bluuebunny/crossref_metadata_2025 huggingface dataset:
1082-P: Safety of SGLT2 Inhibitors in Heart Transplant Recipients
Authors: ZAHALKA SALWA , LOW WANG CECILIA C. , CHOKSI PALAK , LAWLER HELEN M. , GRAU LAURA , JENSEN THOMAS
Published: June 2023

Objective: The safety of SGLT2 inhibitor (SGLT2I) use in patients receiving heart transplants is unknown. We aimed to evaluate key measures of safety after initiation of SGLT2I in a cohort of heart transplant recipients.

Methods: Patients in the University of Colorado Health system who received a heart transplant between 1991 and 2022 were included if an SGLT2I was prescribed post-transplant and continued for at least 1 month. Number of urinary tract infections (UTI), urogenital yeast infections (UGI), and ED visits and hospital admissions for skin and soft tissue infections (SSTI) and euglycemic DKA (eDKA) were collected by chart review for the duration of SGLT2I use. Vital signs and lab values were collected at baseline, 3 months, and 6 months after SGLT2I initiation. Least squared means and mean differences were extracted from a random intercept mixed model with an unstructured covariance matrix for each variable.

Results: Forty-six (46) patients met criteria for analysis. Mean age was 56.1 years, 80.4% had DM, and 84.8% had CKD at the time of SGLT2I initiation. Mean time on SGLT2I was 15 months (range 1-91 months). Three patients (6.5%) developed UTI and one developed UGI. Three (6.5%) had ED visits and admissions for SSTI: 1 had a post-surgical scalp infection and 2 had lower extremity cellulitis (1 led to hallux gangrene and amputation). No patients developed eDKA. Seven patients (15.2%) discontinued their SGLT2I: 2 for UTI and 1 each for hypotension, cost, fatigue, dialysis, and unspecified. Thirty-six (36) patients with adequate data over time were included in the analysis to assess change in vital signs and labs. There were no statistically significant changes from baseline to 3 months or 6 months after SGTL2I initiation for weight, BMI, SBP, DBP, Cr, eGFR, serum Na or serum K.

Conclusions: In this sample of heart transplant recipients on SGLT2I, there were few urogenital and SSTI infections, no eDKA, and no significant change in renal function or electrolytes, which adds support for the safety of SGLT2I in this population.

Disclosure

S.Zahalka: None. C.C.Low wang: Research Support; Dexcom, Inc., Virta Health Corp., CellResearch Corporation. P.Choksi: None. H.M.Lawler: None. L.Grau: None. T.Jensen: Other Relationship; Somalogic.
1084-P: The Trend of Korean Diabetes Patients’ Foot EMG Wave Pattern Age over 65
Authors: KIM WI , SHIK PARK MOON
Published: June 2023

Depending on the healthcare system, ethnicity, and diet, delaying complications related to diabetes differ in each country. Diabetic ulcer accompanied by neuropathy of the foot is the key indicator for the development of complications. Therefore finding the total number of impaired feet with foot muscle dystrophy may understand how the diabetes progression of the patients is controlled by public health organization structures. Korea is one of the nations which adopted a national wide government-organized healthcare insurance system compared with private. In this study, we examined how Korean diabetic feet are controlled by the Korean public health care system. To figure out this, diabetes subjects' foot EMG were examined by STEMG-2 (STUFProject EMG Device-2) by checking 3-second foot up and down movement. Age over 65 who suffered from 50 male and female diabetes patients and 50 male and female nondiabetic patients the foot EMG was tested. After finishing the test results EMG was converted into a digital signal by 1024 arbitrary units and plotted wave pattern with subtracting reference. As a result, 98% of nondiabetics showed constant wave patterns corresponding to muscle relaxation and contraction. Whereas, 86% of diabetes patients have constant EMG wave patterns and only 14% have inconsistent EMG wave patterns. 84% of male and 78% of female diabetes patients have similar wave patterns to nondiabetes individuals Also patients who are BMI less than 23 have 96% of constant patterns. 80% of patients' glucose levels below 180 mg/dl have constant wave patterns. However, 60% of patients over 180mg/dl glucose level have inconsistent patterns. In the conclusion, 86% of Korean diabetes patients are controlling muscle destruction could happen a chronic effect of diabetes. Even 13% of diabetes patients who showed abnormal wave patterns, may have some acute cramp with the foot but visually all toes are intact. This may means the progression of diabetic complications is controlled by the Korean national health system.

Disclosure

W. Kim: None. M. Park: None.

Funding

National Research Foundation of Korea (HNU X-Corps)
109-OR: Prior Cerebrovascular Disease Was Positively Associated with Severe Diabetic Retinopathy and Diabetic Macular Edema in Type 2 Diabetes
Authors: YAMAMOTO MASAHIKO , FUJIHARA KAZUYA , HASEBE HIRUMA , SHIOZAKI HARUKA , KODERA REMI , SATO TAKAAKI , YAGUCHI YUTA , OSAWA TAEKO , MATSUBAYASHI YASUHIRO , IWANAGA MIDORI , YAMADA TAKAHO , SONE HIROHITO
Published: June 2023

Background and Purpose: Although it is well established that diabetic retinopathy (DR) and diabetic macular edema (DME) are risk factors for incident cerebrovascular disease (CVD), whether the CVD history could be a predictor of severe DR or DME remains unknown among people with type 2 diabetes. Also, the effects of aging or systolic blood pressure on incident severe DR or DME in individuals with a history of CVD remains unknown.

Methods: Severe DR and DME were defined as vision-threatening treatment-required diabetic eye diseases (TRDED). Enrolled were 31,638 Japanese patients with type 2 diabetes. We longitudinally explored the existence of such an association not only overall but also according to various factors.

