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Time course of specific AGEs during optimised glycaemic control in type 2 diabetes.
Neth J Med. 2006 Jan; 64(1):10-6.NJ

Abstract

BACKGROUND

Several advanced glycation endproducts (AGEs) are formed in the hyperglycaemic state. Although serum AGEs correlate with average glycaemic control in patients with type 2 diabetes and predict the development of complications, it is not known how serum AGEs change during optimisation of diabetes therapy.

METHODS

We evaluated the change in serum levels of total AGE and the AGEs CML (Nepsilon-carboxymethyllysine) and MGHI (methylglyoxal-derived hydroimidazolone), as well as markers of endothelial function in 28 subjects with type 2 diabetes, who were poorly controlled on oral agents,before and after the institution of insulin therapy.

RESULTS

Mean subject age (+/- SEM) was 58 +/- 2 years,body mass index 27.7 +/- 0.8 kg/m2, and known duration of diabetes was 8.1 +/- 0.9 years. With insulin treatment fasting blood glucose levels dropped from 12.1 +/- 0.9 mmol/l to 6.9 +/- 0.3 and 8.1 +/- 0.4 mmol/l after three and six months, respectively (both p<0.001), while HbA1c decreased from 10.0 +/- 0.3 to 7.8 +/- 0.2% (p<0.001). Endothelial function improved as indicated by a small but significant decrease in soluble intercellular cell adhesion molecule (sICAM-1) (152 +/- 10 to 143 +/- 8 ng/ml, p<0.02)and sE-selectin (111 +/- 16 to 102 +/-12 ng/ml, p<0.02)levels. In contrast, we observed only a tendency towards a decrease in CML levels (110 +/-22 to 86 +/- 13 microg/mg protein, p=ns), but a small increase of MGHI (from 0.23 +/- 0.02 to 0.29 +/- 0.04 U/mg protein, p<0.02). At baseline, 16 patients were on metformin, which is known to reduce methylglyoxal levels and reduce generation of reactive oxygen species. They had similar levels of CML and MGHI to the 12 non-metformin users, although their HbA1c was lower (9.4 +/- 0.3 vs 10.7 +/- 0.6 %). During insulin, patients receiving concomitant metformin therapy showed a similar course of CML and MGHI to those not taking metformin.

CONCLUSION

Although insulin therapy improved HbA1c and markers of endothelial function, the levels of serum AGEs did not follow the same time course. This suggests that these specific AGEs are influenced by other factors in addition to overall glycaemia, such as oxidative stress.

Authors+Show Affiliations

Department of Human Biology, Faculty of Health Sciences, Maastricht University, Maastricht, the Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16421436

Citation

Mentink, C J A L., et al. "Time Course of Specific AGEs During Optimised Glycaemic Control in Type 2 Diabetes." The Netherlands Journal of Medicine, vol. 64, no. 1, 2006, pp. 10-6.
Mentink CJ, Kilhovd BK, Rondas-Colbers GJ, et al. Time course of specific AGEs during optimised glycaemic control in type 2 diabetes. Neth J Med. 2006;64(1):10-6.
Mentink, C. J., Kilhovd, B. K., Rondas-Colbers, G. J., Torjesen, P. A., & Wolffenbuttel, B. H. (2006). Time course of specific AGEs during optimised glycaemic control in type 2 diabetes. The Netherlands Journal of Medicine, 64(1), 10-6.
Mentink CJ, et al. Time Course of Specific AGEs During Optimised Glycaemic Control in Type 2 Diabetes. Neth J Med. 2006;64(1):10-6. PubMed PMID: 16421436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time course of specific AGEs during optimised glycaemic control in type 2 diabetes. AU - Mentink,C J A L, AU - Kilhovd,B K, AU - Rondas-Colbers,G J W M, AU - Torjesen,P A, AU - Wolffenbuttel,B H R, PY - 2006/1/20/pubmed PY - 2006/2/28/medline PY - 2006/1/20/entrez SP - 10 EP - 6 JF - The Netherlands journal of medicine JO - Neth J Med VL - 64 IS - 1 N2 - BACKGROUND: Several advanced glycation endproducts (AGEs) are formed in the hyperglycaemic state. Although serum AGEs correlate with average glycaemic control in patients with type 2 diabetes and predict the development of complications, it is not known how serum AGEs change during optimisation of diabetes therapy. METHODS: We evaluated the change in serum levels of total AGE and the AGEs CML (Nepsilon-carboxymethyllysine) and MGHI (methylglyoxal-derived hydroimidazolone), as well as markers of endothelial function in 28 subjects with type 2 diabetes, who were poorly controlled on oral agents,before and after the institution of insulin therapy. RESULTS: Mean subject age (+/- SEM) was 58 +/- 2 years,body mass index 27.7 +/- 0.8 kg/m2, and known duration of diabetes was 8.1 +/- 0.9 years. With insulin treatment fasting blood glucose levels dropped from 12.1 +/- 0.9 mmol/l to 6.9 +/- 0.3 and 8.1 +/- 0.4 mmol/l after three and six months, respectively (both p<0.001), while HbA1c decreased from 10.0 +/- 0.3 to 7.8 +/- 0.2% (p<0.001). Endothelial function improved as indicated by a small but significant decrease in soluble intercellular cell adhesion molecule (sICAM-1) (152 +/- 10 to 143 +/- 8 ng/ml, p<0.02)and sE-selectin (111 +/- 16 to 102 +/-12 ng/ml, p<0.02)levels. In contrast, we observed only a tendency towards a decrease in CML levels (110 +/-22 to 86 +/- 13 microg/mg protein, p=ns), but a small increase of MGHI (from 0.23 +/- 0.02 to 0.29 +/- 0.04 U/mg protein, p<0.02). At baseline, 16 patients were on metformin, which is known to reduce methylglyoxal levels and reduce generation of reactive oxygen species. They had similar levels of CML and MGHI to the 12 non-metformin users, although their HbA1c was lower (9.4 +/- 0.3 vs 10.7 +/- 0.6 %). During insulin, patients receiving concomitant metformin therapy showed a similar course of CML and MGHI to those not taking metformin. CONCLUSION: Although insulin therapy improved HbA1c and markers of endothelial function, the levels of serum AGEs did not follow the same time course. This suggests that these specific AGEs are influenced by other factors in addition to overall glycaemia, such as oxidative stress. SN - 0300-2977 UR - https://www.unboundmedicine.com/medline/citation/16421436/Time_course_of_specific_AGEs_during_optimised_glycaemic_control_in_type_2_diabetes_ L2 - http://www.njmonline.nl/njm/getarticle.php?v=64&amp;i=1&amp;p=10 DB - PRIME DP - Unbound Medicine ER -