Prediction and prophylactic treatment of type 1 diabetes

An in vitro method for delaying the onset of type 1 diabetes (T1D) in a subject identified as indicative for the likely future onset of T1D within 3 days of the subject's birth said method comprising administering to said subject a composition comprising free carnitine and/or acylcarnitine (L-carnitine), in an amount sufficient to restore free carnitine, acylcarnitine levels to within the normal range, and wherein said subject is identified as indicative for the likely future onset of T1D by the steps of:

• (a) measuring the total concentration of the amino acids alanine, arginine, aspartate, citrulline, glycine, glutamate, glutamine, leucine, isoleucine, methionine, ornithine, phenylanaline, proline, tyrosine and valine in a biological sample taken from the subject;
• (b) measuring the concentration of total carnitine in a sample taken from said subject;
• (c) determining the subject's human leukocyte antigen (HLA) genotype;
• (d) assigning the subject's genetic risk of developing T1D on the basis of the subject's HLA genotype;
• (e) combining the information obtained in step (a) with the information in step (d);
• (f) combining the information obtained in step (b) with the information in step (d);
• and
• (g) predicting the likelihood of onset of T1D based upon the combination of step (e) and (f);
• wherein in step (d) the genetic risk is assigned as “high”, “moderate” or “low” according to the subject's HLA genotype;
• wherein a high risk HLA genotype comprises the genetic markers DRB1*03/*04 (not 0403) and DQB1 0302;
• wherein a moderate/medium risk HLA genotype comprises the genetic markers DRB1*04 (not 0403)/*04 (not 0403), DQB1 0302, DRB1*04 (not 0403)/X, DQB1 0302/DQB1 (not 0602-3), DRB1*03/*03, DRB1*03/X, and DQB1 (not 0602-3, 0301, or 0503);
• wherein X is not DRB1*03, *04, or 0403;
• and wherein a low risk HLA genotype comprises any combination of genetic markers not specified as high or moderate risk;
• wherein a total amino acid concentration of less than approximately 1200 μmol/L and a total carnitine concentration of less than approximately 50 μmol/L in combination with a high risk HLA genotype as identified in step (g) is indicative of the likely future onset of T1D;
• and
• wherein in step (g) a total amino acid concentration of less than approximately 1000 μmol/L and a total carnitine concentration of less than approximately 40 μmol/L in combination with a moderate or low risk HLA genotype as identified in step (g) is indicative of the likely future onset of T1D.