Results: The main outcome of TRDED was observed in 854 (2.7%) patients during a mean follow-up of 5.3 years (5.1/1,000 person-years). Prior CVD was present in 694 of 31,638 (2.2%) patients at baseline. In a multivariate adjusted Cox regression model, prior CVD was positively associated with incident TRDED in analysis of the study population (hazard ratio, 1.63 [95% confidence interval, 1.11-2.37] overall; 1.47 [0.54, 3.99] for age ≤49 y; 1.69 [1.12, 2.55] for age ≥50 y; 1.46 [0.89, 2.39] for SBP ≤139 mmHg; 1.97 [1.09, 3.58] for SBP ≥140 mmHg). All results, including several stratified analyses, correlated with visual inspection of the corresponding Kaplan-Meier analysis with log-rank tests indicating gaps between curves for those with and without prior CVD.

Conclusions: These results indicate that CVD is a predictor of vision-threatening severe retinopathy, and suggested that they shared a common background pathophysiology. It also contributed to preventing severe visual impairment and further deterioration of the quality of life after stroke.

Disclosure

M.Yamamoto: None. M.Iwanaga: None. T.Yamada: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. K.Fujihara: None. H.Hasebe: None. H.Shiozaki: None. R.Kodera: None. T.Sato: None. Y.Yaguchi: None. T.Osawa: None. Y.Matsubayashi: None.

Funding

Japan Society for the Promotion of Science (JP21K11569, JP22K16212)
1094-P: Longitudinal Trajectories of Fasting C-Peptide in Youth-Onset Type 2 Diabetes—The SEARCH for Diabetes in Youth Study
Authors: SHAPIRO ALLISON , BELLATORRE ANNA , STAFFORD JEANETTE M. , SHAH AMY S. , PIHOKER CATHERINE , MALIK FAISAL , LIESE ANGELA D. , PETTITT DAVID J. , DABELEA DANA
Published: June 2023

In youth-onset type 2 diabetes (YO-T2D; diabetes diagnosed <20 years-old) loss of glycemic control is more rapid than in adults, partly attributed to accelerated beta cell decline. However, no studies have investigated the potential heterogeneity in the longitudinal trajectories of beta cell function and whether genetic factors might contribute to heterogeneity. We derived longitudinal trajectories of fasting C-peptide (FCP) levels, a surrogate measure of beta cell function, via discrete mixture modeling of repeated measures collected over 15 years of follow-up in youth with YO-T2D (antibody negative and insulin resistant; n=266) from the SEARCH for Diabetes in Youth cohort study. We tested the association between the derived trajectories and T2D genetic risk score (GRS) using a multinomial logistic regression model with adjustment for relevant covariates. A four-trajectory model best fit the data, classifying youth with YO-T2D as having either “initial low FCP and stable over time” (32%), “initial high FCP and slow incline” (8%), “initial high FCP and slow decline” (53%), or “initial very high FCP and rapid decline” (7%) (Figure). T2D GRS was not associated with FCP trajectory membership. These data demonstrate substantial heterogeneity in trajectories of FCP in YO-T2D and suggest that genetic predisposition to T2D is not a significant determinant of this heterogeneity.

Disclosure

A.Shapiro: None. A.Bellatorre: None. J.M.Stafford: None. A.S.Shah: None. C.Pihoker: None. F.Malik: None. A.D.Liese: None. D.J.Pettitt: None. D.Dabelea: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK127208-01, 1UC4DK108173); Centers for Disease Control and Prevention (U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139)
1097-P: Association between Adipokines and Glycemia in Children under Age 8—The PROGRESS Cohort of Mexico
Authors: BEYH YARA S. , WU HAOTIAN , VENKAT NARAYAN K.M. , STAIMEZ LISA R. , RAMAKRISHNAN USHA , BHASIN MANOJ K. , CRUZ TOLENTINO DOLORES MARI , ESTRADA-GUTIERREZ GUADALUPE , YITSHAK SADE MAAYAN , WRIGHT ROBERT O. , TELLEZ-ROJO MARTHA M. , BACCARELLI ANDREA
Published: June 2023

Background: The increased incidence of type 2 diabetes is closely linked to obesity, in which an accumulation of adipocytes leads to the dysregulated production of adipokines. In adults, several adipokines contribute to the development of glycemic dysregulation, however, the role of adipokines on childhood glycemia is poorly understood. We examine the longitudinal association between adipokines and glycemia using multiple timepoint data from children in Mexico City.

Methods: Children from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort (948 children, 52% male) were followed longitudinally after birth. Leptin, adiponectin, glucose, and HbA1c were measured at 4, 6, and 8 years, and fasting insulin at 8 years. Adiponectin to leptin ratio (ALR) and HOMA2 (B/IR/S) indices were computed. Longitudinal association between adipokines and each of glucose and HbA1c was examined by linear mixed models. Association between adipokines and insulin and the HOMAs at age 8 was examined by multivariable linear regression. All models were adjusted for maternal and child covariates.

Results: Between ages 4 and 8 years, average levels of leptin dropped from 15.7 to 13.7 ug/mL; adiponectin increased from 3.1 to 10.8 ng/mL; and ALR dropped from 9.1 to 3.1 ug/ng. Longitudinally, across timepoints 4, 6, and 8 years after birth, there was no association between adipokines and glycemia. However, the cross-sectional analysis at age 8 years found an association between leptin and insulin (1.03, 95% CI: 1.00, 1.07), HOMA2-B (1.02, 95% CI: 1.00, 1.04), HOMA2-IR (1.03, 95% CI: 1.00, 1.07), and HOMA2-S (0.97, 95% CI: 0.94, 0.99). Similar associations were observed in males and females.

Conclusion: In this prepubertal cohort, leptin was associated with insulin and with HOMA indices at age 8. Further investigation is needed to understand the role of adipokines in the development of T2DM in children and the risk factors that may alter adipokine metabolism.

Disclosure

Y.S.Beyh: None. R.O.Wright: None. M.M.Tellez-rojo: None. A.Baccarelli: None. H.Wu: None. K.Narayan: None. L.R.Staimez: None. U.Ramakrishnan: None. M.K.Bhasin: None. M.Tolentino dolores: None. G.Estrada-gutierrez: None. M.Yitshak sade: None.

