Youth-onset Type Research Articles

Proteomic Analysis Uncovers Multi-Protein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with type 2 diabetes. We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes. Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63. Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions.

Steatotic Liver Disease in Pediatric Obesity and Increased Risk for Youth-Onset Type 2 Diabetes.

To assess 1) the association between metabolic dysfunction-associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, 2) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and 3) the effect of obesity treatment on type 2 diabetes risk. A cohort study using the Swedish Childhood Obesity Treatment Register (Barnobesitas Registret i Sverige [BORIS]) (1999-2020) linked with national registers was conducted. We included 10,346 children with overweight or obesity and 59,336 matched control individuals. MASLD was defined by transaminases and diagnosis code, separately. Type 2 diabetes was ascertained from national registers. In the obesity cohort, median age at type 2 diabetes diagnosis was 16.9 (quartile 1 [Q1], quartile 3 [Q3]: 14.7, 21.4) years, median follow-up was 8.1 (Q1, Q3: 5.1, 11.7) years. Cumulative incidence of type 2 diabetes at age 30 was 22.7% (obesity and MASLD), 9.9% (obesity alone), and 0.7% (control individuals). MASLD was associated with risk for type 2 diabetes (hazard ratio [HR] 2.71 [95% CI 2.14-3.43]), independently of age, sex, degree of obesity, intermediate hyperglycemia, and parental type 2 diabetes. Joint effect of MASLD and intermediate hyperglycemia increased type 2 diabetes risk (HR 9.04 [6.38-12.79]). Optimal response in obesity treatment reduced the risk (HR 0.23 [0.09-0.57]). MASLD, defined by transaminases or diagnosis code, in pediatric obesity is associated with increased risk for youth-onset type 2 diabetes. MASLD interacts synergistically with intermediate hyperglycemia to dramatically increase the risk. Optimal response in obesity treatment reduces type 2 diabetes risk, despite MASLD.

6920 Engagement and Mood assessments in Emerging Adults Attending a Multi-disciplinary Diabetes Transition Clinic

Abstract Disclosure: G.P. Thota: None. S. Glaros: None. S. Dixon: None. S.T. Chung: None. Introduction & Objective: Transitioning to adult diabetes care can be challenging and associated with interruption in care, worsening glycemic control, and social stress. However, most studies have been conducted in emerging adults (YA) with type 1 diabetes (T1D), and contemporary data in multi-disciplinary clinics designed with supportive resources, especially for YA with youth-onset type 2 diabetes (Y2D) is lacking. Our objectives were to assess mood and engagement in psychology therapy services within a structured multidisciplinary diabetes clinic. Methods: This was a single-center observational analysis of YA (18-30y) attending a research diabetes transition clinic supported by clinical coordinators, social navigators, a certified diabetes educator, and a nutritionist between January 2021 and December 2023. All YA were offered free transportation to and from visits. Clinical coordinators communicated regularly for appointment reminders. Mood was assessed with Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder (GAD-7) at each visit and Endocrine Society Transition Readiness Form at initial visit. In January 2023, all YA were given the option to meet with a clinical psychologist during the diabetes visit. Student t-test were used to compare groups using STATA v.18. Results: In 62 YA (73% Y2D, 10% T1D, 17% other) aged 20.2±2.7y, BMI:37.3±9.6 kg/m2, all engaged in nutrition counseling and 52% (32/62) utilized transportation services. A diagnosed psychiatric disorder was present in 16% (10/62). At initial visit, PHQ-9 scores were 6.1±6.3, n=62 and39% (24/62) had score >8 (moderate depression). Within the last 2 weeks, 13% (10/62) reported suicidal ideation. GAD-7 scores were 6.0±6.3 and 54% had anxiety that interfered with activities of daily living. Psychology services were accepted in 61% (38/62) with higher initial GAD-7 scores in those who saw psychologist (8.2±6.8 vs. 4.1±5.3, P=0.02) but no difference in PHQ-9 scores (7.2±6.6 vs. 5.1±5.9, P=0.2). Most YA (81%) reported adequate diabetes knowledge while 25% YA reported diabetes-related challenges including feeling burned out, not knowing how to navigate specialty diabetes care, challenges with medication insurance, transportation, and insurance coverage. Conclusion: Approximately 50% of emerging adults with diabetes reported moderate depression and anxiety scores and were interested in engaging in psychology services. Transition diabetes care programs should focus on increasing access to routine integrated mental health services and social support.Such an initiative could potentially ameliorate psychological stressors associated with diabetes management during the transition to adult care. Presentation: 6/1/2024

