REVERSIBILITY OF INSULIN-RESISTANCE IN OBESE-DIABETIC PATIENTS - ROLEOF PLASMA-LIPIDS

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indi rect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m(2)) at th ree time points: before biliopancreatic diversion (BPD) surgery (Ob); 3 months after surgery. (POI); and after reaching stable body weight, at least 2 years after surgery (POII). A group of 7 control subjects ( C), matched groupwise for sex, age and BMI with POII patients, was als o studied. The M value at POI was significantly higher than at Ob (49. 12 +/- 8.57 vs 18.14 +/- 8.57 mu mol.kg(-1).min(-1)). No statistical d ifference was observed between the POII and C groups. Similarly, gluco se oxidation rate was significantly increased at POI with respect to O b (24.2 +/- 7.23 vs 9.42 +/- 3.91 mu mol.kg(-1).min(-1)) and was not s ignificantly different between POII and C. Basal levels of non-esterif ied fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/-PO II (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mu mol.l(-1 )). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1 .36 +/- 0.49 vs 0.80 +/- 0.19 g.l(-1)). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of tot al decrement). We also report the clinical case of a young woman of no rmal weight, who underwent BPD for chylomicronaemia (secondary to fami lial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabs orption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity a nd glucose tolerance. This improvement in metabolism is noticeable bef ore the surgery has major effects on body weight. These observations s uggest that lowered plasma lipids, rather than weight loss per se: are the cause of the reversibility of insulin resistance.