THE EFFECTS OF CHANGES IN PLASMA NONESTERIFIED FATTY-ACID LEVELS ON OXIDATIVE-METABOLISM DURING MODERATE EXERCISE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Blood levels of intermediary metabolites were measured and indirect calorimetry was performed in 10 otherwise healthy, non-insulin-dependent diabetic (NIDDM) patients before, during, and after 30 minutes of moderate exercise on three occasions in random order at weekly intervals with (1) heparin treatment to increase preexercise plasma nonesterified fatty acid (NEFA) levels (HEPARIN); (2) acipimox, a nicotinic acid analogue, to reduce preexercise plasma NEFA levels (ACIPIMOX); and (3) no manipulation of preexercise plasma NEFA levels (NIL). With ACIPIMOX, preexercise blood levels were significantly reduced for NEFAs and glycerol (P < .01) and marginally reduced for acetoacetate and 3-hydroxybutyrate (NS) compared with preexercise levels for the other two treatments; these low levels seen with acipimox treatment increased only slightly during exercise and the postexercise period. Plasma NEFA levels increased by approximately 150% (P < .001) with HEPARIN at the same times. The levels of ketone bodies during either NIL or HEPARIN increased rapidly postexercise by approximately 90% to 110% for both acetoacetate and 3-hydroxybutyrate (both P < .01). Plasma insulin levels tended to be lowest (despite similar plasma glucose levels during the three treatments) with ACIPIMOX, while growth hormone (hGH) and, perhaps, noradrenaline levels were highest both during and after exercise. The respiratory quotient (RQ) was highest with ACIPIMOX (P < .05 for exercise and postexercise periods compared with the other two treatments), which, compared with NIL, reduced fat oxidation by 27% and 60% and increased carbohydrate oxidation by 29% and 74% during and after exercise, respectively (all P < .05). These changes in substrate oxidation due to ACIPIMOX were almost opposite to those observed with HEPARIN. The increased fat oxidation with exercise during NIL (800%; P < .001 compared with preexercise value) was likely due to increased NEFA supply from the 700% exercise-induced increase in the leg blood flow. In contrast, the 340% increase in NEFA supply with ACIPIMOX could not have accounted for the 900% increase in fat oxidation during exercise (P < .001 compared with preexercise). It is thus likely that alternative (eg, intramuscular) lipid pools are mobilized for oxidative metabolism during exercise with reduced plasma NEFA levels due to ACIPIMOX, and may constitute an adaptive response. These results support the glucose/fatty acid cycle, albeit in the converse, ie, reduced NEFA availability improves glucose oxidation, and are of likely benefit to the diabetic patient. © 1993.