Showing papers by "Andrea De Gaetano published in 1999"

L-carnitine improves glucose disposal in type 2 diabetic patients

Abstract: OBJECTIVE Aim of the present study is to evaluate the effects of L-carnitine on insulin-mediated glucose uptake and oxidation in type II diabetic patients and compare the results with those in healthy controls. DESIGN Fifteen type II diabetic patients and 20 healthy volunteers underwent a short-term (2 hours) euglycemic hyperinsulinemic clamp with simultaneous constant infusion of L-carnitine (0.28 micromole/kg bw/minute) or saline solution. Respiratory gas exchange was measured by an open-circuit ventilated hood system. Plasma glucose, insulin, non-esterified fatty acids (NEFA) and lactate levels were analyzed. Nitrogen urinary excretion was calculated to evaluate protein oxidation. RESULTS Whole body glucose uptake was significantly (p<0.001) higher with L-carnitine than with saline solution in the two groups investigated (48.66+/-4.73 without carnitine and 52.75+/-5.19 micromoles/kg(ffm)/minute with carnitine in healthy controls, and 35.90+/-5.00 vs. 38.90+/-5.16 micromoles/kg(ffm)/minute in diabetic patients). Glucose oxidation significantly increased only in the diabetic group (17.61+/-3.33 vs. 16.45+/-2.95 micromoles/kg(ffm)/minute, p<0.001). On the contrary, glucose storage increased in both groups (controls: 26.36+/-3.25 vs. 22.79+/-3.46 micromoles/kg(ffm)/minute, p<0.001; diabetics: 21.28+/-3.18 vs. 19.66+/-3.04 micromoles/kg(ffm)/minute, p<0.001). In type II diabetic patients, plasma lactate significantly decreased during L-carnitine infusion compared to saline, going from the basal period to the end-clamp period (0.028+/-0.0191 without carnitine and 0.0759+/-0.0329 with carnitine, p<0.0003). CONCLUSIONS L-carnitine constant infusion improves insulin sensitivity in insulin resistant diabetic patients; a significant effect on whole body insulin-mediated glucose uptake is also observed in normal subjects. In diabetics, glucose, taken up by the tissues, appears to be promptly utilized as fuel since glucose oxidation is increased during L-carnitine administration. The significantly reduced plasma levels of lactate suggest that this effect might be exerted through the activation of pyruvate dehydrogenase, whose activity is depressed in the insulin resistant status.

Multivariate identification of metabolic features in inflammatory bowel disease

Abstract: Weight loss and malnutrition are commonly reported in inflammatory bowel disease (IBD), but differences between Crohn's disease (CD) and ulcerative colitis (UC) patients have rarely been pointed out. In this regard, a sample of 102 consecutive patients with a diagnosis of either CD (n = 63, 33 males) or UC (n = 39, 25 males) based on previously reported clinical, morphologic, and histopathologic criteria were studied. Twenty-six anthropometric and metabolic variables were measured upon admission. Body composition was assessed by both anthropometry and bioimpedance measurements, and energy expenditure and substrate oxidation were assessed by indirect calorimetry. The data were subjected to principal-component analysis and to factor rotation to derive a set of a few basic independent descriptors of the metabolic features of each subject. Six descriptors were found to be responsible for greater than 86% of the total sample variability and to associate very well with mutually disjoint subsets of the original variables. The six summarizing factors are listed in order of decreasing percentage of explained variation (size 41.8%, fatness 17.9%, fuel 12.2%, shape 5.4%, energy 5.2%, and steroid 3.9%). CD and UC patients differed significantly with respect to fatness (CD lower, P = .004) and carbohydrate (CHO) fuel preference (CD lower, P = .030). Hence, CD patients showed a reduced fat mass (FM) compared with UC patients, and from a metabolic point of view, too, CD and UC are not superimposable. In fact, the lower CHO oxidation (CHOox) rate and consequent preferential lipid utilization found in CD patients may be taken into account as a contributing cause of lipid tissue wasting and in planning therapeutic enteral regimens.

Comparison between dodecanedioic acid and long-chain triglycerides as an energy source in liquid formula diets.

Abstract: Background: Dicarboxylic acids (DA) are watersoluble substances with high-energy density proposed as an alternative lipid substrate for nutrition purposes. The aim of the present study was to investigate the interaction between glucose and DA or long-chain triglyceride (LCT) metabolism after oral administration. Methods: Two test meals containing either dodecanedioic acid (C12, the 12-atom DA) or LCT, together with glucose and amino acids, were each administered to five healthy volunteers. Tracer amounts of 14 C-dodecanedioic acid were added to the C12 meal to recover expired traced CO 2 and estimate the minimum rate of C12 oxidation. Glucose, insulin, and C12 plasma levels were measured for 360 minutes after the test meal. Indirect calorimetry was performed for the duration of the study. Results: LCTs proved ineffective in promoting their own oxidation after oral administration. On the contrary, C12 was promptly oxidized, a minimum of 21.9% ± 8.3% of the administered amount giving rise to the recovered expired CO 2 . This difference in metabolic fate was reflected in a sparing effect on glucose: suprabasal respiratory quotient and suprabasal carbohydrate oxidation were significantly (p <.05) lower under C12 administration than under LCT administration, with a difference of 0.024 ± 0.015 in respiratory quotient (RQ) and a difference of 0.791 ± 0.197 kJ/min in carbohydrate oxidation. In particular, carbohydrate oxidation increased by 54% over basal with LCT but only by 28% with C12 administration. RQ increased over basal by 5.8% with LCT but only by 3.0% with C12 administration. Conclusions: These results show a fundamental metabolic difference between conventional lipids and DAs, which is the basis for a possible role of DAs in clinical nutrition. The fate of spared glucose is likely to be storage in glycogen form when dodecanedioic acid is made available as an energy source.

