Portillo Sanchez Paola, Bril Fernando, Maximos Maryann, Lomonaco Romina, Biernacki Diane, Orsak Beverly, Subbarayan Sreevidya, Webb Amy, Hecht Joan, Cusi Kenneth
1Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL;
2Division of Endocrinology, Diabetes and Metabolism Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, FL;
J Clin Endocrinol Metab. 2014 Oct 10;100(5). doi: 10.1210/jc.2014-2739.
NAFLD, and its more severe form with steatohepatitis (NASH), are common in patients with T2DM. However, they are usually believed to affect largely those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD (by the gold-standard liver magnetic resonance and spectroscopy or (1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile.
We recruited 103 patients with T2DM and normal plasma aminotransferases (age: 60±8 years, BMI: 33±5 kg/m(2), A1c: 7.6±1.3%). We measured: i) liver triglyceride content by (1)H-MRS; ii) systemic insulin sensitivity (HOMA-IR), and iii) adipose tissue insulin resistance (IR), both fasting (as the adipose tissue IR index: fasting plasma FFA x insulin) and during an OGTT (as the suppression of FFA).
The prevalence of NAFLD and NASH were much higher than expected (76% and 56%, respectively). The prevalence of NAFLD was higher in obese compared to non-obese patients, as well as with increasing BMI (p=0.03 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (p<0.01). Compared to non-obese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle), and particularly, adipose tissue (fasting/postprandial) insulin resistance (all p<0.01).
The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of severe liver disease (NASH). Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.
非酒精性脂肪性肝病(NAFLD)及其更严重的伴有脂肪性肝炎的形式(NASH)在2型糖尿病(T2DM)患者中很常见。然而,通常认为它们主要影响转氨酶升高的患者。本研究的目的是确定T2DM且转氨酶正常患者中NAFLD的患病率(采用金标准肝脏磁共振成像和波谱分析或氢质子磁共振波谱分析(1H-MRS)),并描述其代谢特征。
我们招募了103例T2DM且血浆转氨酶正常的患者(年龄:60±8岁,体重指数(BMI):33±5kg/m²,糖化血红蛋白(A1c):7.6±1.3%)。我们测量了:i)通过1H-MRS测量肝脏甘油三酯含量;ii)全身胰岛素敏感性(稳态模型评估胰岛素抵抗指数(HOMA-IR)),以及iii)脂肪组织胰岛素抵抗(IR),包括空腹时(作为脂肪组织IR指数:空腹血浆游离脂肪酸(FFA)×胰岛素)和口服葡萄糖耐量试验(OGTT)期间(作为FFA的抑制情况)。
NAFLD和NASH的患病率远高于预期(分别为76%和56%)。与非肥胖患者相比,肥胖患者中NAFLD的患病率更高,且随着BMI增加患病率升高(趋势p=0.03)。较高的血浆A1c与NAFLD患病率更高及肝脏甘油三酯蓄积更严重相关(p<0.01)。与无NAFLD的非肥胖患者相比,NAFLD患者存在严重的全身(肝脏/肌肉),尤其是脂肪组织(空腹/餐后)胰岛素抵抗(所有p<0.01)。
在超重/肥胖且转氨酶正常的T2DM患者中,NAFLD的患病率远高于先前的认识。此外,许多患者有发生严重肝病(NASH)的风险增加。医生对T2DM患者进行NAFLD/NASH筛查的阈值应更低。