Nutritional status in post SARS-Cov2 rehabilitation patients.

BACKGROUND & AIMS: After prolonged hospitalization, the assessment of nutritional status and the identification of adequate nutritional support is of paramount importance. In this observational study, we aimed at assessing the presence of a malnutrition condition in SARS-Cov2 patients after the acute phase and the effects of a multidisciplinary rehabilitation program on nutritional and functional status. METHODS: We recruited 48 patients (26 males/22 females) admitted to our Rehabilitation Unit after discharge from acute Covid Hospitals in northern Italy with negative swab for SARS-Cov2. We used the Global Leadership Initiative on Malnutrition (GLIM) criteria to identify patients with different degrees of malnutrition. Patients underwent a 3 to 4-week individual multidisciplinary rehabilitation program consisting of nutritional intervention (energy intake 27to30 kcal/die/kg and protein intake 1-1.3 g/die/kg), exercise for total body conditioning and progressive aerobic exercise with cycle- and arm-ergometer (45 min, 5 days/week). At admission and discharge from our Rehabilitation Unit, body composition and phase angle (PhA) (BIA101 Akern), muscle strength (handgrip, HG) and physical performance (Timed-Up-and-Go, TUG) were assessed. RESULTS: At admission in all patients the mean weight loss, as compared to the habitual weight, was -12.1 (7.6)%, mean BMI was 25.9 (7.9) kg/m2, mean Appendicular Skeletal Muscle Index (ASMI) was 6.6 (1.7) kg/m2 for males and 5.4 (1.4) kg/m2 for females, mean phase angle was 2.9 (0.9)°, mean muscle strength (HG) was 21.1 (7.8) kg for males and 16.4 (5.9) kg for females, mean TUG value was 23.7 (19.2) s. Based on GLIM criteria 29 patients (60% of the total) showed a malnutrition condition. 7 out of those 29 patients (24%) presented a mild/moderate grade and 22 patients (76%) a severe grade. After a rehabilitation program of an average duration of 25 days (range 13-46) ASMI increased, with statistically significant differences only in females (p = 0.001) and HG improved only in males (p = 0.0014). In all of the patients, body weight did not change, CRP/albumin (p < 0.05) and TUG (p < 0.001) were reduced and PhA increased (p < 0.01). CONCLUSIONS: We diagnosed a malnutrition condition in 60% of our post SARS-Cov2 patients. An individualized nutritional intervention with adequate energy and protein intake combined with tailored aerobic and strengthening exercise improved nutritional and functional status.

Non-surgical ablative therapies for inoperable benign insulinoma.

PURPOSE: Benign insulinoma is the most common functioning neuroendocrine tumor of the pancreas. The gold-standard therapeutic approach for insulinoma is surgery, which allows for tumor removal, histology and immunochemical analyses. If surgery is not feasible, minimally invasive ablative procedures performed by interventional radiology can lead to partial or complete remission of hormone hypersecretion and tumor control in insulinoma patients. METHODS: We performed a review of existing literature on non-chemotherapeutic/radioactive ablative techniques employed for the treatment of benign, otherwise inoperable, pancreatic insulinoma. For this purpose, feasibility, effectiveness and safety of ablative treatments for pancreatic insulinoma were reviewed from literature data published from 1982 to date. RESULTS: A total of 44 insulinoma cases treated with non-surgical ablative techniques were desumed, and divided as follows: 7 cases of tumor embolization, 26 ethanol ablations, 7 radiofrequency ablations, 2 high intensity focused ultrasound ablation, 1 irreversible electroporation and 1 percutaneous microwave ablation. Most cases involved single insulinoma, predominantly located in the pancreas head and body. In the majority of patients, ablation was chosen instead of surgery due to severe comorbidities. After an average follow-up of 16 months, the overall success rate of non-surgical ablative treatments of insulinoma was 84%, the recurrence/persistence rate was 16%, and transient adverse events were noted in 23% of cases. Adverse events were usually self-limiting and medically manageable. CONCLUSIONS: Non-surgical ablation is a feasible, safe and repeatable procedure in patients with pancreatic insulinoma, who are not candidate to surgery or refuse it. Partial or complete control of symptoms and tumor growth is experienced by the majority of patients.

Leptin level lowers in proportion to the amount of aerobic work after four weeks of training in obesity.

