Glucose clearance is higher in arm than leg muscle in type 2 diabetes

Skeletal muscle, which makes up ∼40% of the body mass, is the major tissue involved in glucose metabolism and an important site of insulin resistance in obesity and type 2 diabetes (DeFronzo et al. 1992). Glucose transport and uptake are diminished in skeletal muscle in type 2 diabetes (Dela et al. 1995; Zierath et al. 1996). The reduced muscle glucose uptake has been estimated to account for ∼55% (Basu et al. 2000) or even up to ∼100% (DeFronzo et al. 1992) of the decrease in whole body glucose disappearance during a clamp compared to healthy individuals. These numbers are, however, calculated from leg muscle glucose uptake and extrapolated to the whole muscle mass, based on the assumption that glucose uptake is similar in upper and lower body muscles. The possibility exists that there is a difference in glucose uptake between muscles, as for example glucose uptake capacity is larger in red oxidative than in white glycolytic muscle fibres (Lillioja et al. 1987; Goodyear et al. 1991). Although differences in fibre type composition may be larger in other species than man, they could contribute to a difference in insulin sensitivity between arm and leg muscles (Johnson et al. 1973; Schantz et al. 1983). Moreover, the preferential substrate oxidation differs between arm and leg muscles, and in the fasted state during normoinsulinaemia glucose uptake rates are higher in arm compared with leg muscles (Moller-Loswick et al. 1991; Ahlborg & Jensen-Urstad, 1991). Whether upper extremity muscles also maintain their insulin sensitivity better with age than the leg muscles remains to be studied. Recent reports have shown that the same tissue at different areas are not metabolically equal (Enevoldsen et al. 2001; Hagstrom-Toft et al. 2002). We investigated arm and leg glucose uptake in a basal condition and during a physiological isoglycaemic insulin clamp in patients with type 2 diabetes (TYPE 2) and age-matched controls (CON). The hypothesis was that the insulin resistance in TYPE 2 is primarily located in the leg muscles.