Bile acid changes after metabolic surgery are linked to improvement in insulin sensitivity.

BACKGROUND: Metabolic surgery is associated with a prompt improvement in insulin resistance, although the mechanism of action remains unknown. The literature on bile acid changes after metabolic surgery is conflicting, and insulin sensitivity is generally assessed by indirect methods. The aim of this study was to investigate the relationship between improvement in insulin sensitivity and concentration of circulating bile acids after biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). METHODS: This was a prospective observational study of nine patients who underwent BPD and six who had RYGB. Inclusion criteria for participation were a BMI in excess of 40 kg/m2 , no previous diagnosis of type 2 diabetes and willingness to participate. Exclusion criteria were major endocrine diseases, malignancies and liver cirrhosis. Follow-up visits were carried out after a mean(s.d.) of 185·3(72·9) days. Fasting plasma bile acids were assessed by ultra-high-performance liquid chromatography coupled with a triple quadrupole mass spectrometer, and insulin sensitivity was measured by means of a hyperinsulinaemic-euglycaemic clamp. RESULTS: A significant increase in all bile acids, as well as an amelioration of insulin sensitivity, was observed after metabolic surgery. An increase in conjugated secondary bile acids was significantly associated with an increase in insulin sensitivity. Only the increase in glycodeoxycholic acid was significantly associated with an increase in insulin sensitivity in analysis of individual conjugated secondary bile acids. CONCLUSION: Glycodeoxycholic acid might drive the improved insulin sensitivity after metabolic surgery.

Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study.

BACKGROUND/OBJECTIVES: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. SUBJECTS/METHODS: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12kcal/kg body weight of high protein and high fat for 11 months plus 30min of brisk walking daily and at least 3h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. RESULTS: A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P<0.001 vs. medical arm), while ILM+liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P<0.001). More women allocated themselves to the ILM+liraglutide group. Weight loss was 43kg with SG, 26kg with ILM+liraglutide and 15kg with ILM alone. Lean body mass reductions were -11.6kg with SG, -6.3kg with ILM and -8.3kg with ILM+liraglutide. Prevalence of prediabetes was significantly lower with ILM+liraglutide, and insulin resistance was reduced by about 70% by both ILM+liraglutide and SG vs. 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. DISCUSSION: At least in the short-term, liraglutide 3.0mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times greater than ILM alone and only about 25% less than with SG, while preserving lean body mass. Although this study was non-randomised, it was designed to explore the efficacy of medical treatments for obesity in everyday clinical practice.

Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH).

BACKGROUND AND OBJECTIVES: Metabolic alterations are a common feature in patients affected by non-alcoholic steato-hepatitis (NASH). A strong correlation exists between overweight, in particular visceral fat accumulation, and prevalence of NASH, especially in men. Thus, diet-induced weight loss represents a fundamental tool in disease management of these patients. The aim of the present study was to evaluate body composition and nutrient utilisation in patients with NASH, comparing them with patients affected by chronic hepatitis related to hepatitis C virus (HCV) infection and with healthy subjects. MATERIALS AND METHODS: Twenty male outpatients with NASH (age: 41 +/- 11 yr; BMI: 26.2 +/- 2.1 kg/m2) and 14 HCV male patients (age 44.6 +/- 13 yr; BMI: 24.8 +/- 2.8 kg/m2) were enrolled in the study. A group of 20 healthy male subjects (age: 39 +/- 10 yr; BMI: 23.3 +/- 1.1 kg/m2) were studied as controls. Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry; resting metabolic rate and nutrient oxidation by indirect calorimetry. A 7-day food diary was collected. The main biochemical parameters were measured using standardised laboratory techniques. RESULTS: Body weight was higher in NASH patients with respect to HCV patients and control subjects (respectively 75.2 +/- 8.9 vs 68.5 +/- 9.4 and vs 67.0 +/- 8.0 kg; P < 0.01) and this was essentially due to fat mass increase. Fat-free mass reduction was found in HCV patients with respect to both NASH and control subjects. Patients with NASH had a significantly higher waist circumference (P < 0.01) and a lower resting metabolic rate (RMR) with respect to HCV and control subjects. Energy intake was significantly higher in NASH patients (P < 0.01) compared to the other two groups. CONCLUSIONS: NASH patients showed an increase in body weight, fat mass and visceral fat accumulation with respect to HCV and control subjects. The reduction in RMR, coupled with increase energy intake may explain the body composition alterations found in these patients.

