The bile acid composition in duodenal bile was analysed in 22 diet-treated and 11 insulin-treated middle-aged patients with diabetes mellitus and in 20 normoglycaemic controls. In 10 subjects with diabetes mellitus the bile acid profile in urine was also investigated. In the non-insulin-dependent diabetic patients the percentage of cholic acid was reduced and that of deoxycholic acid increased. As a highly significant finding there was a three-fold increase of the percentage of 12-ketolithocholic acid in duodenal bile in non-insulin-dependent diabetics, whereas the bile acid composition in insulin-dependent diabetics was similar to that in a control group. The percentage of 12-ketolithocholic acid in duodenal bile was positively correlated to the percentage in urine. In nine of the subjects studied, 12-ketolithocholic acid was the major individual bile acid in urine. It constituted 36.3 +/- 4.4% of the bile acids analysed and the excretion was 6.1 +/- 2.3 mumol 24 h-1. Together with 3 alpha, 12 beta-dihydroxy-5 beta-cholanoic acid it was predominantly present in the glycine conjugate fraction, whereas in bile its conjugation was similar to that of the other bile acids. The results may reflect an increased formation of secondary bile acids from cholic acid combined with a metabolic disturbance in non-insulin-dependent diabetics affecting the oxidoreduction of bile acids at C-12.

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Previous reports have demonstrated that noninsulin-dependent diabetes mellitus often is associated with hypertriglyceridemia linked to hyperinsulinemia and enhanced cholesterogenesis. Studies with single meals have indicated that rice as compared to potato results in a less pronounced blood glucose and insulin response. These findings initiated the current study in which eight middle-aged patients with adult-onset, noninsulin-dependent diabetes were fed a standardized diet with potato or rice as the major carbohydrate source. Blood glucose control was the same during both dietary periods. When rice was the major carbohydrate source the very low density lipoprotein triglycerides decreased in six patients and the formation of bile acid, especially that of cholic acid, showed a significant drop. The results further underline a link between lipoprotein and bile acid metabolism.

Serum lipids and the kinetics of the two primary bile acids, cholic acid (C) and chenodeoxycholic acid (CD), were studied in six normolipidaemic subjects before and during treatment with cholestyramine (12 g/day). After therapy, total serum and low-density lipoprotein cholesterol decreased by about 15%. These changes were accompanied by significant increases in the pool size, synthesis, and fractional turnover rate (FTR) of C and in the synthesis and FTR of CD. In spite of the enhanced formation of CD, the CD pool size decreased in all subjects, on average by more than 50%. The combined pool size of C and CD remained constant, but the mean total bile acid formation increased by a factor of 2.9. It is suggested that the different responses of C and CD, with an augmented contribution of C to the total amounts of bile acid produced, reflect an enhanced hepatic cholesterogenesis and, possibly, that C and CD to some extent originate from different cholesterol precursor pools.

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