Elevated platelet activation in type I diabetics with chronic complications under long-term near-normoglycemic control.

A prethrombotic state with altered, hyperactive platelets may contribute to the development of diabetic late complications. Whether increased platelet 'in vivo' activation can be reduced by tight metabolic control is controversial. We studied plasma markers of platelet activation in 64 long-term, microangiopathic type I diabetics after at least 18 months of intensive treatment for near-normoglycemia. Both platelet factor 4 and beta-thromboglobulin proved to be significantly (p less than or equal to 0.05) elevated in comparison with healthy controls: 15.8 (sdf 2)/77.6 (sdf 1.9) vs. 8.9 (sdf 1.6)/45.1 (sdf 2) ng/ml (sdf = standard deviation factor). We found no significant correlations with any metabolic parameter (actual blood glucose, mean blood glucose, HbA1, triglycerides, cholesterol) or with the duration of intensive treatment. It is therefore concluded, that platelet 'in vivo' activation takes place in type I diabetics even after long-term near-normoglycemic control. This deviation could be regarded as indicator of an additional risk for the development of vascular complications.

Combined subtotal pancreatectomy with selective streptozotocin infusion--a model for the induction of insulin deficiency in dogs.

Standardized models of type I diabetes-like insulin deficiency in larger laboratory animals hardly exist. It was therefore investigated whether stable long-term insulin deficiency in dogs can be induced by selective beta-cell destruction in a safe and reliable procedure without damage of other organs. In Beagle dogs, the diabetogenic response to systemic streptozotocin administration (38.5-28 mg/kg b.wt.) was tested. In addition, resection of corpus and cauda pancreatis in combination with selective streptozotocin perfusion (25 mg/kg b.wt.) of the remaining pancreas tissue was evaluated. Whereas systemic streptozotocin administration failed to destroy insulin secretion, but led to a variety of intoxication symptoms even in comparatively low doses (28 mg/kg b.wt.), the latter procedure resulted in a complete and persistent insulin depletion (basal serum immunoreactive insulin less than or equal to 3 microU/ml, no stimulated response) without toxic organ damage or other serious side effects. The dogs developed type I-like diabetes, which required continuous exogenous insulin substitution. From these results, subtotal pancreatectomy with selective streptozotocin perfusion of the remaining pancreas is proposed as a safe model of insulin deficiency in dogs, which should be further evaluated in experimental diabetology.