Fasting Serum Leptin Concentrations Research Articles

Dietary Selenium Requirement for the Prevention of Glucose Intolerance and Insulin Resistance in Middle-Aged Mice.

Although dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health. We sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice. Thirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0.01 (basal), 0.04, 0.07, 0.10, and 0.13 (control) mg Se/kg for 4 mo (n=6) until they were middle-aged (8 mo). Droplets of whole blood were used to determine glucose tolerance and insulin sensitivity in the mice from ages 5 to 8 mo. Postmortem serum, liver, and skeletal muscle were collected to assay for selenoprotein expression and markers of glucose metabolism. Data were analyzed by 1-way ANCOVA with or without random effects for time-repeated measurements using live mice or postmortem samples, respectively. Compared with control, the consumption of basal diet increased (P<0.05) fasting serum insulin (95% CI: 52%, 182%) and leptin (95% CI: 103%, 118%) concentrations in middle-aged mice. Dietary Se insufficiency decreased (P<0.05) 1) glucose tolerance (13-79%) and insulin sensitivity (15-65%) at ≤0.10 mg Se/kg; 2) baseline thymoma viral proto-oncogene phosphorylation on S473 (27-54%) and T308 (22-46%) at ≤0.10 and ≤0.07 mg Se/kg, respectively, in the muscle but not the liver; and 3) serum glutathione peroxidase 3 (51-83%), liver and muscle glutathione peroxidase 1 (32-84%), serum and liver selenoprotein P (28-42%), and liver and muscle selenoprotein H (39-48%) and selenoprotein W (16-73%) protein concentrations at ≤0.04, ≤0.10, ≤0.07, and ≤0.10 mg Se/kg, respectively. Mice fed diets containing ≤0.10 mg Se/kg display impaired glucose tolerance and insulin sensitivity, suggesting increased susceptibility to type 2 diabetes by suboptimal Se status at levels ≤23% of nutritional needs.

Relationship between Insulin Sensitivity and Body Fat Composition, and Leptin Sensitivity in Non-Obese and Overweight/Obese Adults

Both insulin and leptin are major contributors for the body energy balance. Obesity is a state of energy imbalance and is also associated with changes in both insulin sensitivity and leptin sensitivity. The aim of this study was to find out the relationship between insulin sensitivity and body fat composition, and leptin sensitivity in non-obese and obese adults. A total of 86 adults participated: 42 non-obese and 44 over-weight/obese. Body fat (BF) percent was determined by skinfold method. Fasting plasma glucose was analyzed by glucose oxidase-phenol and 4 aminophenazone (GOD-PAP) method using spectro-photometer, fasting serum insulin and leptin concentrations by direct sandwich ELISA method and resting energy expenditure (REE) by indirect calorimetry. Leptin sensitivity index and insulin sensitivity were expressed as REE : Leptin ratio and homeostatic model assessment-insulin resistance (HOMA-IR), respectively. It was found that median value of HOMA-IR was significantly higher [2.93 vs 1.72, p&lt;0.01] and leptin sensitivity was significantly lower [116.76 vs 265.66, p&lt;0.001] in the overweight/obese adults than the non-obese adults, indicating that insulin sensitivity and leptin sensitivity were markedly reduced in overweight/obese adults in compare to non-obese adults. There was a moderate degree of positive relationship between HOMA-IR and BF only in the overweight/obese (ρ=0.509, n=44, p&lt;0.001) and all adults (ρ=0.39, n=86, p&lt;0.001). Similarly, a weak negative relationship between leptin sensitivity index and HOMA-IR was found in the overweight/obese (ρ=-0.328, n=44, p&lt;0.05) and all adults (ρ=-0.35, n=86, p&lt;0.01). It can be concluded that the insulin sensitivity was adiposity dependent, but, it did not depend on leptin sensitivity.

Dose-response effects of sex hormone concentrations on body composition and adipokines in medically castrated healthy men administered graded doses of testosterone gel.

