d-Ribose as a Contributor to Glycated Haemoglobin

Area of Science:

• Biochemistry
• Endocrinology
• Metabolic Research

Background:

• Glycated haemoglobin (HbA1c) is a key indicator of chronic hyperglycemia in diabetes mellitus.
• The glycation process, particularly with d-glucose, is well-established.
• The role of other sugars, like d-ribose, in HbA1c formation is less understood.

Purpose of the Study:

• To investigate the role of d-ribose in the formation of HbA1c.
• To explore the potential of targeting d-ribose metabolism for diabetes management.

Main Methods:

• Mass spectrometry was used to detect and quantify glycated hemoglobin products.
• Kinetic analysis compared the rate of fructosamine formation by d-ribose and d-glucose.
• Studies were conducted in Zucker Diabetic Fatty (ZDF) rats and human patients with type 2 diabetes mellitus (T2DM).
• Transketolase (TK) activity was modulated using benfotiamine.

Main Results:

• D-ribose was identified as a significant glycating agent for hemoglobin, forming 10 carboxylmethyllysines (CMLs).
• D-ribose exhibited a fructosamine formation rate approximately 60 times higher than d-glucose initially.
• ZDF rats showed elevated d-ribose and HbA1c, with reduced liver transketolase (TK).
• Benfotiamine administration lowered d-ribose and subsequently HbA1c in ZDF rats.
• T2DM patients with high HbA1c also had high urine d-ribose, irrespective of urine d-glucose levels.

Conclusions:

• D-ribose directly contributes to HbA1c formation.
• Elevated d-ribose may play a role in the pathophysiology of T2DM.
• Targeting d-ribose metabolism, potentially through TK activation, could be a therapeutic strategy for T2DM.