Rasmussen VF, Rasmussen D, Thrysøe M
… +7 more, Karlsson P, Madsen M, Kristensen K, Nyengaard JR, Terkelsen AJ, Vestergaard ET, Ovesen T
Pediatr Diabetes
· 2023 · PMID 40303276
·
Full text
AIM: To determine whether adolescents with type 1 diabetes (T1D) have morphological changes of the corneal nerve fibers and reduced smell and taste function compared to healthy control subjects as a sign of cranial nerve...AIM: To determine whether adolescents with type 1 diabetes (T1D) have morphological changes of the corneal nerve fibers and reduced smell and taste function compared to healthy control subjects as a sign of cranial nerve affection and to evaluate possible associated risk factors for cranial nerve affection. METHODS: The study was a part of the T1DANES study including 60 adolescents (15-<19 years) and 23 healthy age-matched controls. First, clinical and biochemical data on the participants were obtained, and the second step involved a test day with neurological examinations including corneal confocal microscopy (CCM), olfactory testing with Sniffin' Sticks, and gustatory assessment with taste-drop test. RESULTS: The adolescents with T1D (mean diabetes duration 9.8 years, mean HbA1c 61 mmol/mol) had lower CCM parameters (corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, and corneal nerve fiber fractal dimension) compared to control subjects (all < 0.05). No differences in total score for smell test ( = 0.66) and taste test ( = 0.47) were found, but adolescents with T1D had reduced ability to taste sweet ( < 0.01). In total, 24% had two or more reduced CCM parameters, 12% had reduced smell test, and 23% had abnormal taste test. Higher waist to height ratio (WHtR) was the only risk factor found for reduced corneal nerve fiber density, and higher BMI-SDS and WHtR were found for impaired taste function. Having abnormal smell test increased the risk for having abnormal taste perception, and vice versa. CONCLUSION: Up to 29% of adolescents with T1D had abnormal test scores indicating cranial nerve affection. Lower corneal nerve fiber density and reduced ability to taste sweet were found in adolescents with T1D compared to control subjects. Clinical attention to smell and taste function seems important because it requires intervention for advising adolescents with impaired smell and taste function.
Pediatr Diabetes
· 2023 · PMID 40303237
·
Full text
In healthy adults, the association between the glycated hemoglobin A1c (HbA1c) level and intima-media thickness (IMT) is stronger in the femoral artery than that in the carotid artery. However, whether this differential...In healthy adults, the association between the glycated hemoglobin A1c (HbA1c) level and intima-media thickness (IMT) is stronger in the femoral artery than that in the carotid artery. However, whether this differential strength of association also applies to adolescents with type 1 diabetes (T1D) is unknown. Therefore, this study aimed to examine whether IMT increases in extracarotid arteries (specifically in the lower extremities) prior to the carotid artery. In total, 286 adolescents with T1D (15.9 ± 4.9 years; 42.0% male participants) were enrolled, and the B-mode ultrasonographic measurement of IMT in the carotid, femoral, and popliteal arteries was performed. Cardiovascular risk factors, including blood pressure (BP), body mass index, lipid levels, and glycemic parameters, were evaluated. To evaluate the site-dependent relationship between IMT and cardiovascular risk factors, a linear mixed-effects model was developed with repeated IMT measurements at various arterial sites as fixed effects and participants as random effects. Glycemic parameters, lipids, uric acid, high-sensitivity C-reactive protein, and advanced glycation end-products were some cardiovascular risk factors that worsened with increasing HbA1c levels. Patients with a higher HbA1c level (>10% vs. ≤10%) had thicker IMT in the femoral artery but not in the carotid or popliteal arteries. Patients with poorer diabetic control exhibited significant changes in certain cardiovascular functions, including central systolic BP, left ventricular (LV) ejection time, LV dp/dt max, stroke volume, and brachial artery compliance. A standard mediation analysis revealed that none of the aforementioned cardiovascular functions mediated the relationship between higher HbA1c level and greater femoral IMT. In adolescents with T1D, cardiovascular risk factors deteriorate with worsening blood glucose control. In the early stages of T1D, femoral IMT may serve as a more sensitive surrogate marker for hyperglycemia-induced subclinical atherosclerosis, an effect that may not be mediated by alterations in cardiovascular functions.