Serum sex steroid concentrations may alter body composition and glucose homoeostasis in men in a dose-response manner. We evaluated these end-points in healthy men rendered medically castrate through use of a gonadotrophin-releasing hormone antagonist (acyline) with incremental doses of exogenous testosterone (T) gel. Subjects (n=6-9 per group) were randomly assigned to injections of acyline every 2weeks plus transdermal T gel (1.25g, 2.5g, 5.0g, 10g or 15g) daily or double placebo (injections and gel) for 12weeks. Healthy men, ages 25-55years, with normal serum total T concentrations. Serum T, dihydrotestosterone (DHT) and oestradiol (E2) were measured at baseline and every 2weeks. Body composition was analysed by dual-energy X-ray absorptiometry at baseline and week 12. Fasting serum adiponectin, leptin, glucose and insulin concentrations were measured at baseline and week 10. Forty-eight men completed the study. A significant treatment effect was observed for change in lean mass (ANOVAP=.01) but not fat mass (P=.14). Lean mass increased in the 15g T group relative to all lower dose groups, except the 10g T group. When all subjects were analysed together, changes in lean mass correlated directly and changes in fat mass correlated inversely with serum T, E2 and DHT. No changes were noted in serum glucose, insulin or adipokine levels. In healthy men, higher serum concentrations of T, DHT and E2 were associated with greater increases in lean mass and decreases in fat mass but not with changes in serum glucose, insulin or adipokines.

Relationship between adipokines and lipid profile in postmenopausal women with different apolipoprotein E genotypes

ABSTRACTThe aim of the authors of this study was to clarify the relationships among apolipoprotein E (ApoE) genotype, blood pressure, lipid profile, serum leptin, and adiponectin in healthy postmenopausal women. The study was conducted between March 2011 and December 2012 on 266 participants aged 50–65 years from the Institute of Rural Health in Lublin, Poland. Results showed that women had four combinations of genotypes: ɛ2/ɛ3, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4. Carriers of different genotypes did not differ in terms of age, body mass index (BMI), blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, and adiponectin levels. Mean low-density lipoprotein (LDL) cholesterol levels were higher in ε4 carriers compared to non-carriers. Fasting serum leptin concentrations were higher in homozygotes ɛ4/ɛ4. Leptin correlated positively with BMI in all study groups and with LDL in ɛ2/ɛ3, ɛ3/ɛ3, and ɛ3/ɛ4. Adiponectin correlated negatively with triglycerides in ɛ2/ɛ3, ɛ3/ɛ3, and ɛ3/ɛ4 and positively with HDL in ɛ2/ɛ3 carriers. Adipokines were not associated with blood pressure. Multiple regression analyses demonstrated associations among leptin, ApoE ɛ4/ɛ4, BMI, and LDL, and among adiponectin, BMI, and triglycerides. In healthy postmenopausal women ɛ4/ɛ4 genotype was associated with lower leptin levels. Homozygosity ɛ4/ɛ4 was associated with a more atherogenic lipid profile and possibly dysregulation of leptin and adiponectin signaling in lipid metabolism.

Relating Phthalate and BPA Exposure to Metabolism in Peripubescence: The Role of Exposure Timing, Sex, and Puberty.

Exposure to endocrine-disrupting chemicals during development may play a role in the increasing prevalence of metabolic syndrome and type 2 diabetes among children and adolescents by interfering with metabolic homeostasis. To explore associations between in utero and peripubertal urinary phthalate metabolite and bisphenol A (BPA) concentrations and markers of peripubertal metabolic homeostasis. Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT): a longitudinal cohort study of pregnant women in Mexico City and their offspring. Public maternity hospitals in Mexico City. Women recruited during pregnancy; offspring recruited for follow-up at age 8-14 years (n = 250). None. Fasting serum c-peptide, IGF-1, leptin, and glucose concentrations among children at follow-up; calculated measures of insulin secretion and insulin resistance. Phthalate metabolites and BPA were associated with metabolism biomarkers at age 8-14 years in patterns that varied by sex, pubertal status, and exposure timing. For example, in utero monoethyl phthalate was associated with lower insulin secretion among pubertal boys (P = .02) and higher leptin among girls (P = .04). In utero di-2-ethylhexyl phthlate was associated with higher IGF-1 among pubertal girls; peripubertal di-2-ethylhexyl phthlate was associated with higher IGF-1, insulin secretion, and resistance among prepubertal girls. In contrast, peripubertal dibutyl phthalate, monobenzyl phthalate, and mono-3-carboxypropyl phthalate were associated with lower IGF-1 among pubertal boys. Peripubertal BPA was associated with higher leptin in boys (P = .01). Considering the long-term health effects related to metabolic syndrome, additional research on exposure and metabolic outcomes across developmental periods and early adulthood is needed.