Effects of propionyl-L-carnitine topical irrigation in distal ulcerative colitis: a preliminary report.

BACKGROUND/AIMS: To study the tolerability of propionyl-L-carnitine administered as rectal irrigation and its efficacy in improving the clinical picture of distal ulcerative colitis. METHODOLOGY: Ten male subjects (aged 18 to 55 years, with a body mass index ranging from 21 to 25 Kg/m2) with distal ulcerative colitis were treated with propionyl-L-carnitine enemas (6 g in 200 mL physiological solution) twice a day over 120 minutes each. All subjects had a disease activity index from 0 to 1. A clinical, laboratory, endoscopy and biopsy evaluation was performed at baseline and 14 days after treatment. Serum tumor necrosis factor-alpha and interleukin-2 concentration was measured. RESULTS: No side effects were reported by the entire patient population and the clinical conditions remained constant throughout the study period. The disease activity index improved significantly between the beginning and the end of the study in 80% of the patients. Histologic features (mucosal erosion, distortion of crypt architecture, inflammation and lamina propria gap) significantly improved in all treated patients. Serum interleukin-2 levels did not change significantly after propionyl-L-carnitine treatment (respectively: 14.7 +/- 15.8 before vs. 9.9 +/- 13.2 pg/mL), while tumor necrosis factor-alpha levels were undetectable both before and after propionyl-L-carnitine administration. CONCLUSIONS: The topical treatment with a new formulation containing propionyl-L-carnitine seems to be safe and effective in improving the histologic features in patients with inactive or mild ulcerative colitis, as an alternative to conventional therapy.

An update on the medical treatment of Crohn's disease.

Crohn's disease (CD) is a chronic transmural inflammation that may involve any part of the alimentary tract. The affected patients show peculiar metabolic characteristics; they often have a reduced body weight, due to reduction of lipid stores (in spite of lean mass depletion) and an increased utilization of lipids as fuel substrate. An alteration of nutritional status, up to real malnutrition, is common in CD and malnutrition's effects influence the course of disease, acting as independent factors. We will give a description of the main pharmacological approaches in CD management; the first line therapy for CD patients remains the combinations of aminosalicylates, antibiotics, corticosteroids and immunomodulatory agents. The development of new biological agents for the treatment of inflammatory bowel diseases has added to the growing armamentarium of available therapy. We also will explain the importance of enteral nutrition, whose importance goes over the simple amelioration of nutritional status, especially in childhood CD, where it has shown to be as effective as traditional therapy.

Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-alpha reduction and GLUT4 expression enhancement.

AIMS/HYPOTHESIS: The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-alpha and GLUT4 expression and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely obese women (BMI>40 kg/m(2)), before and 6 months after low-dietary intake or bariatric malabsorptive surgery (bilio-pancreatic diversion, BPD), by the euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic triglycerides was chemically measured in needle muscle biopsies. Using reverse transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of TNF-alpha and GLUT4 was also investigated. RESULTS: The weight loss after surgery was 25.98+/-5.81 kg (P<0.001), while that obtained with the diet was 5.07+/-5.99 kg (P=NS). Marked decrease in TNF-alpha mRNA levels (76.67+/-12.59 to 14.01+/-5.21 AU, P<0.001) were observed in comparison with pre-treatment, whereas GLUT4 was significantly increased (62.25+/-11.77-124.25+/-21.01 AU, P<0.001) only in BPD patients. Increased glucose uptake (M) was accompanied by a significant decrease of TNF-alpha mRNA (76.67+/-12.59-14.01+/-5.21 AU, P<0.01) and an increase of GLUT4. The amounts of TNF-alpha mRNAs in skeletal muscle correlated inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels. In a step-down regression analysis (r(2)=0.95) TNFalpha mRNA (P=0.0014), muscular TG levels (P=0.018), and GLUT4 mRNA (P=0.028) resulted to be the most powerful independent variables for predicting M values. CONCLUSION/INTERPRETATION: These findings suggest that insulin resistance in morbidly obese patients is positively associated to the intramyocytic triglycerides content and to TNF-alpha gene expression and inversely correlated to GLUT4 expression.

Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides.

A close relationship between elevated plasma free fatty acid (FFA) levels and insulin resistance is commonly reported in obese subjects. The aim of the present study was to evaluate the role of intramuscular triglyceride (mTG) and FFA levels in insulin sensitivity in 30 nondiabetic normal-weight or obese subjects (18 with body mass index [BMI] = 21.8 +/- 3.3 kg/m2 and 12 with BMI = 34.6 +/- 2.7 kg/m2) who underwent minor abdominal surgery. Body composition was estimated by isotopic dilution, substrate oxidation by indirect calorimetry, and whole-body glucose uptake by euglycemic-hyperinsulinemic clamp (EHC). Glucose uptake (M) value negatively correlated with the MTG level (R2 = -.56, P < .0001), which was increased in obese patients (11.6 +/- 2.2 v 6.2 +/- 1.4 micromol/g wet weight muscle tissue, P < .0001). The TG fatty acid profile was significantly different in the 2 groups: an increased concentration of saturated fat was present in obese patients (unsaturated to saturated ratio, 1.89 +/- 0.40 v2.19 +/- 0.07, P < .0001). Stepwise linear regression analysis of total mTGs and palmitic and oleic fractions on the M value showed that only TGs and palmitic acid were significantly related to glucose uptake (R2 = .66, P < .0001). Furthermore, among the other anthropometric variables, only the BMI was significantly correlated with MTGs (R2 = .71, P < .0001). In conclusion, not only the MTG concentration but also the FFA pattern seems to affect insulin-mediated glucose uptake. A pivotal role might be played by a high saturated fatty acid content in the TGs.

Effect of a vegetable-protein-rich polymeric diet treatment on body composition and energy metabolism in inactive Crohn's disease.

OBJECTIVE: Since malnutrition and lactose intolerance are frequently reported in Crohn's disease (CD), we evaluated the differences in terms of compliance-to-treatment and nutritional status in inactive CD patients after two different treatments using either a standard polymeric diet or a vegetable-protein-rich and lactose-free diet. STUDY DESIGN: A case-control study. SUBJECTS: Forty CD patients with inactive disease were randomly divided into two groups. Group A (10 men; aged 33.9+/-7.2 years; BMI, 21.8+/-1.7 kg/m2) received a conventional polymeric enteral diet, while group B (10 men; aged 35.6+/-6.8 years; BMI, 21.4+/-1.8 kg/m2) was administered a soy-rich and lactose-free polymeric diet, over a 4-week period. METHODS: All the patients had a clinical and laboratory examination. Body composition was assessed by isotopic dilution and resting metabolic rate (RMR), and substrate oxidation rates were measured by indirect calorimetry. RESULTS: Body weight significantly increased after treatment in both groups (A, P<0.05; and B, P<0.01), as well as fat-free mass (A, P<0.05; and B, P<0.05) and fat mass (A, P<0.05; and B, P<0.01). RMR slightly increased, although it did not reach statistical significance. Treatment did not influence substrate oxidation rates. Group B lactose-intolerant patients reported a greater compliance-to-treatment than those in group A. CONCLUSIONS: This study showed that a polymeric enteral diet rich in vegetable protein and not containing milk protein, eaten at home, with no need for positioning a nasogastric tube, significantly improved body composition in inactive and lactose-intolerant CD patients, with no effect on energy metabolism, suggesting that it could be useful in improving nutritional status in these patients.

