Transparent, Compliant 3D Mesostructures for Precise Evaluation of Mechanical Characteristics of Organoids

UNC Libraries · 2026-04-15

Recently developed methods for transforming 2D patterns of thin-film materials into 3D mesostructures create many interesting opportunities in microsystems design. A growing area of interest is in multifunctional thermal, electrical, chemical, and optical interfaces to biological tissues, particularly 3D multicellular, millimeter-scale constructs, such as spheroids, assembloids, and organoids. Herein, examples of 3D mechanical interfaces are presented, in which thin ribbons of parylene-C form the basis of transparent, highly compliant frameworks that can be reversibly opened and closed to capture, envelop, and mechanically restrain fragile 3D tissues in a gentle, nondestructive manner, for precise measurements of viscoelastic properties using techniques in nanoindentation. Finite element analysis serves as a design tool to guide selection of geometries and material parameters for shape-matching 3D architectures tailored to organoids of interest. These computational approaches also quantitate all aspects of deformations during the processes of opening and closing the structures and of forces imparted by them onto the surfaces of enclosed soft tissues. Studies of cerebral organoids by nanoindentation show effective Young's moduli in the range from 1.5 to 2.5 kPa depending on the age of the organoid. This collection of results suggests broad utility of compliant 3D mesostructures in noninvasive mechanical measurements of millimeter-scale, soft biological tissues.

<b>Obstructive Sleep Apnea, Resting Heart Rate and Glycemic Variability in Adults with Maturity-Onset Diabetes of the Young</b>

2025-11-13

<p dir="ltr">Obstructive sleep apnea (OSA) is a common condition strongly linked to increased cardiovascular risk and poor glycemic control. Little is known about OSA, cardiovascular risk and glycemia in maturity onset diabetes of the young (MODY), an inherited form of diabetes, which is different than both type 1 and type 2 diabetes. We assessed OSA, resting heart rate (RHR), an important prognostic marker of cardiovascular disease, and glycemic variability among the most common subtypes of MODY, glucokinase (GCK)-MODY and transcription factor (TF)-related MODY (HNF1A, HNF4A and HNF1B). Adults with GCK-MODY (n=63) and TF-related MODY (n=60), and controls without diabetes (n=65) were screened for OSA by home sleep test. Glycemic variability (continuous glucose monitoring) and RHR (wearable sleep-activity tracker) were concomitantly assessed for 2 weeks at home. Data from 188 subjects (2853 recorded days) were analyzed. TF-related MODY, compared to GCK-MODY or controls, had more OSA (48.3%, 27.0% and 30.8%, respectively; p=0.033), higher RHR (72.8±10.8, 65.2±7.9 and 67.3±7.7 bpm, respectively; p<0.001), and higher glycemic variability (coefficient of variation of glucose 31.6±6.0%, 17.3±4.5% and 17.5±4.0%, respectively; p<0.001). Greater severity of OSA and higher RHR were associated with higher glycemic variability. These findings may have important clinical implications for cardiovascular risk assessment in MODY.</p>

Creation and Evaluation of a Research Participant Portal for the University of Chicago Monogenic Diabetes Registry

Journal of Diabetes Science and Technology · 2025-12-11

The University of Chicago Monogenic Diabetes Registry (UCMDR) developed a participant portal to enhance engagement and data completeness in a large, longitudinal research study. Built in collaboration with the Center for Research Informatics (CRI), the portal integrates with REDCap to provide secure survey access, document exchange, and communication. Since its launch, 40% of invited participants have activated accounts. Among new enrollees, 88% of portal users completed their baseline survey, up from a historical 60%. Portal activation was higher among female participants ( P < .01), with no significant differences by age or income. Overall portal feature use was modest, possibly reflecting lower adoption among historical participants accustomed to legacy processes. These findings support the feasibility of research participant portals while highlighting opportunities to improve equitable engagement and functionality.

