Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes

Abstract

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 [6,6-2 H2]glucose and 1 H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 Ϯ 0.6 and 3.2 Ϯ 0.8 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) similar to OFF (5.3 Ϯ 0.4 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) compared with NOR (8.5 Ϯ 0.5 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.001). Soleus IMCL content was increased in T1DM (112 Ϯ 15 AU), T2DM (108 Ϯ 10 AU) and OFF (82 Ϯ 13 AU) compared with NOR (52 Ϯ 7 AU, P Ͻ 0.05) and the result was inversely proportional to the MCR (R 2 ϭ 0.27, P Ͻ 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R 2 ϭ 0.57, P Ͻ 0.001). Fasting plasma adiponectin was reduced in T2DM (7 Ϯ 1 g/ml, P ϭ 0.01) and OFF (11 Ϯ 1 g/ml, P ϭ 0.03) but not in T1DM (25 Ϯ 6 g/ml), whose plasma level was increased with respect to both OFF (P ϭ 0.03) and NOR (16 Ϯ 2 g/ml, P ϭ 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. intramyocellular triglyceride content; leptin; magnetic resonance spectroscopy

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

“…Then, we performed linear regression analysis in the entire study population (r 2 =0.21, p<0.0003) and separately in the lean individuals (body fat <30%; r 2 =0.42, p<0.01) and in the overweight individuals (body fat >30%; r 2 =0.11, p=0.11). The lack of association between soleus IMCL content and insulin sensitivity in the overweight/obese individuals was similar to a previous report by us on patients with type 2 diabetes [15] and patients with myotonic dystrophy type 1 [19].…”

“…α-TNFR-2 was measured with an enzyme immunoassay following the manufacturer's (Immunotech; Beckman Coulter, Marseille, France) recommendations (intra-and interassay CV <3% and 5%, respectively) as previously described [10,14]. Plasma adiponectin was measured using a commercially available radioimmunoassay kit (Linco Research, St Charles, MO, USA) as previously described [15]. The intra-assay and interassay CVs for adiponectin were 4±1% and 14±3%, respectively.…”

“…Serum urea nitrogen was measured in the postabsorptive and hyperinsulinaemic conditions using an enzymatic method on an Hitachi 747 [10]. The d 2 -glucose enrichment was measured by GCMS as previously described [3,10,14,15].…”

Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications

“…The control group had similar mean age (40.1±10.6 years), BMI (24.0± 3.3 kg/m 2 ) and sex distribution (12 males and 13 females) as the two diabetic groups (Table 1). However, the only purpose of including healthy controls was to confirm that levels of ADPN were increased in type 1 diabetes (controls vs all patients with type 1 diabetes, 13.5±4.7 vs. 23.7± 14.3 mg/l; p<0.0001) as previously reported [22][23][24], and therefore no further statistical analysis was performed in this group.…”

“…Clinically, lean patients with type 2 diabetes suffering from diabetic retinopathy (proliferative as well as non-proliferative) are reported to have lower levels of ADPN than matched patients without retinopathy [19]. On the other hand, lean as well as obese type 2 diabetic patients have normal to subnormal ADPN levels [19][20][21], whereas patients with type 1 diabetes have supranormal levels [22][23][24]. At the time of writing, there is sparse information on the association between serum ADPN and the presence of micro-and macrovascular complications in type 1 diabetes.…”