Kotronen Anna, Juurinen Leena, Tiikkainen Mirja, Vehkavaara Satu, Yki-Järvinen Hannele
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland.
Gastroenterology. 2008 Jul;135(1):122-30. doi: 10.1053/j.gastro.2008.03.021. Epub 2008 Mar 21.
BACKGROUND & AIMS: Liver fat is increased in type 2 diabetes. We determined whether it is associated with impaired insulin clearance and to what extent insulin resistance, impaired insulin clearance, or secretion contribute to fasting hyperinsulinemia. We also examined whether insulin suppression of serum free fatty acid (FFA) correlates with liver fat.
We compared 68 type 2 diabetic patients and age-, gender-, and body mass index (BMI)-matched nondiabetic subjects. Liver fat was determined by (1)H-MRS, body composition by magnetic resonance imaging, and insulin clearance and action on hepatic glucose production (HGP), glucose uptake, and serum FFA by the euglycemic insulin clamp technique (insulin 0.3 mU/kg x min) combined with infusion of [3-(3)H]glucose.
Liver fat was 54% higher and insulin clearance 24% lower in type 2 diabetic patients than nondiabetic subjects. The percent suppression of both HGP and serum FFA by insulin were comparable, but serum insulin concentrations were significantly higher (34 mU/L [interquartile range, 30-39 mU/L] vs 25 mU/L [interquartile range, 22-30 mU/L]; P < .0001) in the type 2 diabetic than the nondiabetic subjects. When this difference was taken into account, both hepatic and adipose tissue insulin sensitivity were impaired in the type 2 diabetic subjects. Liver fat correlated with insulin clearance (r = -0.41; P = .001), and hepatic (r = 0.46; P = .0001) and adipose tissue (r = 0.55; P < .0001) insulin sensitivity. Hepatic but not peripheral insulin sensitivity was independently associated with liver fat content. Insulin clearance and secretion were independent determinants of fasting serum insulin.
We conclude that increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance characterize type 2 diabetic patients.
2型糖尿病患者肝脏脂肪增加。我们确定其是否与胰岛素清除受损相关，以及胰岛素抵抗、胰岛素清除受损或分泌在多大程度上导致空腹高胰岛素血症。我们还研究了胰岛素对血清游离脂肪酸（FFA）的抑制作用是否与肝脏脂肪相关。
我们比较了68例2型糖尿病患者以及年龄、性别和体重指数（BMI）相匹配的非糖尿病受试者。通过氢质子磁共振波谱（1H-MRS）测定肝脏脂肪，通过磁共振成像测定身体成分，并通过正常血糖胰岛素钳夹技术（胰岛素0.3 mU/kg×min）结合输注[3-(3)H]葡萄糖来测定胰岛素清除率以及胰岛素对肝脏葡萄糖生成（HGP）、葡萄糖摄取和血清FFA的作用。
2型糖尿病患者的肝脏脂肪比非糖尿病受试者高54%，胰岛素清除率低24%。胰岛素对HGP和血清FFA的抑制百分比相当，但2型糖尿病患者的血清胰岛素浓度显著高于非糖尿病受试者（34 mU/L[四分位间距，30 - 39 mU/L]对25 mU/L[四分位间距，22 - 30 mU/L]；P <.0001）。考虑到这一差异后，2型糖尿病患者的肝脏和脂肪组织胰岛素敏感性均受损。肝脏脂肪与胰岛素清除率相关（r = -0.41；P =.001），与肝脏（r = 0.46；P =.0001）和脂肪组织（r = 0.55；P <.0001）胰岛素敏感性相关。肝脏而非外周胰岛素敏感性与肝脏脂肪含量独立相关。胰岛素清除率和分泌是空腹血清胰岛素的独立决定因素。
我们得出结论，肝脏脂肪增加、胰岛素清除受损以及肝脏和脂肪组织胰岛素抵抗是2型糖尿病患者的特征。
