The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects.
OBJECTIVE
Improved glycaemic control might reduce both microvascular and macrovascular complications of Type II diabetes (non-insulin-dependent) mellitus. To explore such possible mechanisms, we investigated the effects of intensive treatment on markers of endothelial dysfunction and of acute phase activation, using both sulphonylureas and insulin.


METHODS
In a randomised cross-over study we gave sulphonylureas or insulin each for a period of 16 weeks to 22 poorly controlled Type II diabetic subjects who were being treated by diet. There was a 4 week washout period between each treatment. Subjects were studied at baseline and at the end of each treatment.


RESULTS
Treatment with sulphonylureas and insulin resulted in similar improvements in glycaemic control (glycated haemoglobin, baseline: 11.8 [(SD 2.2)%; after sulphonylureas: 8.6 (1.2)%,p < 0.001; after insulin: 8.6 (1.2)%, p < 0.001] and in insulin sensitivity ¿metabolic clearance rate of glucose, baseline: median 1.75 [interquartile (IQ) range 1.41, 2.27] ml x kg(-1) x min(-1); after sulphonylureas: 2.41 (1.82, 3.01) ml x kg(-1) x min(-1), p = 0.001; after insulin: 2.23 (1.92, 2.75) ml x kg(-1) min(-1), p = 0.027¿. There were no significant changes in concentrations of endothelial markers von Willebrand factor, cellular fibronectin, thrombomodulin, tissue plasminogen activator, soluble E-selectin or soluble intercellular adhesion molecule-1 or in urinary albumin excretion rate after either treatment period. Concentrations of C-reactive protein were not significantly influenced by sulphonylureas but fell after insulin [baseline: median 4.50 (IQ range 1.37, 6.44) microg x ml(-1); sulphonylureas: 2.69 (0.88, 9.65) microg x ml(-1) (p = 0.53); insulin: 2.07 (1.16, 5.24) microg x ml(-1) (p = 0.017)]. There were, however, no significant effects of either treatment on circulating concentrations of fibrinogen (p = 0.28-0.34) or of the proinflammatory cytokines interleukin-6 or tumour necrosis factor-alpha (p = 0.65-0.79).


CONCLUSIONS
Markers of endothelial dysfunction and concentrations of proinflammatory cytokines in Type II diabetes are not influenced by improved glycaemic control over 16 weeks. Improved metabolic control with insulin could, however, be associated with reduced concentrations of the acute phase marker C-reactive protein.
Yudkin
J S
JS
Department of Medicine, University College London Medical School, Whittington Hospital, UK.
Panahloo
A
A
Stehouwer
C
C
Emeis
J J
JJ
Bulmer
K
K
Mohamed-Ali
V
V
Denver
A E
AE
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002097:C-Reactive Protein / Q000032:analysis; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000652:urine; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005353:Fibronectins / Q000097:blood; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D018180:Thrombomodulin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D000209:Acute-Phase Proteins; D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D005340:Fibrinogen; D005353:Fibronectins; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D013453:Sulfonylurea Compounds; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor