Intense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type-2-diabetes--a multicenter, randomised, double-blind, three-arm placebo-controlled clinical trial.

Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.

[Influence of experience on intra- and interindividual variability in assessing peripheral endothelial dysfunction with high resolution ultrasound]. / Einfluss der Untersuchererfahrung auf intra- und interindividuelle Variabilität bei der Erfassung der peripheren Endothelfunktion mittels hochauflösendem Ultraschall.

UNLABELLED: The non-invasive evaluation of endothelial dysfunction with high-resolution ultrasound has become a widely accepted tool in determination of high-risk subjects for early atherosclerosis. Furthermore it is often used as intermediate outcome in intervention studies. AIM: We examined the influence of examiner experience on intra- and inter-individual variability in the measurement of flow-associated vasodilation (FAD) independent of automated analysis systems. METHOD: FAD was measured on two occasions in 7 and 8 subjects respectively (mean age 32 +/- 3 years) by two investigators after different prior training procedures with a 13 MHz linear transducer (LA14A, ESAOTE Biomedica). RESULTS: The intra-individual variability expressed as median absolute difference in the measurements of FAD was 1.1 % (range from 0.03 % to 3.2 %) for examiner one with an experience of more than 50 FAD measurements through former studies and 2.9 % (range from 1.6 % to 9.2 %) for examiner two with only 10 training examinations under supervision. By a further training period of two months, with an increase of examinations of additional 20 measurements by both examiners, the intra-observer variability could be dropped to 0.9 % (range from 0.03 % to 1.3 %) for examiner two (p = 0.0025) with no significant change for examiner one (median 0.6 % with a range from 0.14 % to 3.7 %). As expected, the inter-individual variability was not influenced by this further training (median 1.0 % with a range of 0.5 % to 3.6 % versus a median of 1.6 % with a range from 0.15 % to 7.5 %). CONCLUSION: 30 training measurements of FAD under supervision should be regarded as minimum requirement for valid determination of endothelial function. The reachable result for the intra-observer variability is thereby within the range of computed analysis systems.

Long term effect of a structured inpatient diabetes teaching and treatment programme in type 2 diabetic patients: influence of mode of follow-up.

Structured diabetes teaching and treatment programmes (STTP) are increasingly offered for patients with diabetes to improve metabolic control. We prospectively studied the long term-effect of STTP on metabolic control and knowledge of diabetes in patients with type 2 diabetes. In addition, differences in the mode of follow-up by a university diabetes centre (UDC) versus general practitioner (GP) were assessed. Of the 64 patients with type 2 diabetes (61 +/- 10 years old, diabetes duration 11 +/- 7 years) included in the study 52 could be reevaluated after 2 years. Of those, 31 were followed up by the UDC and 21 by their GPs who received detailed follow-up instructions from the UDC. In all patients, HbA1c decreased from 9.1 +/- 0.3% before the programme to 8.3 +/- 0.3% 2 years after the programme (P = 0.004), whereas body mass index increased from 28.8 +/- 0.8 to 30.3 +/- 0.9 kg/m2 (P < 0.001). Patients had a significantly better knowledge of diabetes and diet 2 years after the programme. For all parameters tested, none of the changes differed between patients managed by the UDC versus those managed by their GP. However, patients who chose follow-up by the UDC were more obese and had a better knowledge of diabetes. In conclusion, the STTP for patients with type 2 diabetes was effective in improving the long-term glycaemic control and knowledge of diabetes. Moreover, with precise therapeutic goals and follow-up instructions given to patient and GP this improvement was independent of the mode of outpatient follow-up.