The steroid resistance of Crohn's disease.

BACKGROUND: A partial or complete steroid resistance, whose cause is not yet clarified, has been documented in many patients with long-standing Crohn's disease (CD). The primary aim of this study was to evaluate the number and affinity of serum protein steroid-binding sites in steroid-resistant patients with Crohn's disease. A secondary goal was to measure insulin sensitivity, an indirect index of steroid effectiveness, in these patients. METHODS: The study included 8 male steroid-resistant patients with active ileal CD and 6 healthy male volunteers. Corticosteroid binding globulin (CBG), binding capacity and affinity for cortisol were measured. The binding of cortisol to normal human serum and to serum of patients with CD was also determined. Whole body glucose uptake and oxidation were assessed by euglycemic hyperinsulinemic clamp and indirect calorimetry. RESULTS: Crohn's patients showed a significantly greater capacity of serum albumin for cortisol than controls (by about 40%, or about 0.15 moles per mole). Conversely, the binding of cortisol to CBG did not show significant differences between groups. Glucose uptake was higher in Crohn's patients than in normal controls (8.82 +/- 2.50 vs 7.01 +/- 2.24 mg/kgFFM/min; P = 0.036). Basal serum nonesterified fatty acid (NEFA) levels were lower in patients than in controls (459.64 +/- 69.95 vs 1026.48 +/- 112.58 mumol/L; P = 0.002). CONCLUSIONS: The observed increase in albumin binding might limit the bioactivity of cortisol in patients with Crohn's disease and contribute to the decreased effectiveness and weaker side effects of glucocorticoid therapy in these patients. The increased number of cortisol binding sites on albumin from patients with CD might be correlated with the significant decrease in serum NEFA, which may compete with steroids for the same sites.

Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids.

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic 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 also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified 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 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-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 total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial 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 malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.