Understanding the role of insulin resistance (IR) in type 1 diabetes (T1D) may help to improve its treatment. Postprandial insulin secretion stimulates amino acid (AA) uptake and protein synthesis. Consequently, impaired insulin-mediated AA clearance could raise postprandial branched-chain AA (BCAA: valine (VAL), leucine (LEU), isoleucine (ILE)) levels and in turn contribute to BCAA-induced IR. We hypothesized that BCAA levels associate negatively with postprandial ß-cell function already in recent-onset T1D. In a cross-sectional study, volunteers of the German Diabetes-Study with T1D (n=10, diabetes duration <1 year) and excellent glycemic control (HbA1C 6.6±0.9%/48±9 mmol/mol), and age-, sex- and BMI- matched glucose tolerant humans (control, CON, n=10, HbA1C 5.1±0.3%/32±3 mmol/mol) underwent a mixed-meal tolerance test (MMT) to assess ß-cell function through disposition index (DI, the product of insulin sensitivity (IS) and acute insulin response to glucose) and postprandial IS (PREDIM index, predicted M-value). Adipose tissue (AT) IR index was calculated as fasting plasma levels of FFA (mmol*l-1) x insulin (pmol*l-1). Postprandial total BCAA, VAL and LEU levels were 25% higher in patients with T1D compared with CON (AUC 11167±5136 vs. 8410±3298, 14363±959 vs. 11754±3890, 11980±4317 vs. 8476±4257 µmol*l-1*3 h-1, p<0.05, respectively). PREDIM was lower in T1D (3.3±1.1 vs. CON 7.0±1.4 ml*min-1*m-2, p<0.01), while fasting and postprandial AT IR were not different. Persons with T1D showed an inverse relationship between BCAA concentrations and C-peptide levels (total BCAA: r=-0.76, p<0.01; VAL: r=-0.80, p<0.01; LEU: r=-0.71, p<0.05; ILE: r=-0.67, p<0.05) and DI (total BCAA: r=-0.71, p<0.05; VAL: r=-0.78, p<0.01; LEU: r=-0.75, p<0.01; ILE: r=-0.69, p<0.05).

In conclusion, persons with even well-controlled recent-onset T1D exhibit elevated postprandial BCAA concentrations, likely due to impaired ß-cell function, which contribute to postprandial IR.


Y. Karusheva: None. K. Strassburger: None. D.F. Markgraf: None. O.P. Zaharia: None. K. Bodis: None. A. Tura: None. G. Pacini: None. V. Burkart: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.