Department of Endocrinology & Diabetes, St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia.
Metabolic & Weight Loss Program, Department of Endocrinology & Diabetes, Blacktown-Mt Druitt Hospital, Blacktown, Sydney, New South Wales, Australia.
J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1131-e1139. doi: 10.1210/clinem/dgaa940.
The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown.
This work aimed to determine whether plasma BAs are elevated in human obesity and/or insulin resistance.
This observational study was conducted at an academic research center. Seventy-one adult volunteers formed 4 groups: lean insulin-sensitive (body mass index [BMI] ≤ 25 kg/m2, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] < 2.0, n = 19), overweight/obese nondiabetic who were either insulin sensitive (Obsensitive, BMI > 25 kg/m2, HOMA-IR < 1.5, n = 11) or insulin resistant (Obresistant, BMI > 25 kg/m2, HOMA-IR > 3.0, n = 20), and type 2 diabetes (T2D, n = 21). Main outcome measures included insulin sensitivity by hyperinsulinemic-euglycemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution, and liver density by computed tomography and plasma BA.
In the Obresistant group, glucose infusion rate/fat-free mass (GIR/FFM, an inverse measure of insulin resistance) was significantly lower, and visceral and liver fat higher, compared to lean and Obsensitive individuals, despite similar total adiposity in Obresistant and Obsensitive. Total BA concentrations were higher in Obresistant (2.62 ± 0.333 mmol/L, P = .03) and T2D (3.36 ± 0.582 mmol/L, P < .001) vs Obsensitive (1.16 ± 0.143 mmol/L), but were similar between Obsensitive and lean (2.31 ± 0.329 mmol/L) individuals. Total BAs were positively associated with waist circumference (R = 0.245, P = .041), visceral fat (R = 0.360, P = .002), and fibroblast growth factor 21 (R = 0.341, P = .004) and negatively associated with insulin sensitivity (R = -0.395, P = .001), abdominal subcutaneous fat (R = -0.352, P = .003), adiponectin (R = -0.375, P = .001), and liver fat (Hounsfield units, an inverse marker of liver fat, R = -0.245, P = .04). Conjugated BAs were additionally elevated in T2D individuals (P < .001).
BA concentrations correlated with abdominal, visceral, and liver fat in humans, though an etiological role in insulin resistance remains to be verified.
胆汁酸（BA）对胰岛素抵抗和肥胖的病因机制尚不清楚。
本研究旨在确定人体肥胖和/或胰岛素抵抗患者中血浆 BA 是否升高。
该观察性研究在学术研究中心进行。71 名成年志愿者分为 4 组：瘦胰岛素敏感组（BMI≤25kg/m2，稳态模型评估的胰岛素抵抗[HOMA-IR]＜2.0，n=19）、超重/肥胖非糖尿病胰岛素敏感组（BMI＞25kg/m2，HOMA-IR＜1.5，n=11）、超重/肥胖胰岛素抵抗组（BMI＞25kg/m2，HOMA-IR＞3.0，n=20）和 2 型糖尿病组（T2D，n=21）。主要观察指标包括高胰岛素-正葡萄糖钳夹法测定的胰岛素敏感性、双能 X 线吸收法测定的身体成分、腹部脂肪分布、计算机断层扫描测定的肝密度和血浆 BA。
在胰岛素抵抗组中，与瘦组和胰岛素敏感组相比，葡萄糖输注率/去脂体重（GIR/FFM，胰岛素抵抗的逆测指标）明显降低，内脏和肝脂肪增加，尽管胰岛素抵抗组和胰岛素敏感组的总脂肪量相似。胰岛素抵抗组（2.62±0.333mmol/L，P=0.03）和 T2D 组（3.36±0.582mmol/L，P＜0.001）的总 BA 浓度高于胰岛素敏感组（1.16±0.143mmol/L），但与瘦组（2.31±0.329mmol/L）相似。总 BA 与腰围（R=0.245，P=0.041）、内脏脂肪（R=0.360，P=0.002）和成纤维细胞生长因子 21（R=0.341，P=0.004）呈正相关，与胰岛素敏感性（R=-0.395，P=0.001）、腹部皮下脂肪（R=-0.352，P=0.003）、脂联素（R=-0.375，P=0.001）和肝脂肪（Hounsfield 单位，肝脂肪的逆测标志物，R=-0.245，P=0.04）呈负相关。T2D 患者的结合型 BA 也升高（P＜0.001）。
BA 浓度与人体腹部、内脏和肝脂肪相关，但在胰岛素抵抗中的病因作用仍有待验证。