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.

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.

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.

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.

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.

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.

Effect of disease localization on the anthropometric and metabolic features of Crohn's disease.

OBJECTIVE: We conducted this study to evaluate the effect of disease localization on the anthropometric and metabolic characteristics of inactive Crohn's disease (CD). METHODS: Forty-three patients with biopsy or radiology proven CD (23 men; age, 33.8 yr; range, 18-54 yr) in clinical remission (simplified Crohn's diseases activity index [SCDAI] < 3) and not receiving steroid therapy or nutritional support were enrolled in the study. Patients were separated into three subgroups according to disease localization: ileal (n = 16), ileo-colonic (n = 13), and colonic CD (n = 14). Sixty healthy volunteers (26 men; age, 32.0 yr; range, 18-60 yr), matched for age and height were used as control subjects. Body composition was assessed by both anthropometry and bioimpedance analysis and indirect calorimetry was performed to measure energy expenditure and substrate oxidation rates. RESULTS: CD patients showed a lower body weight than controls, both as a whole (61.5 kg; range, 41.5-74.0 vs 66.9 kg; range, 55.0-86.0 kg; p < 0.001) and separated by disease localization (ileal; p < 0.001; ileo-colonic; p < 0.001; and colonic; p < 0.05 vs controls). Fat-free mass (FFM) did not differ between the groups, whereas fat mass was significantly lower in CD patients than in controls (p < 0.001), with the lowest values in ileal and ileo-colonic patients. Basal metabolic rate by kg of FFM was higher in CD patients than in healthy individuals (p < 0.01). Nonprotein respiratory quotient was significantly lower in CD than in controls as a whole (0.79; range, 0.73-0.84 vs 0.83; range, 0.79-0.89; p < 0.001) or separated by disease localization (p < 0.001 each subgroup vs controls), with a consequent higher lipid oxidation rate. A lower dietary lipid intake was found in patients than in controls (p < 0.01). CONCLUSIONS: Regardless of disease localization, CD patients showed a lower fat mass and a higher utilization of lipids than control subjects. Patients with ileal and ileo-colonic disease showed the greater reduction in body weight, compared with control subjects, suggesting they were at a higher risk of malnutrition, probably as a consequence of the simultaneous occurrence of both malabsorption and decreased energy intake.

A surgical option for familial chylomicronemia associated with insulin-resistant diabetes mellitus.

BACKGROUND: The goal of the present work is to present an effective surgical approach for the treatment of a medically-resistant form of hyperlipidemia. METHODS: Two siblings with familial lipoprotein-lipase deficiency and subsequent hyperchylomicronemia, widespread skin xanthomas and severe insulin-resistant diabetes mellitus came to our observation after several unsuccessful attempts at medical treatment. In order to lower plasma lipids through lipid malabsorption, a modified bilio-pancreatic diversion operation was employed. The rationale in deciding to use this surgical approach was based also on the likely hypothesis that diabetes, in these subjects, was secondary to high circulating and tissue levels of lipids. Insulin sensitivity in the two treated subjects, as well as in 24 healthy volunteers constituting the control group, was assessed by euglycemic hyperinsulinemic clamp and indirect calorimetry, obtaining total end-clamp glucose uptake (M) and end-clamp glucose oxidation (ECGO) rates. RESULTS: Within 3 weeks of surgery, plasma triglycerides and cholesterol levels had decreased from 4500 and 500 mg/dl (with dietary restrictions) to lower than 450 and 150 mg/dl (on a free, lipid-rich diet) respectively. Fasting plasma glucose levels had decreased from above 300 (under daily repeated subcutaneous injections of insulin) to 80-100 mg/dl (without administration of insulin or oral hypoglycemic agents). Body weight and fat free mass were maintained in both subjects after surgery. In both patients, before surgery M and ECGO were significantly lower than in normal subjects, while after surgery they were not significantly different from normal subjects, confirming the positive metabolic effect of the operation. CONCLUSION: The surgical option used in these patients may represent an interesting and effective new possibility for treatment of those severe cases of hyperlipemia leading otherwise to metabolic complications and a low quality of life.

