Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans

OBJECTIVE: To address the clinical implications of leptin and to re-examine the relationship between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA) and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. DESIGN: Longitudinal study. SETTING: University and foundation hospitals. SUBJECTS: Ten obese men and 10 premenopausal obese women. INTERVENTIONS: Five men and five women took 800 kcal/day LCD and another five men and five women took 1400 kcal/day balanced deficit diet (BDD) during 4 weeks. RESULTS: Plasma leptin levels in the LCD group decreased more markedly (46.2+/-14.6 to 13.2+/-3.6 ng/ml) than that expected for the decrement in percentage fat (39.0+/-1.7 to 35.9+/-1.7%) and body mass index (BMI; 35.4+/-2.4 to 33.1+/-2.2 kg/m(2)), while that in the BDD group did not decrease significantly (14.9+/-3.5 to 13.4+/-2.8 ng/ml). The ratio of the decrease in leptin levels to that of BMI during the first week was significantly greater than that during the following 3 weeks (39.5+/-2.7 vs 29.3+/-2.1%, P=0.017). The plasma insulin and T3 levels also fell substantially in the first week and continued to decrease during the entire course. Plasma leptin levels measured weekly in each subject were correlated well with insulin (r=0.586, P=0.0003) and T3 (r=0.785, P=0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that serum levels of T3 were independently correlated with plasma leptin levels (r=0.928, P<0.0001). The plasma NEFA level was markedly elevated during the first 2 weeks and decreased thereafter. CONCLUSIONS: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness of leptin in combination with caloric restriction for the treatment of obesity. SPONSORSHIP: The Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Labour and Welfare of Japan.     

Changes of ghrelin and leptin in response to hypocaloric diet in obese patients

OBJECTIVE: Hypocaloric diet-induced weight loss produces a coordinated decrease in plasma leptin levels and an increase in plasma ghrelin levels. The aim of the present study was to determine whether subjects who lose significant weight experience changes in circulating ghrelin and leptin levels. METHODS: A population of 66 obese patients was analyzed. Leptin, active ghrelin blood levels, and other cardiovascular risk factors were measured before and after 3 mo of a hypocaloric diet. RESULTS: Sixty-six patients (17 male, 49 female) gave informed consent and were enrolled in the study. Forty-six patients did not lose 5% of initial weight (group I, weight loss 1.4 +/- 2.5 kg) and 20 patients lost weight (>5% of initial weight; group II, weight loss 7.1 +/- 2.6 kg). In group I, active ghrelin levels increased (7.40 +/- 8 versus 19.40 +/- 32 pg/mL, P < 0.05) and leptin levels decreased (102.6 +/- 86 versus 89.30 +/- 76 ng/mL, P < 0.05). In group II, leptin levels also decreased significantly (69.80 +/- 67 versus 53.50 +/- 59 ng/mL, P < 0.05). Active ghrelin in this group did not show differences (24.20 +/- 41 versus 10.30 +/- 12 pg/mL, NS). In the multivariate analysis with a dependent variable (change in active ghrelin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and basal intake of protein remained in the model. In the multivariate analysis with a dependent variable (change in leptin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and BMI remained in the model. CONCLUSION: Patients with weight loss secondary to a hypocaloric diet did not change active ghrelin levels and decreased leptin levels after treatment.     

Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance

OBJECTIVE: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. RESEARCH METHODS AND PROCEDURES: Twenty-four insulin-resistant obese subjects with varying degrees of glucose tolerance completed a 6-month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)] and highly sensitive C-reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. RESULTS: Participants had a 6.9 +/- 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 +/- 3 vs. 23.6 +/- 3 ng/mL, p = 0.01) and IL-6 (2.75 +/- 1.51 vs. 2.3 +/- 0.91 pg/mL, p = 0.012). TNF-alpha levels tended to decrease (2.3 +/- 0.2 vs. 1.9 +/- 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C-reactive protein (r = 0.466, p < 0.05). DISCUSSION: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL-6 and a tendency toward a decrease in circulating TNF-alpha, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Biotin deficiency in a patient with short bowel syndrome during home parenteral nutrition

