Biomedical subjects

G Mingrone

Publications and source records attributed to G Mingrone.

At least 19 recordsLinked to original sources

PubMed2006

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin.

AIMS/HYPOTHESIS: Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance. MATERIALS AND METHODS: We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model. RESULTS: Among 434 consecutive non-diabetic men, the age-adjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513] microg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation. CONCLUSIONS/INTERPRETATION: These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

Adult↗

PubMed2006

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function.

AIMS/HYPOTHESIS: The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing bilio-pancreatic diversion (BPD). SUBJECTS AND METHODS: We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic-hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52+/-7 kg/m(2), mean+/-SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery. RESULTS: BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341+/-79 ml min(-1) m(-2), post-BPD 511+/-57 ml min(-1) m(-2), lean 478+/-49 ml min(-1) m(-2)). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min(-1) m(-2) l mmol(-1), median [interquartile range]) compared with lean subjects (82 [98]; p</=0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r (2)=0.67, partial r=-0.76 and -0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement. CONCLUSIONS/INTERPRETATION: Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity.

Adiponectin↗

PubMed2006

Effect of botulinum toxin antral injection on gastric emptying and weight reduction in obese patients: a pilot study.

BACKGROUND: A potential approach to the treatment of morbid obesity is reduction of gastric emptying to achieve satiety. Botulinum toxin A (Btx-A) is a long-acting inhibitor of acetylcholine-mediated peristalsis, which is mainly responsible for gastric motility. AIM: To investigate whether botulinum toxin A, injected in the antrum of obese patients, delays gastric emptying. METHODS: In a double_blind study, 18 healthy obese subjects (body mass index >30) were randomized into three groups (BTX133, BTX200 and Saline); they received Btx-A133U, Btx-A200U, or saline under endoscopic control. Gastric emptying was tested by scintigraphy before and 10 days after treatment. Body weight variations and appetite sensation were recorded after 5 weeks. RESULTS: Fourteen patients completed the study. The botulinum toxin A-treated groups showed weight reduction, which was not statistically significant. The effects on gastric emptying were variable. Most of the botulinum toxin A treated patients reported a reduced appetite. CONCLUSION: This pilot clinical trial suggests potential activity of botulinum toxin A for the manipulation of appetite.

Adult↗

PubMed2005

Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity?

AIMS/HYPOTHESIS: In obesity the cellular capacity to switch from using lipid to carbohydrate and vice versa as the energy substrate, known as 'metabolic flexibility', is impaired. Mitofusin 2 (MFN2), a mitochondrial membrane protein, seems to contribute to the maintenance and operation of the mitochondrial network, and its expression is reduced in obesity. The aim of this study was to verify whether MFN2 might be implicated in the metabolic inflexibility of obesity. MATERIALS AND METHODS: Insulin sensitivity was measured in six morbidly obese women before and 2 years after malabsorptive bariatric surgery (BMI 53.3+/-10.5 vs 30.3+/-4.0 kg/m2). Skeletal muscle MFN2, SLC2A4 (formerly known as GLUT4), COX3 (encoding cytochrome c oxidase subunit III) and CS (encoding citrate synthase) mRNA levels were measured by real-time PCR. RESULTS: Following bilio-pancreatic surgery, significant increases in MFN2 mRNA (from 0.4+/-0.2 to 1.7+/-1.1 arbitrary units [AU], p=0.019) and SLC2A4 mRNA (0.38+/-0.12 to 0.76+/-0.24 AU, p=0.04) were observed, while increases in COX3 mRNA (from 14.2+/-6.4 to 20.2+/-12.5 AU) and CS mRNA (from 0.4+/-0.1 to 0.7+/-0.3 AU) failed to reach statistical significance. Insulin-mediated whole-body glucose uptake significantly (p<0.0001) increased from 21.2+/-4.1 to 52.8+/-5.9 micromol kg fat-free mass(-1) min(-1) and glucose oxidation rose from 11.1+/-2.1 to 37.7+/-4.7 micromol kg fat-free mass(-1) min(-1) (p<0.0001). Levels of MFN2 mRNA were strongly correlated with the absolute values for the glucose oxidation rate, both during fasting (glucose oxidation =3.55 MFN2 mRNA + 3.93; R2=0.92, p<0.0001) and during the clamp (glucose oxidation=18.8 MFN2 mRNA+34.7; R2=0.80, p<0.0001). The percentage changes in MFN2 mRNA were positively correlated with the percentage change in glucose oxidation during the clamp (glucose oxidation percent (%) change=0.3 MFN2 mRNA percent (%) change+153.2; R2=0.61, p<0.001). CONCLUSIONS/INTERPRETATION: We propose that the significant increase in MFN2 mRNA levels may explain the increase in glucose oxidation observed in morbid obesity following bariatric surgery.

