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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance

Author

  • Ele Ferrannini
  • Andrea Natali
  • Stefania Camastra
  • Monica Nannipieri
  • Andrea Mari
  • Klaus-Peter Adam
  • Michael V. Milburn
  • Gabi Kastemmueller
  • Jerzy Adamski
  • Tiinamaija Tuomi
  • Valeriya Lyssenko
  • Leif Groop
  • Walter E. Gall

Summary, in English

Metabolomic screening of fasting plasma from nondiabetic subjects identified alpha-hydroxybutyrate (alpha-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of alpha-HB and L-GPC for incident dysglycemia, alpha-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, alpha-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with alpha-HB reciprocally related to indices of beta-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, alpha-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 cc-JIB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, alpha-JIB inhibited and L-GPC stimulated glucose-induced insulin release in INS-le cells. alpha-JIB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and beta-cell dysfunction. Diabetes 62:1730-1737, 2013

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2013

Language

English

Pages

1730-1737

Publication/Series

Diabetes

Volume

62

Issue

5

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X