W. Engelen

Platelet prothrombinase activity, a final pathway platelet procoagulant activity, is overexpressed in type 1 diabetes: no relationship with mean platelet volume or background retinopathy

There is overwhelming evidence that platelets from diabetic individuals are hyperreactive, not only when mi crovascular complications are apparent, but already at an early stage of the disease. There is still controversy about the ques tion of whether primary hyperreactive platelets may contribute to the origin or progression of microangiopathy or whether diabetic platelet hyperfunctionality is just a logical conse quence of a continuous low-grade activation of platelets by contact with a diseased microvascular wall. As a consequence of platelet activation, the outer layer of its phospholipid mem brane is more procoagulant than in the quiescent state, stimu lating thrombin formation in plasma. This platelet function is called platelet procoagulant activity. We studied platelet pro thrombinase activity (PPA), a final pathway platelet procoagu lant activity of type 1 diabetic platelets, and looked for an eventual correlation with microvascular disease (background retinopathy) and mean platelet volume (MPV). Stypven clot ting times (SCTs), reflecting PPA expression, and MPV of citrated platelet-rich plasma (PRP), were measured in 21 pa tients with type 1 diabetes—10 with and 11 without back ground retinopathy—under clinically acceptable metabolic control and compared them to 20 disease-free voluntary con trols. We also compared PPA expression and MPV in diabetic individuals with and without retinopathy. With the SCT, a se lective test adapted for studying PPA in PRP, we found hyper expression of PPA in all diabetic patients. We found no differ ence in MPV between diabetic and control PRP. Comparing patients with and without background retinopathy we found no significant difference in PPA expression. From these results, we suggest that the phospholipid surface of diabetic platelets, more than the surface of normal control platelets, stimulate the expression of PPA. This diabetic platelet coagulant anomaly was not related to an increased platelet mass (higher MPV) nor to the presence of microangiopathy. We conclude that PPA hyperexpression is associated with patients with type 1 diabe tes, already occurring in an early stage of the disease, and not necessarily a consequence of early-stage microvascular disease, because the anomaly is also demonstrable, in the same degree, in patients with diabetes without microangiopathy.

Effects of micronized fenofibrate and vitamin E on in vitro oxidation of lipoproteins in patients with type 1 diabetes mellitus

OBJECTIVE The primary objective was to compare the antioxidant activity of micronised fenofibrate 200 mg to 400 IU of vitamin E and placebo, on the LDL and VLDL particles of patients with type 1 diabetes. The secondary objective was to investigate the possible synergy between micronized fenofibrate and vitamin E and to compare the efficacy of these treatments on lipids. METHODS A double-blind, placebo-controlled trial in which patients were randomised into three treatment groups after a wash-out period of 8 weeks: the placebo group (Pla/Pla-group) in which patients received placebo during two consecutive periods of 8 weeks, the vitamin E group (Vit E/Vit E-group) in which patients received Vitamin E during two consecutive periods, and the fenofibrate/Vitamin E group (Fen/Fen + Vit E-group) in which patients received fenofibrate during the first period, followed by fenofibrate and vitamin E during the consecutive period. Blood samples taken at each visit, were analysed for routine biochemistry, blood lipids and copper mediated lipid peroxidation in vitro. RESULTS The lag time of the non-HDL lipoprotein oxidation increased in the group given fenofibrate. The lag-time increased further when fenofibrate and vitamin E were given in association. (This reached significance in the intention-to-treat population, P = 0.034). The AUC of TBARS formation in the Vit E/Vit E group decreased after the first period, but this effect was not enhanced by continuing vitamin E for another 8 weeks. The AUC of TBARS formation did not change significantly after the administration of fenofibrate. Only after the second period, when vit E was given in association, the AUC of TBARS formation decreased significantly (P = 0.004). Fenofibrate caused a significant decrease in total and LDL-cholesterol and triglycerides (P < 0.05). In contrast, vitamin E had no effect on lipids. CONCLUSIONS The combination of micronized fenofibrate 200 mg/day and vitamin E 400 IU/day tended to increase the resistance of non-HDL lipoproteins to copper-mediated oxidation, shown by a prolongation of the lag-time. Vitamin E administration only, decreased the oxidation of non-HDL lipoproteins shown by a reduction of TBARS formation. This protective effect of vitamin E tended to be amplified by micronized fenofibrate.

Epidemiology of microalbuminuria in type 1 diabetic patients (IDDM) in the Antwerp University Hospital

Diabetic nephropathy is the most important cause of increased morbidity and premature mortality in patients with insulin dependent diabetes mellitus. Several longitudinal studies done in different countries have shown that microalbuminuria strongly predicts the development of diabetic nephropathy in insulin dependent diabetes mellitus. Very few data are available about the situation in Belgium. In a retrospective study we analysed the data of 271 insulin dependent diabetic patients attending the University Hospital of Antwerp during the year 1994. Normoalbuminuria was defined as a urinary albumin excretion rate of < or = 20 micrograms/min, microalbuminuria as 20-200 micrograms/min and macroalbuminuria as > 200 micrograms/min. In our population we find an overall prevalence of microalbuminuria of 14%. Patients with microalbuminuria are characterised by an earlier onset and a longer duration of diabetes when compared with patients with normoalbuminuria. Further we find that they have a worse glycemic control, a higher frequency of raised arterial blood pressure and a higher percentage of proliferative retinopathy. These data are comparable with those from other studies done in different countries. They show that patients with microalbuminuria should be regarded as a high risk group and therefore urinary albumin excretion rate should be monitored routinely. Also they stress the importance to strive to a good metabolic control and to an aggressive treatment of arterial hypertension.