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Full-Text Articles in Dietetics and Clinical Nutrition

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero Feb 2026

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …


Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini Feb 2026

Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini

Children’s Nutrition Research Center Staff Publications

Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 …


Conclusions Are Not Supported By The Published Statistical Analysis Comment On López-Toledo Et Al Flaxseed Improves Glucose And Lipid Metabolism In Mexican Subjects With Type 2 Diabetes: A Parallel Randomized Clinical Trial, Robert W Spitz, Deependra K Thapa, Thirupathi Reddy Mokalla, Wasiuddin Najam, Andrew W Brown, David B Allison Jan 2026

Conclusions Are Not Supported By The Published Statistical Analysis Comment On López-Toledo Et Al Flaxseed Improves Glucose And Lipid Metabolism In Mexican Subjects With Type 2 Diabetes: A Parallel Randomized Clinical Trial, Robert W Spitz, Deependra K Thapa, Thirupathi Reddy Mokalla, Wasiuddin Najam, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

López-Toledo et al [...].


Dietary Patterns For Weight And Glycemic Management In Persons With Type 1 Diabetes: A Meta-Analysis Of Clinical Trials, Daria Igudesman, Laura M Nally, Alyssa A Grimshaw, Craig G Gunderson, Elizabeth G Considine, Laura M Jacobsen, Mustafa Tosur, Peter A Gottlieb, Irl B Hirsch, Lori M Laffel, Jennifer L Sherr, Chantal Mathieu, Richard E Pratley Oct 2025

Dietary Patterns For Weight And Glycemic Management In Persons With Type 1 Diabetes: A Meta-Analysis Of Clinical Trials, Daria Igudesman, Laura M Nally, Alyssa A Grimshaw, Craig G Gunderson, Elizabeth G Considine, Laura M Jacobsen, Mustafa Tosur, Peter A Gottlieb, Irl B Hirsch, Lori M Laffel, Jennifer L Sherr, Chantal Mathieu, Richard E Pratley

Children’s Nutrition Research Center Staff Publications

Background: Medical nutrition therapy is fundamental for managing glycemia and weight in type 1 diabetes, yet dietary guidance specific to this population and relevant subgroups is lacking.

Purpose: We synthesized the interventional literature investigating diet patterns for glycemic and weight management in youth and adults with type 1 diabetes, with attention to interindividual variation that suggests the need for precision approaches. The protocol was prospectively registered (CRD42024519941).

Data sources: AMED, CINAHL, Cochrane Library, Ovid MEDLINE, Ovid Embase, Google Scholar, and Web of Science Core Collection were searched from January 2011 to June 2024.

Study selection: Clinical trials ≥4 weeks with …


Amino Acids And Cart Distinguish A-Β+ Ketosis-Prone Diabetes From Type 1 And Type 2 Diabetes During Hyperglycemic Crises, Farook Jahoor, Jean W Hsu, Kelly R Keene, W Frank Peacock, Xiaofang Huang, Danielle Guffey, Jinyoung Byun, Rasmus Bennet, Ake Lernmark, Mustafa Tosur, Ashok Balasubramanyam Sep 2025

Amino Acids And Cart Distinguish A-Β+ Ketosis-Prone Diabetes From Type 1 And Type 2 Diabetes During Hyperglycemic Crises, Farook Jahoor, Jean W Hsu, Kelly R Keene, W Frank Peacock, Xiaofang Huang, Danielle Guffey, Jinyoung Byun, Rasmus Bennet, Ake Lernmark, Mustafa Tosur, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Context: When clinically stable, patients with A-β+ ketosis-prone diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

Objective: Compare serum metabolomics of KPD, T1D, and T2D patients during hyperglycemic crises, and utilize classification and regression tree (CART) modeling to distinguish these forms of diabetes.