Adult↗

PubMed2005

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Adult↗

PubMed2004

Further lowering of muscle lipid oxidative capacity in obese subjects after biliopancreatic diversion.

A reduced lipid oxidative capacity is considered a risk factor for the development of obesity, but a further impairment of lipid oxidative capacity is observed after weight loss. We aimed to define the mechanisms underlying this phenomenon in skeletal muscle and in particular to study the mitochondrial and peroxisomal lipid oxidative pathways. Thus we measured intramyocellular triglyceride content (IMTG) and the expression of genes of lipid oxidation [peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase 1B, and acyl-coenzyme A (acyl-CoA) oxidase 1] and synthesis (acetyl-CoA carboxylase B) using RT-PCR analysis in muscle biopsies of morbidly obese patients before and after biliopancreatic diversion. Weight reduction significantly decreased IMTG while increasing insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Moreover, an increase in glucose and a decline in lipid oxidation, as assessed by respiratory chamber, were observed. Weight loss reduced the expression of peroxisome proliferator-activated receptor-alpha (-46.7%), carnitine palmitoyltransferase 1B (-43.1%), acyl-CoA oxidase 1 (-37.8%), and acetyl-CoA carboxylase B (-48.7%). Our results indicate that a defect of both peroxisomal and mitochondrial oxidative pathways at the muscular level may contribute to the reduced fat oxidation in obese subjects after biliopancreatic diversion. They also suggest that a depression of the de novo lipogenesis may account for IMTG depletion.

Biliopancreatic Diversion↗

PubMed2004

Changes in muscle myostatin expression in obese subjects after weight loss.

Myostatin is a member of transforming growth factor-beta superfamily that plays an important inhibitory role during muscle development; in fact mutations of myostatin gene result in a hypermuscular phenotype. Moreover myostatin-deficient mice have a significant reduction in fat depots and a depression of adipogenesis. Little is known about myostatin function in muscle growth regulation in humans and in particular during caloric restriction. In the present work we quantified by real-time RT-PCR myostatin expression in muscle biopsies of a group of morbidly obese patients before and after weight loss obtained by biliopancreatic diversion (BPD). The patients reduced body weight by 38.9%, mostly due to fat-mass loss, showing also a significant reduction in the 24-hour EE as assessed by the respiratory chamber. Myostatin mRNA levels result clearly decreased after weight loss, suggesting a role in counteracting the progressive decline of muscle mass after BPD. Myostatin may provide therefore another mechanistic explanation for the control of energy partitioning between protein and fat, working against muscle wasting. Our data suggest that myostatin might represent an important regulator of skeletal muscle size also in conditions of food restriction in obese subjects.

Body Composition↗

PubMed2003

VO2, VCO2, and RQ in a respiratory chamber: accurate estimation based on a new mathematical model using the Kalman-Bucy method.

A respiratory chamber is used for monitoring O(2) consumption (Vo(2)), CO(2) production (Vco(2)), and respiratory quotient (RQ) in humans, enabling long term (24-h) observation under free-living conditions. Computation of Vo(2) and Vco(2) is currently done by inversion of a mass balance equation, with no consideration of measurement errors and other uncertainties. To improve the accuracy of the results, a new mathematical model is suggested in the present study explicitly accounting for the presence of such uncertainties and error sources and enabling the use of optimal filtering methods. Experiments have been realized, injecting known gas quantities and estimating them using the proposed mathematical model and the Kalman-Bucy (KB) estimation method. The estimates obtained reproduce the known production rates much better than standard methods; in particular, the mean error when fitting the known production rates is 15.6 +/- 0.9 vs. 186 +/- 36 ml/min obtained using a conventional method. Experiments with 11 humans were carried out as well, where Vo(2) and Vco(2) were estimated. The variance of the estimation errors, produced by the KB method, appears relatively small and rapidly convergent. Spectral analysis is performed to assess the residual noise content in the estimates, revealing large improvement: 2.9 +/- 0.8 vs. 3,440 +/- 824 (ml/min)(2) and 1.8 +/- 0.5 vs. 2,057 +/- 532 (ml/min)(2), respectively, for Vo(2) and Vco(2) estimates. Consequently, the accuracy of the computed RQ is also highly improved (0.3 x 10(-4) vs. 800 x 10(-4)). The presented study demonstrates the validity of the proposed model and the improvement in the results when using a KB estimation method to resolve it.