Pegloticase-Induced Rapid Uric Acid Lowering and Kidney and Cardiac Health Markers in Youth-Onset Type 2 Diabetes: A Pilot Clinical Trial

Rationale & ObjectiveElevated serum uric acid (SUA) is a risk factor for incident hypertension and diabetic kidney disease in young persons with type 2 diabetes (T2D), particularly men. The acute benefit of aggressively lowering SUA on kidney and cardiovascular function in this population remains underexplored. This study was conducted to investigate the impact of a single pegloticase infusion on kidney and cardiovascular function. Study DesignAn open-label pilot trial. Setting & ParticipantsThe study involved 10 young adult males with youth-onset T2D and SUA levels ≥5 mg/dL. Intervention(s)Participants received a single infusion of pegloticase (8 mg). Evaluations were conducted using iohexol-based measured glomerular filtration rate (mGFR) and cardiac/kidney MRI before and one week after infusion. OutcomesThe primary outcomes were changes in SUA and mGFR one week after pegloticase infusion. ResultsNine participants (mean [±SD] age 22±5 years, HbA1c 8.6±3.3%, BMI 40.1±11.0 kg/m2, SUA 6.7±1.1 mg/dL) completed the pegloticase infusion and were included in the analysis. One week after the infusion, median [p25,p75] SUA concentrations dropped from 6.4 [5.6,7.6] to 0.5 [0.5,4.6] mg/dL (p=0.01). Mean mGFR increased from 113±20 to 122±19 ml/min per 1.73 m2 (p=0.004). Among responders (SUA reduction ≥3 mg/dL), an increase in mGFR correlated with an increase in renal artery blood flow (r:0.60, p=0.24) and decrease in SUA (r:-0.79, p=0.05). Mean MRI peak longitudinal cardiac strain additionally decreased from 15.4±2.2 to 13.1±2.2 % (p=0.03) in these responders. LimitationsThe pilot nature of the study and the small sample size limit the generalizability of the findings. ConclusionsIn young adult males with T2D, a single pegloticase infusion decreased SUA levels, which increased mGFR and was strongly associated with increased renal blood flow and impaired cardiac global longitudinal strain. Further research is required to assess the long-term efficacy and safety of pegloticase in patients with T2D.

Reassessing the Burden of Food Insecurity in Youth and Young Adults With Youth-onset Diabetes: The Importance of Marginal Food Security

ObjectivesMarginal food insecurity has been recognized as important in Canadian food security policy, but the category of marginal food security (MFS) is often ignored in food security research in the United States. MethodsThe prevalence of food insecurity was estimated according to the conventional and an alternate classification of MFS with food insecurity among 938 youth and young adults (YYA) with youth-onset type 1 diabetes (T1D) and 156 with youth-onset of type 2 diabetes (T2D) from the SEARCH Food Security Cohort Study (2018–2021). Multivariable regression was used to estimate the association of MFS and conventionally defined food insecurity ascertained with diabetes-related outcomes, including acute diabetes complications, health-care utilization, and diabetes self-management among YYA with T1D. ResultsMFS affected 10% of participants with T1D and 20% of those with T2D. Classifying MFS with food insecurity increased the prevalence of food insecurity from 18.0% to 27.8% in participants with T1D and 34.6% to 55.1% in those with T2D. Compared with those with T1D having high food security, YYA with T1D who were food insecure had a greater odds of hypoglycemia (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.2 to 3.6) and ketoacidosis (1.6, 95% CI 1.0 to 2.6), but no association was seen for MFS. The food insecurity group also had an increased odds of emergency department utilization (OR 2.3, 95% CI 1.5 to 3.4) and hospitalization (OR 2.4, 95% CI 1.5 to 3.9), and a decreased odds of technology use (OR 0.6, 95% CI 0.4 to 0.9) and checking glucose (OR 0.3, 95% CI 0.1 to 0.6). The MFS group exhibited similar associations. ConclusionHealth-care providers should consider care of patients with T1D and MFS the same way they care for patients with food insecurity.

