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  • 1
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    188-OR: Circulating Metabolites and Type 2 Diabetes (T2D) Risk—An Integrated Metabolomics and Genetics Study of ~23,000 Adults
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. Supplement_1 ( 2023-06-20)
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: Metabolome captures complex states of metabolic homeostasis affected by genetic and environmental factors. A systematic understanding of metabolites associated with T2D risk may offer potentials for personalized risk monitoring and prevention. Here, we integrated data for 467 harmonized circulating metabolites, genetics, and diet/lifestyle factors in up to 23,616 racially diverse individuals from 10 cohorts with up to 26-y of follow-up. Through multivariable-adjusted metabolome-wide association analyses, we identified 235 metabolites associated with incident T2D (4,000 incident cases; FDR & lt;0.05). Genetic determinants of these metabolites were mapped to genes implicated in pathways of nutrient/energy metabolism and glucose/lipid dysregulation (pathway enrichment FDR & lt;0.05) and highly expressed in T2D-relevent tissues e.g., liver, adipose tissues, pancreas, and muscles (tissue-specific expression enrichment FDR & lt;0.05). Mendelian randomization analyses further corroborated potential causal associations between 93 of the 235 metabolites and T2D. These included previously known (e.g., valine and isoleucine) and novel associations (e.g., α-ketoisocaproate in leucine metabolism, N-acetylaspartate in glutamate metabolism, and odd-chain fatty acid heptadecanoate). Furthermore, we analyzed metabolome-wide associations with 18 mutually adjusted modifiable risk factors. Several factors e.g., physical activity and whole grain (WG) intake, explained higher proportions of inter-individual variation of T2D-associated vs. other metabolites. We identified specific metabolites as potential mediators linking each risk factor to T2D (e.g., 4 metabolites mediated 22% of the WG-T2D association). In conclusion, we found known and novel metabolites associated with T2D risk, indicating potential biological pathways through which genetic and lifestyle factors contribute to T2D. Our findings may inform future personalized T2D prevention. Disclosure J.Li: None. J.Dupuis: None. E.Selvin: None. S.Bhupathiraju: None. J.A.Brody: None. Y.Liu: None. A.Eliassen: None. J.E.Manson: None. C.B.Clish: None. R.N.Lemaitre: None. K.L.Tucker: None. J.Hu: None. J.I.Rotter: None. M.A.Martinez-gonzalez: None. K.M.Rexrode: None. J.B.Meigs: Consultant; Quest Diagnostics. E.Boerwinkle: None. R.Kaplan: None. F.Hu: None. B.Yu: None. Q.Qi: None. N.The nhlbi topmed metabolomics and proteomics worki: n/a. L.Liang: None. M.Guasch: None. J.Merino: None. M.Ruiz-canela: None. K.Luo: None. C.Rebholz: None. B.Porneala: None. Funding National Institutes of Health (R00DK122128 to J.L.)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-188-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
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  • 2
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    1912-P: Portal Vein Metabolomic Profiling Highlights One-Carbon Metabolism as a Key Pathway Affected by Roux-en-Y Gastric Bypass Surgery
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: After Roux-en-Y gastric bypass (RYGB) surgery, the intestine undergoes structural and metabolic reprogramming and appears to enhance utilization of energetic fuels including glucose and amino acids (AAs), changes that may be related to the surgery’s remarkable metabolic effects. Consistently, RYGB alters serum levels of AAs and other metabolites, changes hypothesized to underlie these benefits. To home in on the intestinal contribution, we performed metabolomic profiling in portal vein (PV) blood from lean, Long Evans rats after RYGB versus sham surgery. After RYGB, systemic blood (SB) metabolomic fingerprinting reflected