Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

• Keywords
• Alzheimer’s disease, GC-MS, differential diagnostics, multivariate statistics, steroidome, type 2 diabetes mellitus,
• MeSH
• Alzheimer Disease * metabolism   MeSH
• Androstenedione MeSH
• Diabetes Mellitus, Type 2 * diagnosis   epidemiology   MeSH
• Comorbidity MeSH
• Humans MeSH
• Steroids metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Androstenedione MeSH
• Steroids MeSH

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.

• MeSH
• 17-alpha-Hydroxypregnenolone blood   chemistry   MeSH
• 17-alpha-Hydroxyprogesterone blood   chemistry   MeSH
• Alanine Transaminase blood   MeSH
• Aspartate Aminotransferases blood   MeSH
• Adult MeSH
• Gestational Age MeSH
• Hydrocortisone blood   chemistry   MeSH
• Cholestasis, Intrahepatic diagnosis   metabolism   pathology   MeSH
• Liver Function Tests MeSH
• Pregnancy Complications diagnosis   metabolism   pathology   MeSH
• Humans MeSH
• Dorsal Raphe Nucleus MeSH
• Area Under Curve MeSH
• Gas Chromatography-Mass Spectrometry MeSH
• Radioimmunoassay MeSH
• ROC Curve MeSH
• Steroids blood   chemistry   metabolism   MeSH
• Pregnancy MeSH
• Bile Acids and Salts analysis   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 17-alpha-Hydroxypregnenolone MeSH
• 17-alpha-Hydroxyprogesterone MeSH
• Alanine Transaminase MeSH
• Aspartate Aminotransferases MeSH
• Hydrocortisone MeSH
• Steroids MeSH
• Bile Acids and Salts MeSH