Perseghin Gianluca, Lattuada Guido, Danna Massimo, Sereni Lucia Piceni, Maffi Paola, De Cobelli Francesco, Battezzati Alberto, Secchi Antonio, Del Maschio Alessandro, Luzi Livio
Section of Nutrition/Metabolism, Università Vita e Salute San Raffaele IRCCS H San Raffaele, 20132 Milan, Italy.
Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1174-81. doi: 10.1152/ajpendo.00279.2003. Epub 2003 Aug 21.
Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 +/- 0.6 and 3.2 +/- 0.8 ml x kg(-1) min(-1)) similar to OFF (5.3 +/- 0.4 ml x kg(-1) x min(-1)) compared with NOR (8.5 +/- 0.5 ml x kg(-1) min(-1), P < 0.001). Soleus IMCL content was increased in T1DM (112 +/- 15 AU), T2DM (108 +/- 10 AU) and OFF (82 +/- 13 AU) compared with NOR (52 +/- 7 AU, P < 0.05) and the result was inversely proportional to the MCR (R2 = 0.27, P < 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R2 = 0.57, P < 0.001). Fasting plasma adiponectin was reduced in T2DM (7 +/- 1 microg/ml, P = 0.01) and OFF (11 +/- 1 microg/ml, P = 0.03) but not in T1DM (25 +/- 6 microg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 +/- 2 microg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.
胰岛素抵抗是2型糖尿病（T2DM）的关键致病因素；相比之下，在1型糖尿病（T1DM）中，它被认为是一种继发性改变。细胞内脂质（IMCL）含量增加和血浆脂联素降低被认为是T2DM中胰岛素抵抗的致病事件。本研究旨在评估IMCL含量和血浆脂联素是否也与T1DM中胰岛素抵抗的严重程度相关。我们研究了18例T1DM患者、7例年龄较大且超重/肥胖的T2DM患者、15例T2DM患者的非糖尿病胰岛素抵抗后代（OFF）以及15例健康个体（NOR）作为适当的对照组，通过正常血糖高胰岛素钳夹技术结合[6,6-2H2]葡萄糖输注和小腿肌肉的1H磁共振波谱分析，使其人体测量特征与T1DM患者相匹配。T1DM和T2DM患者的胰岛素刺激葡萄糖代谢清除率降低（MCR：5.1±0.6和3.2±0.8 ml·kg-1·min-1），与OFF（5.3±0.4 ml·kg-1·min-1）相似，而与NOR（8.5±0.5 ml·kg-1·min-1）相比差异有统计学意义（P<0.001）。与NOR（52±7 AU）相比，T1DM（112±15 AU）、T2DM（108±10 AU）和OFF（82±13 AU）的比目鱼肌IMCL含量增加（P<0.05），且结果与MCR呈负相关（R2 = 0.27，P<0.001）；仅在T1DM中发现IMCL含量与糖化血红蛋白A1c之间存在关联（R2 = 0.57，P<0.001）。T2DM（7±1 μg/ml，P = 0.01）和OFF（11±1 μg/ml，P = 0.03）的空腹血浆脂联素降低，但T1DM（25±6 μg/ml）未降低，其血浆水平相对于OFF（P = 0.03）和NOR（16±
