Strong association between insulin resistance in liver and skeletal muscle in non-diabetic subjects

Objective: To examine the association between insulin resistance in skeletal muscle and liver in non-diabetic subjects. Research design and methods: A total of 182 Mexican American subjects without Type 2 diabetes underwent an oral glucose tolerance test and euglycaemic-hyperinsulinaemic clamp performed with ³[H]glucose. Insulin sensitivity in skeletal muscle was measured as the insulin-stimulated rate of total glucose disposal during the insulin clamp divided by steady-state plasma insulin concentration (TGD/SSPI). Hepatic insulin resistance was measured as the product of basal hepatic glucose production and fasting plasma insulin concentration (HGP × FPI). Results: Hepatic insulin resistance was strongly correlated (r = 0.68, P < 0.0001) with skeletal muscle insulin resistance. Thirty-eight per cent of subjects had increased insulin resistance in both liver and skeletal muscle, while 39% were insulin sensitive in both skeletal muscle and liver. Twenty-three per cent of subjects were discordant for muscle and hepatic insulin resistance (P < 0.0001). Subjects with increased skeletal muscle insulin resistance had a higher 2-h plasma glucose concentration, greater incremental area under the plasma glucose concentration curve, lower fasting plasma insulin concentration and lower rate of basal hepatic glucose production compared with subjects with increased insulin resistance in liver. Conclusion: In non-diabetic subjects, insulin resistance in skeletal muscle is an important determinant of the fasting and 2-h plasma glucose concentrations and strongly correlates with hepatic insulin resistance.