Maghsoodi Negar, Shaw Nicholas, Cross Gemma F, Alaghband-Zadeh Jamshid, Wierzbicki Anthony S, Pinkney Jonathan, Millward Ann, Vincent Royce P
Department of Clinical Biochemistry (Viapath), King's College Hospital, London, UK; Department of Metabolic Medicine/Chemical Pathology, Guy's and St Thomas' Hospitals, London, UK.
NIHR CRN SWP, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Clin Biochem. 2019 Feb;64:12-17. doi: 10.1016/j.clinbiochem.2018.11.016. Epub 2018 Nov 30.
Bile acids (BAs) are known mediators of glucose metabolism that are altered in type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). We hypothesised that post-prandial BA fractions are changed in women with Insulin resistance (IR) after recovery from GDM using homeostatic model assessment (HOMA-IR).
45 women median age 44(31-47) with previous GDM, including 20 with HOMA-IR >2.8 and 25 age-matched controls with HOMA-IR ≤ 2.8 were studied. After an overnight fast, all underwent an oral glucose tolerance test. Blood samples were collected at baseline and every 30 min for 120 min and analysed for glucose on automated platform and for total BAs, their conjugates and fractions using liquid-chromatography tandem mass-spectrometry. Baseline samples were analysed for insulin on automated platform. Delta (Δ) change (difference between baseline and maximal post-prandial response) were calculated. Data is presented as median (IQR).
Fasting primary and unconjugated BAs were higher in women with HOMA-IR >2.8 vs. those with HOMA-IR ≤ 2.8 [0.24 (0.16-0.33) vs 0.06(0.04-0.22) μmol/L and 0.91(0.56-1.84) μmol/L vs. 0.69(0.32-0.89) μmol/L respectively. ∆ taurine-conjugated BAs was higher in women with HOMA-IR ≤ 2.8 than those with HOMA-IR > 2.8 [0.33(0.20-0.54) vs 0.23(0.13-0.34) μmol/L]. Fasting glucose and non-12α-hydroxylated BAs were negatively correlated in women with HOMA-IR >2.8 (all p < 0.05).
Following GDM, individuals with HOMA-IR >2.8 have altered conjugated and non-12α-hydroxylated fractions of BAs. It remains to be elucidated if the altered BA metabolism is a contributing factor to the pathogenesis or a consequence of GDM.
胆汁酸（BAs）是已知的葡萄糖代谢介质，在2型糖尿病（T2DM）和妊娠期糖尿病（GDM）中会发生改变。我们假设，使用稳态模型评估（HOMA-IR），GDM恢复后的胰岛素抵抗（IR）女性餐后胆汁酸组分发生了变化。
研究了45名既往有GDM的女性，年龄中位数为44岁（31 - 47岁），其中20名HOMA-IR > 2.8，25名年龄匹配的对照者HOMA-IR≤2.8。过夜禁食后，所有人都接受了口服葡萄糖耐量试验。在基线和之后每30分钟采集血样，共采集120分钟，在自动平台上分析葡萄糖，并使用液相色谱串联质谱法分析总胆汁酸、其共轭物和组分。在自动平台上分析基线样本中的胰岛素。计算Δ（delta）变化（基线与餐后最大反应之间的差异）。数据以中位数（IQR）表示。
HOMA-IR > 2.8的女性空腹初级和未结合胆汁酸高于HOMA-IR≤2.8的女性[分别为0.24（0.16 - 0.33）μmol/L对0.06（0.04 - 0.22）μmol/L和0.91（0.56 - 1.84）μmol/L对0.69（0.32 - 0.89）μmol/L]。HOMA-IR≤2.8的女性Δ牛磺酸共轭胆汁酸高于HOMA-IR > 2.8的女性[0.33（0.20 - 0.54）μmol/L对0.23（0.13 - 0.34）μmol/L]。HOMA-IR > 2.8的女性空腹血糖与非12α-羟基化胆汁酸呈负相关（所有p < 0.05）。
GDM后，HOMA-IR > 2.8的个体胆汁酸的共轭和非12α-羟基化组分发生了改变。胆汁酸代谢改变是GDM发病机制的一个促成因素还是其结果，仍有待阐明。
