Resistance to insulin-mediated glucose uptake has been implicated in the pathogenesis of Type II (non±insulin-dependent) diabetes mellitus, hypertension and coronary heart disease [1]. Insulin resistance is present in several non-European ethnic groups in which prevalence of' Type II diabetes is higher than in Europeans matched with them for weight, for instance in people of South Asian (Indian, Pakistani, Bangladeshi and Sri Lankan) descent [2]. Insulin resistance is strongly associated with obesity, especially central obesity, but the mechanism of this association is poorly understood. One possibility is that non-esterified fatty acids (NEFA) produced by lipolysis of triglyceride stores in muscle cells block glucose uptake either through substrate competition, as proposed over 30 years ago [3], or through direct inhibition of glucose transport [4].The relation of insulin sensitivity to intramyocellular lipid (IMCL) has been examined in muscle biopsy Diabetologia (1999)
AbstractAims/hypothesis. To compare the relation between intramyocellular lipid content, central obesity and insulin sensitivity in Europeans and South Asians. Methods. Cross-sectional study of 40 South Asian and European non-diabetic men matched for age and body mass index. We measured intramyocellular lipid by proton magnetic resonance spectroscopy of soleus muscle, insulin sensitivity by the short insulin tolerance test, per cent body fat by dual-energy x-ray absorptiometry and visceral fat by single-slice computed tomography of the abdomen. Results. South Asians compared with Europeans had a higher mean per cent body fat (26.8 % vs 22.5 %, p = 0.05) and lower insulin sensitivity (mean ± SEM 2.4 ± 0.2 vs 3.4 %/min ± 0.3, p = 0.013). Mean ( ± SEM) intramyocellular lipid content was higher in South Asians than in Europeans (72.1 ± 7.5 vs 53.6 ± 4.9 mmol/kg dry weight, p = 0.046). In Europeans intramyocellular lipid was correlated with per cent body fat (r = 0.50, p = 0.028), waist:hip ratio (r = 0.74, p < 0.001), visceral fat (r = 0.62, p = 0.004) and insulin sensitivity (r = ±0.53, p = 0.016). In South Asians intramyocellular lipid was not significantly related to insulin sensitivity or obesity, and the strongest associations of insulin sensitivity were with fasting plasma triglyceride and waist:hip ratio. Conclusion/interpretation. The association of intramyocellular lipid with insulin sensitivity and obesity in Europeans is consistent with the hypothesis that muscle triglyceride mediates the effect of obesity on insulin sensitivity. The absence of a similar relation of insulin sensitivity to intramyocellular lipid in South Asians suggests that other mechanisms underlie the high insulin resistance observed in this group. [Diabetologia (1999) 42: 932±935]