A 54-year-old woman with short bowel syndrome was supported with home parenteral nutrition. Six months after receiving 2200 kcal/day of balanced home parenteral nutrition without biotin, she developed biotin deficiency with complete hair loss, eczematous dermatitis, waxy pallor, lethargy, and hypersthesias . Blood and urine samples were collected prior to treatment. Serum zinc was 64 micrograms/dl (nl 50-150 micrograms/dl), and the triene/tetraene ratio was 0.068 (nl 0.4), thereby ruling out zinc and essential fatty acid deficiencies. Serum biotin was 332 pg/ml (nl 520 +/- 220 pg/ml), and urine biotin was 5.22 ng/mg of creatinine (nl 4.3-95 with a mean of 30.2 ng/mg creatinine). The same parenteral nutrition regimen was contained and oral biotin was administered (10 mg/day). After 3 wk, serum and urine biotin levels were 650 pg/ml and 35.6 ng/mg creatinine, respectively. New hair growth was evident and all of her other symptoms resolved. Intravenous biotin was then provided (5 mg/day) for a month after which serum and urine biotin levels were 1316 pg/ml and 178 ng/mg creatine, respectively. The patient has been subsequently maintained on an intravenous multivitamin product containing 60 micrograms biotin per daily dose and remains free of signs and symptoms of biotin deficiency.     

Monosaccharide-enriched diets cause hyperleptinemia without hypophagia

To determine the effect of monosaccharide-enriched diets on plasma leptin and food consumption, body weight, food intake, and serum glucose, insulin, and leptin concentrations were measured in rats maintained on a 10-d course of 60% glucose or 60% fructose diet. The serum leptin concentration in rats fed a high-glucose diet (7.60 +/- 0.6 ng/mL) or a high-fructose diet (5.12 +/- 0.8 ng/mL) was significantly increased compared with that in control rats (2.45 +/- 0.10 ng/mL; P < 0.001). To ascertain that the observed effect was related to hyperinsulinemia, a group of rats were infused with exogenous insulin or rendered insulin resistent with a high-fat diet. When hyperinsulinemia was induced with exogenous infusion, the serum leptin was increased (5.56 +/- 0.23 ng/mL; P < 0.001). High-fat feeding was associated with increased serum leptin (12.1 +/- 1.4 ng/mL) and insulin levels. The increased serum leptin concentration was not associated with decreased food intake. We conclude that monosaccharide-enriched diets, probably through hyperinsulinemia or relative or absolute insulin resistance, cause hyperleptinemia, which does not appear to change feeding behavior.     

Critically-ill patients receiving total parenteral nutrition show altered amikacin pharmacokinetics

The purpose of this clinical study was to characterise the kinetic behavior of amikacin in the parenterally-fed critically-ill adult patient. 22 critically-ill adult patients treated with amikacin (15.5 +/- 7.9 mg/kg/day) for severe gram-negative infections were enrolled into a non-randomised control trial. Malnourished patients were administered total parenteral nutrition (TPN, n = 11), while well-nourished patients received fluid therapy (FT, n = 11). Amikacin pharmacokinetic parameters were estimated by non-linear regression analysis, assuming a one-compartment model and central first-order elimination. Patients receiving TPN showed an expanded amikacin distribution volume (0.403 +/- 0.0961/kg vs. FT 0.298 +/- 0.083 l/kg, p < 0.05), and a tendency towards increased total body clearance (0.089 +/- 0.029 l/kg/h vs. FT 0.069 +/- 0.0201/kg/h, p = 0.09). TPN produced lower peak concentrations (19.3 +/- 3.1 mcg/ml vs. 23.1 +/- 3.5 mcg/ml, p < 0.05), but had no significant influence on trough concentrations (p = 0.56). Patients on TPN also showed increased body temperature (p < 0.05) and fluid intake (p < 0.05), and decreased hematocrit (p < 0.05). Stress, malnutrition, parenteral nutrition itself, fluid and osmotic overload, and fever often occur concurrently in parenterally-fed patients and appear to produce lower amikacin serum levels. Consequently, critically-ill patients receiving TPN need higher amikacin doses and individualised treatment by monitoring serum concentrations, to ensure optimal therapeutic response.     