Mortality in type 1 diabetes mellitus: A single centre experience from the ICMR – Youth onset diabetes registry in India

IntroductionThe prevalence of youth onset diabetes is rising globally along with a greater burden of complications and mortality in them. The current study was undertaken to examine the mortality and causes of death in patients with youth onset diabetesregistered in a tertiary care hospital in North India. MethodsWe analyzed mortality and causes of death in 1088 patients with youth onset diabetes registered from 2006 to 2019 at University College of Medical Sciences, Delhi. Information of death was obtained telephonically or by home visit or from hospital records wherever available. Verbal autopsy according to ICMR questionnaire was performed and cause of death determined as per WHO ICD-10/11. ResultsAmong 898 youth onset type 1 diabetes mellitus (T1D) patients who had a mean follow up of 6.4 years, 105 deaths (11.6 %) occurred. Forty three percent of deaths had diabetes onset at 15 years or below, and 75.6 % had HbA1C > 10 %. Deaths occurred in 24.2 % within 2 years and in 53.6 % within 3 years of diagnosis. Chronic Kidney disease, infections and ketoacidosis were the commonest causes. ConclusionWe found poor glycaemic control and high mortality in people with youth onset T1D being treated at a tertiary care hospital in north India.

Pathophysiology and Treatment of Prediabetes and Type 2 Diabetes in Youth.

Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications. It is often preceded by "prediabetes," a disease phase where defects in β-cell function relative to insulin sensitivity emerge. Herein, we review the current understanding of the pathophysiology of prediabetes and type 2 diabetes in youth. We describe the mechanisms underlying insulin resistance, the precipitous decline of β-cell function, and the role of other hormonal abnormalities in the pathogenesis of the disease. We discuss the critical importance of social determinants of health in the predisposition and progression of these conditions and present current management strategies and the advances in therapeutic approaches. These must adapt to meet the unique needs of the individual patient and family. Significant knowledge gaps remain that need to be addressed in future research.

Endothelial Dysfunction in Youth-Onset Type 2 Diabetes: A Clinical Translational Study.

Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers. We isolated and characterized plasma-derived small extracellular vesicles and evaluated their effects on inflammatory and signaling biomarkers in healthy human coronary artery endothelial cells to validate the imaging findings. Right coronary wall thickness, coronary artery flow-mediated dilation, and brachial artery flow-mediated dilation were measured at baseline and during isometric handgrip exercise using a 3.0T magnetic resonance imaging. Human coronary artery endothelial cells were treated with Y-T2D plasma-derived small extracellular vesicles. Protein expression was measured by Western blot analysis, oxidative stress was measured using the redox-sensitive probe dihydroethidium, and nitric oxide levels were measured by 4-amino-5-methylamino-2',7'-difluororescein diacetate. Y-T2D (n=20) had higher hemoglobin A1c and high-sensitivity C-reactive protein, but similar total and LDL (low-density lipoprotein)-cholesterol compared with healthy peers (n=16). Y-T2D had greater coronary wall thickness (1.33±0.13 versus 1.22±0.13 mm; P=0.04) and impaired endothelial function: lower coronary artery flow-mediated dilation (-3.1±15.5 versus 15.9±17.3%; P<0.01) and brachial artery flow-mediated dilation (6.7±14.7 versus 26.4±15.2%; P=0.001). Y-T2D plasma-derived small extracellular vesicles reduced phosphorylated endothelial nitric oxide synthase expression and nitric oxide levels, increased reactive oxygen species production, and elevated ICAM (intercellular adhesion molecule)-mediated inflammatory pathways in human coronary artery endothelial cells. Coronary and brachial endothelial dysfunction was evident in Y-T2D who were within 5 years of diagnosis and did not have severe hyperglycemia or dyslipidemia. Plasma-derived small extracellular vesicles induced markers of endothelial dysfunction, which corroborated accelerated subclinical coronary atherosclerosis as an early feature in Y-T2D. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02830308 and NCT01399385.