Rose S, Galland BC, Styles SE
… +6 more, Wiltshire EJ, Stanley J, de Bock MI, Tomlinson PA, Rayns JA, Wheeler BJ
Pediatr Diabetes
· 2023 · PMID 40303259
·
Full text
BACKGROUND: The bidirectional relationship between sleep and blood glucose levels may particularly affect adolescents and young adults (AYA), who are more likely to experience less healthy glycemic outcomes and more disr...BACKGROUND: The bidirectional relationship between sleep and blood glucose levels may particularly affect adolescents and young adults (AYA), who are more likely to experience less healthy glycemic outcomes and more disrupted sleep patterns. To date, few data exist describing the impact of intermittently scanned continuous glucose monitoring (isCGM) on habitual sleep patterns and sleep quality in AYA with type 1 diabetes (T1D). OBJECTIVE: To evaluate the impact of 6-month use of isCGM on habitual sleep and wake timing, sleep duration, frequency, and duration of night-time awakenings, sleep efficiency, and perceived sleep quality in young people with T1D and HbA1c ≥ 75 mmol/mol. The study recruited 64 participants aged 13-20 years (mean 16.6 ± 2.1), 48% female, diabetes duration 7.5 ± 3.8 years, 41% Māori or Pasifika, and a mean HbA1c 96.0 ± 18.0 mmol/mol [10.9 ± 3.8%]; 33 were allocated to an isCGM plus self-monitoring blood glucose [SMBG] intervention, and 31 were allocated to the SMBG control group. METHODS: Participants completed 7-day actigraphy measures and the Pittsburgh Sleep Quality Index questionnaire at the baseline and at 6 months. Regression analyses were used to model between-group comparisons, adjusted for baseline sleep measures. RESULTS: At 6 months, subjective measures for overall sleep quality, latency, duration, efficiency, night-time disturbances, use of sleep medications, and daytime dysfunction were similar between the groups. Regression analyses of actigraphy found no significant differences in objectively measured sleep timing and duration across the week after adjusting for age, the period of the school year, and baseline sleep values. CONCLUSIONS: The use of first-generation isCGM in addition to finger-prick testing did not impact objective or subjective sleep measures in AYA with T1D, elevated HbA1c, and highly variable sleep patterns. Research using alternative interventions for improving glycemic outcomes and habitual sleep-wake timing, duration, and perceived sleep quality is warranted in this population group.
Chinchilla P, Dovc K, Braune K
… +4 more, Addala A, Riddell MC, Jeronimo Dos Santos T, Zaharieva DP
Pediatr Diabetes
· 2023 · PMID 40303245
·
Full text
BACKGROUND: Managing glycemia around exercise is challenging for individuals with type 1 diabetes (T1D) and their healthcare professionals (HCP). We investigated HCP knowledge and confidence around exercise counseling fo...BACKGROUND: Managing glycemia around exercise is challenging for individuals with type 1 diabetes (T1D) and their healthcare professionals (HCP). We investigated HCP knowledge and confidence around exercise counseling for youth with T1D worldwide. OBJECTIVE: To assess HCP familiarity with ISPAD Clinical Practice Consensus Guidelines and confidence to deliver recommendations about T1D and exercise. METHODS: A new online survey was developed on strategies and competencies about exercise for youth with T1D, comprising of 64 questions, divided into eight different categories, assessing HCPs perceived exercise knowledge, confidence, training, and barriers to exercise counseling. RESULTS: A total of 125 HCPs mean ± SD age 42 ± 8.2 years (74% female, 73% physicians) completed the survey. The ISPAD exercise guidelines were considered familiar to 68/125 (54%) of responders. Overall, 91/125 (73%) felt confident with giving recommendations about exercise with 47/125 (38%) recommending 45-60 mins/day of physical activity, while 16/125 (13%) recommended >60 mins/day. Several topics related to self-management around exercise were covered by most, but not all responders, and differences were observed in exercise content "confidence" and/or "competence" based on geographic location ( = 0.048). No differences in exercise recommendation dose, confidence, or familiarity with ISPAD guidelines were observed for age, sex, type of HCP, years in practice, or healthcare type. CONCLUSIONS: Exercise counseling for youth with T1D remains a challenge in most healthcare settings, globally. In general, the number of physically active minutes per week is under-prescribed for youth with T1D and many HCPs in various settings around the world feel that more professional education is needed to boost confidence around the education of several exercise-related topics.
