Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a

• Published in: Journal of endocrinological investigation Vol. 45; no. 6; pp. 1227 - 1234
• Main Authors: Simons, P. I. H. G., Valkenburg, O., Telgenkamp, I., van der Waaij, K. M., de Groot, D. M., Veeraiah, P., Bons, J. A. P., Derks, T. G. J., Schalkwijk, C. G., Schrauwen-Hinderling, V. B., Stehouwer, C. D. A., Brouwers, M. C. G. J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2022; Springer Nature B.V
• Subjects: Endocrinology; Fatty acids; Globulins; Glucose-6-phosphatase; Glycogen; Internal Medicine; Lipids; Lipogenesis; Magnetic resonance spectroscopy; Medicine; Medicine & Public Health; Metabolic Diseases; Original; Original Article; Sex hormones; Statistical analysis; Storage diseases; Intrahepatic lipid content; Sex hormone-binding globulin; Glycogen storage disease type 1a; De novo lipogenesis
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-022-01753-2

Purpose
De novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained uncertain. We, therefore, studied individuals with glycogen storage disease type 1a (GSD1a), who are characterized by a genetic defect in glucose-6-phosphatase resulting in increased rates of de novo lipogenesis, to assess the downstream effect on serum SHBG levels.
Methods
A case–control study comparing serum SHBG levels in patients with GSD1a (
n
 = 10) and controls matched for age, sex, and BMI (
n
 = 10). Intrahepatic lipid content and saturated fatty acid fraction were quantified by proton magnetic resonance spectroscopy.
Results
Serum SHBG levels were statistically significantly lower in patients with GSD1a compared to the controls (
p
 = 0.041), while intrahepatic lipid content and intrahepatic saturated fatty acid fraction—a marker of de novo lipogenesis—were significantly higher in patients with GSD1a (
p
 = 0.001 and
p
 = 0.019, respectively). In addition, there was a statistically significant, inverse association of intrahepatic lipid content and saturated fatty acid fraction with serum SHBG levels in patients and controls combined (
β
: − 0.28, 95% CI: − 0.47;− 0.09 and
β
: − 0.02, 95% CI: − 0.04;− 0.01, respectively).
Conclusion
Patients with GSD1a, who are characterized by genetically determined higher rates of de novo lipogenesis, have lower serum SHBG levels than controls.