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Biomedical subjects

G Mingrone

Publications and source records attributed to G Mingrone.

At least 55 records · Page 3Linked to original sources
PubMed1999

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

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.

Animals↗
PubMed1999

Multivariate identification of metabolic features in inflammatory bowel disease.

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.

Adolescent↗
PubMed1999

Acid-base and electrolyte balance in urinary intestinal orthotopic reservoir: ileocecal neobladder compared with ileal neobladder.

OBJECTIVES: To compare acid-base and electrolyte balance in ileocecal and ileal neobladders. METHODS: Acid-base and electrolyte balance were studied in 45 patients with an ileocecourethrostomy and 18 patients with an ileal reservoir. The mean follow-up was 51 months. Results were compared with regard to both the type of operation and the time since surgery. RESULTS: No significant differences were found with regard to either the type of operation or the length of follow-up. A preserved renal function is important in maintaining a healthy status. CONCLUSIONS: The use of 35 to 40 cm of ileum or 10 cm of cecum with the ileocecal junction seems to be safe even after a long follow-up. The length rather than the kind of bowel used for bladder replacement appears to be important in safeguarding hydroelectrolyte and acid-base homeostasis. This is particularly true in the presence of preserved renal function.

Acid-Base Equilibrium↗
PubMed1999

Glucose metabolism and insulin sensitivity in inactive inflammatory bowel disease.

BACKGROUND: Inflammatory mediator concentration was found to be increased in active inflammatory bowel disease, and this could be related to an insulin-resistant state. Moreover, glucocorticoids, which are widely used in the treatment of inflammatory bowel disease, are notoriously related to insulin resistance. AIM: To measure body composition, whole body glucose uptake and oxidation in Crohn's disease and ulcerative colitis patients with inactive disease. METHODS: All patients had clinical, ultrasound and biochemical assessment. Body composition was determined by isotopic dilution technique; basal metabolic rate and substrate oxidation were measured by indirect calorimetry. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Ten patients with inactive Crohn's disease (five males, aged 31.1 +/- 7.0 years) and 10 patients with inactive ulcerative colitis (five males, aged 33.4 +/- 8.8 years) participated in the study. Forty healthy subjects, matched for age and height were used as a control group. RESULTS: Crohn's disease patients showed lower BMI (P < 0.001), fat mass (P < 0.05) and respiratory quotient (P < 0.001) values compared to both ulcerative colitis and control subjects. No difference in peripheral glucose uptake (micromol/kg/min) was found between groups (respectively 42.5 +/- 6.78 in Crohn's disease, 40.2 +/- 8.00 in ulcerative colitis and 41.4 +/- 10.8 in control subjects). Glucose storage and oxidation did not differ between groups. CONCLUSION: Our data showed that inflammatory bowel disease patients in a remission phase of the disease activity had a whole body glucose uptake and oxidation similar to those of control subjects, probably due to fat-free mass preservation and low blood and tissue cytokine concentration.

Adolescent↗
PubMed1999

L-carnitine improves glucose disposal in type 2 diabetic patients.

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.

Analysis of Variance↗
PubMed1999

Carnitine increases glucose disposal in humans.

OBJECTIVE: The goal of this work is to assess the effect of L-carnitine on glucose disposal, particularly on insulin sensitivity, in healthy volunteers. METHODS: Fourteen healthy human volunteers were subjected to the intravenous glucose tolerance test (analyzed by means of the minimal model technique), together with indirect calorimetry and measurement of serum free fatty acids, after a bolus of glucose plus carnitine (C) or a bolus of glucose plus saline (P). RESULTS: The minimal model demonstrated a significant increase in glucose disposal from plasma with carnitine: Glucose effectiveness passed from 2.7%/min to 3.8%/min. No significant changes were observed in the Insulin Sensitivity Index or in Insulin/C-Peptide secretion. Calorimetry showed a significant increase in respiratory quotient, resulting from a significant increase in carbohydrate oxidation rate during carnitine administration by an average of 0.0176+/-0.0118 g/min (p=0.015). Energy expenditure was not modified by treatment. A smaller decrease in plasma fatty acid concentrations was noted with carnitine plus glucose than after glucose alone. CONCLUSIONS: From these data it appears that carnitine stimulates glucose disposal and oxidation in the healthy volunteer. Therefore, carnitine might be useful as an adjunct in the therapy of diabetes mellitus.

Adult↗
PubMed1999

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

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 < 0.001). 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.

Adult↗
PubMed1999

Kinetics of dodecanedioic acid triglyceride in rats.

