AIMS: The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp. PATIENTS AND METHODS: Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L(-1)). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry. RESULTS: Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s(-1), P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s(-1), P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = -0.70, P = 0.007). CONCLUSION: Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.

• MeSH
• Endothelium, Vascular cytology   MeSH
• Diabetes Mellitus, Type 1 physiopathology   therapy   MeSH
• Adult MeSH
• Glucose Clamp Technique * MeSH
• Hyperglycemia physiopathology   therapy   MeSH
• Insulin metabolism   MeSH
• Calibration MeSH
• Diabetes Complications pathology   MeSH
• Blood Glucose metabolism   MeSH
• Laser-Doppler Flowmetry methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Microcirculation MeSH
• Oxidative Stress MeSH
• Perfusion MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Insulin MeSH
• Blood Glucose MeSH

OBJECTIVE: Metformin may influence atherogenesis but the mechanisms are not well understood. A pilot study was undertaken to determine whether metformin administration is associated with changes in oxidative stress and endothelial function. METHODS: Fifteen type 2 diabetic patients were treated for 3 months with metformin (1,700 mg daily) or with a placebo in a crossover study. Laboratory parameters of oxidative stress, fibrinolysis and endothelial function were evaluated both prior to and following the respective treatments. In addition, laser Doppler was used to determine microcirculation changes in the skin. RESULTS: Increases in serum N-acetyl-beta-glucosaminidase activity (p < 0.05) and plasma malondialdehyde concentration were found following 1 month of metformin administration. Three months of treatment was accompanied by significantly increased plasma malondialdehyde (p < 0.001) and ascorbic acid (p < 0.01) concentrations as well as the alpha-tocopherol/(cholesterol + triglyceride) ratio (p < 0.001). The concentration of tissue plasminogen activator (tPA), vascular cell-adhesion molecules (VCAM) and intercellular cell-adhesion molecules (ICAM) were significantly decreased (p < 0.01) compared with placebo. Microcirculation measured by laser Doppler flowmetry was not significantly changed. CONCLUSIONS: We conclude that initiation of metformin treatment in type 2 diabetic patients is associated with improved diabetes control as well as with activation of oxidative stress together with antioxidant system. The atherogenic process measured by biochemical indicators is diminished in parallel. Our results show that in short-term metformin administration in type 2 diabetes promotes endothelium effects associated with a complex of metabolic changes.

• MeSH
• Endothelium, Vascular drug effects   MeSH
• Diabetes Mellitus, Type 2 drug therapy   metabolism   MeSH
• Adult MeSH
• Hypoglycemic Agents pharmacology   therapeutic use   MeSH
• Cross-Over Studies MeSH
• Skin blood supply   drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Malondialdehyde blood   MeSH
• Metformin pharmacology   therapeutic use   MeSH
• Microcirculation drug effects   MeSH
• Oxidative Stress drug effects   MeSH
• Pilot Projects MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Hypoglycemic Agents MeSH
• Malondialdehyde MeSH
• Metformin MeSH