Beta-thromboglobulin and fibrinopeptide A in diabetes mellitus as markers of vascular damage.

Beta-thromboglobulin (BTG) and fibrinopeptide A (FpA) were studied in 68 non-insulin dependent diabetic patients (NIDD) aged 32-81 with a mean duration of diabetes of 9 +/- 0.8 SEM years and 44 healthy controls, comparable for age and sex. Diabetic patients were subdivided into subsets according to the presence of microvascular disease, macrovascular disease or the absence of these lesions. Patients with microangiopathy (micro- and/or macrovascular disease) had higher HbA1 (a-c) (p less than 0.01), higher blood pressure (p less than 0.05) than both healthy controls and uncomplicated diabetics. Plasma BTG was higher in diabetic patients than in healthy controls (p less than 0.02), and was higher in complicated than in non-complicated diabetic subjects. Fpa was higher in complicated than in non-complicated diabetes (p less than 0.05). No differences were observed between the two subsets of complicated patients. In conclusion, we have shown that increased plasma- and platelet-BTG levels are present in non-insulin dependent diabetic subjects, with normal renal function and that plasma BTG is higher in patients with than in those without vascular disease. Fibrinopeptide A, a sensitive marker of in vivo fibrin formation, was significantly increased in NIDD with vascular complications.

Increased production of platelet thromboxane B2 in non-insulin-dependent diabetes. Relationship to vascular complications.

Platelet thromboxane B2 production was studied in forty-seven non-insulin-dependent diabetics by incubating platelets with increasing concentrations of arachidonic acid. In comparison with thirty-two healthy subjects, diabetics showed increased thromboxane B2 production at 0.7 mmol/l (mean: 236 pmol/10(8) platelets, SEM 201-277; v. 135, 105-174; P less than 0.05) and at 1.0 mmol/l (673, 613-739; v. 405, 377-486, P less than 0.01) but not at 0.5 mmol/l. Patients were subdivided according to the presence or absence of vascular complications. Patients without microangiopathy showed significantly greater thromboxane B2 production than healthy subjects at all the arachidonic-acid concentrations (P less than 0.02 or less). Patients with microangiopathy had platelet thromboxane production similar to that observed in healthy subjects at all the arachidonic-acid concentrations (P greater than 0.30) but significantly lower than that of non-microangiopathic patients at 0.5 (P less than 0.01) and at 0.7 mmol/l arachidonic acid (P less than 0.05). These results indicate that non-insulin-dependent diabetics have increased production of platelet thromboxane B2 only when they do not have microvascular complications.

Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus.

Twenty-two hypertensive diabetic patients were admitted to a double-blind, within-patient study, and treated with propranolol 80 mg and metoprolol 100 mg twice daily for 4 weeks according to a cross-over design. Dosages of the two drugs such as to induce comparable cardiovascular effects, did not induce relevant changes of fasting blood glucose levels in patients receiving the oral hypoglycaemic agent glibenclamide (group 1), insulin (group 2) or diet alone (group 3). Glucose tolerance, assessed with a 75 g oral load, was however decreased by propranolol, and not by metoprolol in the glibenclamide-treated group. Glucose-induced insulin secretion was reduced by propranolol and not by metoprolol both in the group treated by diet alone and in the glibenclamide-treated group. It is concluded that cardioselective metoprolol seems to be more suitable than the non-selective propranolol in the treatment of arterial hypertension in diabetic subjects, particularly when sulfonylureas are being used as hypoglycaemic agents.

Chlorpropamide-alcohol flushing in non insulin-dependent diabetes: prevalence of small and large vessel disease and or risk factors for angiopathy.

One hundred and eight non insulin-dependent diabetics were tested for alcohol flushing after chlorpropamide administration (CPAF test). The overall prevalence of patients who flushed at the first challenge was 32%. However, nearly half of them still flushed after alcohol administration, when placebo was given instead of chlorpropamide, so that the prevalence of 'true' flushers was only 17%. Even though the distribution of retinal lesions was similar in 'true' flushers and in non flushers, severe loss of visual acuity was confined to the non flushers and aspecific flushers. The frequency of pathological ECG findings and of peripheral pulse reduction or abolition was significantly higher in the non flushers and aspecific flushers. Blood pressure, serum lipids and hemostatic parameters were similar in the two groups, and therefore do not explain the differences in prevalence of lesions. This study confirms the previous findings of a lower prevalence of large vessel lesions in flushers; however, the prevalence of 'true' CPAF phenomenon in our out-patient population appears to be much lower than previously reported.