We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance.
- Authors
Ferrannini, Ele; Natali, Andrea; Camastra, Stefania; Nannipieri, Monica; Mari, Andrea; Adam, Klaus-Peter; Milburn, Michael V.; Kastenmüller, Gabi; Adamski, Jerzy; Tuomi, Tiinamaija; Lyssenko, Valeriya; Groop, Leif; Gall, Walter E.
- 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.
- Subjects
BLOOD plasma; INSULIN resistance; GLUCOSE intolerance; GLUCOSE tolerance tests; STANDARD deviations
- Publication
Diabetes, 2013, Vol 62, Issue 5, p1730
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db12-0707