Smaller Pancreas Volume in Insulin-Dependent Monogenic Diabetes

Diabetes · 2025-05-22 · 1 citations

Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an INS gene mutation (INS-PND) have a marked reduction in pancreas volume by MRI compared with control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss of pancreas volume in diabetes, we used a standardized and validated MRI protocol to measure pancreas volumes in individuals with various forms of monogenic diabetes, including maturity-onset diabetes of the young (MODY) and PND (HNF4A-MODY, GCK-MODY, HNF1A-MODY, HNF1B-MODY, INS-MODY, or INS-PND; n = 37), and compared their pancreas volumes with those of previously reported individuals with T1D (n = 93) or healthy control participants with ND (n = 90). Across all monogenic diabetes groups, individuals receiving insulin therapy had significantly smaller pancreas volume compared with those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes. ARTICLE HIGHLIGHTS: Individuals with type 1 diabetes (T1D) have a markedly smaller pancreas, but the mechanism responsible for the reduction in size is unknown. How pancreas volume differs in individuals with specific forms of monogenic diabetes and how pancreas volume relates to the severity of insulin deficiency are unknown. Measured by MRI, individuals with permanent neonatal diabetes due to an INS gene mutation (INS-PND) or the HNF1B gene associated with maturity-onset diabetes of the young had smaller pancreas than individuals without diabetes. Across all types of monogenic diabetes, individuals receiving insulin replacement therapy had smaller pancreas than individuals not using insulin. These results support the conclusion that insulin deficiency is a major factor contributing to changes in pancreas volume in T1D, INS-PND, and other forms of monogenic diabetes.

Advancing Monogenic Diabetes Research and Clinical Care by Creating a Data Commons: The Precision Diabetes Consortium (PREDICT)

Journal of Diabetes Science and Technology · 2025-01-09 · 1 citations

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT). Following the D4CG model, PREDICT has successfully established a multicenter MDM data commons. PREDICT has created a consensus data dictionary that will be utilized to address critical gaps in understanding of these rare types of diabetes. This approach may be useful for other rare conditions that would benefit from access to harmonized pooled data.

<b>Smaller pancreas volume in insulin-dependent monogenic diabetes</b>

2025-05-22

<p dir="ltr">Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an <i>INS</i> gene mutation have a marked reduction in pancreas volume by MRI compared to control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss of pancreas volume in diabetes, we used a standardized and validated MRI protocol to measure pancreas volumes in individuals with various forms of monogenic diabetes (HNF4A-MODY, GCK-MODY, HNF1A-MODY, HNF1B-MODY, INS-MODY, or INS-PND, n = 37), and compared their pancreas volumes with those of previously reported individuals with T1D (n = 93) or healthy ND controls (n = 90). Across all monogenic diabetes groups, individuals on insulin therapy had significantly smaller pancreas volume compared to those not requiring insulin. These results support the hypothesis that insulin signaling to the exocrine pancreas determines pancreas volume in multiple types of diabetes.</p>

Antibody-Positive Type 1 Diabetes in a Family With a Pathogenic <i>HNF1A</i>-MODY Variant and Variable Age of Onset

JCEM Case Reports · 2025-09-25

Abstract Monogenic diabetes (MD) is a relatively rare and heterogeneous group of disorders caused by pathogenic single-gene variants or abnormalities resulting in hyperglycemia. MD represents approximately 3.5% of all diabetes cases diagnosed before age 35 years, though it is possible for MD to develop at later ages. MD diagnoses have implications for precision therapy and cascade genetic testing. A hallmark characteristic suggesting MD is a multigenerational family history of nonobese diabetes diagnosed before age 35 with an autosomal dominant inheritance. However, even with a known family history of genetically confirmed MD, it is possible for an individual within that family to have a different form of diabetes. Here, we present a case from the University of Chicago Monogenic Diabetes Registry of an individual with antibody-positive type 1 diabetes in a family with a history of a genetically confirmed known pathogenic HNF1A variant causing maturity-onset diabetes of the young (MODY) with variable age of onset in affected individuals. This family pedigree showcases that HNF1A-MODY can develop at any age and illustrates the importance of every individual receiving a thorough work-up for accurate diabetes classification, including obtaining antibody testing and genetic testing, when indicated, to provide optimal treatment and management.

Sleep patterns in adults and children with less common forms of diabetes

Frontiers in Endocrinology · 2025-10-13

Objective: To review the current evidence on sleep patterns in relation to glucose control in adults and children with type 1 diabetes (T1DM) and monogenic diabetes. Methods: We searched for the literature pertaining to T1DM and monogenic diabetes with reported sleep patterns, along with glycemic control, in PubMed. This review aimed to examine the current evidence on the relationship between sleep patterns and diabetes management and possible mediating mechanisms for this relationship in adults and children with T1DM and monogenic diabetes. We reviewed articles published from inception until 2023. Results: Twenty-five clinical studies met the eligibility criteria and were included. Children with T1DM with higher sleep variability had higher glucose levels, and those with higher glucose variability had more sleep disruptions. Comparing children with suboptimal [hemoglobin A1c (HbA1c) ≥ 7.5%] and optimal glucose control, those with suboptimal control had shorter sleep duration. There was no higher prevalence of obstructive sleep apnea (OSA) in children with T1DM compared to controls, but in T1DM, those who had OSA had higher glucose levels. Adults with T1DM had a high prevalence of poor sleep quality and were also sleeping less than the recommended hours for their age. Poor sleep quality and short sleep duration correlated with higher glycemic variability. First-generation automated insulin delivery systems did not improve sleep patterns in T1DM, but other strategies, including coaching and counseling, proved to be effective. Monogenic diabetes data also suggest poor sleep quality, short sleep duration, and high rates of sleep apnea. Conclusion: T1DM subjects seem to have worse sleep patterns, especially those with suboptimal glucose control. Monogenic diabetes data are limited, but they also suggest poor sleep patterns. Rigorous interventional studies are needed to further elucidate the sleep-diabetes relationship. Future research could provide insights into strategies that could effectively improve sleep in people living with diabetes.