Impact of visceral fat on blood pressure and insulin sensitivity in hypertensive obese women

OBJECTIVE: The relationship among body fat distribution, blood pressure, serum leptin levels, and insulin resistance was investigated in hypertensive obese women with central distribution of fat. RESEARCH METHODS AND PROCEDURES: We studied 74 hypertensive women (age, 49.8 +/- 7.5 years; body mass index, 39.1 +/- 5.5 kg/m(2); waist-to-hip ratio, 0.96 +/- 0.08). All patients were submitted to 24-hour blood pressure ambulatory monitoring (24h-ABPM). Abdominal ultrasonography was used to estimate the amount of visceral fat (VF). Fasting blood samples were obtained for serum leptin and insulin determinations. Insulin resistance was estimated by homeostasis model assessment insulin resistance index (HOMA-r index). RESULTS: Sixty-four percent of the women were postmenopausal, and all patients showed central distribution of fat (waist-to-hip ratio > 0.85). The VF correlated with systolic 24h-ABPM values (r = 0.28, p = 0.01) and with HOMA-r index (r = 0.27; p = 0.01). VF measurement (7.5 +/- 2.3 vs. 5.9 +/- 2.2 cm, p < 0.001) and the systolic 24h-ABPM (133 +/- 14.5 vs. 126 +/- 9.8 mm Hg, p = 0.04), but not HOMA-r index, were significantly higher in the postmenopausal group (n = 48) than in the premenopausal group (n = 26). No correlations were observed between blood pressure levels and HOMA-r index, leptin, or insulin levels. In the multiple regression analysis, visceral fat, but not age, body fat mass, or HOMA-r index, correlated with the 24h-ABPM (p = 0.003). DISCUSSION: In centrally obese hypertensive women, the accumulation of VF, more often after menopause, is associated with higher levels of blood pressure and insulin resistance. The mechanism through which VF contributes to higher blood pressure levels seems to be independent of leptin or insulin levels.     

Differences in glycaemic status do not predict weight loss in response to hypocaloric diets in obese patients

OBJECTIVE: The aim of our study was to detect differences in weigth loss with a hypocaloric diet in obese patients depending on their glycaemic status. SUBJECTS AND METHODS: A population of 76 obesity outpatients was analysed in a prospective way. The following variables were specifically recorded at basal time and after 3 months of hypocaloric diet (1200 kcal/day): weight, blood pressure, body mass index (BMI), waist circumference, and waist-hip ratio. Basal glucose, insulin, fibrinogen, cortisol, c-reactive protein, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides blood levels were measured. HOMA was calculated. An indirect calorimetry, tetrapolar electrical bioimpedance and a serial assessment of nutritional intake with 3 days written food records were performed. RESULTS: The mean age was 46.9 +/- 17.1 years and the mean BMI 34.6 +/- 5.3. All subjects were weight stable during the 2 weeks period preceding the study (body weight change, 0.3 +/- 0.1 kg). Anthropometric measurements showed an average waist circumference (108.7 +/- 15.7 cm), waist-to-hip ratio (0.93 +/- 0.11), and average weight (88.7 +/- 16.9 kg). Bipolar body electrical bioimpedance showed a fat mass of 37 +/- 12.3 kg. Indirect calorimetry showed a resting metabolic rate (RMR) (1674.3 +/- 392 kcal/day). Patients were divided in to two groups by glycaemic status (group I: normal glycaemic metabolism, fasting glucose levels <109 mg/dl; n = 50) and (group II: impaired glycaemic metabolism, fasting glucose levels >110 mg/dl, n = 26). Waist circumference (I: 108 +/- 17.1cm vs. 104.6 +/- 16.7 cm; P < 0.05) and (II: 113.6 +/- 9.8 cm vs. 110.9 +/- 8.9 cm; P < 0.05), weight (I: 90.6 +/- 19.2 kg vs. 86.3 +/- 18.6 kg:P < 0.05) and (II: 89.2 +/- 11.3 kg vs. 86.4 +/- 11.6 kg: P < 0.05) and BMI (I: 34.2 +/- 5.6 vs. 33.7 +/- 5.5; P < 0.05) and (II: 34.8 +/- 4.2 vs. 34.2 +/- 4.6; P < 0.05) improved in both groups with hypocaloric diet. Blood systolic pressure, total cholesterol and LDL cholesterol improved in both groups, without statistical differences. In group II improved glucose levels and HOMA index, too. Patients of group II had higher systolic blood pressure, glucose, total cholesterol, LDL cholesterol, triglycerides, lipoprotein (a), RCP levels and HOMA index than patients in group I. ANOVA analysis did not show differences among weight loss in tertiles of HOMA and glucose. CONCLUSION: Ability to lose weight on a hypocaloric diet over a 3-month time period does not vary in obese patients as a function of glycaemic status. Improvement in cardiovascular risk factors is not related with glycaemic status, too.     