Association of race and ethnicity with the development of cystic fibrosis-related diabetes

BackgroundCF-related diabetes (CFRD) is a common, life-expectancy limiting complication of CF. While Black race and Hispanic ethnicity in youth-onset type 1 and type 2 diabetes are well-recognized risk factors for worse diabetes complications, the potential for racial/ethnic disparities in CFRD has received limited attention. MethodsWe conducted a retrospective cohort study utilizing the CF Foundation Patient Registry from 2010 to 2019 to determine the prevalence and incidence of CFRD by race/ethnicity. Three age cohorts were identified at baseline in 2010 (11–20y, 21–30y, and 31–40y). Logistic regression and Cox regression stratified by age group were used to determine the prevalence and incidence, respectively, among Hispanic, non-Hispanic Blacks (NHB), and non-Hispanic whites (NHW) after adjustment for relevant confounders, including demographics, socioeconomic status, clinical factors, and chronic medication use. ResultsAmong 14,660 registry participants, 510 were NHB and 890 Hispanic. NHB associated with higher odds of CFRD baseline prevalence in all age cohorts (11–20y: OR 2.53 (95 % CI: 1.88–3.41, P < 0.05), 21–30y: OR 1.80 (1.25–2.59, P < 0.05), and 31–40y: OR 1.93 (1.00–3.73, P < 0.05)) relative to NHW. In the 11–20y cohort, the hazard of new-onset CFRD was 40 % higher in NHB (HR 1.40 (1.09–1.8, P < 0.05)) and 19 % higher in Hispanics (HR 1.19 (1.01–1.41, P < 0.05)). ConclusionNHB had a higher prevalence of CFRD across all age groups, with NHB and Hispanics showing higher incidence of CFRD in the youngest group. Multicenter studies performed in diverse CF populations are warranted to identify modifiable factors influencing earlier CFRD development in minoritized groups and their potential contribution to diabetes complication disparities.

SPECTRUM AND CHARACTERISTICS OF THE ELECTROCARDIOGRAPHIC CHANGES IN CHILDREN WITH TYPE I DIABETES MELLITUS

Introduction. Type I diabetes mellitus (T1D) is one of the most widespread and socially significant diseases. Well-known as a co-occurring condition with youth-onset type 1 diabetes mellitus, cardiovascular disease manifests early after initial diagnosis as signs of cardiovascular remodeling. Growing data indicates that type 1 diabetic children and young adults experience subclinical heart dysfunction, central aortic stiffening, and accelerated peripheral vascular disease. Increased morbidity and mortality in adults have been linked to peripheral artery, heart, and cerebrovascular diseases, and early vascular alterations have been demonstrated to exist since childhood. Little is known to date concerning the development of early cardiac structural and functional problems in children with T1D. Early diagnostic is of high importance. Aim. To assess the frequency and spectrum of electrocardiography (ECG) abnormalities in children with type 1 diabetes. Materials and methods. Records of 60 patients with type I diabetes included into the analysis. ECG data, main anamnestic, clinical and laboratory data analyzed. Results. So-called "small ECG abnormalities" were found. Incomplete left/right blockade bundle branch block found in 22.5% of children, shortened PQ interval in 15%, extrasystoles, tachycardia, bradycardia in 52.5%, T wave amplitude decrease in 60%. 87.5% of the examinees have a combination of 2–3 of the above changes on the ECG. Only 12% of the examined children had an ECG without pathological changes. All children with newly diagnosed type 1 DM had at least 1 of the described ECG abnormalities. Correlation analysis done. Substantial positive correlations between Hb1Ac levels and number of ECG changes, serum cholesterol levels and number of ECG changes were found. Conclusions. The results of the study indicate that the majority of children with type I diabetes have so-called "small ECG abnormalities." According to the type of disturbances, they can be classified as rhythm and conduction disturbances and combined changes. These findings are promising in terms of management tactics for children with type I diabetes, early detection and timely therapeutic correction of ECG abnormalities.

Insulin Dynamics and Pathophysiology in Youth-Onset Type 2 Diabetes.

