglycemic agents only, and 52 (78.8%) were combined with insulin therapy at diagnosis. Twelve patients (18.2%) attained remission after a mean of 1.4±0.4 years from the time of diagnosis (at a mean age of 16.1±1.1 years). The remission group showed a higher proportion of males (100.0% vs. 63.0%, P = 0.012). At diagnosis of T2DM, urinary microalbumin-to-creatinine ratio (ACR) was lower in the remission group than in the non-remission group (2.0±1.6 mg/g vs. 11.2±2.9 mg/g, P = 0.010). There were no significant differences between the groups in the presence of initial diabetic ketoacidosis, HbA1c levels at diagnosis, and type of initial treatment. At the time of remission, HbA1c levels were significantly decreased (from 11.8% to 5.4%), while high-density lipoprotein cholesterol levels were increased (from 40.1 mg/dL to 45.7 mg/dL) than those at the time of diagnosis (both P <0.05). Recurrence occurred in three of 12 (25.0%) patients after a mean of 1.9±1.7 years from the time of remission. Conclusion: In Korean youth with T2DM, remission was observed in 18.2% after a mean of 1.4 years of intervention with lifestyle and pharmacotherapy. Youth with T2DM remission showed male predominance, and lower ACR at the time of diagnosis. Further studies about underlying pathophysiology and long-term outcomes after remission are warranted. Presentation: Thursday, June 15, 2023

Antihypertensive and Lipid-Lowering Medication Adherence in Young Adults With Youth-Onset Type 2 Diabetes

Youth-onset type 2 diabetes is associated with early development of chronic complications. Treatment of elevated blood pressure (BP), nephropathy, and dyslipidemia are critical to reduce morbidity. Data are needed on adherence to BP- and lipid-lowering medications in young adults with youth-onset diabetes. To assess adherence and factors associated with adherence to BP- and lipid-lowering medications in young adults with youth-onset type 2 diabetes and diagnoses of hypertension, nephropathy, or dyslipidemia. This cohort study measured medication adherence with 3 monthly unannounced pill counts at 2 time points 1 year apart during iCount, conducted during the last years (2017-2019) of the observational phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth study. Psychosocial factors associated with medication adherence were examined. Participants included individuals with youth-onset type 2 diabetes with hypertension, nephropathy, or dyslipidemia receiving diabetes care in their communities. Data were analyzed from September 2022 to September 2023. The main outcome was BP- and lipid-lowering medication adherence, with low adherence defined as using less than 80% of pills and high adherence, at least 80% of pills. Psychosocial factors were measured using the Beliefs about Medicines Questionnaire and Material Needs Insecurities Survey. Of 381 participants in iCount, 243 participants (mean [SD] age, 26.12 [2.51] years; 159 [65.43%] women) with hypertension, nephropathy, or dyslipidemia were included in analysis. Among 196 participants with hypertension or nephropathy, 157 (80.1%) had low adherence. Participants with low adherence, compared with those with high adherence, were younger (mean [SD] age, 25.99 [2.41] vs 27.26 [2.41] years; P = .005), had higher glycated hemoglobin A1c (mean [SD], 10.33% [2.66 percentage points] vs 8.85% [2.39 percentage points]; P = .001), shorter diabetes duration (mean [SD], 12.32 [1.49] vs 12.90 [1.46] years; P = .03), and less education (eg, 17 participants [10.83%] vs 0 participants with no high school diploma; P = .004). Of 146 participants with dyslipidemia, 137 (93.8%) had low adherence and only 9 participants (6.2%) had high adherence. Of 103 participants with low adherence to BP-lowering medications and using oral hypoglycemic agents, 83 (80.58%) had low adherence to oral hypoglycemic agents. Beliefs that medications are necessary were higher for participants with high adherence to BP-lowering medications than those with low adherence in unadjusted analyses (mean [SD] necessity score, 16.87 [6.78] vs 13.89 [9.15]; P = .03). In adjusted multivariable analyses of participants with hypertension or nephropathy, having at least 1 unmet social need (odds ratio [OR], 0.20; 95% CI, 0.05-0.65; P = .04) and medication concerns (OR, 0.63; 95% CI, 0.40-0.96; P = .01) were associated with worse medication adherence 1 year follow-up. Diabetes distress, self-efficacy, depressive and anxiety symptoms, and self-management support were not associated with 1-year medication adherence. These findings suggest that adherence to BP- and lipid-lowering medications was very poor in this cohort. To improve medication adherence and prevent early vascular events, approaches that identify and address medication concerns and unmet social needs are needed.