Effect of c-reactive protein and interleukins blood levels in postsurgery arginine-enhanced enteral nutrition in head and neck cancer patients

OBJECTIVE: It is known that the immune system is frequently affected in patients with head and neck cancer. Although immune dysfunction could be multifactorial, this immune system may be modulated by specific nutritional substrates, such as arginine. The aim of our study was to evaluate the effect of enteral nutrition supplemented with arginine on c-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor (TNFalpha) in surgical head and neck cancer patients. DESIGN: Randomized trial. SETTING: Tertiary care. SUBJECTS: A population of 36 patients with oral and laryngeal cancer were enrolled. INTERVENTIONS: At surgery patients were randomly allocated to two groups: (a) patients receiving an enteral diet supplements with arginine and dietary fibre (group I, n=18); (b) patients receiving an isocaloric, isonitrogenous enteral formula (group II, n=18). Perioperatively and on postoperative day 5 the following parameters were evaluated: serum values of prealbumin, transferrin, albumin, total number of lymphocytes, interleukin 6, tumour necrosis factor alpha and c-reactive protein. RESULTS: The mean age was 59.6+/-10.9 y (two females/34 males). No significant intergroup differences in the trend of the three plasma proteins and weight were detected. CRP decreased in both groups (group I: 152.9+/-76.9 vs 68.9+/-82.5 mg/dl; P<0.05; and group II: 105.9+/-92 vs 43.6+/-59.1 mg/dl; P<0.05). Interleukin 6 did not change (group I: 16.3+/-12.3 vs 35.6+/-83.4 pg/ml; NS; and group II: 22.8+/-40 vs 9.9+/-17.7 pg/ml; NS). TNFalpha did not show any differences (group I: 4.6+/-1.6 vs 5.1+/-1.5 pg/ml; NS; and group II: 8.8+/-6.1 vs 5.8+/-1.7 pg/ml; NS). Lymphocytes increased in both groups (group I: 1405.6+/-517 vs 1634+/-529 x 10(6)/ml; P<0.05; and group II: 1355+/-696 vs 1561+/-541 x 10(6)/ml; P<0.05). CONCLUSIONS: Enhanced formula did not change IL6 and TNFalpha levels. Further studies are needed to determine whether route of nutrition or type of formula is the key in these patients.     

Hypocaloric enteral tube feeding in critically ill obese patients

OBJECTIVE: We respectively compared the nutritional and clinical efficacies of eucaloric and hypocaloric enteral feedings in 40 critically ill, obese patients admitted to the trauma or surgical intensive care unit. METHODS: Adult patients, 18 to 69 years old, with weights greater than 125% of ideal body weight, normal renal and hepatic functions, and who received at least 7 d of enteral tube feeding were studied. Patients were stratified according to feeding group: eucaloric feeding (>or=20 kcal/kg of adjusted weight per day; n = 12) or hypocaloric feeding (<20 kcal/kg of adjusted weight per day; n = 28). The goal protein intake for both groups was approximately 2 g/kg of ideal body weight per day. Clinical events and nutrition data were recorded for 4 wk. RESULTS: Patients were similar according to sex, age, weight, body mass index, Second Acute Physiology and Chronic Health Evaluation score, Trauma score, and Injury Severity Score. The hypocaloric feeding group received significantly fewer calories than the eucaloric group (P相似文献   

双腔袋肠外营养注射液在胃肠术后应用的安全性评价

目的对双腔袋肠外营养注射液(PN-Twin)在胃肠手术后应用的安全性进行回顾性评价。方法36例胃肠手术后患者分别按使用PN-Twin(2000ml/天)或3升袋“全合一”肠外营养液分为双腔袋组和3升袋组,观察两组患者用药期间的生命体征、不良反应、感染性并发症以及治疗前后的体重改变,检测术前1天和术后1、3、6天的血电解质、血糖、肝、肾功能、血红蛋白及血清内脏蛋白等指标。结果两组患者术后生命体征平稳,未发现腹泻、恶心、呕吐等不良反应和感染性并发症,两组治疗前后的体重改变无显著性差异(P=0.67)。双腔袋组和3升袋组术后血电解质、肝、肾功能指标基本正常,两组比较无显著性差异(P>0.05)。双腔袋组术后血红蛋白、血清白蛋白、前白蛋白、转铁蛋白水平与3升袋组比较无显著性差异(P>0.05),两组血糖均控制在10mmol/L以下。结论胃肠手术后患者短期经中心静脉输注PN-Twin是安全的。     

