Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Diabetes Care. 2012 Apr;35(4):873-8. doi: 10.2337/dc11-1849. Epub 2012 Feb 28.
Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population.
We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[(3)H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR(i)= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR(i)= fasting FFA × FPI).
Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001).
Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD.
糖尿病前期和 2 型糖尿病（T2DM）被认为在非酒精性脂肪性肝病（NAFLD）患者中较为常见，并与更差的代谢特征相关。然而，此前尚无研究对这一人群进行系统筛查。
我们研究了 118 例 NAFLD 患者中糖尿病前期和 T2DM 的患病率及其对代谢的影响。对照组由 20 例年龄、性别和肥胖程度相匹配、无 NAFLD 的个体组成。我们测量了 1）口服葡萄糖耐量试验期间的血浆葡萄糖、胰岛素和游离脂肪酸（FFA）浓度；2）磁共振波谱（MRS）测定的肝脂肪含量；3）血糖钳夹试验（3-[3H]葡萄糖）评估的肝和肌肉胰岛素敏感性；4）肝脏水平的胰岛素抵抗指数（HIR（i）=内源性葡萄糖生成×空腹血浆胰岛素[FPI]）和脂肪组织水平的胰岛素抵抗指数（Adipo-IR（i）=空腹 FFA×FPI）。
糖尿病前期和 T2DM 在患者中的发生率分别为 85%和 30%（P＜0.0001），且均未意识到存在葡萄糖代谢异常。NAFLD 患者的脂肪组织、肝脏和肌肉均存在胰岛素抵抗（均 P＜0.01-0.001）。无论是否患有糖尿病前期或 T2DM，NAFLD 患者的肌肉和肝脏胰岛素敏感性均受损，程度相当。仅 T2DM 患者的脂肪组织胰岛素抵抗恶化，且与肌肉（r=0.34；P＜0.001）和肝脏（r=0.57；P＜0.0001）胰岛素抵抗以及 MRS 评估的肝脂肪变性（r=0.35；P＜0.0001）严重程度相关。
NAFLD 患者可能受益于 T2DM 的早期筛查，因为异常葡萄糖代谢的患病率远高于此前的认识。无论葡萄糖耐量状态如何，严重的胰岛素抵抗都很常见。在 T2DM 患者中，脂肪组织胰岛素抵抗似乎在 NAFLD 的严重程度中起主要作用。