Deterioration of glycemic control in youth-onset type 2 diabetes: What are the early and late predictors?

Deterioration of glycemic control in youth-onset type 2 diabetes: What are the early and late predictors?

Maternal diabetes in youth-onset type 2 diabetes is associated with progressive dysglycemia and risk of complications

Maternal diabetes in youth-onset type 2 diabetes is associated with progressive dysglycemia and risk of complications

The Coronavirus Disease 2019 pandemic is associated with a substantial rise in frequency and severity of presentation of youth-onset type 2 diabetes

The Coronavirus Disease 2019 pandemic is associated with a substantial rise in frequency and severity of presentation of youth-onset type 2 diabetes

Trends in incidence of youth-onset type 1 and type 2 diabetes in the USA, 2002-18: results from the population-based SEARCH for Diabetes in Youth study

Trends in incidence of youth-onset type 1 and type 2 diabetes in the USA, 2002-18: results from the population-based SEARCH for Diabetes in Youth study

Development and Implementation of a Multidisciplinary Clinic Focused on the Care of Adolescents with Youth-Onset Type 2 Diabetes.

Diabetes self-management education and lifestyle interventions are the cornerstones of type 2 diabetes (T2D) care; however, the higher risk of comorbidities among youth with T2D requires a comprehensive care model. Traditionally, sub-specialty care relies on a referral model placing the burden on patients/families. In response, we developed a pediatric T2D multidisciplinary clinic (MDC)-A single physical location where patients can access various sub-specialists. The goals of the MDC are to aid with lifestyle modifications and provide referral/access to sub-specialists within the MDC, as determined through screening labs and assessment tools. We conducted a retrospective chart review of youth seen in the T2D MDC clinic at Cincinnati Children's Hospital from 1/2020 to 12/2021. We evaluated the frequency that youth met with each specialist and completion rates of annual screening labs. The cohort consisted of 227 youth with T2D (mean age 17.6 years, mean BMI 40.9kg/m2, 64% female, 50% Black or African American, 65% public insurance). All patients met with a diabetes provider and 81.2% met with a registered dietitian/certified diabetes education specialist. Exercise physiology met with 51.5% of patients, gastroenterology met with 34.8% of patients, social work met with 44.1% of patients, clinical psychology met with 27.3% of patients, and bariatric surgery met with 9.7% of patients. Percent completion of annual labs were: 98.2% for HbA1c, 84.6% for urine microalbumin, 83.7% for lipids, 90% for liver function, 59.5% for retinopathy, and 45.4% for the Patient Health Questionnaire-9. The majority of patients received diabetes and nutrition education and annual screening labs. Exercise counseling and sub-specialty care remain below 60% in part due to services not being available at every MDC. Our goals are to increase access to subspecialty care within the MDC's and consider additional care delivery methods to provide comprehensive care to youth with T2D.

Reevaluating First-line Therapies in Youth-Onset Type 2 Diabetes.

The prevalence of youth-onset type 2 diabetes is growing worldwide and current first-line treatment with metformin and intensive behavior and lifestyle changes are suboptimal in over 50% of youth within 2 years of diagnosis. This perspective article is a call to action for reevaluation of existing strategies and critical appraisal of metformin as first-line therapy in youth-onset type 2 diabetes. Increased attention should be given to novel therapeutics approved in youth, including glucagon-like 1 receptor agonists, sodium glucose cotransporter-2, and sociocultural interventions that will promote diabetes self-management.

Approach to the Patient: Youth-Onset Type 2 Diabetes.