Serum leptin levels in girls with precocious puberty

Few data are available regarding leptin levels in children with different pubertal stages or with precocious puberty (PP). The aim of this study was to assess the changes in serum leptin levels in patients with PP. We studied 20 girls with PP, with Tanner stage II-III; the age at the beginning of pubertal signs ranged from 4.2 to 7.1 yr; all the girls had an advantaged bone age. Controls were subdivided in two groups: group 1: 20 pre-pubertal girls with the same chronological age of the patients, without any signs of pubertal development (Tanner stage I); group 2: 20 additional girls with the same bone age, pubertal stage and body mass index (BMI) of the girls with PP. Serum leptin levels in females with PP are similar to those found in subjects with normal puberty (9.0 +/- 0.8 vs 9.1 +/- 0.9 ng/ml; ns) and different from subjects with the same chronological age without activation of puberty (5.6 +/- 0.9 ng/ml, p < 0.001). In all groups leptin levels correlated significantly with BMI (girls with PP: r = 0.5 1, p < 0.02; control group 1 girls: r = 0.71; p < 0.0001; control group 2 girls: r = 0.49; p < 0.02), there was no significant relationship between leptin and activation of hypothalamic-pituitary-gonadal axis. Our results indicate that the serum leptin levels in the girls with PP are not significantly different from levels in healthy girls at a similar stage of pubertal development, suggesting that the relationship between serum leptin levels and BMI is also present in this pathological situation.     

Leptin responses to weight loss in postmenopausal women: relationship to sex-hormone binding globulin and visceral obesity

OBJECTIVE: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. RESEARCH METHODS AND PROCEDURES: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone-binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0+/-4.5 kg/m2; mean +/- SD), women (60+/-6 years) before and after a 6-month hypocaloric diet (250 to 350 kcal/day deficit). RESULTS: Body weight decreased by 5.8+/-3.4 kg (7.1%) and leptin levels decreased by 6.6+/-11.9 ng/mL (14.5%) after the 6-month treatment. Insulin levels decreased 10% (p< 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p<0.0001), fat mass (r = 0.38, p<0.01), subcutaneous fat area (r = 0.52, p<0.0001), and with baseline values of SHBG (r = 0.38, p<0.01) and baseline intra-abdominal fat area (r = -0.27, p<0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r2 = 0.24, p<0.01), relative changes in body weight (cumulative r2 = 0.40, p<0.05), and baseline intra-abdominal fat area (cumulative r2 = 0.48, p<0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. DISCUSSION: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Leptin and insulin response to long-term total parenteral nutrition depends on body fat mass

BACKGROUND & AIMS: Circulating leptin and insulin concentrations are physiologically representing energy homeostasis. However, the artificial situation of long-term total parenteral nutrition (TPN) and its effects on serum leptin and insulin is not fully understood. METHODS: We studied 42 gastroenterological patients who received TPN for 19+/-11 days. Serum leptin and insulin levels as well as body composition assessed by bioelectrical impedance analysis were evaluated on days 0, 7 and 14. Insulin sensitivity was estimated by calculating the QUICKI. RESULTS: Before the start of TPN, leptin correlated positively with female gender (P<0.03), BMI (P<0.02), fat mass (P<0.02), insulin levels (P<0.001) and QUICKI (P<0.001). Within the first week of TPN, an increase of leptin levels was found only in patients with a body fat mass of >30% (P<0.02). As these were predominantly women, their leptin levels increased likewise (P<0.003). In regression analysis, fat mass (P<0.001), female gender (P<0.04), insulin levels (P<0.03), and i.v. glucose supply rates (P<0.05) were independently associated to leptin levels. CONCLUSIONS: TPN-especially glucose-induces a neurohumoral response as shown here for leptin and insulin that is mainly depending on the fat mass. Better understanding of this regulatory mechanism during artificial nutrition could offer a new approach to improve its therapeutic effects.     