Funding

National Institute of Environmental Health Sciences (R01ES032242, R01ES021357, R01ES013744, P30ES009089)
1099-P: Plasma Amino Acid Profiles in Childhood Predict 10-Year Risk of Insulin Resistance in Adulthood—The BCAMS Study
Authors: GAO SHAN , LI MING , GROUP BCAMS
Published: June 2023

Objective Insulin resistance (IR) is the critical step in the development of type 2 diabetes. Recent cross-sectional studies in children demonstrate plasma amino acids such as branched-chain and aromatic amino acids are associated with IR, however, information is scant regarding whether these associations in childhood persist over time and predict diabetes risk in young adults. We aimed to examine whether circulating amino acids in childhood predict 10-year risk of IR in early adulthood.

Research design and Methods: This was a 10-year longitudinal study from childhood to early adulthood. A total of 961 subjects aged 6-18 years at baseline participated in the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS). Serum insulin was determined by in-house ELISA with no cross-reaction with proinsulin, and plasma amino acids were profiled using targeted LC-MS/MS. IR was determined by the homeostatic model assessment of insulin resistance (HOMA-IR).

Results: At baseline, after adjusting for age, gender, tanner stage, diet score, exercise, residence and BMI, 17 amino acids were closely correlated with HOMA-IR and nine with impaired fasting glucose (IFG) in childhood (p < 0.05 for all). Among them, Isoleucine showed the strongest association with IR (OR=2.04, 95% CI 1.65-2.54, P<0.001), and alanine was the strongest predictor of IFG (OR =1.52, 95%CI 1.22-1.91, P<0.001). Prospectively, after adjusting for the covariates at baseline, four amino acids have a significant predictive effect on the risk of IR at 10-years follow-up, of which alanine was the strongest predictor [OR=1.38, 95% CI (1.02, 1.85), P=0.035].

Conclusion: Our findings suggest the changes in amino acid metabolism not only link IR in childhood, but also persist into adulthood and may heighten type 2 diabetes risk later in life.

Disclosure

S.Gao: None. M.Li: None. Bcams group: n/a.

Funding

National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014); National Natural Science Foundation of China (81970732, 82270924); CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-016); Capital's Funds for Health Improvement and Research (2020-2Z-40117); Key Program of Beijing Municipal Science &Technology Commission (D111100000611001, D111100000611002)
1102-P: Joint Effect of GLP-1R and Exposure to Gestational Diabetes on Glucose Regulation in Adolescents—The EPOCH Study
Authors: HARRALL KYLIE K. , GLUECK DEBORAH H. , SAUDER KATHERINE A. , CREE-GREEN MELANIE , DABELEA DANA
Published: June 2023

Exposure to gestational diabetes (GDM) and polymorphisms of the glucagon-like-peptide-1 receptor gene (GLP-1R) are both associated with type 2 diabetes risk. In adults, GLP-1R mutations were associated with altered first phase insulin secretion and glucose levels during an oral glucose tolerance test (OGTT). We explored a potential joint association between GLP-1R and GDM exposure on glucose regulation in youth. Exploring Perinatal Outcomes among Children (EPOCH) participants with (N = 86) and without (N = 189) GDM exposure had 2-hour 75g OGTT at ~17 years. DNA was genotyped by microarray. Plink 2.0 was used to extract genotyped and imputed GLP-1R polymorphisms. Glucose and insulin measured at 0, 30 and 120 minutes were used to calculate areas under the curve (AUC), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulinogenic index (IGI), and disposition index (DI). Linear models tested the interaction of GLP-1R rs1042044 homozygosity of the minor allele and GDM on each outcome. Homozygotes exposed to GDM had higher baseline, 30, 120 minute and AUC for glucose (p < 0.0001), and lower insulin AUC (p = 0.046) than others (Figure 1), but not significantly different HOMA-IR, IGI and DI. Our data indicates a joint effect of GDM exposure and GLP-1R on glucose levels in youth, potentially due to reduced first phase insulin secretion. Further studies are needed to replicate this finding.

Disclosure

K.K.Harrall: None. D.H.Glueck: None. K.A.Sauder: None. M.Cree-green: Consultant; Pollie Inc, Research Support; Amino Corp LLC. D.Dabelea: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068001)
1103-P: Prediabetes and Associated Characteristics among Asian/Pacific Islander Adolescents with Obesity
Authors: CHU CLARENCE , RODRIGUEZ LUIS A. , CHANDRA MALINI , GREENSPAN LOUISE , BACONG ADRIAN M. , LO JOAN C.
Published: June 2023

Background: There are limited data regarding modifiable lifestyle behaviors and prediabetes among US Asian/Pacific Islander (API) children. This study characterizes the association of obesogenic behaviors and weight with prediabetes among API adolescents with obesity receiving pediatric care.

Methods: We used retrospective data from 3,233 API adolescents aged 13-17 years in a US healthcare system who had well child visits in 2016-2019, provided well-check information on health behaviors, had BMI ≥95th percentile, and HbA1c level (within 1 year). Age, sex, self-reported daily obesogenic behaviors (eating <5 servings of fruits/vegetables, drinking ≥12 oz juice/soda, exercising for <60 minutes, >2 hours screen time), obesity level (Class I,2,3) and neighborhood deprivation index (NDI) were examined. Prediabetes was defined as HbA1c 5.7-6.4%; those with HbA1c ≥6.5% or diabetes diagnosis were excluded. Multivariable logistic regression was used to examine the association of these factors and prediabetes.

Results: Among 3,233 API adolescents (mean age 14.6 ± 1.4 y; 63.8% male) with obesity, 22.4% had prediabetes (84.4% had HbA1c 5.7-5.9%). Prediabetes did not differ by age or sex but increased with obesity level (20.1%, 25.2%, 33.2% for Class 1, 2, 3 obesity, respectively). In unadjusted analyses, low exercise was marginally associated with prediabetes (p=0.07) but not diet or screen time. In fully adjusted multivariable analyses, obesity severity (OR 1.98 [95% CI 1.47-2.64] for class 3, OR 1.34 [1.10-1.63] for class 2 vs 1), and low exercise (OR 1.20 [1.01-1.44]) were associated with increased odds of prediabetes, whereas other modifiable behaviors were not.

