Youth-onset Type 2 Diabetes and Heart Disease

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Abstract

A. Youth-onset Type 2 Diabetes and Heart Disease: The Young at Heart Prospective Cohort Study (001819-DK) This study will evaluate the pathophysiological features of cardiovascular disease in youth-onset type 2 diabetes (Y-T2DM) using a multi-level, multi-domain approach of socio-ecological risk factors (societal, community, and individual). We will employ a prospective, observational study design in youth aged 12-25 years to compare Y-T2DM with age and BMI-matched youth with overweight or obesity (Y-OW) and age-matched healthy lean peers (Y-Lean). The study will also include a single-day visit for biological parents of enrolled Y-T2DM, Y-OW and Y- lean, to assess parental factors involved in the pathophysiology of cardiovascular disease in Y-T2DM. Primary Objectives: 1. To compare pulse wave velocity (PWV) at baseline and 5 years in Y-T2DM vs Y-OW and age-matched peers Y-Lean. 2. To compare augmentation index (Aix) at baseline and 5 years in Y-T2DM vs Y-OW and age-matched peers Y-Lean. 3. To evaluate coronary artery structure & endothelial function at baseline and 5 years. 4. To evaluate the relationship of pulse wave velocity and coronary artery structure & endothelial function with atherogenic and remnant lipoproteins. 5. To evaluate annual change in vascular aging (measured by the change in pulse wave velocity and endothelial function). 6. To evaluate the relationship of physiologic, psychological stress (measured with the allostatic load score, ALS), psychosocial and behavioral factors with vascular aging. 7. To evaluate biomarkers for vascular aging; ex. β-cell function, insulin resistance, inflammatory markers, and novel lipid parameters. 8. To evaluate the association of polygenic risk scores (PRS) in Y-T2DM and with changes in glucose and metabolism B. Evaluation of the Clinical Spectrum of Diabetes and Obesity in youth and adults (002229-DK and 07-DK-0115 ) Our joint NIDDK-CNH Young Adult Transition Clinic that was established in January 2021 enrolling participants at the NIH Clinical Center. This clinic enrolls youth and young adults who have suspected or established endocrinological or metabolic conditions or those who require clinical screening for such conditions. The clinic provides standard clinical care and facilitates diabetes management and screening for diabetes-related complications. The data repository protocol will store and retain data and samples obtained during regular clinical care for future research. Primary Objective: To collect data and samples during clinical evaluation, treatment, and follow-up of participants for future use in studies of endocrine and metabolic disorders. C. Allostatic load and cardiometabolic health In collaboration with North West University and Dr. Annemarie Wentzel, we are investigating the relationship of cumulative physiologic stress with vascular and metabolic risk markers. Allostasis is the adaptation in response to a stressful challenge that involves the activation of central neural, neuro-endocrine, CV, metabolic and immune mechanisms. Allostatic load is ideal for assessing cumulative burden of physiological stress because it describes a common pathway that connects obesity and Y-T2DM with the above-mentioned mediating factors. The study utilizes data collected in The African Prospective Study on Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT) cohort study that was designed to identify and describe the development of hypertension in screened to be healthy South African Black and White individuals, aged 20–30 yr, over a period of 15 yr. Primary Objectives: 1. Compare allostatic load by age and determine the relationship with vascular health, masked hypertension and prediabetes. 2. Determine the relationship of allostatic load score (ALS) with metabolomic markers (urine and plasma) and psychological scores such as meaning of life. D. Transitioning Care in Youth-onset Type 2 Diabetes, A Crossroads for Navigating Heart Disease Risk Transitioning from pediatric to adult-centered diabetes care may be challenging, especially for young individuals at risk for and with youth-onset type 2 diabetes (Y-T2D) who have a high disease burden and rapidly progressive disease. However, the scope of transition readiness, range of psychosocial factors, and perceived barriers and how they relate to heart disease risk and cumulative stress among Y-T2D are understudied. Primary Objectives: 1. Characterize attitudes toward transition readiness 2. Examine relationships among depressive and anxiety-related symptoms and transition readiness 3. Identify perceived barriers and facilitators of diabetes self-care 4. Examine the relationship of mood symptoms and diabetes burnout experienced during the transition period with allostatic load and vascular aging. The following results are were published related to this project Endothelial Dysfunction in Youth-Onset Type 2 Diabetes: A Clinical Translational Study. Circ Res. 2024 Jul 29. doi:10.1161/CIRCRESAHA.124.324.272. We used a powerful, non-invasive approach to visualize coronary structure and endothelial function and validate our findings with biological experiments. Magnetic resonance imaging was used to examine the size and function of the right coronary artery and the right brachial artery. Young adults with type 2 diabetes had thicker right coronary arteries and abnormally restricted blood flow in the heart (coronary) and arm (brachial) arteries during a simple hand exercise test. In laboratory experiments we confirmed our findings by showing that blood samples from the same young adult subjects with diabetes contained small, extracellular vesicles that impaired vessel function. This study is important because it provides crucial insights into early signs of heart disease among young adults undergoing treatment for recent (<5 years) development of diabetes. Allostatic load and cardiometabolic health in a young adult South African population: the African-PREDICT study Am J Physiol Heart Circ Physiol 328: H581–H593, 2025. doi:10.1152/ajpheart.00845.2024 This is the first study to assess the effect of stress, as a composite allostatic load score, on micro-, macrovascular, and central cardiac features in healthy emerging and young adults, independent of traditional cardiovascular risk markers. It exemplifies independent stress-induced changes throughout the cardiovascular tree, which may increase the risk of cardiometabolic complications, masked hypertension, and prediabetes. Sustained stress may be a key etiological factor in cardiometabolic disease development in a young population. Navigating Transition to Adult Care in Youth-Onset Type 2 Diabetes: Facilitators, Attitudes, Barriers, and Behaviors The Journal of Clinical Endocrinology & Metabolism, 2025, 00, 1–8, https://doi.org/10.1210/clinem/dgaf239 This study provided a detailed understanding of the mood symptoms, facilitators, and barriers to diabetes self-care among Y-T2D attending a multidisciplinary transition care clinic. Using both quantitative and qualitative methods, the study explored insights into necessary targeted interventions for this population, thereby emphasizing the importance of psychological support, executive functioning, systems navigation, and social support. Most Y-T2D reported adequate diabetes self-care knowledge that did not interfere with daily activities. Though only 15% of Y-T2D believed diabetes negatively affected their daily routine, one-third of Y-T2D reported difficulty with transition-related tasks such as scheduling diabetes appointments, refilling prescriptions, managing diabetes when sick, and navigating transportation to and from clinic visits. Mood symptoms significantly increased the odds of mild cognitive challenges such as forgetfulness and poor attentiveness by approximately 10-fold. Mild or greater depressive and anxiety-related symptoms independently increased the odds of perceived social, emotional, and cognitive challenges. Collectively, the range of the complexities experienced in this young adult cohort highlight the need for Y-T2D–specific transitional programs that systematically address social worries and mood symptoms to optimize health outcomes in these emerging adults in the modern era.