Non-esterified fatty acids do not contribute to insulin resistance in persons at increased risk of developing type 2 (non-insulin-dependent) diabetes mellitus.

The mechanisms underlying insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus are not fully understood. An enhanced lipid/non-esterified fatty acid oxidation could provide an explanation. To test this hypothesis we examined the relationship between glucose and lipid metabolism in 44 first-degree relatives (28 glucose-tolerant and 16 glucose-intolerant) of Type 2 diabetic patients and in 18 healthy control subjects. Total body glucose disposal was impaired among both glucose-tolerant and glucose-intolerant relatives compared with control subjects (36.3 +/- 3.8 and 30.4 +/- 2.7 vs 47.7 +/- 3.4 mumol.kgLBM-1. min-1; p less than 0.05). The impairment in glucose disposal among the relatives was primarily accounted for by impaired non-oxidative glucose metabolism (14.8 +/- 3.0 and 12.5 +/- 1.8 vs 25.3 +/- 3.1 mumol.kgLBM-1.min-1; p less than 0.05). Plasma non-esterified fatty acid concentrations were similar in both glucose-tolerant and glucose-intolerant relatives and control subjects (646 +/- 36, 649 +/- 43 and 615 +/- 41 mumol/l) and showed the same degree of suppression by insulin (99 +/- 8, 86 +/- 7 and 84 +/- 9 mumol/l). Basal lipid oxidation was similar in all groups (1.29 +/- 0.09, 1.52 +/- 0.13 and 1.49 +/- 0.21 mumol.kgLBM-1. min-1). Furthermore, insulin suppressed lipid oxidation to the same degree in glucose-tolerant, glucose-intolerant relatives and control subjects (0.65 +/- 0.13, 0.88 +/- 0.15 and 0.59 +/- 0.09 mumol.kgLBM-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)