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The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects

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Author: Yudkin, J.S. · Panahloo, A. · Stehouwer, C. · Emeis, J.J. · Bulmer, K. · Mohamed-Ali, V. · Denver, A.E.
Institution: Gaubius Instituut TNO
Source:Diabetologia, 9, 43, 1099-1106
Identifier: 235682
doi: doi:10.1007/s001250051500
Keywords: Biology · Acute-Phase Proteins · Albuminuria · Biological Markers · Blood Glucose · C-Reactive Protein · Cross-Over Studies · Diabetes Mellitus, Type 2 · Drug Therapy, Combination · Endothelium, Vascular · Female · Fibrinogen · Fibronectins · Glyburide · Hemoglobin A, Glycosylated · Humans · Hypoglycemic Agents · Insulin · Interleukin-6 · Male · Middle Aged · Sulfonylurea Compounds · Thrombomodulin · Tumor Necrosis Factor-alpha · von Willebrand Factor


Aims/hypothesis. 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 · kg-1 · min-1; after sulphonylureas: 2.41 (1.82, 3.01) ml · kg-1 · min -1, p = 0.001; after insulin: 2.23 (1.92, 2.75) ml · 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) μg · ml-1; sulphonylureas: 2.69 (0.88, 9.65) μg · ml-1 (p = 0.53); insulin: 2.07 (1.16, 5.24) μg. m1-1 (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-α (p = 0.65-0.79). Conclusion/interpretation. 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. Chemicals/CAS: Acute-Phase Proteins; Biological Markers; Blood Glucose; C-Reactive Protein, 9007-41-4; Fibrinogen, 9001-32-5; Fibronectins; Glyburide, 10238-21-8; Hemoglobin A, Glycosylated; Hypoglycemic Agents; Insulin, 11061-68-0; Interleukin-6; Sulfonylurea Compounds; Thrombomodulin; Tumor Necrosis Factor-alpha; von Willebrand Factor