Related Experiment Videos
Activated platelets in subjects at increased risk of IDDM. DENIS Study Group. Deutsche Nikotinamid
D Tschoepe1, E Driesch, B Schwippert
1Diabetes Research Institute, Düsseldorf, Germany.
Insights
Platelets in individuals at high risk for insulin-dependent diabetes mellitus (IDDM) show increased activation, indicated by elevated P-selectin (CD62) and other markers. This early platelet activation may be a key factor in the development of IDDM.
Area of Science:
- Immunology
- Endocrinology
- Hematology
Background:
- Activated platelets link inflammation and thrombosis through adhesion molecules.
- Platelet activation in recent-onset insulin-dependent diabetes mellitus (IDDM) is independent of metabolic control.
- Early detection of platelet activation may identify individuals at increased risk for IDDM.
Purpose of the Study:
- To evaluate circulating activated platelet levels in first-degree relatives of IDDM patients who are at increased risk.
- To assess platelet surface markers such as P-selectin (CD62), thrombospondin, and lysosomal GP53 (CD63) in prediabetic individuals.
- To determine if platelet activation is an antecedent feature of IDDM.
Main Methods:
- Flow cytometry was used to measure platelet surface marker expression.
- Study included 19 islet cell antibody-positive first-degree relatives of IDDM patients with normal metabolism.
- A control group of 50 healthy volunteers matched for age, BMI, and metabolic parameters was included.
Main Results:
- Prediabetic subjects showed a 3.2-fold increase in CD62+ platelets compared to controls (p < 0.0001).
- Levels of thrombospondin+ and CD63+ platelets were also significantly elevated in prediabetic individuals (p < 0.0001).
- These findings indicate heightened platelet activation in individuals at risk for IDDM.
Conclusions:
- Intravascular platelet activation is present in potentially prediabetic subjects.
- This platelet activation may represent an antecedent, potentially pathogenic feature of IDDM.
- Early platelet activation could be a significant factor in the pathogenesis of IDDM.
Abstract:
Activated platelets respond to activated leukocytes and endothelial cells via adhesion molecules linking inflammation and thrombosis. Platelets of recent-onset insulin-dependent diabetic (IDDM) patients have been shown to be activated independent of metabolic control. This study evaluates the levels of circulating activated platelets exposing adhesion molecules in healthy subjects at increased risk of IDDM (surface markers were: P-selectin (CD62), thrombospondin, lysosomal GP53 (CD63). From the DENIS and the ENDIT screening programmes 19 identified islet cell antibody positive (titre > or = 20 Juvenile Diabetes Foundation units) first degree relatives of IDDM patients (male/female 9/10; age 22 +/- 15 years; body mass index (BMI): 20.0 +/- 4.3 kg/m2) with clearly normal metabolism (HbA1: 6.1 +/- 0.8%; fasting blood glucose: 4.95 +/- 0.67 mmol/l) were available for this investigation. Platelet CD62 as well as thrombospondin and CD63 expression were determined by flow cytometry. We matched 50 normal volunteers for age (29 +/- 6 years), anthropometric measures (male/female 26/24; BMI: 22.3 +/- 2.8 kg/m2) and metabolic parameters (HbA1: 5.8% +/- 0.3; fasting blood glucose: 4.41 +/- 0.53 mmol/1) served as control subjects. The mean number of CD62+ platelets was increased 3.2-times in prediabetic patients: 1.94 x 2.91 (+/- 1) vs 0.60 x 1.83 (+/- 1%), p < 0.0001. Thrombospondin+ and CD63+ platelet levels were concomitantly increased (1.45 x 2.38( +/- 1)/5.97 x 2.89 (+/- 1)% vs 0.52 x 2.01 (+/-1)/1.64 x 2.26 (+/-1)%, p < 0.0001 for both comparisons). Thus, intravasal platelet activation is already present in potentially prediabetic subjects representing an antecedent, potentially pathogenic feature of IDDM.