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.

State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting.

OBJECTIVES: To evaluate state and trait form of anxiety and current depression in patients affected by gastrointestinal diseases. METHODS: We studied 1641 outpatients with gastrointestinal disorders, consecutively referred to our Internal Medicine outpatients from 1997 to 2005. State and trait anxiety were assessed by the State and Trait Anxiety Inventory. Current depression was assessed by the Zung self-rating depression scale. RESULTS: Among patients, 1379 (84.1%) showed state anxiety, 1098 (67%) showed trait anxiety and 442 (27%) showed current depression. The number of gastrointestinal diseases was directly correlated to state anxiety (p < 0.001) and trait anxiety (p = 0.04). Females showed higher levels of anxiety and depression than males (p < 0.001). State anxiety was related to food allergies (p < 0.001), small intestinal bacterial overgrowth (SIBO) (p = 0.001), Hp infection (p = 0.01) and ulcerative colitis in active phase (p = 0.03). Trait anxiety was related to irritable bowel syndrome (IBS) (p < 0.001), Helicobacter pylori (Hp) infection (p = 0.001), food allergies (p = 0.001) and SIBO (p = 0.001). Current depression was related to IBS (p < 0.001) and coeliac disease (p = 0.01), SIBO (p = 0.02). A predicted probability of 0.77 +/- 0.16 to have state anxiety, of 0.66 +/- 0.12 to have trait anxiety and of 0.39 +/- 0.14 to have depression was found in these patients. CONCLUSIONS: Most of the patients who seek medical consultation for gastrointestinal problems show an associated affective disorder. These patients should be managed by a team including gastroenterologists, psychologists and/or psychiatrists, or by a gastroenterologist having expertise in the treatment of psychological disorders.

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.

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.

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.

An independent, inverse association of high-density-lipoprotein-cholesterol concentration with nonadipose body mass.

BACKGROUND: Increasing body mass index (BMI) is associated with progressively lower serum HDL-cholesterol concentrations, although the underlying body-composition compartment accounting for this unfavorable lipid change remains uncertain. OBJECTIVE: Because growing evidence favors a role of lean tissue in HDL homeostasis, the hypothesis was tested that non-adipose tissue components of body mass explain the inverse association of HDL cholesterol and BMI. DESIGN: Fasting serum lipid concentrations and body composition [total, subcutaneous, and visceral adipose tissue; adipose tissue-free mass (ATFM); and skeletal muscle by whole-body magnetic resonance imaging and body cell mass by 40K counting) were evaluated in healthy adults. Body-composition compartments were expressed as height2-normalized indexes. RESULTS: An inverse correlation was observed between serum HDL cholesterol and BMI in women (n = 68; R2 = 0.08, P = 0.023) and men (n = 61; R2 = 0.07, P = 0.046). Significant inverse correlations (P = 0.005-0.02) were also observed between HDL cholesterol and nonadipose components (ie, ATFM, skeletal muscle, and body cell mass) but not between HDL cholesterol and any adipose tissue component. The association between HDL cholesterol and ATFM remained significant after serum triacylglycerol was controlled for. When BMI was entered into the HDL cholesterol-ATFM regression model, BMI was not a significant independent variable. The strongest correlate of serum triacylglycerol was visceral adipose tissue (P = 0.002 for both women and men). CONCLUSIONS: Lean tissues and body cell mass appear to account in part for the long-observed inverse association of HDL cholesterol and BMI. These observations suggest a link between nonadipose tissue compartments and the greater cardiovascular risk associated with high BMI.

Glucose-induced thermogenesis in postobese women who have undergone biliopancreatic diversion.

We evaluated the metabolic response to a standard (75-g) oral-glucose-tolerance test (OGTT) in eight post-obese women (PO) who underwent biliopancreatic diversion and in eight healthy control women (C). All subjects had been weight-stable for > or = 2 y. Blood samples for glucose, insulin, C-peptide, and nonesterified free fatty acids were taken at baseline and during 180 min after the glucose load. Plasma glucose and insulin concentrations at baseline and during the OGTT were similar in the two groups, suggesting the absence of an insulin-resistant state in the PO. Continuous indirect calorimetry was performed throughout the test. Glucose-induced thermogenesis (GIT) was higher in PO than in C (8.6 +/- 2.6 vs 4.3 +/- 1.9%; P < 0.01). These data indicate that GIT and insulin-glucose metabolism are not impaired in postobese patients when a near ideal body weight is reached and maintained after weight loss; this suggests that thermogenic deficiencies and hyperinsulinemia-insulin resistance are alterations secondary to obesity.