Serum leptin concentrations in patients with short-bowel syndrome

BACKGROUND: Short-bowel syndrome is a state of severe malabsorption resulting from absence or removal of the small bowel for several causes. A number of short-bowel patients develop hyperphagia. Leptin, a protein secreted from adipose tissue, signals the amount of energy stores to the brain. OBJECTIVE: To study body composition and leptin regulation in short-bowel patients and to determine whether or not leptin concentrations are linked with hyperphagia. DESIGN: We studied 25 short-bowel patients (remnant bowel less than 150 cm) and 31 controls and 10 oral nutrition. Fifteen patients received total parenteral nutrition and 10 oral nutrition. Anthropometric measurements, body composition (by bioelectrical impedance), and cholesterol, triacylglycerol and leptin concentrations were studied in all subjects. RESULTS: There were no differences between short-bowel patients and controls in anthropometric variables, body composition, or leptin concentrations. Leptin concentrations were higher in short-bowel women than men (9.21+/-8.54 vs. 3.22+/-1.86 ng/ml, P=0.01). Leptin concentrations correlated positively with age (r=0.4, P=0.045), body mass index (r=0.52, P=0.007), fat mass (r=0.67, P=0.001) and body fat (r=0.68, P=0.0001); there were no correlations with other body composition parameters. We found no correlations between parenteral or oral nutrition and body composition parameters, or between leptin concentrations and the presence of hyperphagia. Logistic regression analysis showed that body fat correctly identified leptin concentrations in 60% of patients. CONCLUSIONS: Body composition, leptin concentrations and leptin regulation in patients with short-bowel syndrome are similar to those of controls. Leptin concentrations do not correlate with hyperphagia in short bowel-patients.     

The effects of different intravenous feeding regimens on the rates of synthesis of alpha1-antitrypsin after surgery

The effects of two nutritional regimens on the synthesis of alpha-1 antitrypsin were investigated postoperatively in gynaecological cancer patients. Total parenteral nutrition (TPN) or a hypocaloric amino acid mixture was administered on the day of surgery and continued for 3 days. The rate of synthesis of alpha-1 antitrypsin was estimated by a computer model from serial plasma concentrations of this protein and a reference protein, albumin. The hypocaloric amino acid mixture resulted in a more negative nitrogen balance than that produced during administration of TPN containing the same amount of nitrogen but more non-protein energy. Urinary excretion of 3-methylhistidine was significantly greater (p = 0.017) in the hypocaloric amino acid group (350 +/- 40 mumol/day; mean +/- SE) on the third postoperative day, as compared to the TPN group (240 +/- 20 mumol/day). In spite of this the synthesis of alpha-1 antitrypsin was apparently greater in the hypocaloric amino acid than in the TPN group. The accumulated plasma appearance rate of alpha-1 antitrypsin was significantly higher (p = 0.0465) in HAA group, at 70 h it was 490 +/- 40 compared to 400 +/- 20 times the pre-operative synthesis in the TPN group.     

Basal and stimulated plasma leptin in diabetic subjects

OBJECTIVE: To determine whether leptin secretion is impaired in diabetes, we compared basal and stimulated plasma leptin levels in diabetic subjects and healthy controls. RESEARCH METHODS AND PROCEDURES: Blood samples for assay of leptin and other hormones were obtained at baseline in 54 diabetic patients and 65 controls, and 8 hours, 16 hours, and 40 hours following ingestion of dexamethasone (4 mg) in 6 healthy and 12 controls. C-peptide status was defined as "negative" if < or =0.1 ng/mL or "positive" if > or =0.3 ng/mL, in fasting plasma. RESULTS: Basal plasma leptin levels were 19.7+/-2.2 ng/mL in nondiabetic subjects, 13.4+/-1.5 ng/ml in C-peptide negative (n = 28) and 26.1+/-3.7 ng/mL in C-peptide positive (n = 26, p = 0.001) diabetic patients. Dexamethasone increased leptin levels of controls (n = 6) to 145+/-17% of baseline values at 8 hours (p = 0.03), 224+/-18% at 16 hours (p = 0.01), and 134+/-18% at 40 hours (p=0.05). The corresponding changes were 108+/-13%, 126+/-23%, and 98+/-16% in C-peptide negative (n=6), and 121+/-10%, 144+/-16% (p=0.03), and 147+/-23% (p=0.11) in C-peptide positive (n = 6) diabetic patients, respectively. The peak stimulated leptin levels were lower in the diabetic patients, compared with controls. Plasma insulin increased (p = 0.02) in controls, but not in the diabetic patients, following dexamethasone. DISCUSSION: Although diabetic patients have normal plasma leptin levels under basal conditions, their leptin responses to glucocorticoid are impaired, probably because of the concomitant insulin secretory defect. A subnormal leptin secretory response could worsen obesity and insulin resistance in diabetes.     