Leptin values are higher in obesity. Physical exercise reduces fat mass (FM) and decreases leptin levels. Intensity of physical training seems to play a role in reducing circulating leptin. In 16 obese subjects (8 men and 8 women, age 38.6±3.9 years, BMI 35.9±1.8 kg/m(2)), leptin was sampled before and after 4 weeks of controlled training. Eight subjects (4 men and 4 women) performed an aerobic training schedule (Group A), the remainders an aerobic training program with a bout of work beyond the anaerobic threshold (AT) (Group B). Training determined a reduction in leptin levels in both groups, which was significant in Group A (12.2 vs. 27.8 µg/l, p<0.05), even when related to the change in FM (0.372 vs. 0.762 µg/l/kg, p<0.05). FM decreased significantly in Group B when compared to Group A (-7.4 vs. -2.6 kg, respectively, p<0.001). While in Group A the slight loss of FM was aggregated to a significant decrease in leptin levels, the opposite occurred in Group B. In Group A, leptin lowering was proportional to the amount of total work performed (p<0.001, R(2)=0.89). In obesity, a reduction is observed in leptin levels after short-term training, which is seemingly dissociated from concomitant decrease of FM. Aerobic training alone appears to be linked to a greater leptin reduction, which is well correlated with the amount of work performed.

Assessing the appropriateness of the level of care for morbidly obese subjects: validation of the CASCO-R scale.

AIM: Aim of this study was to validate the Comprehensive Appropriateness Scale for the Care of Obesity in Rehabilitation (CASCO-R) and to determine the cut-off score for indicating the most appropriate health care setting for patients with obesity. METHODS: The CASCO-R scale was developed according to the available scientific literature and expertise of an expert panel working for a Consensus document endorsed by the Italian Society of Obesity (SIO) and the Italian Society for the Study of Eating Disorders (SISDCA). 16 Italian centres, specialized in the treatment of obesity, characterised by different settings of care (specialist outpatient service, day-hospital service, intensive inpatient rehabilitation), participated in the study. RESULTS: 449 obese subjects were enrolled in the study (30.5% males and 69.5% females): 38.3% from outpatient services, 20.7% from day-hospital services and 40.9% from intensive inpatient rehabilitation units. After 2-month of treatment, a workload summary sheet, including medical and nursing interventions, number of expert advices and diagnostic procedures, and adverse clinical events (ACEs) was fulfilled for each patient. Statistically significant correlation was found between the CASCO-R scale score, overall workload and ACEs. The CASCO-R scale demonstrated also an excellent performance in terms of internal validity and test-retest analysis. Three total score cut-off have been proposed: >25 for inpatient intensive rehabilitation; 20-25 for day-hospital service; <20 for outpatient treatment. CONCLUSIONS: In conclusion, the CASCO-R scale was demonstrated to be a valid tool for assessing the appropriateness of the choice of the level of care. Hence, it can be used to verify the proper allocation of patients, as it was well correlated with measures of workload and the incidence of ACEs.

Acute post-exercise oxygen uptake, hormone and plasma metabolite response in obese men.

This study aimed to compare oxygen uptake ( VO2), hormone and plasma metabolite responses during the 30 min after submaximal incremental exercise (Incr) performed at the same relative/absolute exercise intensity and duration in lean (L) and obese (O) men. Eight L and 8 O men (BMI: 22.9 ± 0.4; 37.2 ± 1.8 kg · m(-2)) completed Incr and were then seated for 30 min. VO2 was monitored during the first 10 min and from the 25-30(th) minutes of recovery. Blood samples were drawn for the determination of hormone (catecholamines, insulin) and plasma metabolite (NEFA, glycerol) concentrations. Excess post-exercise oxygen consumption (EPOC) magnitude during the first 10 min was similar in O and in L (3.5 ± 0.4; 3.4 ± 0.3 liters, respectively, p=0.86). When normalized to percent change ( VO2END=100%), % VO2END during recovery was significantly higher from 90-120 s in O than in L (p ≤ 0.04). There were no significant differences in catecholamines (p ≥ 0.24), whereas insulin was significantly higher in O than in L during recovery (p=0.01). The time-course of glycerol was similar from 10-30 min of recovery (-42% for L; -41% for O, p=0.85), whereas significantly different patterns of NEFA were found from 10-30 min of recovery between groups (-18% for L; +8% for O, p=0.03). Despite similar EPOC, a difference in VO2 modulation between groups was observed, likely due to faster initial rates of VO2 decline in L than in O. The different patterns of NEFA between groups may suggest a lower NEFA reesterification during recovery in O, which was not involved in the rapid EPOC component.

