Sandby Karoline, Krarup Thure, Chabanova Elizaveta, Geiker Nina R W, Magkos Faidon
Department of Nutrition, Exercise and Sports, University of Copenhagen, 1958 Frederiksberg C, Denmark.
Department of Endocrinology, Copenhagen University Hospital Bispebjerg and Frederiksberg, 2400 Copenhagen NV, Denmark.
J Clin Endocrinol Metab. 2025 Apr 22;110(5):e1395-e1403. doi: 10.1210/clinem/dgae572.
Studies in heterogeneous groups of people with respect to sex, body mass index (BMI), and glycemic status (normoglycemia, impaired glucose tolerance, diabetes), indicate no relationship between liver fat accumulation and pancreatic insulin secretion.
This work aimed to better understand the association of liver fat with insulin secretion.
A cross-sectional analysis was conducted of 61 men with abdominal obesity who had high liver fat (HLF, ≥ 5.6% by magnetic resonance spectroscopy, n = 28) or low liver fat (LLF, n = 33), but were balanced on BMI, total body fat, visceral adipose tissue (VAT), and pancreatic fat. A frequently sampled 5-hour oral glucose tolerance test with 11 samples, in conjunction with mathematical modeling, was used to compute indices of insulin sensitivity and insulin secretion (oral minimal model).
Compared to individuals with LLF, those with HLF had significantly greater fasting glucose, insulin, C-peptide, and triglycerides; lower high-density lipoprotein cholesterol; but similar glycated hemoglobin A1c. Areas under the 5-hour curve for glucose, insulin, and C-peptide were greater in the HLF group than the LLF group (by ∼10%, ∼38%, and ∼28%, respectively); fasting and total postprandial insulin secretion rates were approximately 37% and approximately 50% greater, respectively (all P < .05); whereas the insulinogenic index was not different. HLF participants had lower whole-body and hepatic insulin sensitivity, disposition index, and total insulin clearance than LLF participants (all P < .05).
Accumulation of liver fat is associated with increased insulin secretion independently of total adiposity, abdominal fat distribution, and pancreatic fat. Thereby, hyperinsulinemia in fatty liver disease is partly because of insulin hypersecretion and partly because of impaired insulin clearance.
针对不同性别、体重指数（BMI）和血糖状态（正常血糖、糖耐量受损、糖尿病）人群的研究表明，肝脏脂肪堆积与胰腺胰岛素分泌之间没有关联。
本研究旨在更好地了解肝脏脂肪与胰岛素分泌之间的关联。
对61名腹部肥胖男性进行横断面分析，这些男性肝脏脂肪含量高（HLF，磁共振波谱法测定≥5.6%，n = 28）或低（LLF，n = 33），但在BMI、全身脂肪、内脏脂肪组织（VAT）和胰腺脂肪方面保持平衡。采用11个样本的频繁采样5小时口服葡萄糖耐量试验，并结合数学建模，计算胰岛素敏感性和胰岛素分泌指标（口服最小模型）。
与LLF个体相比，HLF个体的空腹血糖、胰岛素、C肽和甘油三酯显著更高；高密度脂蛋白胆固醇更低；但糖化血红蛋白A1c相似。HLF组葡萄糖、胰岛素和C肽的5小时曲线下面积比LLF组更大（分别约大10%、约38%和约28%）；空腹和餐后总胰岛素分泌率分别约高37%和约50%（所有P < 0.05）；而胰岛素生成指数无差异。HLF参与者的全身和肝脏胰岛素敏感性、处置指数和总胰岛素清除率均低于LLF参与者（所有P < 0.05）。
肝脏脂肪堆积与胰岛素分泌增加相关，独立于总体脂、腹部脂肪分布和胰腺脂肪。因此，脂肪肝疾病中的高胰岛素血症部分是由于胰岛素分泌过多，部分是由于胰岛素清除受损。