Youth-onset type 2 diabetes is a growing epidemic with a rising incidence worldwide. Although the pathogenesis and diagnosis of youth-onset type 2 diabetes are similar to adult-onset type 2 diabetes, youth-onset type 2 diabetes is unique, with greater insulin resistance, insulin hypersecretion, and faster progression of pancreatic beta cell function decline. Individuals with youth-onset type 2 diabetes also develop complications at higher rates within short periods of time compared to adults with type 2 diabetes or youth with type 1 diabetes. The highest prevalence and incidence of youth-onset type 2 diabetes in the United States is among youth from minoritized racial and ethnic groups. Risk factors include obesity, family history of type 2 diabetes, comorbid conditions and use of medications associated with insulin resistance and rapid weight gain, socioeconomic and environmental stressors, and birth history of small-for-gestational-age or pregnancy associated with gestational or pregestational diabetes. Patients with youth-onset type 2 diabetes should be treated using a multidisciplinary model with frequent clinic visits and emphasis on addressing of social and psychological barriers to care and glycemic control, as well as close monitoring for comorbidities and complications. Intensive health behavior therapy is an important component of treatment, in addition to medical management, both of which should be initiated at the diagnosis of type 2 diabetes. There are limited but growing pharmacologic treatment options, including metformin, insulin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Although long-term outcomes are not fully known, metabolic/bariatric surgery in youth with type 2 diabetes has led to improved cardiometabolic outcomes.

Impact of youth onset type 2 diabetes during pregnancy on microvascular and cardiac outcomes

AimsTo examine the impact of pregnancy on microvascular and cardiovascular measures in women with youth-onset T2D. MethodsMicrovascular and cardiovascular measures were compared in in a cohort of 116 women who experienced a pregnancy of ≥ 20 weeks gestation and 291 women who did not among women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. ResultsCox regression models adjusted for participant characteristics at baseline including age, race/ethnicity, household income, diabetes duration, HbA1c (>6%), and BMI, demonstrated those who experienced pregnancy had 2.76 (1.38–5.49; p = 0.004) fold increased risk of hyperfiltration (eGFR ≥ 135 ml/min/1.73 m2), compared to those without a pregnancy. No differences were observed in rates of retinopathy (48.9% vs. 41.1%) or neuropathy (23.3% vs. 16.3%) in women who experienced pregnancy vs. women who did not, respectively. In fully adjusted models, pregnancy did not impact changes in echocardiographic or arterial stiffness compared to changes in women who were never pregnant. ConclusionsThese results indicate that pregnancy increases the risk of hyperfiltration in women with youth-onset T2D, but not other micro or macrovascular complications. The rates of vascular complications are very high in youth-onset T2D potentially obscuring micro- and macrovascular changes attributable to pregnancy.Clinical Trial Information: ClinicalTrials.gov numbers,NCT01364350andNCT02310724.

Food Insecurity and Adequacy of Dietary Intake in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes.

Household food insecurity is associated with poor dietary intake in the general population, but little is known about this association in persons with diabetes. We examined the degree of adherence to the dietary reference intakes and 2020-2025 Dietary Guidelines for Americans overall and according to food security status and diabetes type among youth and young adults (YYA) with youth-onset diabetes. The SEARCH for Diabetes in Youth study includes 1,197 YYA with type 1 diabetes (mean age= 21 ± 5 years) and 319 YYA with type 2 diabetes (25 ± 4 years). Participants (or parents if younger than age 18 years) completed the US Department of Agriculture Household Food Security Survey Module, wherein ≥3 affirmations indicate food insecurity. Diet was assessed via food frequency questionnaire and compared with age- and sex-specific dietary reference intakes for 10 nutrients and dietary components (calcium; fiber; magnesium; potassium; sodium; vitamins C, D, and E; added sugar; and saturated fat). Median regression models controlled for sex- and type-specific means for age, diabetes duration, and daily energy intake. Prevalence of guideline adherence was overarchingly poor, with <40% of participants meeting recommendations for eight of 10 nutrients and dietary components; however, higher adherence (>47%) was observed for vitamin C and added sugars. YYA with type 1 diabetes who were food insecure were more likely to meet recommendations for calcium, magnesium, and vitamin E (P < 0.05), and less likely for sodium (P < 0.05) than those with food security. In adjusted models, YYA with type 1 diabetes who were food secure had closer median adherence to sodium (P= 0.002) and fiber (P= 0.042) guidelines than those food insecure. No associations were observed in YYA with type 2 diabetes. Food insecurity is associated with lesser adherence to fiber and sodium guidelines in YYA with type 1 diabetes, which may lead to diabetes complications and other chronic diseases.