Conclusion: About 1 in 5 API adolescents with obesity had prediabetes, associated with obesity severity and low exercise. These findings support efforts that address obesity and promote physical activity in API children to reduce the risk of diabetes. Further studies should examine potential differences by ethnic group.

Disclosure

C.Chu: None. L.A.Rodriguez: None. M.Chandra: None. L.Greenspan: None. A.M.Bacong: None. J.C.Lo: None.

Funding

Kaiser Permanente Northern California
1104-P: South Asian vs. White Adolescents Have Lower Insulin Sensitivity and Higher Insulin AUC
Authors: HITT TALIA A. , STEFANOVSKI DARKO , MALINA SARA , WANG CYNTHIA X.D. , ZEMEL BABETTE S. , KELLY ANDREA , MAGGE SHEELA N.
Published: June 2023

Background: T2D occurs at higher rates in South Asian (SA) adults, even at non-overweight/obese BMI. OGTT metrics were compared in SA vs White (W) adolescents to identify early contributors to increased T2D risk.

Methods: Healthy SA and W adolescents, ages 12-21y, with BMI ≥80%ile (or ≥23kg/m2 if ≥18y) underwent 10-sample 180-min OGTT to determine incremental insulin AUC (iAUC), Oral Minimal Model insulin sensitivity (Si), and disposition index (DI: Si x insulin iAUC at 180min). Ancestry differences in OGTT outcomes were compared using linear regression adjusted for age, sex, and BMI.

Results: For n=21, age [median (IQR) W: 20.1y (16.1, 21.3), SA: 21.0 (20.3, 21.6)], sex [W: 6F, SA: 4F], and BMI [W: 25.2kg/m2 (24.7, 31.4), SA: 24.6 (24.1, 27.9)] were not different for SA vs W. Fasting glucose [β=7.1, p=0.01; SA: 98.0mg/dL (92.0, 102.5), W: 89.0mg/dL (87.0, 93.5)], fasting insulin [β=7.0, p=0.005], insulin iAUC at 30min [β=1192, p=0.02], and log-transformed insulin iAUC at 180min [β=0.98, p=0.002] were higher, and log-transformed Si [β=-1.07, p=0.008] lower in SA than W. HbA1c, OGTT 1h and 2h glucose, and DI did not differ.

Conclusions: Higher OGTT insulin in overweight SA adolescents contrast with reduced insulin found in SA adults and suggests reduced Si and insulin hyper-secretion are precursors to β-cell failure and T2D in SA adults. Understanding T2D mechanistic differences by ancestry may lead to improved T2D treatments.

Disclosure

T.A.Hitt: None. D.Stefanovski: None. S.Malina: None. C.X.D.Wang: None. B.S.Zemel: None. A.Kelly: None. S.N.Magge: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK115648); National Institutes of Health (UL1TR001878, UL1TR001079)
1105-P: Development and Implementation of a Multidisciplinary Clinic Focused on Youth-Onset Type 2 Diabetes
Authors: SCHAAF LISA R. , CRAIL JENNIFER , XANTHAKOS STAVRA , SIZEMORE JENNIFER , CRIMMINS NANCY A. , HELMRATH MICHAEL , LEY SANITA , MORWESSEL NANCY , RIEGLER ALLEN , TARIQ FATIMA , SHAH AMY S.
Published: June 2023

Diabetes self-management education and lifestyle interventions are the cornerstone of type 2 diabetes (T2D) care; however, the higher risk of comorbidities, including depression, among youth with T2D requires a comprehensive care model. Traditionally sub-specialty care relies on a referral model placing the burden on the patient. In response, we developed a pediatric T2D multidisciplinary clinic (MDC) - a single physical location where patients have access to various sub-specialists. The goals of the MDC are to provide access to lifestyle modifications, identify patients who need access to sub-specialty care through screening labs, and improve health care access.

We conducted a retrospective chart review of youth seen in the T2D MDC clinic at Cincinnati Children's Hospital from 1/2020 - 12/2021. We evaluated the frequency that youth met with each specialist and completion rates of annual screening labs.

The cohort consisted of 227 youth with T2D (mean age 17.6 years, mean BMI 40.9%, 64% female, 50% Black or African American, 65% public insurance). All patients met with a diabetes provider and 81.2% met with a registered dietitian/certified diabetes education specialist. Gastroenterology met with 55.8% of the patients who had elevated liver enzymes, exercise physiology met with 51.6% of patients, social work met with 44.1% of patients, clinical psychology met with 27.3% of patients, and bariatric surgery met with 9.7% of patients. Percent completion of annual labs were: 98.2% for HbA1c, 84.6% for urine microalbumin, 83.7% for lipids, 89.9% for liver function, and 59.5% for retinopathy.

The majority of patients received diabetes and nutrition education and annual screening labs. Exercise counseling and sub-specialty care remain below 60% in part because these services are not available at every MDC clinic. Our goals are to increase access to subspecialty care within the MDC's and consider additional care delivery methods to provide comprehensive care to youth with T2D.

Disclosure

L.R.Schaaf: None. F.Tariq: None. A.S.Shah: None. J.Crail: None. S.Xanthakos: None. J.Sizemore: None. N.A.Crimmins: None. M.Helmrath: None. S.Ley: None. N.Morwessel: None. A.Riegler: None.
1107-P: Insulin Sensitivity Changes from Adolescence to Young Adulthood
Authors: BRAXTON MORGAN , JAGER JUSTIN , AYERS STEPHANIE , OLSON MICAH , SHAIBI GABRIEL Q.
Published: June 2023

Background: Latino youth are disproportionately impacted by type 2 diabetes (T2D) and youth onset T2D is more aggressive and resistant to conventional treatment. Early prevention efforts are warranted for high-risk pediatric populations, but little is known about the long-term effects of such interventions. The purpose of this study was to examine health trajectories following a diabetes prevention program for Latino adolescents with obesity who are now young adults.