Brady RP, Jensen ET, Rigdon J
… +11 more, Crimmins NA, Mallon D, Dolan LM, Imperatore G, Kahkoska AR, Mottl AK, Honor A, Pettitt DJ, Merjaneh L, Dabelea D, Shah AS
Pediatr Diabetes
· 2023 · PMID 39845332
·
Full text
AIMS: Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study,...AIMS: Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study, we aimed to assess the frequency of CD and the potential for undiagnosed CD among youth with childhood onset type 1 diabetes. In addition, we assessed the burden of cardiovascular risk factors and diabetes-associated complications in youth with type 1 diabetes by CD status and IgA tissue transglutaminase autoantibody (tTGA) levels. METHODS: 2,444 youths with type 1 diabetes completed a CD questionnaire and underwent tTGA testing. Integrating the celiac disease questionnaire and tTGA results for this cross-sectional analysis, participants were categorized as follows: (1) reported CD; (2) seropositive for CD (no reported CD and seropositive tTGA); and (3) type 1 diabetes only (comparison group: no reported CD and seronegative tTGA). Subanalyses were performed on those with no reported CD and tTGA ≥10x ULN, designated potentially undiagnosed CD. Cardiovascular risk factors and diabetes-associated complications were evaluated by CD status and tTGA levels utilizing a Poisson model to estimate relative risk. RESULTS: Reported CD in youths with type 1 diabetes was 7%. Seropositivity for tTGA with no reported CD was present in 4%, and 1.2% had potentially undiagnosed CD. Youths with potentially undiagnosed CD had a 2.69x higher risk of diabetic retinopathy than comparison group. In addition, CD with tTGA <0.05 (controlled CD) was associated with lower HbA1c. CONCLUSIONS: Undiagnosed CD is likely present in youths with type 1 diabetes and potentially undiagnosed CD is associated with a higher risk of diabetic retinopathy. These findings indicate the importance of routine screening for CD in type 1 diabetes in youths.
Tatum JD, Hornung L, Bellin MD
… +6 more, Elder DA, Thompson T, Vitale DS, Wasserfall CH, Shah AS, Abu-El-Haija M
Pediatr Diabetes
· 2023 · PMID 39600796
·
Full text
INTRODUCTION: The underlying pathophysiology of diabetes mellitus after acute pancreatitis is unknown and overall risk of developing diabetes postacute pancreatitis in children is understudied. The objective of our study...INTRODUCTION: The underlying pathophysiology of diabetes mellitus after acute pancreatitis is unknown and overall risk of developing diabetes postacute pancreatitis in children is understudied. The objective of our study was to describe the frequency of islet cell autoimmunity and abnormal glucose testing in pediatric patients in the year following their index case of acute pancreatitis. MATERIALS AND METHODS: Data were obtained from a single-center observational cohort study of patients with their first episode of acute pancreatitis. Islet cell autoantibody titers were measured on stored plasma collected from acute pancreatitis diagnosis, at 3 months and at 12 months postacute pancreatitis attack. Abnormal glucose testing was defined as the presence of prediabetes or diabetes, as defined by American Diabetes Association criteria. RESULTS: Eighty-four patients with acute pancreatitis and islet cell autoantibody data were included, 71 had available glucose measures. Median age at first acute pancreatitis attack was 14 years (IQR 8.7-16.3) and 45/84 (54%) were females. Twenty-four patients (29%) were positive for at least one of four islet cell autoantibodies (IAA, GADA, IA-2A, and ZnT8A) and 6 (7%) had two or more positive islet cell autoantibodies. Nineteen patients out of 71 (27%) had abnormal glucose testing at or postacute pancreatitis diagnosis. A higher proportion (37%, 7/19) with abnormal glucose testing had severe acute pancreatitis compared to those with normal glucose testing (13%, 7/52) ( = 0:04). Patients with normal glucose testing were more likely to be positive for one or more islet cell autoantibodies (31%, 16/52) compared to those with abnormal glucose testing (0%, 0/19) ( = 0:004). CONCLUSIONS: Islet cell autoimmunity is more common in children after their index acute pancreatitis attack (29%) than in the general population (7%-8%). While the frequency of prediabetes and diabetes postacute pancreatitis is high, other mechanisms besides islet cell autoimmunity are responsible.