Rationale for hospital-based rehabilitation in obesity with comorbidities.

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to-date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.

Effectiveness of in-patient rehabilitation in obesity-related orthopedic conditions.

BACKGROUND: The aim of the present paper is to provide initial evidence that in-patient multidisciplinary rehabilitation is effective in minimizing the obesity-related disability and enhancing functional capacities in obese patients with motor disability. SUBJECTS: Four hundred and sixty-four obese patients with orthopedic conditions admitted to our Rehabilitation Unit for multidisciplinary rehabilitation were enrolled in this study. METHODS: At admission and discharge (after 4 weeks), the following outcome measures were computed: body weight (BW) (kg), body mass index (BMI) (kg/m2), Functional Independence Measure (FIM) motor and cognitive, Obesity-related disability test (TSD-OC), Visual Analogue Score (VAS) for functioning, Timed-Up-Go (TUG). Intensive rehabilitation addressed to obese patients with orthopedic conditions and motor difficulties consisted of a 4-week and 3-h daily multidisciplinary program covering nutritional, motor and psychological aspects. RESULTS: All of the outcomes measured, except the FIM cognitive score, improved significantly after in-patient rehabilitation. The obesity-specific disability scale appears sensitive to changes among groups with different grades of disability and the percentage of change does not differ among groups. Younger obese individuals generally showed to benefit more from rehabilitation interventions than the older ones. CONCLUSIONS: In-patient rehabilitation interventions appear effective in reducing both mild and severe disabilities related to obesity with orthopedic co-morbidities. This paper provides initial evidence that in-patient multidisciplinary intensive rehabilitation is effective in minimizing the obesity-related disability and initial support to the indications of the Italian Ministry of Health for such rehabilitation pathway. The disability grading could help the decision making of allocating patients to appropriate rehabilitation settings.

Measuring changes after multidisciplinary rehabilitation of obese individuals.

BACKGROUND: In 2009, the Italian Society of Obesity developed the short-form questionnaire for Obesity-related Disabilities (TSD-OC). AIMS: To stage the degree of disability in obese patients using TSD-OC; to verify its sensitivity to change after rehabilitation. SUBJECTS: Three hundred and fifty-five adult obese individuals [body mass index (BMI) >30 kg/m2] undergoing rehabilitation. Exclusion criteria were severe cardiovascular or respiratory diseases, neurological and psychological conditions. Sensitivity to change of TSD-OC was evaluated in 194 patients out of the initial sample. METHODS: To define the disability levels according to TSD-OC, the method of interquartile range was applied to the initial sample. The 194 in-patients were assessed with Roland-Morris Disability Questionnaire, Functional Independence Measure (FIM), Functional Visual Analogue Scale, and TSD-OC before (S0) and after 4 weeks (S1) of intensive (3 h daily) rehabilitation multidisciplinary program. Individuals were grouped according to age (1: age 30-59 yr; 2: age over 60 yr) and degree of obesity (BMI: A, 30-40 kg/m2; B, 40-50 kg/m2). RESULTS: At S1, BMI and all the clinical scores improved significantly in the whole study sample. The younger individuals with higher level of obesity showed a higher functional improvement (-51.3%). In the older subjects, improvement was not statistically different when varying BMI (A2 -13.7% vs B2 -14.6%). In the whole group, the TSD-OC improvement was statistically greater than the physical FIM gain (-25.9% vs +5.4%, p<0.05). CONCLUSIONS: Our data evidenced that the TSD-OC is a sensitive measure of short-term changes in disability status of obese individuals after rehabilitation.

[Applicability of the test SIO on obesity-related disability (TSD-OC) in occupational medicine for the evaluation of work problems linked to overweight-obesity condition]. / Applicabilità del Test SIO sulla disabilità correlata all'obesità (TSD-OC) in Medicina del Lavoro per la valutazione di problematiche lavorative legate al sovrappeso-obesità.

Obesity is frequently associated with functional changes that may affect work capacity, so we administered to a group of 198 overweight-obese subjects with median BMI of 32.7 and median waist circumference of 101 cm, the test-TSD OC which consists of 7 sections (pain, stiffness, activities of daily life, activities of the house, instrumental activities of daily living, work, social relations) for a total of 36 visual analogical scales. After the identification of 4 workers categories (health, services, administration, commerce/industry), resulted homogeneous for age, BMI, CV, we saw that the work section was more compromised for health and services. The overall disability increases especially in relation to BMI and seems influenced by age and sex.