Methods: At an urban hospital emergency center, adults with KPD, T1D, and T2D during hyperglycemic crises with or without diabetic ketoacidosis (DKA), and healthy controls, underwent comparisons of serum metabolite and hormonal profiles and CART analyses. …


Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong Jul 2025

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …


The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group Jul 2025

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …


Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian Jul 2025

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …


The Maturity-Onset Diabetes Of The Young (Mody) Calculator Overestimates Mody Probability In Hispanic Youth, Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur Jun 2025

The Maturity-Onset Diabetes Of The Young (Mody) Calculator Overestimates Mody Probability In Hispanic Youth, Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur

Children’s Nutrition Research Center Staff Publications

Context: The applicability of the maturity-onset diabetes of the young (MODY) risk calculator to non-White European populations remains unknown.

Objective: We aimed to test its real-world application in Hispanic youth.

Methods: We conducted a retrospective chart review of Hispanic youth (< 23 years) with diabetes (n = 2033) in a large pediatric tertiary care center in the United States. We calculated MODY probability for all subjects, splitting them into 2 cohorts based on the original model: individuals who were started on insulin within 6 months of diabetes diagnosis (Cohort 1) and those who were not (Cohort 2).

Results: Cohort 1 consisted of 1566 individuals (median age [25p, 75p]: 16 [13, 19] years, 49% female), while Cohort 2 comprised 467 youth (median age [25p, 75p]: 17 [15, 20] years, 62% female). The mean MODY probability was 5.9% and 61.9% in Cohort 1 and Cohort 2, respectively. The mean probability for both cohorts combined was 18.8%, suggesting an …


The Effect Of Dietary Strawberry Supplementation On Glycemic Control Factors In Overweight And Obese Postmenopausal Women With At-Risk Diabetes Mellitus Pathogenesis, Jennifer Herrera Jun 2025

The Effect Of Dietary Strawberry Supplementation On Glycemic Control Factors In Overweight And Obese Postmenopausal Women With At-Risk Diabetes Mellitus Pathogenesis, Jennifer Herrera

Master's Theses

Glycemic control is directly related to type II diabetes mellitus (T2DM). As of 2023, 30.5 million Americans have T2DM, and this number only continues to increase exponentially across the world (“Facts & Figures,” n.d.). T2DM is only a precursor to fatal conditions including cardiovascular disease, the number one cause of death in the United States. Extensive research has revealed that strawberries, a high polyphenolic food, may pose positive effects on glycemic control biomarkers. This study aimed to investigate the effect of three servings of strawberries in the form of 39-g of freeze-dried strawberry powder (FDSP) for six weeks on glycemic …


Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo Mar 2025

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …


Insulin Clearance At Randomisation And In Response To Treatment In Youth With Type 2 Diabetes: A Secondary Analysis Of The Today Randomised Clinical Trial, Kristen J Nadeau, Silva A Arslanian, Fida Bacha, Sonia Caprio, Lily C Chao, Ryan Farrell, Kara S Hughan, Maria Rayas, Melinda Tung, Kaitlyn Cross, Laure El Ghormli Mar 2025

Insulin Clearance At Randomisation And In Response To Treatment In Youth With Type 2 Diabetes: A Secondary Analysis Of The Today Randomised Clinical Trial, Kristen J Nadeau, Silva A Arslanian, Fida Bacha, Sonia Caprio, Lily C Chao, Ryan Farrell, Kara S Hughan, Maria Rayas, Melinda Tung, Kaitlyn Cross, Laure El Ghormli

Children’s Nutrition Research Center Staff Publications

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin …


Snap Participation As A Moderator Of Food And Nutrition Security And Combined Cardiometabolic Conditions: A Mixed Regression Approach, Maha Almohamad, Ruosha Li, Natalia I Heredia, Jayna M Dave, Eric E Calloway, Anjail Sharrief, Shreela V Sharma Feb 2025

Snap Participation As A Moderator Of Food And Nutrition Security And Combined Cardiometabolic Conditions: A Mixed Regression Approach, Maha Almohamad, Ruosha Li, Natalia I Heredia, Jayna M Dave, Eric E Calloway, Anjail Sharrief, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: To examine the relationships between food security, nutrition security, Supplemental Nutrition Assistance Program (SNAP) participation, and cardiometabolic outcomes, including hypertension, hyperlipidemia, or diabetes, among low-income U.S. individuals.

