Thiazolidinedione increases serum soluble receptor for advanced glycation end-products in type 2 diabetes.
OBJECTIVE
Interfering with the activation of receptor for AGE (RAGE) by using a soluble form of the AGE receptor (sRAGE) prevents or ameliorates the vascular complications of diabetes in experimental studies. Relatively little is known about factors that influence endogenous circulating sRAGE in humans. We investigated the impact of improving glycaemic control on serum total sRAGE and endogenous secretory RAGE (esRAGE), a splice variant of sRAGE, and compared the effect of rosiglitazone with that of sulfonylurea.


METHODS
A randomised, open-label, parallel group study was performed with 64 participants randomised to receive add-on therapy with either rosiglitazone or sulfonylurea. Serum total sRAGE and esRAGE and metabolic parameters were measured before and after 6 months of treatment.


RESULTS
At 6 months, both rosiglitazone and sulfonylurea resulted in a significant reduction in HbA(1c), fasting glucose and AGE. However, significant increases in total sRAGE and esRAGE were only seen in the rosiglitazone group. As a result, serum esRAGE was higher in the rosiglitazone group than in the sulfonylurea group at 6 months (p < 0.01), whereas the differences in sRAGE between the two groups did not reach statistical significance. Stepwise linear regression analysis showed that treatment modality made a greater contribution than the changes in HbA(1c) to the subsequent changes in esRAGE levels at 6 months.


CONCLUSIONS
Treating type 2 diabetic patients with thiazolidinedione can increase circulating levels of esRAGE and sRAGE. Whether modulation of circulating sRAGE has a beneficial effect on diabetic complications will have to be evaluated in long-term prospective studies.
Tan
K C B
KCB
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China. kcbtan@hkucc.hku.hk.|Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR, People's Republic of China. kcbtan@hkucc.hku.hk.
Chow
W S
WS
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.
Tso
A W K
AWK
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.
Xu
A
A
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR, People's Republic of China.
Tse
H F
HF
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR, People's Republic of China.
Hoo
R L C
RLC
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.
Betteridge
D J
DJ
Department of Medicine, Royal Free and University College London Medical School, London, UK.
Lam
K S L
KSL
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR, People's Republic of China.
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005905:Glyburide