Methods: Participants (N=61) completed a 3-month lifestyle intervention as adolescents (Mage = 15.4) and were re-contacted ~5 years post-intervention (Mage = 20.7 years). Measures included BMI and the Matsuda Index to estimate insulin sensitivity. Latent profile analysis was used to examine heterogeneity in changes in insulin sensitivity over time.

Results: Participants exhibited significant reductions in BMI post-intervention (from 34.8±4.7 to 34.1±4.7, p <.001); however, BMI increased at 5-year follow up (40.5±8.4, p <.001). Similarly, insulin sensitivity increased by 23.5% post-intervention (from 1.7±1.0 to 2.1±1.0, p <.001) but returned to baseline levels at 5-years (1.8±1.4). Latent profile analysis identified two distinct trajectories in insulin sensitivity. Profile 1 was characterized by lower baseline insulin sensitivity (1.4 [1.2, 1.7]) followed by a 36% increase post-intervention (1.9 [1.6, 2.2]) that remained above baseline at 5 years (1.7 [1.3, 2.1]). Profile 2 exhibited a 31% increase from baseline insulin sensitivity (2.9 [1.6, 4.2]) after the intervention (3.8 [2.8, 4.8]) that fell below baseline at 5 years (2.7 [0.6-4.8]) Female sex significantly differentiated the trajectories and was associated with profile 1.

Discussion: Despite improvements in diabetes-related health immediately following the intervention, weight gain and decreased insulin sensitivity persisted into young adulthood. The unique profiles suggest that there may be specific factors such as sex that can differentiate health trajectories over time.

Disclosure

M.Braxton: None. J.Jager: None. S.Ayers: None. M.Olson: Advisory Panel; Rhythm Pharmaceuticals, Inc. G.Q.Shaibi: None.

Funding

National Institute on Minority Health and Health Disparities (U54MD002316)
1119-P: Improved Glycemic Control with Less Effort during Real-World MiniMed 780G Advanced Hybrid Closed-Loop (AHCL) System Use by Children with T1D
Authors: MCVEAN JENNIFER , ARRIETA ARCELIA , CORDERO TONI L. , CASTAÑEDA JAVIER , COHEN OHAD
Published: June 2023

Objective: To evaluate real-world glycemic outcomes and insulin delivery based on TIR (70-180mg/dL) before and after MiniMed™ 780G system use by children with T1D.

Methods: MiniMed™ 780G system data from 2,516 users aged ≤15 years (from Europe, the Middle East and Africa) who provided assent, were uploaded between Aug 2020 and Jun 2022. For users with ≥10 days of sensor glucose (SG) data, glycemic outcomes (e.g., SG, time in SG ranges and glucose management indicator [GMI]), insulin delivered, and use of the 100mg/dL* glucose target and 2hrs active insulin time (recommended settings) were summarized and stratified by baseline TIR quartiles. Results: After AHCL initiation, overall glycemic control (GMI) improved and TIR increased in all TIR quartiles, with increased system-initiated insulin (auto basal and auto correction) delivery and fewer user-initiated boluses (Figure). Greater recommended settings use was associated with a higher TIR (4th quartile) and less recommended settings use was associated with a lower TIR (1st quartile).

Conclusion: Children with T1D using the MiniMed™ 780G system had improved glycemic control evidenced by increased TIR with less effort (i.e., fewer user-initiated boluses). Glycemic control was improved across the spectrum of users and use of recommended settings enhanced outcomes.

Disclosure

J.Mcvean: Employee; Medtronic. A.Arrieta: Employee; Medtronic. T.L.Cordero: Employee; Medtronic. J.Castañeda: Employee; Medtronic. O.Cohen: Employee; Medtronic.
1120-P: Higher Real-World Time in Range Demonstrated in Children Using Recommended MiniMed 780G (AHCL) Settings
Authors: MCVEAN JENNIFER , ARRIETA ARCELIA , CORDERO TONI L. , CASTRO MATIAS , CASTAÑEDA JAVIER , COHEN OHAD
Published: June 2023

Objective: The present study evaluated real-world pediatric glycemia during use of MiniMed™ 780G recommended settings (100 mg/dL* glucose target [GT] and 2hrs active insulin time [AIT]).

Methods: Overall mean TIR, after AHCL initiation, in the pediatric pivotal trial (ages 7-17 years) was 70.3% (N=160).1 For participants using recommended settings >95% of the time, mean TIR was 73.4% (N=19). In this abstract, we present real-world glycemic outcomes in children (≤15 years) from multiple continents using a range of GT and AIT settings, versus the recommended GT and AIT settings. Assented real-world users with ≥10 days of sensor glucose (SG) data from EMEA (N=3,211 in Europe, the Middle East, and Africa) and Latin America (N=332) uploaded system data between Aug 2020-Sep 2022. Outcomes included the mean of SG, glucose management indicator and percentage of time spent below, within and above target (70-180 mg/dL) range.

Results: Real-world outcomes from children in EMEA and Latin America using overall AHCL settings met consensus goals (Figure)2 and TIR increased further when recommended settings were used.

Conclusion: Findings in a population of children from around the world with T1D who used MiniMed™ 780G AHCL at recommended settings (versus a range of settings) had the highest time in range, without compromising time below range.

Disclosure

J.Mcvean: Employee; Medtronic. A.Arrieta: Employee; Medtronic. T.L.Cordero: Employee; Medtronic. M.Castro: Employee; Medtronic. J.Castañeda: Employee; Medtronic. O.Cohen: Employee; Medtronic.
1128-P: Changes in Gut Bacteriome Composition on Low-Carbohydrate Diet in Children with Type 1 Diabetes
Authors: NEUMAN VIT , HLINÁKOVÁ LUCIE , PLACHY LUKAS , PETRUZELKOVA LENKA , OBERMANNOVA BARBORA , PRUHOVA STEPANKA , KOLOUSKOVA STANISLAVA , HAVLIK JAROSLAV , SUMNIK ZDENEK , CINEK ONDREJ
Published: June 2023

Objectives: Low-carbohydrate diet (LCD) is a controversial but popular dietary choice for many children and adolescents with type 1 diabetes (CwD). In a cross-over trial with LCD (clinicaltrials.gov NCT05078658), we assessed whether even a short period of tightly controlled LCD is able to change the gut bacteriome in CwD.