changes in AA metabolism including serine/glycine/threonine metabolism, an important mechanism of one-carbon donation for folate metabolism. Principal component analysis (PCA) confirmed, among the metabolites most influential to the post-RYGB SB metabolome (PC1, P=0.0008), enrichment for these pathways as well as for sphingolipid and glycerophospholipid metabolism. PV profiling largely mirrored that of SB; using PCA to identify the PV metabolites most affected after RYGB (PC2, P=0.016), we found one-carbon metabolism (OCM) to be enriched. Among those metabolites significantly altered in PV versus SB, 15 were uniquely affected in sham-operated animals and 33 in RYGB-operated animals. Pathway analysis of the latter revealed overrepresentation of nitrogen, serine/glycine/threonine, and sphingolipid metabolism as well as ubiquinone biosynthesis. Together, our data provide novel insight into RYGB’s effects on the gut-liver axis and highlight a role for OCM as a key metabolic pathway affected by RYGB. OCM links cellular nutrient status to homeostatic mechanisms including purine biosynthesis, AA homeostasis, and epigenetic maintenance, and we hypothesize that in the intestine and liver, it might serve as a key fuel sensing pathway to mediate local changes in glucose metabolism, perhaps via epigenetic reprogramming. Disclosure M.A. Stefater: None. J. Avila: None. C.B. Clish: None. N. Stylopoulos: None. Funding National Institutes of Health
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1912-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 3
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    Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. 12 ( 2019-12-01), p. 2337-2349
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. 12 ( 2019-12-01), p. 2337-2349
    Abstract: Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET] , or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-0236
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 4
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    1994-LB: Metabolites Link Infections to Type 2 Diabetes in the Multiethnic Study of Atherosclerosis (MESA)
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Introduction & Objective: Prior to T2D, patients experience increased infections, yet no pathways account for this immune/endocrine system cross-talk. We aimed to identify metabolites that link pathogens to T2D. Methods: Using plasma from 4,424 adults (61 ±9 y; 53% female), taxonomic classification was conducted on reads from sequencing that aligned with a microbial reference panel, and metabolites quantified. Incident T2D (ADA 2003 criteria) was assessed over ~18 y. A cox-proportional hazard model identified baseline microbes as ‘variables of importance’ to incident T2D, with a penalty function to minimize sparse data bias. Metabolome-wide associations identified metabolites shared between T2D-related microbes at baseline, and incident T2D. All models adjusted for age, gender, race/ethnicity, education, and AHA’s Life’s Simple 8 score. Results: Total microbes differed by race/ethnicity (X2= 30.4, df = 9, P= 3.8*10-4), but not any other covariates (all P & gt;.05). Incident T2D was associated with 2 microbes: Rahnella (HR=1.90 (1.09-3.30), P=.02) and Plasmodium falciparum (HR=1.34 (1.05-1.73), P=.02). 23 metabolites were associated with incident T2D (P & lt;.05 after an FDR-correction) and at least one of these microbes (P & lt;.05; Fig). Conclusions: These analyses indicate molecules linking exposure to, and / or continued presence in the plasma of, infectious microbes, and increased risk of T2D. Disclosure A. Wood: Research Support; Beef Checkoff. Consultant; Lundquist. M.O. Goodarzi: Advisory Panel; Nestlé Health Science, Organon. Z. Chen: None. X. Guo: None. S.S. Rich: None. C.B. Clish: None. R.E. Gerszten: None. J.I. Rotter: None. K. Taylor: None. Funding USDA/ARS cooperative agreement (#58-3092-5-001). Advancing Translational Sciences (UL1TR001420, UL1TR001881).
