Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes.
Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes.
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DOI：
10.2337/dc15-1876
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发表时间：
2016-04
期刊：
影响因子：
16.2
通讯作者：
Cusi K
中科院分区：
文献类型：
--
作者：
Lomonaco R;Bril F;Portillo-Sanchez P;Ortiz-Lopez C;Orsak B;Biernacki D;Lo M;Suman A;Weber MH;Cusi K
非酒精性脂肪性肝炎（NASH）在肥胖患者中越来越常见。然而，其对2型糖尿病（T2DM）患者的代谢影响尚不清楚。我们研究了154例肥胖患者，分为四组：1)对照组（无T2DM或NAFLD）， 2)无NAFLD的T2DM， 3)孤立性脂肪变性T2DM， 4)合并NASH的T2DM。我们通过质子MRS （1H-MRS）评估肝内甘油三酯，并在口服葡萄糖耐量试验和葡萄糖周转测量的正糖-高胰岛素钳中评估胰岛素分泌/抵抗。各组间在性别、体重指数或总体脂方面均无显著差异。随着T2DM的出现和肝脂肪变性的发展，代谢参数逐渐恶化，NASH患者出现更严重的高胰岛素血症、胰岛素抵抗和血脂异常（高甘油三酯血症和低HDL胆固醇）（P < 0.001）。与孤立性脂肪变性相比，NASH与更多功能失调和胰岛素抵抗的脂肪组织相关（胰岛素抑制血浆FFA[33±3比48±6%]或脂肪组织胰岛素抵抗指数[9.8±1.0比5.9±0.8 mmol/L⋅µIU/mL]， P均< 0.03）。此外，胰岛素抑制血浆FFA与肝脏脂肪变性（r = -0.62, P < 0.001）和脂肪性肝炎的严重程度（rs = - 0.52, P < 0.001）密切相关。与其他组相比，T2DM和NASH患者的肝脏胰岛素敏感性也更明显受损，无论是空腹还是胰岛素水平在生理范围内（10至140 μ IU/mL）升高。在肥胖T2DM患者中，与没有NAFLD的患者相比，NAFLD的存在与更严重的高胰岛素血症、血脂异常和脂肪组织/肝脏胰岛素抵抗相关。与NAFLD相关的不利代谢特征应提示早期识别和治疗该人群的策略。
Nonalcoholic steatohepatitis (NASH) is increasingly common in obese patients. However, its metabolic consequences in patients with type 2 diabetes mellitus (T2DM) are unknown. We studied 154 obese patients divided in four groups: 1) control (no T2DM or NAFLD), 2) T2DM without NAFLD, 3) T2DM with isolated steatosis, and 4) T2DM with NASH. We evaluated intrahepatic triglycerides by proton MRS (1H-MRS) and assessed insulin secretion/resistance during an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp with glucose turnover measurements. No significant differences among groups were observed in sex, BMI, or total body fat. Metabolic parameters worsened progressively with the presence of T2DM and the development of hepatic steatosis, with worse hyperinsulinemia, insulin resistance, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol) in those with NASH (P < 0.001). Compared with isolated steatosis, NASH was associated with more dysfunctional and insulin-resistant adipose tissue (either as insulin suppression of plasma FFA [33 ± 3 vs. 48 ± 6%] or adipose tissue insulin resistance index [9.8 ± 1.0 vs. 5.9 ± 0.8 mmol/L ⋅ µIU/mL]; both P < 0.03). Furthermore, insulin suppression of plasma FFA correlated well with hepatic steatosis (r = –0.62; P < 0.001) and severity of steatohepatitis (rs = −0.52; P < 0.001). Hepatic insulin sensitivity was also more significantly impaired among patients with T2DM and NASH, both fasting and with increasing insulin levels within the physiological range (10 to 140 µIU/mL), compared with other groups. In obese patients with T2DM, the presence of NAFLD is associated with more severe hyperinsulinemia, dyslipidemia, and adipose tissue/hepatic insulin resistance compared with patients without NAFLD. The unfavorable metabolic profile linked to NAFLD should prompt strategies to identify and treat this population early on.
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影响因子：
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作者：
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