Trajectories of eGFR and risk of albuminuria in youth with type 2 diabetes: results from the TODAY cohort study.

We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories. At baseline, participants' mean age was 14years, type 2 diabetes duration was 6months, mean HbA1c was 6%, and mean eGFR was 120ml/min/1.73m2. Five eGFR trajectories associated with different rates of albuminuria were identified, including a "progressive increasing eGFR" group (10%), three "stable eGFR" groups with varying starting mean eGFR, and an "eGFR steady decline" group (1%). Participants who exhibited the greatest peak eGFR also had the highest levels of elevated albuminuria at year 10. This group membership was characterized by a greater proportion of female and Hispanic participants. Distinct eGFR trajectories that associate with albuminuria risk were identified, with the eGFR trajectory characterized by increasing eGFR over time associating with the highest level of albuminuria. These descriptive data support the current recommendations to estimate GFR annually in young persons with type 2 diabetes and provide insight into eGFR-related factors which may contribute to predictive risk strategies for kidney disease therapies in youth with type 2 diabetes. ClinicalTrials.gov Identifier: NCT00081328, date registered 2002. A higher resolution version of the Graphical abstract is available as Supplementary information.

Virtual Learning and Youth-Onset Type 2 Diabetes during the COVID-19 Pandemic

Introduction: Cases and severity of presentation of youth-onset type 2 diabetes (Y-T2D) increased during the COVID-19 pandemic, yet the potential drivers of this rise remain unknown. During this time public health mandates paused in-person education and limited social interactions, resulting in radical lifestyle changes. We hypothesized that the incidence and severity of presentation of Y-T2D increased during virtual learning amidst the COVID-19 pandemic. Materials and Methods: We conducted a single-center retrospective chart review to identify all newly diagnosed cases of Y-T2D (n = 387) at a pediatric tertiary care center in Washington, DC during three predetermined learning periods as defined by learning modality in Washington, DC Public Schools: pre-pandemic in-person learning (March 11, 2018–March 13, 2020), pandemic virtual learning (March 14, 2020–August 29, 2021), and pandemic in-person learning (August 30, 2021–March 10, 2022) periods. Results: Incident cases were stable during pre-pandemic in-person learning (3.9 cases/month, 95% CI: 2.8–5.4 cases/month), increased to a peak during virtual learning (18.7 cases/month, 95% CI: 15.9–22.1 cases/month), and declined with return to in-person learning (4.3 cases/month, 95% CI: 2.8–6.8 cases/month). Y-T2D incidence was 16.9 (95% CI: 9.8–29.1, p < 0.001) and 5.1-fold higher (95% CI: 2.9–9.1, p < 0.001) among non-Hispanic Black and Latinx youth, respectively, throughout the study period. Overall COVID-19 infection rates at diagnosis were low (2.5%) and were not associated with diabetes incidence (p = 0.26). Conclusions: This study provides timely insights into an important and modifiable correlate of Y-T2D incidence, its disproportionate impact on underserved communities, and the need to consider the effects on long-term health outcomes and preexisting healthcare inequities when designing public policy.

Effect of Early Glycemic Control in Youth-Onset Type 2 Diabetes on Longer-Term Glycemic Control and β-Cell Function: Results From the TODAY Study.