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1994-LB
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 5
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    Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis
    American Diabetes Association ; 2016
    In:  Diabetes Care Vol. 39, No. 5 ( 2016-05-01), p. 833-846
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 39, No. 5 ( 2016-05-01), p. 833-846
    Abstract: To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 diabetes. RESEARCH DESIGN AND METHODS We searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite. RESULTS We identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 [1.24–1.48]; I2 = 9.5%), 36% for leucine (1.36 [1.17–1.58] ; I2 = 37.4%), 35% for valine (1.35 [1.19–1.53]; I2 = 45.8%), 36% for tyrosine (1.36 [1.19–1.55] ; I2 = 51.6%), and 26% for phenylalanine (1.26 [1.10–1.44]; I2 = 56%). Glycine and glutamine were inversely associated wit h type 2 diabetes risk (0.89 [0.81–0.96] and 0.85 [0.82–0.89] , respectively; both I2 = 0.0%). CONCLUSIONS In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc15-2251
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2016
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  • 6
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    553-P: Changes in Circulating Bile Acids and the Improvements in Glucose and Insulin Metabolism in Response to Weight-Loss Diets: The POUNDS Lost Trial
    American Diabetes Association ; 2022
    In:  Diabetes Vol. 71, No. Supplement_1 ( 2022-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Bile acids (BAs) are synthesized from cholesterol in the liver and are essential for nutrient absorption. The host-derived primary BAs are transformed into secondary BAs in the intestine. Various BA subtypes may play pivotal roles as endocrine molecules to affect glucose and insulin metabolism. We tested whether changes in distinct BA subtypes were associated with improved glucose and insulin metabolism among adults with overweight and obesity who participated in a weight-loss diet intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after the intervention; 6-month changes in BAs were calculated (n=515) . When we analyzed associations of BA changes with changes in fasting glucose, insulin, and insulin resistance at 6 months, more decreases in several primary BAs (CDCA, taurocholate [TCA], and taurochenodeoxycholate [TCDCA] ) and secondary TDCA were associated with larger reductions of glucose (PFDR & lt;0.for all) , although the associations were dependent on concurrent weight changes. The decreases in primary BAs (including CA, CDCA, TCA, TCDCA) and secondary BAs (including DCA, GDCA, TDCA, GUDCA) were significantly related to improved hyperinsulinemia and insulin resistance, independent of weight changes. Also, we found significant interactions between dietary fat intake and changes in lithocholate and glycolithocholate for changes in insulin metabolism. Further, the initial changes in several primary and secondary BAs showed significant associations for 2-year improvements in glucose/insulin metabolism. In conclusion, decreases in distinct primary and secondary BAs during weight-loss dietary interventions were associated with improved glucose and insulin metabolism. Changes in various BA subtypes were related to the improved insulin metabolism independent of weight loss status during the interventions. Disclosure Y.Heianza: None. X.Wang: None. H.Ma: None. J.Rood: None. C.B.Clish: None. G.Bray: None. F.Sacks: None. L.Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db22-553-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 7
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    Metabolite Profiles During Oral Glucose Challenge
    American Diabetes Association ; 2013
    In:  Diabetes Vol. 62, No. 8 ( 2013-08-01), p. 2689-2698
    Details
    In: Diabetes, American Diabetes Association, Vol. 62, No. 8 ( 2013-08-01), p. 2689-2698
    Abstract: To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m2) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db12-0754
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
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  • 8
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    1507-P: Baseline Metabolite Profiles of Incident Type 2 Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program (DPP)
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Novel biomarkers of T2D and preventative treatment response could predict outcomes in high-risk individuals. We used Cox models to assess the association of 334 profiled metabolites in 2,019 baseline plasma samples with incident T2D after 3.2 years in a DPP substudy. We further assessed if associations out of the 334 metabolites differed by treatment (lifestyle (ILS), metformin (MET), and placebo (PLA)) and if, after stratification into concentration quartiles, the metabolite levels modified treatment effect in pair-wise treatment comparisons. We found 69 metabolites associated with incident T2D in the entire cohort (FDR-q & lt;0.05) including the novel association of cytosine, which had the lowest risk (HR of 0.77 per 1 SD, 95% CI 0.67-0.89, FDR-q 0.008). The associations of 35 metabolites differed across the three treatments (p for homogeneity & lt;0.05) and the quartiles of several of these metabolites modified treatment effects in pair-wise comparisons (Table 1). For example, individuals in higher quartiles of specific phospholipids had decreased T2D risk with ILS compared to PLA and MET, but not with MET when compared to PLA. In conclusion, we identified baseline metabolites associated with T2D risk prediction and efficacy of prevention interventions. This motivates further studies to validate interactions between biomarkers and diabetes prevention strategies. Disclosure Z. Chen: None. J. Liu: None. J. Morningstar: None. B.M. Heckman-Stoddard: None. C. Lee: None. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc. J.F. Ferguson: None. R.F. Hamman: None. W.C. Knowler: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. L. Perreault: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. J.C. Florez: None. T. Wang: None. C.B. Clish: None. M. Temprosa: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Other Relationship; Self; Merck KGaA. R.E. Gerszten: None. DPP Research Group: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1507-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 9
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    1476-P: Metabolomic and Genetic Diabetes Predictors in the Diabetes Prevention Program (DPP)
    American Diabetes Association ; 2024
    In:  Diabetes Vol. 73, No. Supplement_1 ( 2024-06-14)
    Details
    In: Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
    Abstract: Objective: Type 2 diabetes (T2D) can be prevented, but the risk is heterogeneous even among high-risk individuals. We aimed to create a metabolite T2D risk model and evaluate its utility compared to a genetic risk score (GRS) and traditional clinical factors in 1,635 participants with available genomics and metabolomics. Methods: Predictors were picked using elastic net from 3,145 mass spectrometry measured metabolites in baseline fasting plasma. Predictive performance after 3.2 years follow-up was assessed using AUC and IDI of Cox models that included the metabolites, the 120-SNP GRS, and clinical factors. Results: The composite monosaccharide measurement of glucose/fructose/galactose and a 50 carbon:1 double bond triacylglycerol (TG 50:1) were selected and minimally increased the AUC beyond the clinical model (AUC=0.71 vs AUC=0.69, Fig1A). There was no change with the addition of the GRS (AUC=0.69). When added to FPG, TG 50:1 provided the same increase in the integrated discrimination index (IDI) as with clinical triglycerides (Fig1B), but glucose/fructose/galactose provided a significant increase in IDI beyond clinical FPG. Conclusion: Metabolites minimally improve DM prediction beyond clinical risk factors in a high-risk adult population. A glucose/fructose/galactose composite metabolite significantly improves IDI. Disclosure Z. Chen: None. R. Shu: None. M. Tripputi: None. X. Shi: None. J. Avila: None. W.C. Knowler: None. S.E. Kahn: Advisory Panel; AltPep, Boehringer-Ingelheim, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk A/S. B.M. Heckman-Stoddard: None. C.B. Clish: None. Q. Pan: None. J.C. Florez: Research Support; Novo Nordisk. Other Relationship; Novo Nordisk, AstraZeneca. R.E. Gerszten: None. M. Temprosa: None. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db24-1476-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2024
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  • 10
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    1938-P: The Gut Microbiota Is Critical for the Beneficial Metabolic Effects of Palmitic Acid Hydroxy Stearic Acids (PAHSAs) in Diet-Induced Obese Mice
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: The gut microbiome contributes to host health and has therapeutic potential to treat metabolic disease. A newer class of lipids, PAHSAs, have antidiabetic effects in high-fat diet (HFD)-fed mice. We aimed to determine whether the gut microbiome contributes to the beneficial metabolic effects of PAHSAs and if these effects are transmissible by Fecal Microbiota Transplantation (FMT) in mice. In HFD-fed germ-free (GF) mice, PAHSA treatment for 35 days did not improve glucose homeostasis vs. vehicle-treated mice, in contrast to previous data in conventional HFD mice. Feces from conventional Chow fed mice with enhanced insulin sensitivity after PAHSA treatment for 21 days were used for oral FMT in HFD-GF mice. HFD-GF mice treated with feces from PAHSA-treated chow mice gained less weight, had reduced glycemia 5-hrs after food removal, and were more glucose tolerant and insulin sensitive than HFD-GF-mice that received feces from vehicle-treated Chow mice. Metagenome sequencing and metabolomics analysis performed on cecal contents from conventional Chow-fed PAHSA- and Vehicle-treated mice showed that 26 fatty acids (out of 600 metabolites) and several microbial species and their metabolic pathways correlated most highly with PAHSA-mediated insulin sensitivity. Also, Bacteroides thetaiotaomicron (Bt), a gut microbe associated with leanness in humans, and cecal C34:2 Phosphatidylethanolamine (PE), an abundant phospholipid class that is reduced in obese humans, were most strongly associated with the beneficial PAHSA effects. Initial studies with Bt treatment in male chow mice show improved glucose tolerance and lower glycemia 5-hrs after food removal vs. controls. Thus, the gut microbiota is necessary for the effects of PAHSAs to improve glucose homeostasis in HFD-fed mice. These effects can be conferred by FMT. PAHSA-associated microbes could provide novel gut-based therapeutic strategies to treat obesity and insulin resistance. Disclosure J. Lee: None. A. Rahnavard: None. K. Wellenstein: None. A.T. Nelson: None. C.B. Clish: None. D. Siegel: None. B. Kahn: Advisory Panel; Self; Harrington Discovery Institute, Janssen Pharmaceuticals, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1K01DK114162-01A1, DK1NADK-057521-01 to J.L.); JPB Foundation (to B.K.)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-1938-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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