Lipid-carbohydrate interactions in post-absorptive non-insulin-dependent diabetic patients

Substrate competition is an important mechanism of insulin resistance, although its role in the post-absorptive hyperglycemia of NIDDM is not clear: lipid infusion does not raise plasma glucose levels in normal subjects, and total lipid oxidation, the elevation of which is a hallmark of disrupted carbohydrate metabolism, is normal in non-insulin-dependent diabetes mellitus (NIDDM). To examine further these two arguments against the involvement of lipid-carbohydrate interactions in the hyperglycemia of NIDDM, we compared the effect of a 3-hour lipid infusion ('Ivélip') on post-absorptive blood glucose levels, plasma lipids and respiratory exchanges in 15 patients with NIDDM, with that of an infusion of saline in 15 other patients with similar metabolic profiles. The lipid infusion significantly slowed the natural post-absorptive decline in blood glucose levels (saline -0.47 +/- 0.14 and Ivélip -0.10 +/- 0.12 mmol.l-1.h-1, p < 0.05), with marked interindividual differences. Substrate oxidation rates were unchanged during saline infusion, and were immediately (within 30 min) and reciprocally modified by the lipid infusion (lipid oxidation enhanced: 0.90 +/- 0.14 to 1.06 +/- 0.13 mg.kg-1.min-1 at time 30 min, p < 0.05; glucose oxidation inhibited: 1.27 +/- 0.19 to 0.87 +/- 0.18, p < 0.05), but this was not correlated with the alteration in blood glucose levels. In contrast, the increase in plasma lipids was continuous, and positively correlated with the change in blood glucose levels (r = 0.58, p < 0.05 for change of plasma free fatty acids; r = 0.55, p < 0.05 for change of plasma triglycerides, TGs). In line with the Randle mechanism, the lipid infusion affected oxidation rates, but another mechanism, depending on intravascular lipolysis of the infused TGs, was thought to occur in certain individuals whose blood glucose levels rose during the infusion.