Carbon Dioxide↗

PubMed2003

Intramyocitic lipid accumulation and SREBP-1c expression are related to insulin resistance and cardiovascular risk in morbid obesity.

The aim of this study was to investigate the sterol regulatory element-binding protein 1c (SREBP1c) mRNA muscle expression in morbid obese subjects before and after massive lipid malabsorption due to bariatric surgery (bilio-pancreatic diversion, BPD). We studied 11 obese subjects (BMI 49+/-2 kg/m2) before and 24 months after BPD. Skeletal muscle SREBP1c mRNA expression was determined using RT-competitive PCR. Intramyocytic triglycerides were quantified by HPLC. Insulin sensitivity (M/I) was assessed by euglycemic-hyperinsulinemic clamp. Energy expenditure and respiratory quotient (RQ) were measured over 24 h in a calorimetric chamber. Total cardiovascular risk dropped from 2 before to -2.5 after BPD (P<0.0001). The M/I value was normalized after surgery (0.036+/-0.0148 to 0.095+/-0.0147 micromol kgFFM(-1) min(-1) pmoles(-1) P<0.001). SREBP-1c mRNA levels were decreased (from 4.12+/-2.43 to 2.69+/-1.83% of cyclophilin mRNA, P=0.02) after BPD. In a multiple regression analysis, M/I values (P<0.0001) as well as the intramyocytic triglyceride levels (P=0.039) were the most powerful independent variables for predicting cardiovascular risk. Our results show that the reduction of cardiovascular risk after bariatric massive weight loss is strongly related to the reversion of insulin resistance and to the lowering of intramyocytic triglyceride depots. These two parameters are associated with a significant reduction in SREBP-1c mRNA expression in skeletal muscle, suggesting that this transcription factor might be involved in the accumulation of triglycerides in muscle cells of morbidly obese subjects.

Adipose Tissue↗

PubMed2002

Computing DIT from energy expenditure measures in a respiratory chamber: a direct modeling method.

The possibility of computing Diet Induced Thermogenesis (DIT) is an important feature of metabolic investigations. However, methodological problems have affected the determination of DIT in the indirect calorimetric chamber. DIT has been commonly estimated by regressing energy expenditure on a measure of physical activity. Although used for many years as the only feasible approach to calculate DIT in a respiratory chamber, this traditional method has been criticized because of an apparent underestimation of the DIT, but no alternative method has been suggested so far. The present work proposes to estimate DIT directly by means of a mathematical model. This approach also allows to simultaneously estimate other parameters, namely resting energy expenditure (REE), physical activity (PA) and physical exercise (PE).

Adult↗

PubMed2002

Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery.

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.

Adult↗

PubMed2002

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.

Adult↗

PubMed2002

Mechanisms of hyperinsulinaemia in Child's disease grade B liver cirrhosis investigated in free living conditions.