Changes in body composition, substrate oxidation, and resting metabolic rate in adult celiac disease patients after a 1-y gluten-free diet treatment.

BACKGROUND: The incidence of celiac disease has been on the rise in both Europe and the United States. Celiac disease patients are at high risk of undernutrition because of nutrient malabsorption. OBJECTIVE: The aim of the present study was to evaluate changes in body composition and energy metabolism in a group of patients with celiac disease before and after consumption of a gluten-free diet (GFD). DESIGN: Body composition (by anthropometry and isotopic dilution), resting metabolic rate (RMR), and substrate oxidation rates (by indirect calorimetry) were assessed in 39 adult celiac disease patients (16 men and 23 women) with a mean (+/-SD) age of 29. 9 +/- 7.6 y, weight of 58.3 +/- 6.6 kg, and percentage body fat of 20.1 +/- 6.7%, and in 63 (29 men and 34 women) age- and height-matched control subjects (age: 33.2 +/- 8.1 y; weight: 66.8 +/- 6.6 kg; and percentage body fat: 25.4 +/- 3.7%). Celiac disease patients were studied twice, at diagnosis and 1 y after treatment with a GFD. RESULTS: Before treatment, celiac disease patients had a lower body weight (P < 0.05) and a higher carbohydrate oxidation rate (P < 0.01) than did control subjects. Carbohydrate oxidation rates correlated positively with fecal lipid loss in untreated celiac disease patients (r = 0.80, P < 0.0001). After the GFD, percentage body fat was higher in celiac disease patients than in control subjects (P < 0.01), and lipid intakes tended to be higher than before treatment. CONCLUSIONS: This longitudinal study showed that the GFD treatment significantly increased body fat stores. Untreated patients preferentially utilized carbohydrates as a fuel substrate, probably as a consequence of both lipid malabsorption and a high carbohydrate intake, and lipid utilization increased with the restoration of the intestinal mucosa.

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.

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.

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.

Psychological support counselling improves gluten-free diet compliance in coeliac patients with affective disorders.

BACKGROUND: Anxiety and depression are common features of coeliac disease. Depression is cause of non-compliance to treatment in chronic illness. AIM: To evaluate the useful of psychological support counselling to improve affective disorders and gluten-free diet adherence in coeliac disease with anxiety and depression. METHODS: A total of 66 coeliac disease patients with state anxiety and current depression were enrolled. Patients were randomized in two groups: in group A psychological support was started at the beginning of gluten-free diet, while group B was free of psychological support. Both groups were followed every 2 weeks for 6 months. State and Trait Anxiety Inventory test Y-1 and the modified Zung self-rating depression scale were administered before (T0) and after 6 months of gluten-free diet (T1). RESULTS: At T1 no difference was found between groups in the percentage of state anxiety, while a significant lower percentage of depressed subjects was found in group A with respect to group B (15.1% vs. 78.8%; P=0.001). In the follow-up period, a significant lower compliance to gluten-free diet was found in group B with respect to group A (39.4% vs. 9.1%; P=0.02). CONCLUSIONS: In coeliac disease patients with affective disorders psychological support seems to be able to reduce depression and to increase gluten-free diet compliance.

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.

Blunted glucose metabolism in anorexia nervosa.