Little is known about the impact of early attainment of tight glycemic control on long-term β-cell function and glycemic control in youth-onset type 2 diabetes. We examined the effect of the initial 6 months of glycemic control on β-cell function and glycemic control longitudinally over 9 years and the impact of sex, race/ethnicity, and BMI on these relationships in adolescents with youth-onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Oral glucose tolerance tests were performed longitudinally through year 9 to derive estimates of insulin sensitivity and secretion. Early glycemia was defined by mean HbA1c during the first 6 months postrandomization, categorized into five HbA1c groups (<5.7%, 5.7 to <6.4%, 6.4 to <7.0%, 7.0 to <8.0%, and ≥8.0%). The long-term period was defined as the period between years 2 and 9. A total of 656 participants (64.8% female, baseline mean age 14 years, diabetes duration <2 years) had longitudinal data available over an average of 6.4 ± 3.2 years of follow-up. HbA1c significantly increased in all early glycemic groups during years 2-9, with a steeper increase (+0.40%/year) among participants with the tightest initial control (mean early HbA1c <5.7%), in parallel to a decline in the C-peptide-derived disposition index. Nevertheless, the lower HbA1c categories continued to have relatively lower HbA1c over time. Early tight glycemic control in the TODAY study was related to β-cell reserve and translated to better long-term glycemic control. However, tight early glycemic control on the randomized treatment in the TODAY study did not prevent deterioration of β-cell function.

43-OR: Beliefs about Medicines, Self-Efficacy, and Health Care Coverage Predict Glycemic Control in Young Adults with Youth-Onset Type 2 Diabetes—The TODAY2 iCount Study

Background: Little is known about psychosocial factors that predict glycemic control (A1c) in young adults with youth-onset type 2 diabetes. Aim: To identify psychosocial predictors of A1c in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. Design: Longitudinal, measured at T1 (baseline) and T2 (1 year later). Logistic and linear regressions, adjusted for covariates (including T1 A1c), identified T1 predictors of A1c at T2. Participants: N= 348 participants in TODAY2. Mean age=26.0 years, 65.8% female, 37.6% non-Hispanic Black, 36.5% Hispanic, 20.4% non-Hispanic white, mean A1c=9.4%. Measures: Reliable, valid measures of beliefs about medicines, depressive and anxiety symptoms, diabetes distress, diabetes self-efficacy, diabetes attitudes, self-management support and material need insecurities. A1c was examined categorically (high vs. low: high ≥8%) and continuously (percent). Key Results: The high A1c group had more belief in the necessity of (p=0.023), but concerns about (p=0.029), medicines, higher diabetes distress (p&amp;lt;0.001), and lower diabetes self-efficacy (p=0.017). In adjusted analyses, every 5-point higher score measuring beliefs that medicines are overused predicted 3.6 times higher odds of high A1c at T2 (p=0.010). Every 5-point higher self-efficacy score predicted 16.7% lower odds of high A1c at T2 (p=0.033). Surprisingly, those who lacked healthcare coverage were less likely to have high A1c at T2 vs. those with coverage (p=0.10). Every 5-point higher medicines are overused score predicted 48.5% higher % A1c at T2 (p=0.017). No other psychosocial measures predicted A1c. Conclusions: High A1c is common in young adults with youth-onset type 2 diabetes and is predicted over time by beliefs about medicines, diabetes self-efficacy and healthcare coverage status. We must address these factors to help this vulnerable group establish optimal glycemic control. Disclosure P.M.Trief: None. D.Uschner: None. B.Anderson: None. H.Wen: None. J.D.Bulger: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110456)

160-LB: Circulating MicroRNAs as Predictors of Microvascular Complications in Youth Onset Type 2 Diabetes—The TODAY Study