Metabolic features of inflammatory bowel disease in a remission phase of the disease activity.

OBJECTIVES: To evaluate the anthropometric and metabolic characteristics of patients with Crohn's disease (CD) and ulcerative colitis (UC), comparing both groups with healthy volunteers. DESIGN: A cross-sectional study. SETTING: The Department of Internal Medicine, Catholic University Hospital, Rome, Italy. SUBJECTS: Thirty-four patients with biopsy-proven inflammatory bowel disease (18 CD; 16 UC) in clinical remission (SCDAI < 3 and Powell-Tuck index < 4) not receiving steroid therapy. INTERVENTIONS: All patients had a clinical examination. MAIN OUTCOME MEASURES: Blood indicators of inflammation and nutritional status. Body composition was assessed by both anthropometry and bioimpedance and metabolic variables were measured by indirect calorimetry over a 60-90 min period. RESULTS: CD had a lower body weight than both controls (58.1 kg, range 41.5-71.0 vs. 66.4 kg, range 57.0-76.0; P < 0.001) and UC) 58.1 kg, range 41.5-71.0 vs. 69.6 kg, range 50.5-94.0; (P < 0.001). Fat-free mass (FFM) did not differ between the groups, whilst fat mass was significantly lower in CD than in UC (P < 0.05) and controls (P < 0.001). Normalizing the basal metabolic rate by FFM, a higher value was found in CD compared with UC (143 kJ kg-1) d-(-1), range 97.5-179 vs. 133 kJ kg-1 d-1, range 123-148; P < 0.05) and control subject 143 kj kg-1 d-1, range 97.5-179 vs. 134 kj kg-1 d-1, range 122-162; P < 0.05). The nonprotein respiratory quotient was significantly lower in CD compared to UC 0.80, range 0.73-0.84 vs. 0.84, range 0.79-0.91; P < 0.01) and controls (0.80, range 0.73-0.84 vs. 0.83, range 0.81-0.87; P < 0.001), with a consequently higher lipid oxidation rate in CD. CONCLUSIONS: CD subjects showed a decreased fat mass and enhanced utilization of lipids compared with UC and controls. These data could be explained by the larger intestinal involvement and considered as a contribution to lipid tissue wasting in CD.

Twenty-four-hour energy balance in Crohn disease patients: metabolic implications of steroid treatment.

Several hypotheses have been proposed to explain the nutritional deficiencies seen in Crohn disease patients, including inadequate food intake, decreased assimilation and increased loss of nutrients, and increased energy expenditure. To assess the effect of steroid therapy on body composition, energy expenditure, and fuel selection in Crohn disease, we compared 12 patients (6 men and 6 women) with biopsy-proven ileal Crohn disease with 11 healthy volunteers (6 men and 5 women). Five patients [Crohn's disease activity index (CDAI) = 98.4 +/- 3.78] took no medication and seven patients (CDAI = 283.9 +/- 22.5) were administered 29 +/- 18 mg prednisone/d. Body composition was evaluated by isotopic dilution and bioelectrical impedance analysis, and 24-h energy expenditure and basal metabolic rate were measured in a respiratory chamber. Fat-free mass was not significantly different among groups, whereas fat mass was lower in patients than in control subjects. Energy intake was higher in treated patients than in both untreated patients (P = 0.004) and control subjects (P = 0.005). Fecal losses were not significantly different between untreated patients and control subjects, but were higher (and proportional to the CDAI) in treated patients than in control subjects (P = 0.001). Metabolizable energy was not significantly different among groups, whereas energy balance was significantly higher in treated patients than in both control subjects (P = 0.0057) and untreated patients (P = 0.018). Nitrogen balance was mildly negative in treated patients compared with both control subjects and untreated patients, but not significantly so. In conclusion, prednisone treatment in Crohn disease patients stimulates food intake, promoting an overall positive energy balance despite large fecal nutrient losses.