Methods: A cross-sectional survey of 486 participants (April–June 2021) assessed food and nutrition security and cardiometabolic outcomes. Mixed-effects logistic regression models adjusted for covariates and included a random effect for state of residence. Moderation analyses evaluated SNAP participation’s impact.

Results: Very low food security was associated with higher odds of having at least one cardiometabolic condition, such as hypertension, hyperlipidemia, or diabetes (AOR = 1.96; 95% CI: 1.04–3.69; p = 0.04). SNAP …


Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam Dec 2024

Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and …


The Association Of Self-Reported Sleep And Circadian Measures With Glycemic Control And Diabetes Complications Among Young Adults With Type 2 Diabetes, Dorit Koren, Kristen L Knutson, Brian K Burke, Kimberly L Drews, Fida Bacha, Lorraine Katz, Marsha D Marcus, Siripoom Mckay, Kristen Nadeau, Babak Mokhlesi, Today Study Group Jun 2024

The Association Of Self-Reported Sleep And Circadian Measures With Glycemic Control And Diabetes Complications Among Young Adults With Type 2 Diabetes, Dorit Koren, Kristen L Knutson, Brian K Burke, Kimberly L Drews, Fida Bacha, Lorraine Katz, Marsha D Marcus, Siripoom Mckay, Kristen Nadeau, Babak Mokhlesi, Today Study Group

Children’s Nutrition Research Center Staff Publications

We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were …


Prevalence Of Distal Symmetrical Polyneuropathy By Diabetes Prevention Program Treatment Group, Diabetes Status, Duration Of Diabetes, And Cumulative Glycemic Exposure, Christine G Lee, Adam Ciarleglio, Sharon L Edelstein, Jill P Crandall, Dana Dabelea, Ronald B Goldberg, Steven E Kahn, William C Knowler, Maxwell T Ma, Neil H White, William H Herman, Diabetes Prevention Program Research Group May 2024

Prevalence Of Distal Symmetrical Polyneuropathy By Diabetes Prevention Program Treatment Group, Diabetes Status, Duration Of Diabetes, And Cumulative Glycemic Exposure, Christine G Lee, Adam Ciarleglio, Sharon L Edelstein, Jill P Crandall, Dana Dabelea, Ronald B Goldberg, Steven E Kahn, William C Knowler, Maxwell T Ma, Neil H White, William H Herman, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

Research design and methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms …


An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo Apr 2024

An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide …


Glycemia And Gluconeogenesis With Metformin And Liraglutide: A Randomized Trial In Youth-Onset Type 2 Diabetes, Katrina B Dietsche, Sheela N Magge, Sydney A Dixon, Faith S Davis, Andrea Krenek, Aruba Chowdhury, Lilian Mabundo, Michael Stagliano, Amber B Courville, Shanna Yang, Sara Turner, Hongyi Cai, Kannan Kasturi, Arthur S Sherman, Joon Ha, Eileen Shouppe, Mary Walter, Peter J Walter, Kong Y Chen, Robert J Brychta, Cody Peer, Yi Zeng, William Figg, Fran Cogen, D Elizabeth Estrada, Shaji Chacko, Stephanie T Chung Apr 2024

Glycemia And Gluconeogenesis With Metformin And Liraglutide: A Randomized Trial In Youth-Onset Type 2 Diabetes, Katrina B Dietsche, Sheela N Magge, Sydney A Dixon, Faith S Davis, Andrea Krenek, Aruba Chowdhury, Lilian Mabundo, Michael Stagliano, Amber B Courville, Shanna Yang, Sara Turner, Hongyi Cai, Kannan Kasturi, Arthur S Sherman, Joon Ha, Eileen Shouppe, Mary Walter, Peter J Walter, Kong Y Chen, Robert J Brychta, Cody Peer, Yi Zeng, William Figg, Fran Cogen, D Elizabeth Estrada, Shaji Chacko, Stephanie T Chung

Children’s Nutrition Research Center Staff Publications

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D.

METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before …


Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi Mar 2024

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …


Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium Feb 2024

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …


Feasibility Of A Food-Based Diabetes Self-Management Education Intervention For Food Insecure Patients With Type 2 Diabetes: A Convergent Mixed Methods Study, Eliza Short, Debbe Thompson, Douglas Taren, Holly Bryant, Rhonda Gonzalez, Jessi Sheava, Melanie Hingle Dec 2023

Feasibility Of A Food-Based Diabetes Self-Management Education Intervention For Food Insecure Patients With Type 2 Diabetes: A Convergent Mixed Methods Study, Eliza Short, Debbe Thompson, Douglas Taren, Holly Bryant, Rhonda Gonzalez, Jessi Sheava, Melanie Hingle

Children’s Nutrition Research Center Staff Publications

Objective: To assess the feasibility of a food-based diabetes self-management education and support (DSMES) intervention delivered to persons with type 2 diabetes (T2DM) and food insecurity.

Design: This single arm pre-/post convergent mixed methods study tested the feasibility of a 3-month intervention using food boxes, recipes, DSMES and dietitian visits. Feasibility benchmarks assessed were acceptability (> 50 % participants satisfied), demand (> 50 % used program components) and implementation (75 % adherence, 80 % retention). Assessments included: self-reported food security, health-related quality of life, diabetes self-efficacy, socio-demographic and dietary intake, height, weight, and HbA1c and one in-depth interview with participants …


Associations Between Avocado Intake And Measures Of Glucose And Insulin Homeostasis In Hispanic Individuals With And Without Type 2 Diabetes: Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Mackenzie K Senn, Mark O Goodarzi, Gautam Ramesh, Matthew A Allison, Mariaelisa Graff, Kristin L Young, Gregory A Talavera, Amanda C Mcclain, Tanya P Garcia, Jerome I Rotter, Alexis C Wood Dec 2023

Associations Between Avocado Intake And Measures Of Glucose And Insulin Homeostasis In Hispanic Individuals With And Without Type 2 Diabetes: Results From The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Mackenzie K Senn, Mark O Goodarzi, Gautam Ramesh, Matthew A Allison, Mariaelisa Graff, Kristin L Young, Gregory A Talavera, Amanda C Mcclain, Tanya P Garcia, Jerome I Rotter, Alexis C Wood

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry.

METHODS AND RESULTS: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by …


Associations Between Metabolomic Biomarkers Of Avocado Intake And Glycemia In The Multi-Ethnic Study Of Atherosclerosis, Alexis C Wood, Mark O Goodarzi, Mackenzie K Senn, Meghana D Gadgil, Goncalo Graca, Matthew A Allison, Ioanna Tzoulaki, Michael Y Mi, Philip Greenland, Timothy Ebbels, Paul Elliott, Russell P Tracy, David M Herrington, Jerome I Rotter Oct 2023

Associations Between Metabolomic Biomarkers Of Avocado Intake And Glycemia In The Multi-Ethnic Study Of Atherosclerosis, Alexis C Wood, Mark O Goodarzi, Mackenzie K Senn, Meghana D Gadgil, Goncalo Graca, Matthew A Allison, Ioanna Tzoulaki, Michael Y Mi, Philip Greenland, Timothy Ebbels, Paul Elliott, Russell P Tracy, David M Herrington, Jerome I Rotter

Faculty, Staff and Students Publications

BACKGROUND: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.

OBJECTIVES: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.