The kinetics of the triglyceride of dodecanedioic acid (TGDA) has been investigated in 30 male Wistar rats after a rapid intravenous bolus injection. TGDA and its product of hydrolysis, nonesterified dodecanedioic acid (NEDA), were measured in plasma samples taken at different times using an improved high-performance liquid chromatographic method. The 24-h urinary excretion of TGDA was 1.54 +/- 0.37 micromol, corresponding to approximately 0.67% of the administered amount. Several kinetics models were considered, including central and peripheral compartments for the triglyceride and the free forms and expressing transports between compartments with combinations of linear, carrier-limited, or time-varying mechanisms. The parameter estimates of the kinetics of TGDA and of NEDA were finally obtained using a three-compartment model in which the transfer of TGDA to NEDA was assumed to be linear, through a peripheral compartment, and the tissue uptake of NEDA was assumed to be carrier limited. TGDA had a large volume of distribution ( approximately 0.5 l/kg body wt) with a fast disappearance rate from plasma (0.42 min-1), whereas NEDA had a very small volume of distribution ( approximately 0.04 l/kg body wt) and a tissue uptake with maximal transport rate of 0.636 mM/min. In conclusion, this first study on the triglyceride form of dodecanedioic acid indicates that it is rapidly hydrolyzed and that both triglyceride and nonesterified forms are excreted in the urine to a very low extent. The tissue uptake rate of NEDA is consistent with the possibility of achieving substantial energy delivery, should it be added to parenteral nutrition formulations. Furthermore, the amount of sodium administered with the triglyceride form is one-half of that necessary with the free diacid.

Animals↗
PubMed1999

Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency.

Raised plasma triglycerides (TGs) and nonesterified fatty acid (NEFA) concentrations are thought to play a role in the pathogenesis of insulin-resistant diabetes. We report on two sisters with extreme hypertriglyceridemia and overt diabetes, in whom surgical normalization of TGs cured the diabetes. In all of the family members (parents, two affected sisters, ages 18 and 15 years, and an 11-year-old unaffected sister), we measured oral glucose tolerance, insulin sensitivity (by the euglycemic-hyperinsulinemic clamp technique), substrate oxidation (indirect calorimetry), endogenous glucose production (by the [6,6-2H2]glucose technique), and postheparin plasma lipoprotein lipase (LPL) activity. In addition, GC-clamped polymerase chain reaction-amplified DNA from the promoter region and the 10 coding LPL gene exons were screened for nucleotide substitution. Two silent mutations were found in the father's exon 4 (Glu118 Glu) and in the mother's exon 8 (Thr361 Thr), while a nonsense mutation (Ser447 Ter) was detected in the mother's exon 9. Mutations in exons 4 and 8 were inherited by the two affected girls. At 1-2 years after the appearance of hyperchylomicronemia, both sisters developed hyperglycemia with severe insulin resistance. Because medical therapy (including high-dose insulin) failed to reduce plasma TGs or control glycemia, lipid malabsorption was surgically induced by a modified biliopancreatic diversion. Within 3 weeks of surgery, plasma TGs and NEFA and cholesterol levels were drastically lowered. Concurrently, fasting plasma glucose levels fell from 17 to 5 mmol/l (with no therapy), while insulin-stimulated glucose uptake, oxidation, and storage were all markedly improved. Throughout the observation period, plasma TG levels were closely correlated with both plasma glucose and insulin concentrations, as measured during the oral glucose tolerance test. These cases provide evidence that insulin-resistant diabetes can be caused by extremely high levels of TGs.

Adolescent↗
PubMed1999

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.

Adult↗
PubMed1999

Alterations of nutritional status in the main gastrointestinal pathologies.

An impairment of nutritional status up to real malnutrition can frequently be associated to gastrointestinal diseases. The diseases of the gastrointestinal tract can be divided into five groups: those hampering the nutrient physiological transit (especially neoplastic diseases); those affecting the intestinal mucosa (such as chronic inflammatory bowel disease); those determining intraluminal maldigestion; the hepato-biliary diseases and finally, the diseases of the pancreas. In order to correctly evaluate the nutritional status of an individual, besides the determination of the common biochemical parameters, body composition by direct and indirect techniques and energy metabolism by indirect calorimetry should be measured. Patients affected by Crohn's disease showed a lower fat mass content along with higher lipid oxidation compared to patients affected by ulcerative colitis. Patients with coeliac disease at diagnosis had a reduction in both fat and fat-free mass content along with an increased utilisation of carbohydrates as fuel substrate. There are many factors potentially leading to severe malnutrition in pancreatic diseases, especially in the acute form. Due to the primary role played by the liver in the metabolism of energy substrates, an impaired nutritional status might be commonly found in cirrhotic patients. In this connection, our group reported an increased energy expenditure and lipid oxidation, and an insulin-resistant state in compensated liver cirrhotic patients. These alterations seemed to precede and probably to lead to liver-disease-related malnutrition.

Journal Article↗
PubMed1999

Wasting in gastrointestinal tract cancers: clinical and etiologic aspects.