Youth-onset type 2 diabetes (T2D) is increasing around the globe. The mounting disease burden of youth-onset T2D portends substantial consequences for the health outcomes of young people and for health care systems. The pathophysiology of this condition is characterized by insulin resistance and initial insulin hypersecretion ± an inherent insulin secretory defect, with progressive loss of stimulated insulin secretion leading to pancreatic β-cell failure. Research studies focusing on youth-onset T2D have illuminated key differences for youth- vs adult-onset T2D, with youth having more profound insulin resistance and quicker progression to loss of sufficient insulin secretion to maintain euglycemia. There is a need for therapies that are targeted to improve both insulin resistance and, importantly, maintain sufficient insulin secretory function over the lifespan in youth-onset T2D.

Circulating Metabolite Biomarkers of Glycemic Control in Youth-Onset Type 2 Diabetes.

We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10-17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0-36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance.

With changes in lifestyle behaviors, including dietary structure and habits, the prevalence of Youth-onset Type 2 Diabetes Mellitus (YODM) has increased 2 to 3 times compared to 30 years ago. YODM patients experience complications earlier, progress faster, and exhibit more severe symptoms. However, limited and inconclusive direct evidence, coupled with poor patient compliance, poses challenges in the clinical management of YODM. Apart from the continuous decline in pancreatic β-cell function and quantity, tissue-specific insulin resistance (IR) is also a typical characteristic of YODM. The main mechanisms of IR in YODM involve different aspects such as obesity, dietary imbalance, abnormal substance metabolism, chronic inflammation, oxidative stress, and hormonal fluctuations during adolescence. For the comprehensive management of YODM, besides achieving good control of blood glucose levels, it may be necessary to apply the most appropriate methods considering the uniqueness of the patient population and the specifics of the disease. Early identification and detection of the disease are crucial. Precise screening of patients with well-functioning pancreatic insulin β-cells, primarily characterized by IR and obesity, represents the population most likely to achieve diabetes remission or reversal through lifestyle modifications, medications, or even surgical interventions. Additionally, considering potential emotional disorders or the impact of adolescent hormones in these patients, health education for patients and caregivers is essential to make them aware of the long-term benefits of well-controlled blood glucose. In conclusion, adopting comprehensive management measures to achieve diabetes remission or reversal is the ideal goal. Controlling high blood glucose, obesity, and other risk factors related to diabetes complications is the next priority to delay the occurrence and progression of complications. A comprehensive perspective on IR provides insights and references for identifying YODM and its management strategies.

1141-P: Increased Predicted Risk for Fatal/Nonfatal Cardiac Events in Youth-Onset Type 2 Diabetes

1141-P: Increased Predicted Risk for Fatal/Nonfatal Cardiac Events in Youth-Onset Type 2 Diabetes

1160-P: Continuous Glucose Monitoring in Youth-Onset Type 2 Diabetes—Interim Results from Pilot Randomized Controlled 12-Week Trial

1160-P: Continuous Glucose Monitoring in Youth-Onset Type 2 Diabetes—Interim Results from Pilot Randomized Controlled 12-Week Trial

1152-P: Treatment Trends in Youth-Onset Type 2 Diabetes—Changing Landscape after GLP-1RA Approval

1152-P: Treatment Trends in Youth-Onset Type 2 Diabetes—Changing Landscape after GLP-1RA Approval

1142-P: Fat Distribution in Youth-Onset Type 2 Diabetes

1142-P: Fat Distribution in Youth-Onset Type 2 Diabetes

1304-P: MODY Calculator Overestimates MODY Probability in Multiethnic Cohort with Youth-Onset Type 2 Diabetes Phenotype

1304-P: MODY Calculator Overestimates MODY Probability in Multiethnic Cohort with Youth-Onset Type 2 Diabetes Phenotype