METHODS: Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an …


Identification Of Genetic Variation Influencing Metformin Response In A Multiancestry Genome-Wide Association Study In The Diabetes Prevention Program (Dpp), Josephine H Li, James A Perry, Kathleen A Jablonski, Shylaja Srinivasan, Ling Chen, Jennifer N Todd, Maegan Harden, Josep M Mercader, Qing Pan, Adem Y Dawed, Sook Wah Yee, Ewan R Pearson, Kathleen M Giacomini, Ayush Giri, Adriana M Hung, Shujie Xiao, L Keoki Williams, Paul W Franks, Robert L Hanson, Steven E Kahn, William C Knowler, Toni I Pollin, Jose C Florez, Diabetes Prevention Program Research Group Aug 2023

Identification Of Genetic Variation Influencing Metformin Response In A Multiancestry Genome-Wide Association Study In The Diabetes Prevention Program (Dpp), Josephine H Li, James A Perry, Kathleen A Jablonski, Shylaja Srinivasan, Ling Chen, Jennifer N Todd, Maegan Harden, Josep M Mercader, Qing Pan, Adem Y Dawed, Sook Wah Yee, Ewan R Pearson, Kathleen M Giacomini, Ayush Giri, Adriana M Hung, Shujie Xiao, L Keoki Williams, Paul W Franks, Robert L Hanson, Steven E Kahn, William C Knowler, Toni I Pollin, Jose C Florez, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide …


Factors Associated With Choice Of Behavioural Weight Loss Program By Adults With Obesity, Yasaman Jamshidi-Naeini, Susan B Roberts, Stephanie Dickinson, Arthur Owora, Jon Agley, Roger S Zoh, Xiwei Chen, David B Allison Aug 2023

Factors Associated With Choice Of Behavioural Weight Loss Program By Adults With Obesity, Yasaman Jamshidi-Naeini, Susan B Roberts, Stephanie Dickinson, Arthur Owora, Jon Agley, Roger S Zoh, Xiwei Chen, David B Allison

Children’s Nutrition Research Center Staff Publications

We assessed the preference for two behavioural weight loss programs, Diabetes Prevention Program (DPP) and Healthy Weight for Living (HWL) in adults with obesity. A cross-sectional survey was fielded on the Amazon Mechanical Turk. Eligibility criteria included reporting BMI ≥30 and at least two chronic health conditions. Participants read about the programs, selected their preferred program, and answered follow-up questions. The estimated probability of choosing either program was not significantly different from .5 (N = 1005, 50.8% DPP and 49.2% HWL, p = .61). Participants' expectations about adherence, weight loss magnitude, and dropout likelihood were associated with their choice (p <  .0001). Non-White participants (p = .040) and those with monthly income greater than $4999 (p = .002) were less likely to choose DPP. Participants who had postgraduate education (p = .007), did not report high serum cholesterol (p = .028), and reported not having tried losing weight before (p = .025) were more likely to choose DPP. Those who chose HWL were marginally more likely to report that being offered two different programs rather than one would likely affect their decision to enrol in one of the two (p = .052). The enrolment into DPP and HWL was balanced, but race, educational attainment, income, previous attempt to lose weight, and serum cholesterol levels had significant associations with the choice of weight loss program.


Metabolomic Profile Of The Healthy Eating Index-2015 In The Multiethnic Study Of Atherosclerosis, Meghana D Gadgil, Alexis C Wood, Ibrahim Karaman, Goncalo Graça, Ioanna Tzoulaki, Victor W Zhong, Philip Greenland, Alka M Kanaya, David M Herrington Aug 2023

Metabolomic Profile Of The Healthy Eating Index-2015 In The Multiethnic Study Of Atherosclerosis, Meghana D Gadgil, Alexis C Wood, Ibrahim Karaman, Goncalo Graça, Ioanna Tzoulaki, Victor W Zhong, Philip Greenland, Alka M Kanaya, David M Herrington

Children’s Nutrition Research Center Staff Publications

Background: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version) are limited.

Objectives: The goal was to determine a pattern of metabolites associated with the Healthy Eating Index (HEI)-2015, which measures adherence to the Dietary Guidelines for Americans.