From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, 60% of the participants demonstrated diabetes-related complications by 10 years. We aimed to identify circulating microRNA (miRNA) species associated with microvascular disease in TODAY participants with youth-onset type 2 diabetes. Using nCounter Human v3 miRNA Panel (NanoString Technologies) to identify relevant miRNAs in two groups of participants who lost glycemic control and either developed microvascular complications during follow-up (n=6) or not (n=11), 53 miRNA species were differentially expressed at baseline (p&amp;lt;0.05) and 2 at the end of study visit (p&amp;lt;0.05). Polymerase chain reaction validations were carried out for 17 miRNAs from 365 participants with samples obtained at baseline, 24, 60, 96, and 120 months. During follow-up, 250 (68%) of the participants (mean 14 years old and diabetes duration &amp;lt;2 years at entry) developed at least one microvascular complication. Using backward elimination modeling and adjusting for demographic characteristics, a set of four baseline miRNA log2 fold changes remained significant predictors of microvascular complications (p&amp;lt;0.05). Increased levels of miR-122 (OR:1.17, 95%CI:1.03-1.32) and miR-221 (OR:1.51, 95%CI: 1.51-1.98) were associated with higher risk of complication, while increased levels of miRNA-let 7g (OR:0.75, 95%CI: 0.60-0.94) and miRNA-130a (OR:0.82, 95%CI: 0.68-0.99) were associated with lower risk of complication. miR-122 abundance was also positively correlated with urine albumin/creatinine ratio at baseline and 24-months (R=0.11, p=0.041 and R=0.16, p=0.005, respectively). The alterations in miR-122, 221, 130a, and let 7g in circulation are all consistent with in vitro alterations that promote endothelial dysfunction suggesting that these early alterations in circulation may predict those at highest risk of microvascular disease in the future. Disclosure D. Redling: None. S. Bialek: None. S. Chernausek: Advisory Panel; Ascendis Pharma A/S. L. El ghormli: None. J. B. Tryggestad: None. Funding National Institutes of Health (5U01DK061230-16)

61-LB: Blood Pressure and Lipid-Lowering Medication Adherence in Young Adults with Youth-Onset Type 2 Diabetes and Hypertension or Dyslipidemia—The TODAY2 iCount Study

Youth-onset type 2 diabetes (T2D) is associated with early development of vascular complications. Treatment of hypertension and dyslipidemia are critical to reduce morbidity. iCount examined adherence to blood pressure (BP) and lipid-lowering medications in young adults with youth-onset T2D (mean age 26 y, duration of T2D 12 y, BMI 37 kg/m2) and hypertension/nephropathy (n=196) or dyslipidemia (n=146) during the observational phase of the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY)2 study (2017-2019). They were receiving diabetes care in their communities. Adherence was assessed with 3 monthly unannounced phone pill counts at 2 times 1 year apart. Percent low adherent (&amp;lt;80% pill-taking) and high-adherent (≥80% pill-taking) did not change over time. Of participants with hypertension and/or nephropathy, 80.1% were low adherent, 19.9% were high adherent. Those who were low adherent had fewer years of education (p=0.004), higher HbA1c (p=0.001) and shorter diabetes duration (p=0.031). Of those with dyslipidemia, 93.8% were low adherent, 6.2% high adherent. Those low adherent to BP (p&amp;lt;0.001) and lipid-lowering (p≤0.008) medications were also low adherent to oral hypoglycemic medications or insulin. Beliefs that medications are necessary were lower for those low adherent to BP and lipid-lowering medications (unadjusted analyses); concerns about medications also were lower for those low adherent to lipid-lowering medications. In adjusted multivariable analyses of participants with hypertension or nephropathy, having ≥1 material need insecurity predicted medication adherence 1 year later (p=0.010). Belief about medicines, diabetes distress, self-efficacy, depressive and anxiety symptoms, and self-management support were not 1 yr predictors of medication adherence. To prevent early vascular events, approaches that further identify and address unmet needs should be studied. Disclosure P. M. Trief: None. R. S. Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. B. K. Burke: None. H. Wen: None. S. Kalichman: None. J. D. Bulger: None. B. J. Anderson-thomas: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110456)

625-P: Psychosocial Factors Predict Health Care Usage in Young Adults with Youth-Onset Type 2 Diabetes—TODAY2 iCount Study

