1681-P: Metabolomic Signatures of Adiposity in Young Adults with Type 1 Diabetes
Authors: IGUDESMAN DARIA A. , CARNERO ELVIS A. , CASU ANNA , MAYER-DAVIS ELIZABETH J. , MAAHS DAVID M. , PRATLEY RICHARD E. , CORBIN KAREN 
Published: June 2024

Introduction & Objective: Obesity is purported to be phenotypically distinct in persons with T1D due to exogenous insulin administration and metabolic derangements, yet empirical data are lacking. We explored biomarkers of adiposity and energy metabolism in young adults diagnosed with T1D &gt;1y prior and age-, sex-, and BMI-matched controls across a range of BMI (19.1-36.9 kg/m²).

Methods: Total body adiposity, gynoid fat, and android fat (DXA); bioenergetic parameters (24h energy expenditure [24h EE], sleeping metabolic rate, and fat and carbohydrate oxidation—whole-room indirect calorimetry); and untargeted fasting serum metabolites were compared between cases and controls. Metabolites were correlated with DXA and bioenergetic measures, stratified by T1D status. Analyses were FDR-corrected (MetaboAnalyst 6.0; SAS 9.4).

Results: Gynoid fat was 0.8kg (95%CI 0.25, 1.29) higher adjusting for HbA1c, total body mass (g), and sex; and 24h EE was 212 kcal/d (95%CI 85, 339) higher adjusting for total lean mass (g) in cases with T1D (n=20) vs. controls (n=21). Of 952 retained metabolites, those related to phosphatidylcholine (PC) and phosphatidylethanolamine (PE) biosynthesis, and mono- and disaccharide degradation were higher in cases; while those related to essential omega-3 and omega-6 fatty acid metabolism, beta oxidation, and carnitine synthesis were lower vs. controls. HbA1c adjustment nullified differences. In cases, gynoid fat correlated positively with 1 PC-related metabolite (r = 0.87) and negatively with 2 PE-related metabolites (r = -0.79 to -0.80) after HbA1c, total body mass, and sex adjustment.

Conclusion: Metabolites of PC and PE biosynthesis may be biomarkers of gynoid adiposity in young adults with T1D, inviting speculation that these lipids relate to increased peripheral fat storage when insulin is administered exogenously. These metabolite classes may modulate insulin sensitivity; thus, our findings should be confirmed in prospective studies of adiposity-related cardiometabolic risk in T1D.

Disclosure

D.A. Igudesman: None. E.A. Carnero: None. A. Casu: None. E.J. Mayer-Davis: None. D.M. Maahs: Advisory Panel; Medtronic. Consultant; Abbott, LifeScan Diabetes Institute, Sanofi, Provention Bio, Inc., Bayer Inc., Kriya Therapeutics, BioSpex. R.E. Pratley: Other Relationship; Bayer AG, Dompé, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals Ltd., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sun Pharmaceutical Industries Ltd. Consultant; AbbVie Inc., AstraZeneca. Other Relationship; Bayer HealthCare Pharmaceuticals, Inc., Biomea Fusion, Carmot Therapeutics, Inc., Corcept Therapeutics, Fractyl Health, Inc., Genprex. Consultant; Getz Pharma. Other Relationship; Lilly USA LLC, Sanofi. Consultant; Scholar Rock, Inc. K. Corbin: Research Support; BPG Bio. Advisory Panel; Target RWE. Research Support; Target RWE, Merck & Co., Inc. Consultant; Weight Watchers International. Research Support; Rivus Pharmaceuticals Inc., Eli Lilly and Company.

Funding

National Institutes of Diabetes and Digestive and Kidney Diseases (DP3DK113358-01)