Improvement of glucose metabolism in patients with type II diabetes after treatment with a hemodialysate.
Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Previous studies have shown that Actovegin, a hemodialysate of calf blood, which has been used for treatment of circulatory disorders for many years, improves glucose tolerance in NIDDM without affecting insulin levels; in vitro studies found an improvement of insulin-stimulated glucose uptake in adipocytes. This pilot study was initiated to see whether this compound augments insulin sensitivity after repeated treatment. Ten patients with NIDDM received the hemodialysate (Actovegin 2.000 pro infusions, 500 ml as daily infusions) over a period of 10 days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11; oral glucose tolerance test (oGTT) was done on day -4 and day 12. Parenteral administration of the hemodialysate markedly augmented insulin stimulated glucose disposal (glucose infusion rate and metabolic clearance rate) by more than 80% (p < 0.003 day 11 vs. day 0). Although tested 44 h after the last infusion, oGTT also improved significantly, as documented by the diminished area under the curve (AUC) for glucose, whereas the AUC for insulin remained unchanged. This is the first clinical study to show that parenteral administration of the tested hemodialysate results in a significant increase of insulin-stimulated glucose disposal in NIDDM. The exact mode of action of the hemodialysate in improving insulin sensitivity is currently not known. The hemodialysate possibly acts via a supplementation of inositol-phosphate-oligosaccharides (IPO), as in experimental studies IPOs isolated from the hemodialysate improved glucose uptake in adipocytes in an insulin-independent manner. Further studies are needed to elucidate the underlying mechanisms.
Jacob
S
S
Department of Internal Medicine, Stadtklinik, Baden-Baden, Germany.
Dietze
G J
GJ
Machicao
F
F
Kuntz
G
G
Augustin
H J
HJ
D000368:Aged; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D006418:Heme / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D010865:Pilot Projects
D007004:Hypoglycemic Agents; D008055:Lipids; D006418:Heme; C015646:Actovegin; D005947:Glucose