Axe Endocrinologie et Néphrologie, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada.
Département de Médecine, Faculté de Médecine, Université Laval, Québec, Quebec, Canada.
Am J Physiol Endocrinol Metab. 2024 May 1;326(5):E616-E625. doi: 10.1152/ajpendo.00294.2023. Epub 2024 Mar 13.
Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic β-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45-65) vs. 57 (44-63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group ( < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic β-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI ( < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase β-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D. Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic β-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes.
代谢相关性脂肪性肝病（MAFLD）已被确定为 2 型糖尿病（T2D）的发病危险因素，但潜在的餐后机制仍不清楚。我们比较了 MAFLD 患者和非 MAFLD 患者口服葡萄糖耐量试验（OGTT）后的葡萄糖代谢、胰岛素抵抗、胰岛素分泌和胰岛素清除率。我们纳入了 50 名 BMI 在 25 至 40kg/m2 之间且存在 1 种以上代谢异常的个体：空腹甘油三酯或胰岛素升高、血浆葡萄糖 5.5-6.9mmol/L 或糖化血红蛋白 5.7-5.9%。参与者根据 MAFLD 状态分组，定义为 MRI 上肝脂肪分数（HFF）≥5%。我们使用口服最小模型对频繁采样的 3 小时 75g-OGTT 进行分析，以估计胰岛素敏感性、胰岛素分泌和胰岛β细胞功能。50%的参与者患有 MAFLD。两组间的中位年龄（IQR）[57（45-65）比 57（44-63）岁]和性别（60%比 56%为女性）相当。OGTT 后血糖浓度在两组间无差异，而 MAFLD 组 OGTT 后胰岛素浓度较高（<0.03）。MAFLD 患者的胰岛素清除率、胰岛素敏感性和第一时相胰岛β细胞功能较低。在所有个体中，在校正年龄、性别和 BMI 后，胰岛素增量 AUC 增加和胰岛素清除率降低与 HFF 相关（<0.02）。在存在代谢异常的个体中，MAFLD 的特征主要是 OGTT 后高胰岛素血症和胰岛素清除率降低，同时表现出较低的第一时相β细胞功能和胰岛素敏感性。这表明 MAFLD 与胰岛素代谢受损有关，这种受损可能早于 T2D 发生。使用口服葡萄糖耐量试验，我们发现 MAFLD 患者存在高胰岛素血症、胰岛素敏感性降低、胰岛素清除率降低和第一时相胰岛β细胞功能降低。这可以解释该人群 2 型糖尿病发病风险增加的部分原因。这些数据还突出了高胰岛素血症和胰岛素清除受损在 MAFLD 进展为 2 型糖尿病中的作用。