Only few studies have specifically investigated diet-induced thermogenesis in anorexia nervosa. Twenty women, 10 anorectics (body mass index [BMI] = 14.98 +/- 1.02 kg/m(2)) and 10 controls (BMI = 22.53 +/- 0.75 kg/m(2)) were studied. Body composition was evaluated by isotopic dilution. Respiratory gas exchange was measured by indirect calorimetry. An oral glucose load (75 g) was administered to the anorectics (A) and the controls (CA). The controls underwent a second load (CB) with a higher glucose amount (1.85 +/- 0.11 g/kg body weight [BW]) to compare with the load taken by anorectics. Glucose-induced thermogenesis (GIT) was computed for 300 minutes following the load as the percent increase of energy expenditure (EE) above resting-EE (REE). Serum glucose levels were lower in anorectic patients both in fasting (3.46 +/- 0.66 v 5.23 +/- 0.23 in CA, P <.01 v 5.32 +/- 0.34 mmol in CB, P <.01) and in the postprandial state (glucose area under the curve [AUC] 175.51 +/- 6.40 v 289.80 +/- 7.30 in CA, P <.01 v 324.65 mmol in CB, P <.001); insulin AUC was lower, 1,926 +/- 452 versus 41,148 +/- 2,071 in CA, P <.0001 versus 60,765.5 pmol in CB, P <.0001. REE, normalized by fat-free mass (FFM), was similar between groups. GIT was lower in anorectics (3.58 +/- 1.20 v 5.45 +/- 1.83 in CA, P <.05 v 9.09% +/- 1.05% in CB, P <.01). Glucose oxidation was higher in anorectics than in CA (689.44 +/- 72.22 v 333.32 +/- 32.98 micromol/L/min, P <.001), but similar to CB. Lipid oxidation become negative after 30 minutes in anorectics (postprandial lipid oxidation = -93.58 +/- 39.86 v 370.61 +/- 21.73 in CA, P <.0001 v 119.01 +/- 12.32 micromol/L/300 min in CB, P <.0001). Anorectic patients displayed a low REE and GIT. Carbohydrate oxidation was similar between groups; lipid oxidation was extremely reduced. An increased protein catabolism was observed.

Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus.

To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/- 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.48 mumol/kg/min [P < .05] and 11.92 +/- 2.74 v 8.43 +/- 1.86 mumol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucose level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg/dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration. In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play an important role in weight reduction. In addition, dF shows a weight-independent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion.

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.

Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients.

Little information is available in the literature on the effect of L-carnitine to improve glucose disposal in healthy control subjects and type 2 diabetic patients. No data are reported on the pharmacological properties of acetyl-L-carnitine (ALC) in type 2 diabetes mellitus. The present study evaluates glucose uptake and oxidation rates with either ALC or placebo administration in 18 type 2 diabetic patients. On different days, each patient received both a primed-constant infusion of ALC (5 mg/kg body weight [BW] priming bolus and either 0.025, 0.1, or 1.0 mg/kg BW/min constant infusion) and a comparable placebo formulation. During the infusion period, continuous indirect calorimetric monitoring and a euglycemic-hyperinsulinemic clamp (EHC) study were performed. The total end-clamp glucose tissue uptake (M value) was significantly increased by the administration of ALC (from 3.8 to 5.2 mg/kg/min, P = .006), and the dose dependence of this effect reached borderline statistical significance (P = .037). The increase in the M/I ratio was also highly significant after ALC administration (from 3.9 to 5.8 x 10(-2) mg/kg/min/(microUI/mL, P < .001), while no statistically significant effect was attributable to the different dosages. The increase in the M value was related to increased glucose storage (highly significant effect of ALC) rather than increased glucose oxidation (no statistical significance). In conclusion, the effect of ALC on glucose disposal has no relationship to the amount administered. This could be due to an effect of ALC on the enzymes involved in both the glycolytic and gluconeogenetic pathways, and a possible reversibility of glycogen synthase inhibition in diabetic subjects.

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.

Different limit to the body's ability of increasing fat-free mass.

It is a common understanding that fat-free mass (FFM) increases with body weight. However, limited information is available as to the relationship between weight increase and changes in body composition. We performed the present study to determine quantitatively the relationship between body composition, total body weight, age, and sex. Body composition data were obtained by isotopic dilution on 273 subjects ranging in body mass index (BMI) from about 13 to 70 kg/m(2). Adipose free tissue (AFT) was modeled as a nonlinear, increase-limited function of body weight. Model parameters were evaluated as functions of sex, age, and height. The relationship between AFT and body weight was very well approximated by means of the nonlinear model (R(2) =.95), with maximal AFT being determined by both sex and height and with AFT growth rate determined only by sex. AFT clearly shows a nonlinear behavior, tending to increase less and less with progressively increasing body weight. With the proposed model, an asymptotic maximal AFT may be postulated. The organism seems to have an intrinsic limitation to how much skeletal muscle development may take place to accommodate the necessities of an ever-increasing load. These limits are different between the sexes, with women tending to approach more rapidly than men a lower maximal AFT for the same height.