Brown AD, Liese AD, Shapiro ALB
… +13 more, Frongillo EA, Wilkening G, Fridriksson J, Merchant AT, Henkin L, Jensen ET, Reboussin BA, Shah AS, Marcovina S, Dolan LM, Dabelea D, Pihoker C, Mendoza JA
Pediatr Diabetes
· 2023 · PMID 38765732
·
Full text
OBJECTIVE: 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). DESIGN: In this cross-sectional study, age-adjusted...OBJECTIVE: 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). DESIGN: In this cross-sectional study, age-adjusted scores for composite Fluid Cognition, and sub-domain scores for Receptive Language and Inhibitory Control and Attention, were modeled stratified by diabetes-type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure composite Fluid Cognition score. The NIHT-CB Picture Vocabulary Test was used to assess Crystallized Cognition score and rapid identification of congruent versus noncongruent items were used to assess Inhibitory Control and Attention score. SETTING: The SEARCH for Diabetes in Youth study, representative of 5 U.S. states. PARTICIPANTS: Included 1574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c). RESULTS: Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite Fluid Cognition score (β= -2.5, 95% confidence interval (CI)= -4.8, -0.1) and a lower Crystallized Cognition score (β= -3.4, CI= -5.6, -1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D effect modification by glycemic levels were found in the association between FI and composite Fluid Cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p=0.0531). CONCLUSIONS: Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors.
Johnson RK, Ireton AJ, Carry PM
… +11 more, Vanderlinden LA, Dong F, Romero A, Johnson DR, Ghosh D, Yang F, Frohnert B, Yang IV, Kechris K, Rewers M, Norris JM
Pediatr Diabetes
· 2023 · PMID 38765731
·
Full text
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 cont...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.
Shapiro ALB, Bellatorre A, Dabelea D
… +12 more, Stafford JM, D'Agostino R, Shah AS, Urbina EM, Barrett CE, Pihoker C, Marcovina S, Liese AD, Mottl AK, Jensen ET, Wilkening G, SEARCH for Diabetes in Youth Study Group
Pediatr Diabetes
· 2023 · PMID 38706530
·
Full text
AIMS/HYPOTHESES: 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...AIMS/HYPOTHESES: 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. METHODS: Using data from the SEARCH for Diabetes in Youth study cohort, a prospective longitudinal cohort, we examined clustering of complications and their underlying clinical factors with performance on cognitive tests in young adults with youth-onset T1D or T2D. Cognition was assessed via the NIH Toolbox Cognition Battery. The main cognitive variables were age-corrected scores for composite fluid cognition and associated cognitive subdomains. Diabetes complications included retinopathy, microalbuminuria, and peripheral neuropathy (PN). Lipids, systolic blood pressure (SBP), hemoglobin A1c, and other clinical factors were included in the analyses. Clustering was applied separately to each group (T1D=646; T2D=165). A three-cluster(C) solution was identified for each diabetes type. Mean values and frequencies of all factors were compared between resulting clusters. RESULTS: The average age-corrected score for composite fluid cognition differed significantly across clusters for each group (p<0.001). People with T1D and the lowest average fluid cognition scores had the highest frequency of self-reporting at least one episode of hypoglycemia in the year preceding cognitive testing and the highest prevalence of PN. Persons with T2D and the lowest average fluid cognition scores had the highest SBP, the highest central systolic and diastolic blood pressures, and highest prevalence of PN. CONCLUSIONS/INTERPRETATIONS: These findings highlight shared (PN) and unique factors (hypoglycemia in T1D; SBP in T2D) that could be targeted to potentially mitigate cognitive issues in young people with youth-onset diabetes.