One of the major complications found in patients affected by malignancy of the gastrointestinal tract is represented by an alteration of nutritional status, up to real cachexia. The factors responsible for the severe nutritional deficiencies are: metabolic alterations, which involve carbohydrate, lipid and protein metabolism; the reduced availability of nutritional substrates, due to neoplastic growth that, by expanding locally or destroying the affected organ, determines alterations of deglutition, digestion and food absorption; the effects of surgical therapy, radiotherapy and chemotherapy, which are able to cause temporary or permanent nutritional deficiencies; the effects of immunological mediators, and above all of tumor necrosis factor-alpha (TNF-alpha). In fact, TNF-alpha is considered the main mediator of cancer cachexia as it is responsible for different metabolic alterations, both directly and by the activation of other mediators, such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). In addition, a negative energy balance in cancer patients could occur as a consequence of increased energy requirements. In this connection, patients with different neoplasia localisation, show high or within the normal range energy expenditure values. These data indicate that the increase in energy metabolism is not likely to represent the main determining factor in neoplastic cachexia. In conclusion, since patients affected by malignancy of the gastrointestinal tract showed a reduction in body weight, fat and fat-free mass, accurate evaluation of nutritional status should be useful in the management and follow-up of these patients.

Journal Article↗
PubMed1998

Daily energy and substrate metabolism in patients with cirrhosis.

Twenty-four-hour energy expenditure (EE) and substrate oxidation (respiratory chamber), and whole-body glucose uptake and oxidation rates (euglycemic hyperinsulinemic clamp [EHC] and indirect calorimetry) were measured in 10 male patients with posthepatitis, Child B cirrhosis, and 8 healthy male controls matched for age, body size, and body composition. Twenty-four-hour EE was higher in cirrhotic patients than in controls (8,567 +/- 764 vs. 6,825 +/- 507 kJ/d; P < .001). Resting energy expenditure (REE) was also higher in cirrhotic patients than in controls (7,881 +/- 1,125 vs. 5,868 +/- 489 kJ/d; P < .01). Twenty-four-hour respiratory quotient (RQ) (trend) and fasting RQ (0.76 +/- 0.05 vs. 0.82 +/- 0.04; P < .05) were lower in cirrhotic patients than in controls, reflecting higher lipid oxidation rates in the former group. Whole-body glucose uptake was markedly reduced in cirrhotic patients when compared with controls (22.4 +/- 3.2 vs. 44.5 +/- 7.6 mmol/kg/min; P < .001). Carbohydrate oxidation rates, computed during the last 40 minutes of the clamp, were 8.5 +/- 1.1 mmol/kg/min in cirrhotic patients and 22.6 +/- 6.1 mmol/kg/min in controls (P < .001). Nonoxidative glucose disposal was 13.9 +/- 2.5 mmol/kg/min in cirrhotic patients and 22.0 +/- 5.5 mmol/kg/min in normal controls (P < .01). In conclusion, our data indicate that patients with Child B cirrhosis who still maintain a nutritional status (i.e., body composition) comparable with healthy controls are characterized by a cluster of metabolic defects that include hypermetabolism, increased lipid utilization, and insulin resistance. This suggests that the above metabolic syndrome precedes and probably leads to malnutrition in the natural history of the liver disease. In fact, in spite of the absence of a significant difference in caloric intake between cirrhotic patients and normal controls, the elevated 24-hour EE might allow for a relevant weight loss in cirrhotic patients, because, with time, the differences may be cumulative. However, whether this hypermetabolism can lead to a real weight loss remains to be evaluated in a longitudinal study.

Adult↗
PubMed1998

Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris.

BACKGROUND & AIMS: The etiology of cholesterol gallstones is multifactorial, with interactions of genes and the environment. The hypothesis that aborigine cholesterol lithogenic genes are widely spread among Chileans, a population with a high prevalence of gallstones, was tested. METHODS: Medical history and anthropometric measurements were obtained and abdominal ultrasonography was performed in 182 Mapuche Indians, 225 Maoris of Easter Island, and 1584 Hispanics. Blood groups, DNA, lipids, and glucose were analyzed. The Amerindian Admixture Index and mitochondrial DNA (mtDNA) assessed the ethnicity and degree of racial admixture. RESULTS: Amerindian Admixture Index was 0.8 in Mapuches and 0.4 in Hispanics. All Mapuches, 88% of Hispanics, but none of Maoris had Amerindian mtDNA haplotypes. Age- and sex-adjusted global prevalence of gallstone disease was higher in Mapuches (35%) than in Hispanics (27%) and Maoris (21%). Compared with Hispanics, the youngest group of Mapuches had the greatest corrected risk of gallstones: odds ratios of 6.0 in women and 2.3 in men. In contrast, the gallstone risk in Maoris was lower compared with Hispanics: odds ratios of 0.6 for women and 0.5 for men. CONCLUSIONS: Cholesterol lithogenic genes appear widely spread among Chilean Indians and Hispanics. They could determine the early formation of gallstones and explain the high prevalence of gallbladder diseases among some South American populations.

Adult↗