Effect of glycaemic control, metformin and gliclazide on platelet density and aggregability in recently diagnosed type 2 (non-insulin-dependent) diabetic patients.

Platelet density profiles, intraplatelet nucleotides, intraplatelet beta thromboglobulin (beta TG), plasma beta TG levels, intraplatelet cyclic AMP (cAMP) levels, platelet release reaction, platelet thromboxane (TX)B2 production and plasma fibrinogen levels were investigated in 24 newly diagnosed, non-insulin-dependent diabetic patients and 12 comparable controls. These variables were measured at diagnosis, after a 3-6 week dietary run-in period, and again after 6 months on treatment with either metformin or gliclazide therapy. With dietary restriction of refined carbohydrate and oral hypoglycaemic therapy, there was a reduction in platelet density (p less than 0.05), intraplatelet nucleotides (p less than 0.001), intraplatelet beta TG (p less than 0.001), plasma beta TG (p less than 0.001) and there was an increase in intraplatelet cAMP levels (p less than 0.05). Although these platelet variables returned towards normal, only the platelet density mean returned to within the normal range. There was no significant change in the platelet TXB2 production and plasma fibrinogen levels with treatment. Metformin and gliclazide were equally effective in the glycaemic control of non-insulin-dependent diabetes, and there was no difference between the platelet variables measured in the two groups. We would therefore suggest that improvement of glycaemic control, rather than any specific effect of the oral hypoglycaemic agent employed, is the most important factor in returning these parameters towards normality.

Platelet-density analysis and intraplatelet granule content in young insulin-dependent diabetics.

This study was designed to assess the density characteristics of platelets from controls (N = 10) and three groups of diabetics (N = 32) exhibiting various degrees of glycemic control. With continuous gradients of Percoll, platelets from controls and diabetics (N = 8) with an HbA1 less than or equal to 9% formed a band extending from 1.0625 g/ml to 1.0925 g/ml with a mean platelet density of 1.0775 g/ml. In the two groups of diabetics with HbA1 greater than or equal to 10%, there was an increase in the proportion of low-density platelets recovered on the gradients and the mean platelet density was reduced to 1.0750 g/ml (HbA1 = 10-13%) and 1.070 g/ml (HbA1 greater than or equal to 14%). All three groups of diabetics had normal levels of intraplatelet ATP/ADP and beta-thromboglobulin. It is unlikely that in vivo degranulation of platelets after activation was responsible for the altered density profiles. We propose that abnormal platelet subpopulations with low density but normal intraplatelet granule content were responsible for the changed density profiles.

Survival of 111-indium platelet subpopulations of varying density in normal and post splenectomized subjects.

The present study was designed to investigate the survival of platelets of differing densities in normal and post-splenectomized subjects. Autologous platelets, labelled with 111In-oxine, were reinjected into normal subjects (n = 12); 63% were recovered in the circulation and their survival curve was linear with a T 1/2 of 4.5 d. When the platelets were layered onto a continuous Percoll gradient, they formed a band extending between 1.040 and 1.080 g ml-1. After fractionation of the gradient the specific radioactivity of 111In platelets recovered was measured. The specific activity of low density platelets (average 1.050 g ml-1) decreased rapidly with a T 1/2 of 2.0 d, whilst medium density platelets (average 1.060 g ml-1) survived with a T 1/2 of 4.5 d; high density platelets (average 1.073 g ml-1) exhibited a T 1/2 greater than 5.0 d. This latter population of high density platelets also showed a significant increase in specific activity on the first day following injection. In post-splenectomy subjects a similar relationship between density and 111In associated activity was observed but no increase in the specific activity of the dense platelets on day 1 was observed. We conclude that high density autologous 111In-platelets are preferentially retained in the spleen and have a more prolonged survival than those of lower density.

Sulphated glycosaminoglycans in regenerating rat liver.

The total weight percentage glycosaminoglycan content of rat liber was found to increase by 50% in the first 30 h after partial hepatectomy. The content returned to near normal by the third day, but then increased again to a second maximum at 5-6 days, only to gradually decline to normal by the ninth day, when regeneration was nearly complete. This biphasic pattern was most marked in the chondroitin sulphate A/C component, with a 6-fold increase by the sixth day. Dermatan sulphate showed the same temporal trend, whereas heparan sulphate remained relatively unaltered. No such changes were detected in the livers of rats subjected to sham operation. The possible molecular mechanisms underlying the apparent link between cellular glycosaminoglycan content and proliferative tendency are discussed.