Methods: Twenty CwD (aged 15.1±3.0 years) were recruited into an intervention trial with a 5-week period of LCD (95±3 g carbs daily) followed by 5 weeks of regular carbohydrate diet (RCD) (193±18 g carbs daily) with the order randomized. The diets did not differ in energy intake (8360 vs. 8392 kJ, P=0.08). The fecal samples were collected regularly before, after and throughout the interventions (median number of samples collected per subject was 12, IQR 10-15). The fecal bacteriome was assessed using massively parallel sequencing of the variable regions V3-V4 of 16S rDNA. Mixed effects regression models were built where responses were principal components of the bacteriome community, alpha diversity indices and individual taxa. The predictors were the type of the diet, time since start of the diet and randomized order of the diets.

Results: We observed shifts in the bacteriome community composition on the LCD which were apparent at all taxonomic levels (P for various principal components ranging from 5×10-4 to 0.015); their magnitude was however moderate. Of individual taxa, Bifidobacterium sp. and its higher taxonomic categories were negatively associated with LCD; the overall effects observed on the community composition were however broader than could be explained by changes in this single taxon. The alpha diversity decreased with time regardless of the intervention sequence, but did not associate with LCD.

Conclusions: Even a short period of LCD is associated with subtle yet significant changes in the stool bacteriome community composition mainly in the Bifidobacterium sp. The observed changes may help us understand the possible effects of LCD on T1D.

Disclosure

V.Neuman: None. O.Cinek: None. L.Hlináková: None. L.Plachy: None. L.Petruzelkova: None. B.Obermannova: None. S.Pruhova: None. S.Kolouskova: None. J.Havlik: None. Z.Sumnik: None.

Funding

Czech Ministry of Health (AZVNU21-01-00085)
1130-P: Language and Ethnicity in the Experience of Social Determinants of Health in Pediatric Type 1 Diabetes
Authors: ADDALA ANANTA , MEDINA PENARANDA RICARDO , HANES SARAH , SHAW GARY M. , CHAMBERLAIN LISA , NARANJO DIANA , RAYMOND JENNIFER , MAAHS DAVID M. , HOOD KOREY K.
Published: June 2023

Social determinants of health (SDOH) are recognized as drivers of health outcomes. In this pilot study, we explored SDOH in parents/guardians (PG) of youth with type 1 diabetes (T1D) and public insurance for differences across preferred language and ethnicity.

PG of youth <12 years with T1D and public insurance were recruited to complete nine validated surveys in English or Spanish measuring perceived discrimination, childhood trauma, technology acceptance, and mental health. PG and child characteristics were gathered via self-report. Descriptive differences in survey responses were evaluated by three language and ethnicity groups: non-Hispanic English preferred (NHE), Hispanic English preferred (HE), and Hispanic Spanish preferred (HS).

We recruited 28 PG (37±7 yrs, youth 8±2 yrs, 68% Hispanic, 54% Spanish preferred, 71% with income <$50K). Most children use sensors (93%) and, less frequently, pumps (54%). Compared to NHE and HS, HE PG score higher on discrimination scales, had lower technology acceptance, and poorer mental health (Table). Interestingly adverse childhood experiences were highest in the NHE group.

Language may play a role in the experience of discrimination, technology acceptance, and mental health for Hispanic PG. Although only two surveys were statistically significant, mean survey differences between the groups are clinically meaningful and warrant further investigation.

Disclosure

A.Addala: None. R.Medina penaranda: None. S.Hanes: None. G.M.Shaw: None. L.Chamberlain: None. D.Naranjo: None. J.Raymond: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. K.K.Hood: Consultant; Cecelia Health.

Funding

Maternal & Child Health Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases (K23DK13134201)
1133-P: Body Mass Index Trajectories in Youth with Type 1 Diabetes
Authors: GANTA AVANI , HAS PHINNARA , WARNICK JENNIFER , SWARTZ TOPOR LISA
Published: June 2023

Background: About 35% of youth in Rhode Island (RI) meet criteria for overweight/obesity (OW/OB). Though previously rare, rates of OW/OB in youth with T1D are reportedly increasing.

Objective: To examine BMI trajectories of youth with T1D in RI from initial diagnosis over 5 years. We hypothesized that BMI would increase after diagnosis, continue to rise over time, and be similar to the general population.

Methods: A retrospective chart review was conducted. Youth ≥5 years old with new onset T1D diagnosed in 2015-2016, followed at least annually for 5 years were included. Linear growth curve models specifying visit date as a random effect were used to assess BMI percentiles and z-scores across time. P<0.05 were considered significant.

Results: Subjects (n=76) were 57.9% male; mean (SD) age at T1D diagnosis=11 (2.9) years. At initial outpatient visit 35.5% had OW/OB, with M:F ratio of 1.4:1. By 2021, 53% had OW/OB, with equal M:F distribution. More males were observed to have obesity in 2021. Mean BMI percentile and z-score per subject per year increased gradually over time (p <0.001).

Conclusion: Youth with T1D in RI experienced a steady increase in BMI over time and within 5 years of T1D diagnosis. Males were more likely to have obesity 5 years after diagnosis. The combination of T1D with OW/OB compounds the risks for metabolic syndrome. Targeted interventions to address OW/OB in these youths are needed, as are further studies of glycemic trajectory and clinical course.