AIMS: Human liver cirrhosis is commonly associated with increased fasting and glucose induced insulin concentrations. However, whether the hyperinsulinaemia is a consequence of increased pancreatic insulin secretion, decreased hepatic insulin removal, or impaired feedback regulation of insulin secretion is still doubtful. To investigate these issues, insulin secretion-during 24 hours of standardised living conditions-insulin sensitivity, and hepatic insulin extraction were assessed in cirrhotic patients compared with matched healthy subjects. PATIENTS: Nine Child's disease grade B cirrhotic patients and seven healthy volunteers, participated in the study. The subjects were studied on two separate days, one for the assessment of insulin secretion during a standardised 24 hour life period (calorimetric chamber), and one for the determination of insulin sensitivity. METHODS: Insulin secretion rates were reconstructed from plasma C peptide concentrations by deconvolution, and indices of beta cell function were derived using a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations. Insulin sensitivity was determined using the euglycaemic hyperinsulinaemic clamp technique. RESULTS: Cirrhotic patients showed a marked hypersecretory response, both in absolute terms (mean (SEM) 295 (53) versus 138 (11) nmol/m(2), p<0.02), and in relation to glucose (175 (26) versus 57 (5) pmol/min/m(2), p<0.02). In particular, the beta cell dose-response function was shifted upward compared with controls. The sensitivity of insulin secretion to the rate of glucose change was also increased. Insulin sensitivity, markedly reduced in cirrhosis (157 (10) versus 296 (30) ml/min/m(2), p<0.002), was strongly inversely correlated (r=0.89, p<0.002) in these patients with insulin secretion at 5 mM glucose. Insulin clearance and hepatic insulin extraction were not reduced. A frank hypermetabolism with increased lipid oxidation was found in this series. CONCLUSIONS: This study suggests that hyperinsulinaemia, at least in Child's disease grade B cirrhotic patients, is the consequence of increased beta cell sensitivity to glucose, while hepatic insulin extraction does not seem to play a significant part.

Biomarkers↗

PubMed2002

New bioimpedance model accurately predicts lower limb muscle volume: validation by magnetic resonance imaging.

Conventional bioimpedance analysis (BIA) methods now simplify the representation of lower limb geometry and electrical properties for body composition estimation. In the present study, a three-dimensional model of the lower limb was assembled by segmentation of magnetic resonance cross-sectional images (MRI) for adipose tissue, skeletal muscle, and bone. An electrical network was then associated with this model. BIA and MRI measurements were made in six lean subjects (3 men and 3 women, age 32.2 +/- 6.9 yr). Assuming 0.85 S/m for the longitudinal conductivity of the muscle, the model predicted in the examined subjects an impedance profile that conformed well to the BIA impedance profile; predicted and measured resistances were similar (261.3 +/- 7.7 vs. 249 +/- 9 Omega; P = not significant). The resistance profile provided, through a simpler model, muscle area estimates along the lower limb and total leg muscle volume (mean 4,534 cm(3) for men and 4,071 cm(3) for women) with a mean of the absolute value of relative error with respect to MRI of 6.2 +/- 3.9. The new approach suggests that BIA can reasonably estimate the distribution and volume of muscles in the lower extremities of lean subjects.

Adipose Tissue↗

PubMed2002

Enteral diet in Crohn's disease. Nutritional and therapeutic implications in patient's management.

Inflammatory bowel diseases (IBD) are often characterized by impairment of nutritional status. Crohn's disease (CD) patients, especially in the active phase of disease, show a reduced body weight, due to the reduction of lipid stores, in spite of lean mass depletion. Fat mass reduction has been correlated to an increased utilization of lipids as fuel substrate. The alterations of nutritional status are able, in turn, to influence, as independent factors, the disease course and patient prognosis. A disease's treatment based only on pharmacologic therapy, especially on corticosteroid use in the active phases, often does not take into account the relevant need for preserving a normal nutritional status. In this connection, enteral nutrition has been shown to be able to improve nutritional status and induce and maintain remission. We present some of the possible mechanisms of efficacy of enteral feeding and some rules to attempt to treat patients with IBD, especially those with Crohn's disease.

Journal Article↗

PubMed2002

Main physiopathologic mechanisms involved in hepatic drug reactions.

The liver has a pivotal role in drug metabolism and hepatic drug reactions are frequent events, accounting for 5% of cases of jaundice or acute hepatitis in the community. The importance of hepatic drug reactions lies not only in their frequency, but also in the great number of molecules that can cause this type of lesions and in their variable gravity. This review will show the main factors implicated in drug metabolism which can explain the different susceptibility in developing hepatic drug reaction, the possibility that it may manifest as a wide spectrum of clinical syndromes or that a single agent may cause more than one lesion (a relevant problem not only for the clinician, but also for the pathologist).

Journal Article↗

PubMed2001

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.

Anorexia Nervosa↗

PubMed2001

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.

Adipose Tissue↗