Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by near-normoglycemia.
It has been suggested that platelet hyperactivity contributes to the early evolution of diabetic vascular disease per se. This study directly evaluates the level of intravascular platelet activation in newly diagnosed IDDM patients before and after tight metabolic control. Platelet activation was determined by the Duesseldorf-III flow cytometry assay in 21 recent-onset hyperglycemic IDDM patients before insulin, after 3 days of treatment with intravenous insulin, and after 14 and 60 days of intensified conventional insulin therapy. The intravasal platelet activation status was quantified by the percentage of platelets exposing the activation-dependent molecules CD62 (P-selectin), thrombospondin (TSP), and CD63 (GP53) as well as the activated fibrinogen receptor (GPIIB/IIIA). Fifty matched normal subjects served as control subjects. Fourteen patients completed the 60-day study design. After initial recompensation, near-normoglycemic control was achieved after 14 days (fasting blood glucose, 117.0 +/- 19.0 mg/dl), and the HbA1 concentration was 7.6 +/- 1.2% after 60 days. CD62+ (4.0 +/- 4.5%), TSP+ (2.0 +/- 1.8%), CD63+ (11.0 +/- 7.0%), and activated-GPIIB/IIIA+ (7.6 +/- 7.7%) platelet levels were initially 5, 3.3, 5.7, and 2.8 times higher than the mean level of normal. There was no correlation with any of the nearly normalized metabolic parameters. Thus, more activated platelets circulate in newly diagnosed IDDM patients, which supports the assumption of a prethrombotic condition even in disease stages without apparent vascular damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Tschoepe
D
D
Diabetes Research Institute, Heinrich Heine University, Duesseldorf, Germany.
Driesch
E
E
Schwippert
B
B
Nieuwenhuis
H K
HK
Gries
F A
FA
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis / Q000502:physiology*; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000097:blood*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D019007:P-Selectin; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000097:blood / Q000378:metabolism; D012016:Reference Values; D060149:Tetraspanin 30; D019699:Thrombospondins; D013997:Time Factors
D015703:Antigens, CD; D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D006442:Glycated Hemoglobin; D008562:Membrane Glycoproteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D019699:Thrombospondins; C554586:CD63 protein, human