[Evaluation of the work-related disability in people affected by Ehlers-Danlos syndrome]. / Valutazione della disabilità in ambito lavorativo in soggetti con sindrome di Ehlers-Danlos.

The Ehlers-Danlos syndrome (EDS), inherited disorder of connective tissue, frequently leads to impairment of various functional areas, including employment. In 35 subjects with classic type EDS, 14 hypermobile, 3 vascular was administered 7 visual analogical scales (pain, stiffness, activities of daily living, instrumental activities of daily living, work, social relations). An impairment of particular significance in total score and in individual areas emerges is in the hypermobile group, followed by classic, less for the vasculature. Overall there is a significant alteration of the quality of life that deserves proper evaluation to facilitate the definition of fitness and the improvement of job insertion in patients with EDS.

[Impact of obesity-related disability in different work categories]. / Impatto dello disabilità correlata all'obesità nelle diverse categorie professionali.

Absenteeism and sick leave are often reported in obese workers. To evaluate disability work related we assess 180 overweight-obese subjects [BMI 34,6 + 6,4, range 26,0-59,0) with TSD-OC questionnaire divided into 7 items (pain; stiffness; ADL; housework; IADL; occupational activities; social life) with a total of 36 visual analogue scales. Among the job categories, health-care workers showed the highest TSD-OC total score (26,9 + 22,5%, ANOVA p < 0,05) and BMI (BMI 37,7 + 6,9 kg/m2). Among the items, pain was statistically significant in health-care workers (16,1 + 13,2%), in Services (16,3 + 14,3%), in Education (15,1 + 11,4%) and in Administration (13,3 +11,0%) ( p <0,05). "Occupational activities" item was statistically significant in health-care (11, 6 +10,6%, p <0,05).

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patients.

AIM: In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. METHODS: From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18-65 years and body mass index 35-50 kg/m(2) and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. RESULTS: A significant weight loss and reduction of fat mass was demonstrated with metformin (-9.7 +/- 1.8 kg and -6.6 +/- 1.1 kg) and also with rosiglitazone (-11.0 +/- 1.9 kg and -7.2 +/- 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 +/- 1.5 vs. 8.0 +/- 0.,7 microU/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 +/- 8.8 vs. 109.9 +/- 10.3, p < 0.005) with a concomitant decrease in beta-cell function as measured by HOMA of beta-cell function (163.2 +/- 16.1 vs. 127.4 +/- 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. CONCLUSION: Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction.

D2 dopamine receptor (DRD2) gene Taq1A polymorphism and the eating-related psychological traits in eating disorders (anorexia nervosa and bulimia) and obesity.

OBJECTIVE: Food is considered a reinforcing agent, like a variety of substances such as alcohol and other drugs of abuse that produce pleasure. Psychopathological traits related to food intake are demonstrated in eating disorders as in obesity with different genetic aspects for these diseases. Recently, the prevalence of TaqA1 allele has been associated to alcohol, drug abuse and carbohydrate preference. For this reason, the aim of this study was to evaluate if the presence of A1 allele, in eating disorders and obesity, is associated with some particular psycho-pathological characteristics. METHODS: We studied the presence of TaqA1 in Italian subjects affected by obesity (n=71), anorexia (n=28), bulimia (n=20) and in control group (n=54). The Eating Disorders Inventory (EDI test) was used to evaluate the psychological profiles. Patients without alcohol and drugs abuse were selected (>125 ml/day). RESULTS: The A1+ allele, both in A1/A1 and A1/A2 genotypes, was not differently distributed among disease groups; on the contrary two EDI subscales (Drive for thinness and Ineffectiveness) resulted associated with A1+ allele without effect of the eating disease or obesity. CONCLUSION: These results confirm that the presence of A1+ allele is not simply related to body weight but the A1+ allele might be a marker of a genetic psychological condition in people with high risk to develop pathological eating behaviour.

Effect of small doses of dexamethasone on plasma leptin levels in normal and obese subjects: a dose-response study.