Disclosure

A.Ganta: None. P.Has: None. J.Warnick: None. L.Swartz topor: None.
1134-P: Determination of Glucose-Independent Racial Disparity in HbA1c in Youth with Type 1 Diabetes in the Era of Continuous Glucose Monitoring
Authors: CHRISTAKIS NICHOLAS J. , FELIPE DANIA , GOMEZ RICARDO , CHALEW STUART
Published: June 2023

Introduction: The extent and importance of higher HbA1c levels not due to mean blood glucose (MBG) in non-Hispanic Black (B) versus non-Hispanic White (W) individuals is controversial. We sought to clarify the relationship of HbA1c with metrics of glycemia derived from continuous glucose monitoring (CGM) in a young biracial population.

Methods: Glycemic data of 33 B and 85 W, otherwise healthy youth with type 1 diabetes (age 14.7±4.8 years, M/F=51/67, duration of diabetes 5.4±4.7 years) was derived from a factory calibrated CGM and compared with assayed HbA1c. Hemoglobin glycation index (HGI) a metric of MBG difference in HbA1c not due to MBG =assayed HbA1c - Glucose Management Index (GMI).

Results: B patients had higher unadjusted levels of HbA1c, MBG, MBGSD, GMI and HGI than W patients. Percent glucose time in range (TIR) and percent sensor use (PSU) were lower for B patients. HbA1c remained higher in B patients (8.6%) versus (7.7%) for W (p<0.0001) after statistical adjustment for MBG, MBGSD, age, gender, insulin delivery method and PSU. MBG and race accounted for 80% of the variation in HbA1c in the model. Results were similar when TIR was substituted for MBG (R2=0.64, p<0.0001). The 95% for HGI=0.47% in W patients, 52% of B patients had HGI ≥0.5%. Percent time below range was similar for both groups.

Conclusions: Young B patients have clinically relevant higher HbA1c (~0.9%) at any given level of MBG or TIR than W patients, which may pose an additional risk for diabetes complications. HGI ≥0.5% may be an easy way to identify high risk patients.

Disclosure

N.J.Christakis: None. D.Felipe: None. R.Gomez: None. S.Chalew: Advisory Panel; Medtronic.

Funding

National Institutes of Health (1R21DK118643-01A1, U54GM104940)
114-OR: Genetic Variants in GIPR and Effects of Dietary Carbohydrate Quantity and Quality on Glycemic Responses to an Oral Glucose Load—The OmniCarb Trial
Authors: HEIANZA YORIKO , WANG XUAN , XUE QIAOCHU , APPEL LAWRENCE J. , SACKS FRANK , QI LU
Published: June 2023

The gut incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), may play a pivotal role in mediating adverse effects of high glycemic index (GI) foods on metabolic diseases. GIP exerts its effects by binding to a receptor, GIPR; genome-wide association studies have identified variants in the GIPR region related to type 2 diabetes (T2D) and glycemic/GIP responses to glucose tolerance tests. We examined whether GIPR variants were related to impaired glycemic responses during oral glucose tolerance tests (OGTTs) after consuming 4 diets (each for 5 weeks) with different carbohydrate (Carb) content and GI levels in the OmniCarb randomized crossover feeding trial. A genetic risk score (GRS) was calculated by counting T2D-risk alleles of SNPs rs1800437, rs11671664, and rs2238689 at GIPR (n=146). We found that GRS was related to greater glycemic responses after consuming a high GI/high Carb diet, regardless of baseline glycemic status (Fig). When testing diet replacement effects, combined effects of high GI and high Carb (vs. low GI/low Carb) on glycemic responses were significantly modified by GRS (Pinteraction<0.05). In conclusion, T2D-risk-related GIPR variants modified the effects of dietary carbohydrates on glucose tolerance. GIPR variants may be related to deteriorating glucose tolerance after eating a high GI, high Carb diet.

Disclosure

Y.Heianza: None. X.Wang: None. Q.Xue: None. L.J.Appel: None. F.Sacks: None. L.Qi: None.

Funding

National Institutes of Health (2P20GM109036-06A1-7233, DK091718, DK100383, DK115679)
1141-P: Characterizing Clinical Characteristics of 6q24-Related Transient Neonatal Diabetes
Authors: MCCULLOUGH MICHAEL , LETOURNEAU-FREIBERG LISA R. , BOWDEN TIANA L. , KANDASAMY BALAMURUGAN , DEL GAUDIO DANIELA , PHILIPSON LOUIS H. , GREELEY SIRI ATMA W.
Published: June 2023

Introduction: Transient neonatal diabetes mellitus (TNDM) is a heterogeneous subtype of neonatal diabetes that usually presents within the first days or weeks of life, spontaneously remits in infancy, but can recur in childhood or adolescence as a permanent form of diabetes. Approximately 70% of TNDM cases are due to overexpression of genes at chromosome 6q24 caused by one of three potential mechanisms: uniparental disomy (UPD6), paternal duplication, or hypomethylation of the maternal allele. Our aim was to further elucidate clinical characteristics of a relatively large group of individuals with this rare condition.

Methods: Participants with a confirmed or suspected diagnosis of 6q24 TNDM were identified through the University of Chicago Monogenic Diabetes Registry. Research based genetic testing was provided. Clinical information was extracted from survey responses and medical records.

Results: There were thirty-three participants with 6q24-TNDM (58% male). Eight (24%) had hypomethylation of the maternal allele, seven (21%) had paternal duplication, seventeen (52%) had UPD6, and one had UPD6 vs. hypomethylation of the maternal allele. The mean age of initial diabetes presentation was 4.6 days (n=33). Remission occurred at a mean age of 4.5 months (n=28). Nine participants reported having relapse of diabetes, with a mean age of relapse of 17.4 years (range 12 - 31 years). There were six participants who reported umbilical hernia (22%, n=27), fifteen participants reported macroglossia (54%, n=27), and ten (36%, n=28) indicated speech therapy was required. No significant differences in clinical characteristics were identified across the three mechanisms (UPD6, paternal duplication, hypomethylation).

Conclusions: Clinical characteristics were not different across mechanism groups, suggesting that genetic testing is required to definitively determine a mechanism and diagnosis of 6q24 TNDM. Early assessment for speech therapy should be considered for this patient population.

