Objective: High levels of bile acids (BA) stimulate insulin release and therefore decrease serum
glucose levels; vice versa, high glucose levels can upregulate BA synthesis from cholesterol by stimulating
the enzyme Cyp7a1. Type 1 diabetes (T1D) leads to hyperglycaemia due to lack of endogenous
insulin. We hypothesized that in adolescents with T1D BA levels vary co-ordinately
with HbA1c, a long time marker of glycaemic control.
Design: Concentrations of glucose, HbA1c, and serum total BA (tBA) were measured in 86 fasted
adolescents with T1D (age 11 – 20 years) under insulin therapy. Patients were divided
into three groups: Group 1: HbA1c < 59 mmol/mol; n = 21; Group 2: HbA1c 59 – 75 mmol/mol;
n = 49 and Group 3: high HbA1c > 75 mmol/mol; n = 16. TBA values were compared to
healthy adolescents (n = 88). In 10 µl of serum a BA profile was determined by high-performance
liquid chromatography – mass spectrometry including 15 unconjugated and taurine (T)-
or glycine (G)-conjugated BA.
Results: In Group 1 mean tBA values lay below reference values (3.1 µmol/l ± 2.4 µmol/l vs.
3.7 µmol/l ± 1.9 µmol/l). In Group 2 mean tBA values were significantly lower compared
to controls with 2.3 µmol/l ± 1.8 µmol/l (p < 0.05). Group 3 comprised patients who
showed highest tBA concentration (5.5 µmol/l ± 10.1 µmol/l). BA profile showed a significant
decline in G-conjugates of Group 1 and Group 2, respectively, compared to controls
(1.6 µmol/l ± 1.8 µmol/l and 1.3 µmol/l ± 1.2 µmol/l vs. 2.5 µmol/l ± 1.4 µmol/l;
p < 0.05). T-conjugates were significantly increased in Group 3 (0.8 µmol/l ± 2.4
µmol/l vs. 0.4 µmol/l ± 0.4 µmol/l; p ≤0.001).
Conclusion: This study shows that insulin therapy in T1D may influence the concentration of serum
tBA. Adequate insulin therapy, as judged by HbA1c values, is associated with normal
or low tBA levels, whereas chronically high HbA1c levels are associated with high
tBA levels. Hence, tBA may act as a new marker for glycaemic control.
