Dr. Frank Pistrosch

Insulin resistance, endothelial dysfunction and diabetic nephropathy

Previous and current research

Insulin resistance is an independent risk factor for arteriosclerosis and cardiovascular mortality of patients with type 2 diabetes mellitus. A possible mechanism by which insulin resistance contributes to arteriosclerosis could be endothelial dysfunction.

1. Using venous occlusion plethysmography we demonstrated an amelioration of endothelial dysfunction in the human forearm by treatment with the PPAR gamma activator rosiglitazone. This improvement of endothelial dysfunction was independent of glycemic control. We found a close association between improvement of insulin resistance by rosiglitazone and the corresponding improvement of endothelial dysfunction.

2. Because of potential relevance of endothelial dysfunction for development of diabetic nephropathy we proceeded to human studies of renal hemodynamics. Microalbuminuria, an early stage of diabetic nephropathy, might reflect the renal manifestation of a global vascular dysfunction. We demonstrated that treatment of microalbuminuric type 2 diabetic patients with a PPAR gamma activator reduced the urinary albumin excretion and glomerular hyperfiltration. Furthermore we found an improvement of intrarenal nitric oxide bioavailability in these patients after treatment – a widely accepted marker of an intact endothelium.

Future prospects and goals

Based on our previous findings we will proceed to confirm our observations in patients with overt diabetic nephropathy.

Selected publications

1. Pistrosch F, Herbrig K, Kindel B, Passauer J, Fischer S Gross P (2005): Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction and microalbuminuria of incipient diabetic nephropathy in patients. Diabetes. 54(7): 2206-11.
2. Pistrosch F, Herbrig K, Oelschlaegel U, Richter S, Passauer J, Fischer S, Gross P (2005): PPARgamma-agonist increases number and migratory activity of cultured endothelial progenitor cells. Atherosclerosis. 20(5).
3. Pistrosch F, Passauer J, Fischer S, Fuecker K, Hanefeld M, Gross P (2004): In type 2 diabetes rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glycemic control. Diabetes Care 27(2): 484-90

Curriculum vitae

2000: MD at the Freie Universität of Berlin

1999-2000: Research fellow at the Institut of Clinical Metabolic Research, University Clinic of Dresden

since 2001: Resident and research fellow, Medical Clinic III, Dept of Nephrology, University Clinic of Dresden