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.