Biliary lipid and bile acid composition in insulin-dependent diabetes mellitus. Arguments for increased intestinal bacterial bile acid degradation.

Bile cholesterol saturation and bile acid composition was studied in 12 nonobese male insulin-dependent diabetics and 28 controls. The total bile lipid concentration in the bile rich duodenal aspirate was lower in the diabetics. The bile cholesterol saturation index was lower in the diabetics if calculated according to Thomas and Hofmann, but not if calculated according to Carey's critical tables. A negative correlation was observed between the cholesterol saturation index of the bile of the diabetics and their long-term metabolic control, as measured by the percentage HbA1c. No correlation existed between the saturation index and the metabolic control at the time of bile sampling as measured by serum glucose, beta-hydroxybutyrate, free fatty acids, and triglycerides. There was also a negative correlation between the cholesterol saturation index and the serum cholesterol concentrations. The glycine-taurine ratio of the conjugated bile acids was increased in the diabetics, as was the percentage concentration of secondary bile acids (deoxycholic acid and lithocholic acid). No correlation was found between the metabolic control of the diabetic state and either the glycine-taurine ratio or the percent concentration of secondary bile acids. These results do not favor a higher incidence of cholesterol gallstones in male juvenile-onset insulin-dependent diabetics. The increased glycine-taurine ratio of the conjugated bile acids and the elevated concentration of secondary bile acids may be due to increased bacterial invasion of the small intestine or decreased absorption of bile acids in the terminal ileum in these insulin-dependent diabetics.

Hepatotoxic effect of bile acids in inflammatory bowel disease.

Lithocholate, a secondary bile acid, is hepatotoxic in many animal species including nonhuman primates. The induced histologic changes resemble those observed in patients with hepatic damage associated with inflammatory bowel disease. Accordingly, we have examined the hypothesis that lithocholate is of etiologic importance in causing this association by measuring serum and biliary lithocholates in inflammatory bowel disease patients with and without liver disease. Serum and biliary lithocholates and isolithocholates were normal in all patients. Because defective sulfation in the nonhuman primate which allows lithocholate to accumulate in the enterohepatic circulation is thought to be responsible for inducing liver damage and because secondary bile acids are reduced after colectomy and in established liver disease, we examined thae capacity of all patients to sulfate labeled lithocholate. Effective sulfation of lithocholate was demstrated in all groups. Despite the hepatotoxic effects observed in nonhuman primates, we have found no evidence so far to implicate lithocholate as an etiologic factor in inflammatory bowel disease and hepatic dysfunction nor have we detected other potentially hepatotoxic bile acids in these patients.

Effect of a standardized wheat bran preparation on serum lipids in young healthy males.

Feeding of a chemically standardized coarse wheat bran product in a dose of 0.5 g/kg body weight per day over a period of 4 weeks in young healthy male volunteers did cause a significant reduction in total serum cholesterol as well as in total serum triglycerides of 10 and 24%, respectively. Very low density lipoprotein-, high density lipoprotein-, and low density lipoprotein-cholesterol levels tended to diminish during bran feeding. The most marked reduction was observed in the high density lipoprotein- cholesterol fraction. Although the duration of this study was relatively short, it is concluded, that these results could have therapeutic consequences for the dietary management of hyperlipidemia. However, the lowering of high density lipoprotein-cholesterol could also be interpreted as unfavorable since an inverse relationship between high density lipoprotien-cholesterol levels and the occurrence of coronary heart disease has been established.