Methods: The analysis examined 3557 adult men and women from the longitudinal cohort Multiethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens and diet and demographic questionnaires were assessed at baseline. Untargeted 1H 1-dimensional nuclei magnetic …


Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson Apr 2023

Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device …


Diabetes Of Unclear Type In An Adolescent Boy With Multiple Islet-Cell Autoantibody Positivity Successfully Managed With Glucagon-Like Peptide-1 Receptor Agonist Alone: A Case Report, Olivia Z B Ginnard, Maria J Redondo, Sarah K Lyons Feb 2023

Diabetes Of Unclear Type In An Adolescent Boy With Multiple Islet-Cell Autoantibody Positivity Successfully Managed With Glucagon-Like Peptide-1 Receptor Agonist Alone: A Case Report, Olivia Z B Ginnard, Maria J Redondo, Sarah K Lyons

Children’s Nutrition Research Center Staff Publications

Diabetes classification has traditionally considered type 1 and type 2 diabetes as 2 separate entities with different pathogenic mechanisms. However, clinicians and researchers see increasingly more exceptions to this conventional paradigm, leading to a concept of mixed phenotypes in diabetes classification. Herein we report the case of an adolescent with unclear diabetes type due to the presence of obesity, robust endogenous insulin production, multiple islet autoantibody positivity and severe hyperglycemia at diabetes diagnosis that has been successfully treated with liraglutide therapy alone. Our case report highlights the difficulty of diabetes classification and subsequent need for personalized medicine with regard to …


Initial Insights Into The Genetic Variation Associated With Metformin Treatment Failure In Youth With Type 2 Diabetes, Shylaja Srinivasan, Ling Chen, Miriam Udler, Jennifer Todd, Megan M Kelsey, Morey W Haymond, Silva Arslanian, Philip Zeitler, Rose Gubitosi-Klug, Kristen J Nadeau, Katherine Kutney, Neil H White, Josephine H Li, James A Perry, Varinderpal Kaur, Laura Brenner, Josep M Mercader, Adem Dawed, Ewan R Pearson, Sook-Wah Yee, Kathleen M Giacomini, Toni Pollin, Jose C Florez Jan 2023

Initial Insights Into The Genetic Variation Associated With Metformin Treatment Failure In Youth With Type 2 Diabetes, Shylaja Srinivasan, Ling Chen, Miriam Udler, Jennifer Todd, Megan M Kelsey, Morey W Haymond, Silva Arslanian, Philip Zeitler, Rose Gubitosi-Klug, Kristen J Nadeau, Katherine Kutney, Neil H White, Josephine H Li, James A Perry, Varinderpal Kaur, Laura Brenner, Josep M Mercader, Adem Dawed, Ewan R Pearson, Sook-Wah Yee, Kathleen M Giacomini, Toni Pollin, Jose C Florez

Faculty, Staff and Students Publications

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 (P < 1 × 10−6), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P …


Diabetes-Related Worries And Coping Among Youth And Young Adults With Type 1 Diabetes, Lindsay Taraban, Rachel Wasserman, Viena T Cao, Sahar S Eshtehardi, Barbara J Anderson, Debbe Thompson, David G Marrero, Marisa E Hilliard Oct 2022

Diabetes-Related Worries And Coping Among Youth And Young Adults With Type 1 Diabetes, Lindsay Taraban, Rachel Wasserman, Viena T Cao, Sahar S Eshtehardi, Barbara J Anderson, Debbe Thompson, David G Marrero, Marisa E Hilliard

Children’s Nutrition Research Center Staff Publications

Objective: Although mood and anxiety symptoms are common in youth with type 1 diabetes (T1D), little research has described their worries across developmental stages or the strategies they use to cope with these worries. This secondary data analysis aimed to describe and characterize common T1D-related worries and coping strategies from middle childhood through young adulthood.

Methods: Twenty-three youth (9 children, 7 adolescents, and 7 young adults) completed semistructured qualitative interviews about health-related quality of life. We coded interview transcripts using thematic analysis to generate common themes of diabetes-related worries and coping strategies.

Results: Participants' worries fell into four major themes: …