城市居民血清瘦素水平与体质指数、血脂和胰岛素关系的研究

目的　测量城市居民血清瘦素 (leptin)水平并探讨其与体质指数 (BMI)、血脂、胰岛素的关系。方法　选取 15 8例 17～ 72岁济南市社区居民作为研究对象 ,测量其身高、体重、腰围 (W)、臀围 (H) ,检测其血清胰岛素、血脂、血清leptin水平。结果　 15 8名城市居民血清leptin水平为 (17. 4 7± 13. 5 2 )ng ml,男性血清leptin水平为 (8.38± 6 . 31)ng ml,女性血清leptin水平为 (2 4. 98± 13. 2 9)ng ml。Leptin与BMI、腰围、臀围呈显著正相关 ,与腰臀比 (WHR)没有相关性 ;女性leptin与WHR相关 ;男性和女性血清leptin水平和胰岛素水平均无相关性 ;男性载脂蛋白B(ApoB)和leptin呈正相关 ,女性的总胆固醇 (TC)、低密度脂蛋白 (LDL- c)与leptin呈正相关。结论　BMI是影响血清leptin水平的重要因素。男性ApoB和leptin有相关性 ,女性的TC、LDL- c与leptin呈正相关。胰岛素、血脂、与leptin的关系均受性别的影响。     

Glycosylated haemoglobin and serum insulin antibodies in type I diabetes

Type 1 diabetics receiving once (Group 1, n = 72) and twice (Group 2, n = 48) daily subcutaneous injections of conventional beef insulin were compared, on a cross-sectional basis, in respect of insulin antibody binding by serum and total glycosylated haemoglobin (HbA1). Patients in Group 1 had higher insulin antibody binding (25.2 +/- 15.8% vs 17.0 +/- 13.9%; p less than 0.01) and higher HbA1 levels (12.5 +/- 2.0% vs 11.0 +/- 1.8%; p less than 0.001) than patients in Group 2. An inverse correlation (tau = -0.28, p less than 0.01) was observed between HbA1 and insulin antibody binding in C-peptide non-secretors of Group 1 but not in Group 1 C-peptide secretors, nor in C-peptide secretors and/or non-secretors of Group 2. It is suggested that in Type 1 diabetics who receive a single daily insulin injection and who have no endogenous insulin secretion, insulin antibodies may aid glycaemic control by prolonging insulin action.     

Role of insulin and free fatty acids in the regulation of ob gene expression and plasma leptin in normal rats

OBJECTIVE: It is under debate whether free fatty acids (FFAs) play an independent role in the regulation of adipose cell functions. In this study, we evaluated whether leptin secretion induced by FFA is due directly to an increased FFA availability or whether it is mediated by insulin levels. RESEARCH METHODS AND PROCEDURES: To test this hypothesis, we compared the effects of six different experimental designs, with different FFA and insulin levels, on plasma leptin: euglycemic clamp, euglycemic clamp + FFA infusion, FFA infusion alone, FFA + somatostatin infusion, somatostatin infusion alone, and saline infusion. RESULTS: Our results showed that euglycemic clamp, FFA infusion, or both in combination induced a similar increment of circulating leptin (3.31 +/- 0.30, 3.40 +/- 0.90, and 3.35 +/- 0.80 ng/mL, respectively). Moreover, the inhibition of FFA-induced insulin increase by means of somatostatin infusion completely abolished the rise of leptin in response to FFA (1.05 +/- 0.30 vs. 3.40 +/- 0.90 ng/mL, p < 0.001). DISCUSSION: In conclusion, our data showed that the effects of high FFA levels on plasma leptin were mediated by the rise of insulin concentration. These data confirm a major role for insulin in the regulation of leptin secretion from rat adipose tissue and support the hypothesis that leptin secretion is coupled to net triglyceride synthesis in adipose tissue.