Is diabetes an acquired disorder of reactive glucose metabolites and their intermediates?

Abstract

AIMS/HYPOTHESIS:

We hypothesised that diabetic patients would differ from those without diabetes in regard to the handling of glucose-derived reactive metabolites, evidenced by triosephosphate intermediates (TP(INT)) and methylglyoxal (MG), irrespective of the type of diabetes, plasma glucose level or HbA(1c) value.

METHODS:

To test this hypothesis, erythrocytes were isolated from patients with type 1 (n = 12) and type 2 (n = 12) diabetes with varying blood glucose and HbA(1c) levels. These were then compared with erythrocytes isolated from individuals without diabetes (n = 10), with respect to MG, as determined by HPLC, and TP(INT), as determined by endpoint enzymatic assays.

RESULTS:

The concentrations of intracellular TP(INT) and MG were significantly elevated in erythrocytes from diabetic patients. Normalisation of either TP(INT) or MG to intracellular glucose concentration (nmol glucose/mgHb) confirmed that erythrocytes from diabetic patients accumulated more reactive metabolites than did those from healthy controls.

CONCLUSIONS/INTERPRETATION:

Diabetic patients can be characterised by an increased formation of TP(INT) and MG. The 25-fold increase of MG in type 1 and the 15-fold increase in type 2 diabetes, together with a several-fold increase in TP(INT) and decreased glyceraldehyde-3-phosphate dehydrogenase activity even under normal glucose conditions, imply that normalising glucose level cannot completely prevent late diabetic complications until this acquired error of metabolism has been restored.

• Authors: T Fleming, J Cuny, G Nawroth, Z Djuric, P M Humpert, M Zeier, A Bierhaus, P P Nawroth
• Journal: Diabetologia (Diabetologia) Vol. 55 Issue 4 Pg. 1151-5 (Apr 2012) ISSN: 1432-0428 [Electronic] Germany
• PMID: 22270223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Pyruvaldehyde
• Glyceraldehyde-3-Phosphate Dehydrogenases
• Glucose

Topics

• Adult
• Aged
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 1 (metabolism)
• Diabetes Mellitus, Type 2 (metabolism)
• Erythrocytes (metabolism)
• Female
• Glucose (metabolism)
• Glycated Hemoglobin (metabolism)
• Glyceraldehyde-3-Phosphate Dehydrogenases (metabolism)
• Humans
• Male
• Middle Aged
• Pyruvaldehyde (metabolism)