Disclosure

M.Mccullough: None. L.R.Letourneau-freiberg: None. T.L.Bowden: Stock/Shareholder; Procter & Gamble, OPKO Biologics, Ltd. B.Kandasamy: None. D.Del gaudio: None. L.H.Philipson: Advisory Panel; Nevro Corp., Research Support; Novo Nordisk, Dompé, Provention Bio, Inc., Imcyse, Novo Nordisk Foundation. S.W.Greeley: None.

Funding

National Institutes of Health (R01DK104942, P30DK020595)
1146-P: Changes in Parent/Guardian and Youth Patient Reported Outcomes (PROs) after T1D Diagnosis for Families in the 4T Study 1
Authors: ALAMARIE SELMA A. , PANG ERICA , CORTES-NAVARRO ANA L. , ARRIZON-RUIZ NORA , BALISTRERI ILENIA , LOYOLA ALONDRA , SCHNEIDER-UTAKA AIKA , RITTER VICTOR , SHAW BLAKE , BISHOP FRANZISKA K. , ZAHARIEVA DESSI P. , PRAHALAD PRIYA , DESAI MANISHA , MAAHS DAVID M. , HOOD KOREY K. , ADDALA ANANTA
Published: June 2023

The 4T Study 1 is a clinical pragmatic research trial that starts continuous glucose monitoring (CGM) within 30 days of T1D diagnosis and monitors PROs. We report the longitudinal relationship of PROs between newly diagnosed youth and parents/guardians (PG). PROs surveys were administered to youth and PG at baseline, 3, and 6 months. PG PROs included the 20-item parent Diabetes Distress Scale (DDS-P) and youth PROs were the 2-item Diabetes Distress Scale (DDS-2) and the 7-item PROMIS Pediatric Global Health Scale (PGH-7). Pearson correlations evaluated the relationship between scores on the PG and youth PROs. Youth (n=60 who were aged ≥11 years) with new onset T1D and their PG (n=125) were eligible to complete PROs, yet response rates varied (at baseline, 3-, 6-months: Youth 59%, 53%, and 50% vs PG 74%, 70%, and 66%). Correlations showed that PG diabetes distress was positively correlated with child diabetes distress at baseline (r=0.48, p=0.003) and at 3 months (r= 0.35, p=0.058). However, by 6 months, this association decreased in strength and significance (r=0.16, p=0.42). Youth global health was inversely correlated with PG diabetes distress at baseline (r=-0.36, p=0.029) and 3 months (r=-0.53, p=0.002) and this correlation was not significant at 6 months (r =-0.049, p=0.81). These data suggest that the relationship between PG diabetes distress and youth psychosocial states are dynamic. PG and youth psychosocial states are strongly associated after diagnosis and decrease over time. Utilization of CGM, age, T1D duration, response rate, and changes in the PG-youth relationship (such as decreased adult involvement or increased independence of youth) may contribute to our findings. Further investigation of longitudinal relationships between PG and youth PROs may provide additional insight into PG and youth psychosocial states and diabetes outcomes and indicate optimal timing for assessment and treatment referral.

Disclosure

S.A.Alamarie: None. F.K.Bishop: None. D.P.Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. P.Prahalad: None. M.Desai: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. K.K.Hood: Consultant; Cecelia Health. A.Addala: None. E.Pang: None. A.L.Cortes-navarro: None. N.Arrizon-ruiz: None. I.Balistreri: None. A.Loyola: None. A.Schneider-utaka: None. V.Ritter: None. B.Shaw: None.

Funding

National Institutes of Health (R18DK122422)
1149-P: Health Literacy and Numeracy Based on The Newest Vital Sign Is Not Associated with Hemoglobin A1c in Caretakers or Youth with Type 1 Diabetes
Authors: SANCRAINTE LEANNE , SHAH AMY S. , BOWERS KATHERINE A. , LEYENDECKER ANASTASIA C. , YAYAH JONES NANA-HAWA
Published: June 2023

Management of type 1 diabetes (T1D) requires the ability to perform, process, and understand the clinical importance of mathematical calculations to correctly dose insulin. This degree of comprehension is the backbone of health literacy and numeracy (HLN). The Newest Vital Sign (NVS) is a valid and reliable tool to assess HLN in a clinic setting. Few studies have evaluated the NVS in youth living with T1D and its relationship to glycemic control. We hypothesized lower HLN in caretakers and patients would be associated with higher HbA1c among youth with T1D.

A cross sectional study was conducted to assess the degree of HLN in caretakers (for patient ages 6-18 years) and adolescent patients (ages 13-18 years) living with T1D. The NVS consists of 6 questions based on a fictitious nutrition label from an ice cream container. Total scores reflect probable level of HLN (0-1 likely limited; 2-3 possibly limited; 4-6 adequate literacy).

Data from 44 adult caretakers and 23 patients living with T1D was collected. Mean±SD HbA1c for youth was 8.0±1.8% (range 5.4-12.8%). Of the 44 caretakers, 42 (95.5%) scored 4-6, indicating adequate HLN, and 0 caretakers scored 0-1 points. Of 23 adolescent patients with T1D, 16 (69.5%) had adequate HLN, with 5 (21.7%) scoring 2-3, and 1 (4.3%) scoring only 1 point: high likelihood of low HLN. Youths’ HLN scores increased with age with the lowest HLN score of 1 in a patient that was 13.08 years. Mean age of those scoring 2-3 was 15.3 years and those scoring >4 was 16.5 years. HbA1c levels did not correlate with HLN scores in either caretakers or patients.

In caretakers of youth living with T1D, the NVS was unable to capture variations in HLN, possibly because this tool is based on a nutrition label which underlies all diabetes education. Given the importance of HLN in diabetes care, future work is needed to identify the best tool to assess HLN in those providing and receiving care for T1D.

Disclosure

L.Sancrainte: None. A.S.Shah: None. K.A.Bowers: None. A.C.Leyendecker: None. N.Yayah jones: Consultant; Medtronic.