Comparison between dodecanedioic acid and long-chain triglycerides as an energy source in liquid formula diets

Abstract: Background: Dicarboxylic acids (DA) are watersoluble substances with high-energy density proposed as an alternative lipid substrate for nutrition purposes. The aim of the present study was to investigate the interaction between glucose and DA or long-chain triglyceride (LCT) metabolism after oral administration. Methods: Two test meals containing either dodecanedioic acid (C12, the 12-atom DA) or LCT, together with glucose and amino acids, were each administered to five healthy volunteers. Tracer amounts of 14 C-dodecanedioic acid were added to the C12 meal to recover expired traced CO 2 and estimate the minimum rate of C12 oxidation. Glucose, insulin, and C12 plasma levels were measured for 360 minutes after the test meal. Indirect calorimetry was performed for the duration of the study. Results: LCTs proved ineffective in promoting their own oxidation after oral administration. On the contrary, C12 was promptly oxidized, a minimum of 21.9% ± 8.3% of the administered amount giving rise to the recovered expired CO 2 . This difference in metabolic fate was reflected in a sparing effect on glucose: suprabasal respiratory quotient and suprabasal carbohydrate oxidation were significantly (p <.05) lower under C12 administration than under LCT administration, with a difference of 0.024 ± 0.015 in respiratory quotient (RQ) and a difference of 0.791 ± 0.197 kJ/min in carbohydrate oxidation. In particular, carbohydrate oxidation increased by 54% over basal with LCT but only by 28% with C12 administration. RQ increased over basal by 5.8% with LCT but only by 3.0% with C12 administration. Conclusions: These results show a fundamental metabolic difference between conventional lipids and DAs, which is the basis for a possible role of DAs in clinical nutrition. The fate of spared glucose is likely to be storage in glycogen form when dodecanedioic acid is made available as an energy source.

A new HPLC method for the direct analysis of triglycerides of dicarboxylic acids in biological samples

Abstract: Dicarboxylic acids (DA) are alternate lipid substrates recently proposed in parenteral nutrition. Two new derivatives of DA, a triglyceride of sebacic (TGC10) and one of dodecanedioic (TGC12) acid have been synthesised in order to reduce the amount of sodium given with the unesterified forms. The present paper describes a rapid and direct high-performance liquid chromatographic method (HPLC) for the analysis of these substances in both plasma and urine. Thirty-six male Wistar rats were rapidly injected with 64 mg of TGC10 or 53 mg of TGC12. The triglycerides and their products of hydrolysis were measured in plasma samples taken at different times. For the dose of 500 ng the intra-assay variations ranged from 6. 80+/-0.35% for TGC10 to 18.6+/-3.20% for TGC12 and the inter-assay variations were from 4.44+/-2.21% for TGC10 to 15.0+/-6.72% for TGC12. The detection limit for both triglycerides was 5 ng. This rapid and direct HPLC method could have practical implications in monitoring the concentration of both triglycerides and free forms of DA in biological samples of patients who might benefit from the administration of these substances during parenteral nutrition regimens.

Elevated diet-induced thermogenesis and lipid oxidation rate in Crohn disease

Abstract: Background: Although malnutrition is frequently observed in Crohn disease (CD), its cause is not clear. Regulation of energy metabolism and diet-induced thermogenesis (DIT) have not been adequately studied in CD. Objective: The aim was to study DIT and substrate oxidation in patients with inactive ileal CD. Design: After a test meal providing 50.2 kJ/kg body wt, DIT was assessed by indirect calorimetry performed over 360 min in 18 CD patients and 12 healthy volunteers matched for age, sex, weight, and height. Body composition was evaluated with the labeled-water-bolus injection technique. Results: Fat-free mass did not differ significantly between groups, but CD patients had markedly lower fat mass than control subjects (13.8 ± 5.63 compared with 19.0 ± 3.49 kg; P < 0.001). Nonprotein respiratory quotient was lower in CD patients than control subjects (0.80 ± 0.04 compared with 0.86 ± 0.03; P <0.001). Average respiratory quotient between 75 and 150 min after the test meal was 0.85 ± 0.03 in CD patients and 0.91 ± 0.02 in control subjects (P < 0.001). Lipid oxidation rate was higher in CD patients than in control subjects (2.26 ± 1.13 compared with 1.50 ± 0.75 kJ/min: P < 0.05). DIT was higher in CD patients than in control subjects (9.89 ± 1.93% compared with 5.67 ± 0.91% of energy intake; P < (1.001). Conclusions: Patients with inactive ileal CD had significantly higher DIT and lipid oxidation rate than do healthy volunteers. These results may explain why CD patients have difficulty maintaining adequate nutritional status, and the findings also suggest that a diet relatively rich in fat may attain better energy balance.