Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold ( < 1 × 10), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in was associated with worse metformin response in the Metformin Genetics Consortium ( = 7,812), though statistically not being significant after Bonferroni correction ( = 0.06). A higher -cell pPS was associated with a lower insulinogenic index ( = 0.02) and C-peptide ( = 0.047) at baseline and higher pPS related to two insulin resistance processes were associated with increased C-peptide at baseline ( = 0.04,0.02). Although pPS were not associated with changes in glycemic traits or metformin response, our results indicate a trend in the association of the -cell pPS with reduced -cell function over time. Our data show initial evidence for genetic variation associated with metformin response in youth with T2D.

Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

The relationship of HbA1c versus the mean blood glucose (MBG) is an important guide for diabetes management but may differ between ethnic groups. In Africa, the patient's glucose information is limited or unavailable and the management is largely guided by HbA1c. We sought to determine if the reference data derived from the non-African populations led to an appropriate estimation of MBG from HbA1c for the East African patients.

People with type 1 (T1D) or type 2 diabetes (T2D) who also have diabetes complications can have pronounced cognitive deficits. It remains unknown, however, whether and how multiple diabetes complications co-occur with cognitive dysfunction, particularly in youth-onset diabetes.

Given the differential risk of type 1 diabetes (T1D) in offspring of affected fathers versus affected mothers and our observation that T1D cases have differential DNA methylation near the imprinted gene compared to controls, we examined whether methylation near mediates the association between T1D family history and T1D risk. In a nested case-control study of 87 T1D cases and 87 controls from the Diabetes Autoimmunity Study in the Young, we conducted causal mediation analyses at 12 region CpGs to decompose the effect of family history on T1D risk into indirect and direct effects. These effects were estimated from two regression models adjusted for the human leukocyte antigen DR3/4 genotype: a linear regression of family history on methylation (mediator model) and a logistic regression of family history and methylation on T1D (outcome model). For 8 of the 12 CpGs, we identified a significant interaction between T1D family history and methylation on T1D risk. Accounting for this interaction, we found that the increased risk of T1D for children with affected mothers compared to those with no family history was mediated through differences in methylation at two CpGs (cg27351978, cg00565786) in the region, as demonstrated by a significant pure natural indirect effect (odds ratio (OR) = 1.98, 95% confidence interval (CI): 1.06-3.71) and nonsignificant total natural direct effect (OR = 1.65, 95% CI: 0.16-16.62) (for cg00565786). In contrast, the increased risk of T1D for children with an affected father or sibling was not explained by DNA methylation changes at these CpGs. Results were similar for cg27351978 and robust in sensitivity analyses. Lastly, we found that DNA methylation in the region was associated (<0:05) with gene expression of nearby protein-coding genes , , , and . Results indicate that the maternal protective effect conferred through exposure to T1D may operate through changes to DNA methylation that have functional downstream consequences.

Using continuous glucose monitoring (CGM), we examined patterns in glycemia during school hours for children with type 1 diabetes, exploring differences between school and non-school time.

The prevalence of overweight and obesity in youth with type 1 diabetes mellitus (T1D) now exceeds that of youth without T1D. Comorbid T1D and excess adiposity are associated with multiple serious negative health outcomes. Unfortunately, youth with T1D are often excluded from and/or not referred to standard behavioral lifestyle interventions. This is often attributed to the complexities of managing T1D and an effort not to overburden persons who have T1D. Furthermore, standard behavioral weight management intervention recommendations can be perceived as contradicting T1D disease management (e.g., removing sugar-sweetened beverages from diet, energy balance with exercise, and caloric restriction). A weight management intervention specifically designed for youth with T1D is needed to provide treatment to youth with comorbid T1D and overweight/obesity. The current study interviewed adolescents with T1D and overweight/obesity ( = 12), their caregivers ( = 12), and pediatric endocrinologists ( = 9) to understand (a) whether they would be interested in a weight management intervention adapted for youth with T1D and (b) specific adaptations they would want and need. Five central themes emerged following applied thematic analysis: (1) program content, (2) programmatic messaging, (3) program structure, (4) social support, and (5) eating disorder risk. Results provide detailed recommendations for the adaptation of a behavioral weight management intervention for youth with T1D.

Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI.

Adolescents and young adults with type 1 diabetes have high HbA1c levels and often struggle with self-management behaviors and attention to diabetes care. Hybrid closed-loop systems (HCL) like the t:slim X2 with Control-IQ technology (Control-IQ) can help improve glycemic control. The purpose of this study is to assess adolescents' situational awareness of their glucose control and engagement with the Control-IQ system to determine significant factors in daily glycemic control.

There is a paucity of data on the risk factors for the hyperosmolar hyperglycemic state (HHS) compared with diabetic ketoacidosis (DKA) in pediatric type 2 diabetes (T2D).

To understand the practices, attitudes, and beliefs of type 1 diabetes (T1D) providers towards school-based diabetes care (SBDC), including counseling families and communicating with schools, and explore the barriers and facilitators which affect their support of SBDC.

The incidence of pediatric diabetic ketoacidosis (DKA) increased during the peak of the COVID-19 pandemic. The objective of this study was to investigate whether rates of hyperosmolar therapy administration for suspected clinically apparent brain injury (CABI) complicating DKA also increased during this period as compared to the three years immediately preceding the pandemic and to compare the characteristics of patients with suspected CABI before the pandemic, patients with suspected CABI during the peak of the pandemic, and those with DKA but without suspected CABI during the pandemic. Patients aged ≤18 years presenting with DKA before (March 11, 2017-March 10, 2020) and during the peak of the pandemic (March 11, 2020-March 10, 2021) were identified through a rigorous search of two databases. Predefined criteria were used to diagnose suspected CABI. Biochemical, clinical, and sociodemographic data were collected from a comprehensive review of the electronic medical record. The proportion of patients with DKA who received hyperosmolar therapy was significantly higher ( = 0.014) during the pandemic compared to the prepandemic period; however, this was only significant among patients with newly diagnosed diabetes. Both groups with suspected CABI had more severe acidosis, lower Glasgow Coma Scale scores, and longer hospital admissions (< 0.001 for all) than cases without suspected CABI. During the pandemic, the blood urea nitrogen concentration was significantly higher in patients with suspected CABI than those without suspected CABI, suggesting they were more severely dehydrated. The clinical, biochemical, and sociodemographic characteristics of patients with suspected CABI were indistinguishable before and during the pandemic. In conclusion, administration of hyperosmolar therapy for suspected CABI was more common during the peak of the COVID-19 pandemic, possibly a result of delayed presentation, highlighting the need for increased awareness and early recognition of the signs and symptoms of diabetes and DKA, especially during future surges of highly transmissible infections.

Adolescents with type 1 diabetes (T1D) are particularly vulnerable to poor psychosocial outcomes-high rates of diabetes distress and poor quality of life are common among this cohort. Previous work in the general population demonstrated positive associations between quality of life and increases in moderate-to-vigorous physical activity (MVPA), as well as decreased sedentary behavior. While survey-based assessments of young adults with T1D observed similar trends, these studies were limited by their use of subjective assessments of MVPA and sedentary behavior. The use of direct activity monitoring is needed to establish the association between psychosocial outcomes and MVPA and sedentary behavior among adolescents with T1D.

The Diabetes Device Confidence Scale (DDCS) is a new scale designed to evaluate school nurse confidence with diabetes devices. We hypothesized that DDCS score would be associated with related constructs of school nurse diabetes knowledge, experience, and training.

We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D).

ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved -cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric KPD within this cohort.