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

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 effect s 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 sub jects who were being treated by diet. There was a 4 week washout period bet ween each treatment. Subjects were studied at baseline and at the end of ea ch treatment. Results. Treatment with sulphonylureas and insulin resulted in similar impr ovements 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 glucos e, 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 marke rs von Willebrand factor, cellular fibronectin, thrombomodulin, tissue plas minogen activator, soluble E-selectin or soluble intercellular adhesion mol ecule-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) mu g . ml(-1); sulphonylureas: 2.69 (0.88, 9.65) mu g . ml(-1) (p=0 .53); insulin: 2.07 (1.16, 5.24) mu g . ml(-1) (p = 0.017)], There were, ho wever, no significant effects of either treatment on circulating concentrat ions of fibrinogen (p = 0.28-0.34) or of the proinflammatory cytokines inte rleukin-6 or tumour necrosis factor-a (p = 0.65-0.79). Conclusion/interpretation. Markers of endothelial dysfunction and concentra tions of proinflammatory cytokines in Type II diabetes are not influenced b y improved glycaemic control over 16 weeks. Improved metabolic control with insulin could, however, be associated with reduced concentrations of the a cute phase marker C-reactive protein.