Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance.
Ele Ferrannini,Andrea Natali,Stefania Camastra,Monica Nannipieri,Andrea Mari,Klaus-Peter Adam,Michael V. Milburn,Gabi Kastenmüller,Jerzy Adamski,Tiinamaija Tuomi,Valeriya Lyssenko,Leif Groop,Walter Gall +12 more
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TLDR
In this paper, α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively.Abstract:
Metabolomic screening of fasting plasma from nondiabetic subjects identified α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of α-HB and L-GPC for incident dysglycemia, α-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, α-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with α-HB reciprocally related to indices of β-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, α-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00–1.60] and 1.26 [1.07–1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48–0.85] and 0.67 [0.54–0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting α-HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, α-HB inhibited and L-GPC stimulated glucose-induced insulin release in INS-1e cells. α-HB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and β-cell dysfunction.read more
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Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis
Marta Guasch-Ferré,Adela Hruby,Estefanía Toledo,Clary B. Clish,Miguel Ángel Martínez-González,Miguel Ángel Martínez-González,Jordi Salas-Salvadó,Frank B. Hu,Frank B. Hu +8 more
TL;DR: In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
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The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis
TL;DR: The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance.
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Human Insulin Resistance is Associated with Increased Plasma Levels of 12α−hydroxylated Bile Acids
TL;DR: In this paper, the relationship between clamp-measured insulin sensitivity and BA composition in a cohort of 200 healthy subjects and 35 type 2 diabetic (T2D) patients was examined.
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Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance
Melania Gaggini,Fabrizia Carli,Chiara Rosso,Emma Buzzigoli,Milena Marietti,Veronica Della Latta,Demetrio Ciociaro,Maria Lorena Abate,Roberto Gambino,Maurizio Cassader,Elisabetta Bugianesi,Amalia Gastaldelli +11 more
TL;DR: Increased plasma AA concentrations were observed mainly in subjects with obesity and NAFLD, likely as a consequence of increased IR and protein catabolism, and the GSG‐index is a possible marker of severity of liver disease independent of body mass index.
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Is there a "metabolic-mood syndrome"? A review of the relationship between obesity and mood disorders.
TL;DR: Accumulating evidence indicates that there is a consistent association of multiple abnormalities in neuropsychological constructs, as well as correspondent brain abnormalities, with broad-based metabolic dysfunction, suggesting, therefore, that the existence of a "metabolic-mood syndrome" is possible.
References
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Journal ArticleDOI
Homeostasis model assessment : insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
TL;DR: The correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
Journal ArticleDOI
Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.
TL;DR: A novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the oral glucose tolerance test (OGTT).
Journal ArticleDOI
A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance
Christopher B. Newgard,Jie An,James R. Bain,Michael J. Muehlbauer,Robert Stevens,Lillian F. Lien,Andrea M. Haqq,Svati H. Shah,Michelle Arlotto,Cris A. Slentz,James Rochon,Dianne Gallup,Olga Ilkayeva,Brett R. Wenner,William S. Yancy,Howard Eisenson,Gerald Musante,Richard S. Surwit,David S. Millington,Mark D. Butler,Laura P. Svetkey +20 more
TL;DR: Findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.
Journal ArticleDOI
Metabolite profiles and the risk of developing diabetes
Thomas J. Wang,Martin G. Larson,Martin G. Larson,Ramachandran S. Vasan,Ramachandran S. Vasan,Susan Cheng,Susan Cheng,Susan Cheng,Eugene P. Rhee,Eugene P. Rhee,Elizabeth L. McCabe,Elizabeth L. McCabe,Gregory D. Lewis,Gregory D. Lewis,Caroline S. Fox,Caroline S. Fox,Paul F. Jacques,Céline Fernandez,Christopher J. O'Donnell,Christopher J. O'Donnell,Christopher J. O'Donnell,Stephen A Carr,Vamsi K. Mootha,Vamsi K. Mootha,Jose C. Florez,Jose C. Florez,Amanda Souza,Olle Melander,Clary B. Clish,Robert E. Gerszten,Robert E. Gerszten +30 more
TL;DR: Findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment.
Journal ArticleDOI
Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.
Michael Stumvoll,Asimina Mitrakou,W P Pimenta,T. Jenssen,Hannele Yki-Järvinen,T.W. van Haeften,Walter Renn,John E. Gerich +7 more
TL;DR: Predicting insulin sensitivity and insulin release with reasonable accuracy from simple demographic parameters and values obtained during an OGTT is possible and should be used in various clinical settings in which the use of clamps or the minimal model would be impractical.
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