To further elucidate the role of glucocorticoids in the regulation of leptin secretion, we studied the effects of overnight small doses of dexamethasone on plasma leptin levels in normal weight controls and in obese patients and correlated the results with indexes of insulin sensitivity and body fat distribution. In 114 subjects (81 obese patients, 49 women and 32 men, BMI 37.4 +/- 0.77 kg/m2 and 33 normal-weight subjects, 17 women and 16 men, BMI 22.1 +/- 0.41 kg/m2) plasma F and leptin levels were measured at 08:00 h basally and after the administration of different doses of dexamethasone (a fixed dose of 1-mg and 0.0035, 0.007, 0.015-mg/kg bw, given po at 23:00 h the night before). Tests were performed one week apart with bw remaining stable over the study period. Basal leptin levels were significantly higher in obese than in normal subjects (31.9 +/- 2.41 vs 7.7 +/- 0.93 ng/ml, p<0.0001). In obese patients, leptin levels increased significantly by 1-mg (from 31.9 +/- 2.41 to 35.0 +/- 2.59 ng/ml, p<0.005) and the 0.015-mg/kg bw dose (from 31.5 +/- 2.34 to 33.7 +/- 2.44 ng/ml, p<0.05), while they were unaffected by each dose of dexamethasone in normal subjects. However, after splitting subjects by gender, mean leptin levels rose from 39.3 +/- 2.97 to 43.3 +/- 3.12 ng/ml after the 1-mg dose, p<0.005, from 39.1 +/- 2.87 to 43.6 +/- 2.91 ng/ml after the 0.015-mg/kg bw dose, p<0.005, from 39.3 +/- 2.90 to 42.2 +/- 2.90 ng/ml after the 0.007-mg/kg bw dose, p<0.05 and from 38.8 +/- 2.66 to 41.1 +/- 2.87 ng/ml after the 0.0035-mg/kg bw dose, p=0.055, only in obese women. Conversely, no leptin changes were seen in the other groups and no differences were observed in the leptin response between groups. After the 1-mg dose, in the whole group, the absolute leptin variation was weakly but significantly related to BMI values (r=0.231, p<0.02) while in all sessions the percent leptin changes over baseline were not significantly correlated with age, BMI, waist, WHR, insulin, HOMA index, a marker of insulin sensitivity, plasma dexamethasone concentrations and to the percent cortisol variation following dexamethasone. In conclusion, in obese women but not in obese men and in normal weight subjects, small overnight increases in plasma glucocorticoid concentrations induced gender-related plasma leptin elevations that were unrelated to body fat distribution and insulin sensitivity. A greater sensitivity of female adipose tissue to glucocorticoids probably underlies this sexually dimorphic pattern of leptin response. These findings provide an additional piece of information on the regulation of leptin secretion exerted by glucocorticoids.

Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians.

The importance of the genetic component on adipose tissue accumulation has been clearly demonstrated. Among the candidate genes investigated, there are those that regulate thermogenesis and, thus, can affect energy expenditure. The uncoupling proteins (UCPs) are a family of proteins that uncouple respiration leading to generation of heat and increased energy expenditure. Contradictory data indicate that allelic variants in their coding genes might be associated with obesity. In this study we evaluated the role of two allelic variants of the UCP2 gene in obesity and the association with its sub-phenotypic characteristics. To this aim, 360 morbidly obese patients [age: 45 +/- 15 yr, body mass index (BMI): 46 +/- 7 kg/m2] and 103 normal weight subjects (BMI < 24 kg/m2) were genotyped for the 45 bais-pair (bp) insertion/deletion (I/D) in the 3'-untraslated region of exon 8 of the UCP2 gene while the presence of an Ala/Val substitution at codon 55 (Ala55Val) of the same gene was studied in 104 obese and 50 lean subjects. Patients also underwent a study protocol including measurements of BMI, waist-to-hip ratio (WHR), resting energy expenditure (REE), energy intake, fat mass (FM) and free fat mass (FFM), total cholesterol (TCH), high density lipoprotein (HDL) cholesterol, triacylglyceroles (TG), leptin levels, basal glucose, immunoreactive insulin (IRI), glycated haemoglobin (HbA1c), insulin sensitivity and thyroid hormones. No significant association between the two polymorphisms studied and the clinical, metabolic and anthropometric parameters characteristic of the obese phenotype was found. These results, in accordance with similar findings previously obtained in other ethnic groups, suggest that these two UCP2 allelic variants may not have a direct role in the pathogenesis and development of obesity.

The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.

BACKGROUND: The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. METHODS: We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. RESULTS: The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. CONCLUSIONS: These data indicate that circulating concentrations of TNF-alpha do not reflect the degree of insulin resistance in obesity and GHDA. They, however, do not exclude that TNF-alpha may induce insulin resistance at tissue level.

Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.