Obstructive Sleep Apnea, Resting Heart Rate, and Glycemic Variability in Adults With Maturity-Onset Diabetes of the Young

Diabetes · 2025-11-13 · 1 citations

Obstructive sleep apnea (OSA) is a common condition strongly linked to increased cardiovascular risk and poor glycemic control. Little is known about OSA, cardiovascular risk, and glycemia in maturity-onset diabetes of the young (MODY), an inherited form of diabetes, which is different than both type 1 and type 2 diabetes. We assessed OSA, resting heart rate (RHR), an important prognostic marker of cardiovascular disease, and glycemic variability among the most common subtypes of MODY, glucokinase (GCK)-MODY, and transcription factor (TF)-related MODY (HNF1A, HNF4A, and HNF1B). Adults with GCK-MODY (n = 63) and TF-related MODY (n = 60) and control adults without diabetes (n = 65) were screened for OSA by home sleep test. Glycemic variability (continuous glucose monitoring) and RHR (wearable sleep-activity tracker) were concomitantly assessed for 2 weeks at home. Data from 188 individuals (2,853 recorded days) were analyzed. Individuals with TF-related MODY, compared with those with GCK-MODY or control individuals, had more OSA (48.3%, 27.0%, and 30.8%, respectively; P = 0.033), higher RHR (72.8 ± 10.8, 65.2 ± 7.9, and 67.3 ± 7.7 bpm, respectively; P < 0.001), and higher glycemic variability (coefficient of variation of glucose 31.6 ± 6.0%, 17.3 ± 4.5%, and 17.5 ± 4.0%, respectively; P < 0.001). Greater severity of OSA and higher RHR were associated with higher glycemic variability. These findings may have important clinical implications for cardiovascular risk assessment in MODY. ARTICLE HIGHLIGHTS: Obstructive sleep apnea (OSA) has been strongly linked to increased cardiovascular risk and poor glycemic control in the general population. Resting heart rate (RHR) is a prognostic marker of cardiovascular morbidity and mortality and has been linked to dysglycemia. Little is known about OSA, RHR, and glycemia in maturity-onset diabetes of the young (MODY), an inherited form of diabetes with discrete clinical features. Adults with transcription factor-related MODY (HNF1A, HNF4A, and HNF1B) had more OSA and higher RHR and greater glycemic variability compared with those with glucokinase-MODY or control adults without diabetes, which may have important clinical implications for future cardiovascular risk.

&lt;b&gt;Obstructive Sleep Apnea, Resting Heart Rate and Glycemic Variability in Adults with Maturity-Onset Diabetes of the Young&lt;/b&gt;

2025-11-13

&lt;p dir="ltr"&gt;Obstructive sleep apnea (OSA) is a common condition strongly linked to increased cardiovascular risk and poor glycemic control. Little is known about OSA, cardiovascular risk and glycemia in maturity onset diabetes of the young (MODY), an inherited form of diabetes, which is different than both type 1 and type 2 diabetes. We assessed OSA, resting heart rate (RHR), an important prognostic marker of cardiovascular disease, and glycemic variability among the most common subtypes of MODY, glucokinase (GCK)-MODY and transcription factor (TF)-related MODY (HNF1A, HNF4A and HNF1B). Adults with GCK-MODY (n=63) and TF-related MODY (n=60), and controls without diabetes (n=65) were screened for OSA by home sleep test. Glycemic variability (continuous glucose monitoring) and RHR (wearable sleep-activity tracker) were concomitantly assessed for 2 weeks at home. Data from 188 subjects (2853 recorded days) were analyzed. TF-related MODY, compared to GCK-MODY or controls, had more OSA (48.3%, 27.0% and 30.8%, respectively; p=0.033), higher RHR (72.8±10.8, 65.2±7.9 and 67.3±7.7 bpm, respectively; p&lt;0.001), and higher glycemic variability (coefficient of variation of glucose 31.6±6.0%, 17.3±4.5% and 17.5±4.0%, respectively; p&lt;0.001). Greater severity of OSA and higher RHR were associated with higher glycemic variability. These findings may have important clinical implications for cardiovascular risk assessment in MODY.&lt;/p&gt;