Piloya-Were T, Mungai LW, Moran A
… +5 more, Yauch LM, Christakis N, Zhang L, McCarter R, Chalew S
Pediatr Diabetes
· 2023 · PMID 38706529
·
Full text
INTRODUCTION: 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 u...INTRODUCTION: 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. METHODS: We examined the relationship of HbA1c versus MBG obtained by the continuous glucose monitoring in a group of East African youth having type 1 diabetes in Kenya and Uganda ( = 54) compared with the data obtained from A1c-derived average glucose (ADAG) and glucose management indicator (GMI) studies. A self-identified White (European heritage) population of youth ( = 89) with type 1 diabetes, 3-18 years old, living in New Orleans, LA, USA metropolitan area (NOLA), was studied using CGM as an additional reference. RESULTS: The regression equation for the African cohort was MBG (mg/dL) = 32.0 + 16.73 × HbA1c (%), = 0.55, < 0.0001. In general, the use of the non-African references considerably overestimated MBG from HbA1c for the East African population. For example, an HbA1c = 9% (74.9 mmol/mol) corresponded to an MBG = 183 mg/dL (10.1 mmol/L) in the East African group, but 212 mg/dL (11.7 mmol/L) using ADAG, 237 mg/dL (13.1 mmol/L) using GMI and 249 mg/dL (13.8 mmol/L) using NOLA reference. The reported occurrence of serious hypoglycemia among the African patients in the year prior to the study was 21%. A reference table of HbA1c versus MBG from the East African patients was generated. CONCLUSIONS: The use of non-African-derived reference data to estimate MBG from HbA1c generally led to the overestimation of MBG in the East African patients. This may put the East African and other African patients at higher risk for hypoglycemia when the management is primarily based on achieving target HbA1c in the absence of the corresponding glucose data.
Abbasi M, Tosur M, Astudillo M
… +3 more, Refaey A, Sabharwal A, Redondo MJ
Pediatr Diabetes
· 2023 · PMID 38694145
·
Full text
BACKGROUND: 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 w...BACKGROUND: 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. METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI -score and hemoglobin A1c at the time of diagnosis, and non-HDL cholesterol within first year of diagnosis. RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: Cluster 1 was characterized by higher A1c; Cluster 2, by higher non-HDL; Cluster 3, by lower age at diagnosis and lower A1c; Cluster 4, by lower BMI and higher A1c; and Cluster 5, by lower A1c and higher age. Youth in Cluster 1 had the highest rate of diabetic ketoacidosis (DKA) ( = 0.0001) and were most prescribed metformin ( = 0.06). Those in Cluster 2 were most prone to polycystic ovarian syndrome ( = 0.001). Younger individuals with lowest family history of diabetes were least frequently diagnosed with diabetic ketoacidosis ( = 0.001) and microalbuminuria ( = 0.06). Low-BMI individuals with higher A1c had the lowest prevalence of acanthosis nigricans ( = 0.0003) and hypertension ( = 0.03). CONCLUSIONS: Utilizing clinical measures gathered at the time of diabetes diagnosis can be used to identify subgroups of pediatric T2D with prognostic value. Consequently, this advancement contributes to the progression and wider implementation of precision medicine in diabetes management.
Srinivasan S, Chen L, Udler M
… +20 more, Todd J, Kelsey MM, Haymond MW, Arslanian S, Zeitler P, Gubitosi-Klug R, Nadeau KJ, Kutney K, White NH, Li JH, Perry JA, Kaur V, Brenner L, Mercader JM, Dawed A, Pearson ER, Yee SW, Giacomini KM, Pollin T, Florez JC
Pediatr Diabetes
· 2023 · PMID 38590442
·
Full text
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...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.