Background: Established diabetes care (“diabetes home”) and regular healthcare visits are important to achieve good outcomes. Nothing is known about psychosocial factors that predict healthcare usage (HCU) in young adults with youth-onset type 2 diabetes. Objective: To identify psychosocial predictors of HCU in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. Design: Longitudinal, measured at T1 (baseline) and T2 (1 year later). Logistic and linear regressions, adjusted for covariates, were used to identify predictors of sub-optimal HCU (defined as no diabetes home, 0 routine care visits, ≥1 urgent care visit in prior 6 months). Participants: N= 366 TODAY2 participants. Mean age=26.0 years, 67.8% female, 37.7% non-Hispanic Black, 35.8% Hispanic, 20.2% non-Hispanic white, mean HbA1c=9.4%. Main measures: HCU survey; reliable, valid measures of diabetes self-efficacy, depressive symptoms, anxiety symptoms, diabetes distress, beliefs about medicines, diabetes attitudes, material need insecurities and self-management support. Key Results: 25.4% had no diabetes home, 23.7% had 0 routine care visits, 46% had ≥1 urgent care visit in prior 6 months. Beliefs in the necessity of (p&amp;lt;0.001), and concerns about (p=0.004), diabetes medicines, and diabetes having negative psychosocial impacts (p=0.034), predicted higher odds of having a diabetes home at T2. Beliefs that medicines are harmful predicted lower odds of having a diabetes home (p=0.006). Necessity beliefs (p=0.002), concerns (p=0.025), and self-management support (p=0.014) predicted higher odds of having ≥ 1 diabetes care visit in prior 6 months, harm beliefs predicted lower odds (p=0.005). Conclusions: Sub-optimal healthcare usage is common in young adults with youth-onset type 2 diabetes and is predicted by beliefs about medicines and self-management support. We must address these factors to help this vulnerable group establish a stable foundation for diabetes care. Disclosure P.M.Trief: None. D.Uschner: None. B.Anderson: None. H.Wen: None. J.D.Bulger: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110456)

317-OR: Metabolomic Analyses Identify Novel Predictors of Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes

Background: Diabetic kidney disease (DKD) develops by young adulthood in up to 50% of people with youth-onset type 2 diabetes (Y-T2D), increasing risk of dialysis and premature death. Understanding mechanisms responsible for early DKD is key to management and prevention; accordingly, we sought to identify metabolite signatures of DKD in Y-T2D. Methods: We measured 57 metabolites in 374 baseline plasma and urine samples from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study, using mass spectrometry with a targeted ZipChip based assay. Urine albumin-to-creatinine ratio (UACR) was assessed annually for up to 15 years. Incident moderate and severe albuminuria were defined as UACR ≥30 and ≥300 mg/g, respectively, on ≥2 of 3 measures. We evaluated prediction of moderate and severe albuminuria in separate Cox proportional hazards models adjusted for HbA1c, triglycerides, systolic blood pressure, and estimated insulin sensitivity. Urine metabolites were normalized by urine creatinine. Results: Participants were 14±2 years of age, 37% male; 43% developed either moderate or severe albuminuria. Four urine metabolites predicted time to moderate albuminuria, while 8 urine metabolites predicted time to severe albuminuria, with 3 metabolites in common: 2-hydroxybutyric acid (moderate: HR: 0.82 per 1 SD [95% CI 0.70, 0.96]; severe: 0.70 [0.55, 0.88]), glycine (moderate: 0.81 [0.69, 0.94]; severe: 0.62 [0.45, 0.85]), citric acid (moderate: 0.78 [0.67, 0.91]; severe: 0.76 [0.58, 0.99]). Four plasma metabolites predicted time to moderate albuminuria and severe albuminuria, such as glutamic acid for moderate albuminuria (1.23 [1.03, 1.47]) and citric acid for severe albuminuria (1.39 [1.09, 1.77]). Conclusion: Higher urine metabolites involved in mitigating oxidative stress (glycine), glomerular epithelial cell injury (2-hydroxybutyric acid) and preserving mitochondrial function (citrate) predicted lower risk of albuminuria in Y-T2D. Disclosure L.Pyle: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. A.S.Shah: None. K.Drews: None. J.R.Ryder: None. R.Gubitosi-klug: None. K.Sharma: Advisory Panel; Reata Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. T.B.Vigers: None. L.El ghormli: None. I.De boer: Advisory Panel; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Boehringer Ingelheim International GmbH, Otsuka America Pharmaceutical, Inc., Bayer Inc., Consultant; George Clinical, Gilead Sciences, Inc., Medscape, Research Support; Dexcom, Inc. R.G.Nelson: None. S.Waikar: None. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck &amp; Co., Inc., Janssen Research &amp; Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.White: None. K.L.Tommerdahl: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61242)