No abstract

Thallium tomographic imaging and exercise electrocardiography were performed on 136 diabetic patients without symptoms of heart disease. Thirty three patients had post-exercise thallium defects and 19 had ST 1 mm greater than or equal to segment depression during exercise electrocardiography. Both tests were positive in 13 patients. Coronary angiography was subsequently performed on 33 patients with either scintigraphic and/or electrocardiographic evidence of myocardial ischaemia. Angiographically significant coronary artery disease (greater than or equal to 50% narrowing of the coronary artery lumen) was detected in 13 patients. Six patients had minimal coronary artery stenosis (less than 50%), and 14 had normal coronary arteries. Six patients refused cardiac catheterisation. In 14 out of 27 patients with post-exercise thallium defects coronary angiography did not show any coronary artery stenoses (positive predictive accuracy 48%). Exercise electrocardiography showed only one false positive result (positive predictive accuracy 94%) but failed to detect coronary artery disease in three patients with a positive scintigraphic result. The accuracy of a positive exercise electrocardiographic test seems to be better than that of a positive thallium tomographic scan for detecting asymptomatic coronary artery disease in diabetic patients. The high number of false positive thallium defects may be the result of technical features inherent in thallium tomography and/or the possible disease of the small intramyocardial arteries in diabetic patients.

Liver blood flow and indices of hepatic drug metabolism (antipyrine elimination rate and cytochrome P-450 concentration in liver biopsy specimens) were studied in 19 epileptics on long-term anticonvulsant treatment, and in 18 controls. The size of the liver and the total estimated liver blood flow were greater inthe epileptics than in the controls, whereas the relative liver blood flow (per unit weight of the liver) was not significantly different. The epileptics had higher cytochrome P-450 levels and they eliminated antipyrine faster than the controls. It was concluded that long-term ingestion of enzyme-inducing anticonvulsants is associated with an increase in the total hepatic blood flow in parallel with the increase in liver size, and not as an independent phenomenon. Since the relative perfusion rate of the hepatocytes was unchanged, the enhanced activity of drug metabolizing enzymes is presumed to be mainly responsible for the increased drug clearance observed in epileptic subjects.

Serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentration and the ratio between them, major risk factors of coronary heart disease, and liver size were investigated in 18 subjects who were on enzyme-inducing anticonvulsants, phenytoin alone or in combination with phenobarbital and/or carbamazepine. The subjects with a high liver cytochrome P-450, indicating hepatic microsomal enzyme induction, who showed an increase in liver size, had an elevated high-density lipoprotein concentration and high-density lipoprotein cholesterol/total cholesterol ratio, and a reduced low/high-density lipoprotein cholesterol ratio. The high-density lipoprotein cholesterol concentration and its ratio to total cholesterol were directly and related to the ratio between low and high-density lipoprotein cholesterol were inversely related to the extent of liver enlargement. The serum cholesterol distribution profile associated with an increase in liver size was typical of subjects with a low risk of coronary heart disease. The results suggest that enzyme-inducers, such as phenytoin and phenobarbital, induce structural and functional changes in hepatocellular membranes associated with liver enlargement and cholesterol distribution characteristic of low susceptibility to atherosclerotic vascular disease.

Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in 21 subjects (mean age 48 yr) with insulin-dependent diabetes mellitus (IDDM) and without evidence of ischemic heart disease and in 21 healthy control subjects of similar age and sex distribution. The peak mitral valve flow velocities during the early rapid filling phase (E) and during late atrial filling (A) were measured, and the ratio of these peak flow velocities (E:A) was calculated. E was similar in both groups, but A was higher (P less than .01) in the diabetic group. Thus, E:A was lower (1.19 +/- 0.24 vs. 1.65 +/- 0.67; P less than .01) in the diabetic subjects than in the control subjects. On subgroup analysis, 6 patients with cardiac autonomic neuropathy had lower E:A than the patients with no such disorder (0.99 +/- 0.15 vs. 1.29 +/- 0.25; P less than .05). E:A was not related to the duration of diabetes, presence of retinopathy, HbA1, or blood glucose levels. In conclusion, the atrial contribution to left ventricular filling seems to be augmented in diabetic subjects. This finding indirectly supports the view that left ventricular compliance is already reduced in asymptomatic diabetic subjects.