Prediabetes Prevalence by Adverse Social Determinants of Health in Adolescents

Several clinical practice guidelines advise race- and ethnicity-based screening for youth-onset type 2 diabetes (T2D) due to a higher prevalence among American Indian and Alaska Native, Asian, Black, and Hispanic youths compared with White youths. However, rather than a biological risk, this disparity likely reflects the inequitable distribution of adverse social determinants of health (SDOH), a product of interpersonal and structural racism. To evaluate prediabetes prevalence by presence or absence of adverse SDOH in adolescents eligible for T2D screening based on weight status. This cross-sectional study and analysis used data from the 2011 to 2018 cycles of the National Health and Nutrition Examination Survey. Data were analyzed from June 1, 2023, to April 5, 2024. Participants included youths aged 12 to 18 years with body mass index (BMI) at or above the 85th percentile without known diabetes. The main outcome consisted of an elevated hemoglobin A1c (HbA1c) level greater than or equal to 5.7% (prediabetes or undiagnosed presumed T2D). Independent variables included race, ethnicity, and adverse SDOH (food insecurity, nonprivate health insurance, and household income <130% of federal poverty level). Survey-weighted logistic regression was used to adjust for confounders of age, sex, and BMI z score and to determine adjusted marginal prediabetes prevalence by race, ethnicity, and adverse SDOH. The sample included 1563 individuals representing 10 178 400 US youths aged 12 to 18 years (mean age, 15.5 [95% CI, 15.3-15.6] years; 50.5% [95% CI, 47.1%-53.9%] female; Asian, 3.0% [95% CI, 2.2%-3.9%]; Black, 14.9% [95% CI, 11.6%-19.1%]; Mexican American, 18.8% [95% CI, 15.4%-22.9%]; Other Hispanic, 8.1% [95% CI, 6.5%-10.1%]; White, 49.1% [95% CI, 43.2%-55.0%]; and >1 or other race, 6.1% [95% CI, 4.6%-8.0%]). Food insecurity (4.1% [95% CI, 0.7%-7.5%]), public insurance (5.3% [95% CI, 1.6%-9.1%]), and low income (5.7% [95% CI, 3.0%-8.3%]) were each independently associated with higher prediabetes prevalence after adjustment for race, ethnicity, and BMI z score. While Asian, Black, and Hispanic youths had higher prediabetes prevalence overall, increasing number of adverse SDOH was associated with higher prevalence among White youths (8.3% [95% CI, 4.9%-11.8%] for 3 vs 0.6% [95% CI, -0.7% to 2.0%] for 0 adverse SDOH). Adverse SDOH were associated with higher prediabetes prevalence, across and within racial and ethnic categories. Consideration of adverse SDOH may offer a more actionable alternative to race- and ethnicity-based screening to evaluate T2D risk in youth.

Circulating MicroRNAs as Predictors of Beta Cell Function in Youth-Onset Type 2 Diabetes: The TODAY study.

In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, an intervention trial followed by an observational phase, half the participants reached the primary outcome (HbA1c ≥ 8% for at least 6 months) within 4 years which was associated with a decrease in C-peptide oral disposition index (oDI). We aimed to identify circulating miRNA species associated with decline in beta cell function. Following a preliminary survey of select participants using nCounter Human v3 miRNA Panel (NanoString Technologies), polymerase chain reaction analyses were carried out for 17 miRNAs from 365 participants from samples at baseline, 24, 60, 96, and 120 months. Using a backward selection approach, four baseline miRNA log2 fold changes independently predicted treatment failure; however, baseline HbA1c was higher in those with treatment failure. Three baseline miRNA log2 fold changes remained significant predictors of this C-peptide oDI decline ≥20% (p < 0.05). Increased levels of miRNA-155 (OR:1.2, 95%CI:1.1-1.4) and miRNA-130b (OR:1.3, 95%CI: 1.0-1.7) were associated with oDI decline, while decreased levels of miRNA-126 (OR:0.6, 95%CI: 0.4-0.8) were associated with oDI decline. miRNA-122 was negatively correlated with C-peptide oDI at baseline and 24-months (R = 0.22, p < 0.01 and R = 0.19, p < 0.01, respectively), and positively correlated with proinsulin, at baseline, 24-, and 60- months (R = 0.26, p < 0.01, R = 0.26, p < 0.01, R = 0.18, p < 0.01, respectively). The miRNA species associated with beta cell function are associated with alterations in cellular metabolism and apoptosis, suggesting that differences in baseline abundance may serve as circulating markers of beta cell dysfunction and provide potential mechanistic insights into the aggressive nature of youth-onset type 2 diabetes.