Hyperleptinemia Is a Risk Factor for the Development of Central Arterial Stiffness in Kidney Transplant Patients

BackgroundArterial stiffness could cause adverse outcomes in kidney transplant (KT) patients. Leptin has a role in influencing vascular smooth muscle that may contribute to atherosclerosis. The aim of this study was to evaluate the relationship between fasting serum leptin concentration and carotid-femoral pulse wave velocity (cfPWV) in KT patients. Materials and MethodsFasting blood samples were obtained from 55 KT patients and 65 subjects from the outpatient department were enrolled as the control group. The cfPWV values of >10 m/s were used to define as the high arterial stiffness group and <10 m/s as the low arterial stiffness group. The predictive ability of leptin for arterial stiffness of KT was assessed using receiver operating characteristic (ROC) curve and multivariate logistic regression analyses. ResultsKidney transplant patients had lower hemoglobin, but higher blood urea nitrogen, creatinine, total cholesterol, diastolic blood pressure, intact parathyroid hormone levels, and leptin levels than controls. Although cfPWV levels were higher in KT patients, there is no difference of cfPWV levels between KT patients and control (P = .595). Fifteen KT patients (27.3%) were defined in the high arterial stiffness group, and serum leptin level was higher in the high arterial stiffness group compared with the low arterial stiffness group in KT patients (P < .001). Multivariate logistic regression analysis showed that leptin (odds ratio: 1.044, 95% confidence interval [CI]: 1.016–1.072, P = .002) was an independent predictor of arterial stiffness in KT patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve predicting arterial stiffness in KT patients were 73.33%, 87.5%, 68.7%, 89.7%, and 0.828 (95% CI: 0.703–0.917, P < .001), and the leptin cut-off value was 74.14 ng/mL. ConclusionSerum fasting leptin level could predict the development of central arterial stiffness of KT patients.

Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women.

Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin.

Effects of photoperiod on food intake, activity and metabolic rate in adult neutered male cats.

With the continued rise in feline obesity, novel weight management strategies are needed. To date, strategies aimed at altering physical activity, an important factor in weight maintenance, have been lacking. Photoperiod is known to cause physiological changes in seasonal mammals, including changes in body weight (BW) and reproductive status. Thus, our objective was to determine the effect of increased photoperiod (longer days) on voluntary physical activity levels, resting metabolic rate (RMR), food intake required to maintain BW, and fasting serum leptin and ghrelin concentrations in adult cats. Eleven healthy, adult, neutered, male domestic shorthair cats were used in a randomized crossover design study. During two 12-week periods, cats were exposed to either a short-day (SD) photoperiod of 8 h light: 16 h dark or a long-day (LD) photoperiod of 16 h light: 8 h dark. Cats were fed a commercial diet to maintain baseline BW. In addition to daily food intake and twice-weekly BW, RMR (via indirect calorimetry), body composition [via dual-energy X-ray absorptiometry (DEXA)] and physical activity (via Actical activity monitors) were measured at week 0 and 12 of each period. Fasting serum leptin and ghrelin concentrations were measured at week 0, 6 and 12 of each period. Average hourly physical activity was greater (p = 0.008) in LD vs. SD cats (3770 vs. 3129 activity counts/h), which was primarily due to increased (p < 0.001) dark period activity (1188 vs. 710 activity counts/h). This corresponded to higher (p < 0.0001) daily metabolizable energy intake (mean over 12-week period: 196 vs. 187 kcal/day), and increased (p = 0.048) RMR in LD cats (9.02 vs. 8.37 kcal/h). Body composition, serum leptin and serum ghrelin were not altered by photoperiod. More research is needed to determine potential mechanisms by which these physiological changes occurred and how they may apply to weight management strategies.

Roux-en-Y gastric bypass and calorie restriction induce comparable time-dependent effects on thyroid hormone function tests in obese female subjects

Obesity and weight loss influence thyroid hormone physiology. The effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass (RYGB) in obese subjects have not been studied in parallel. We hypothesized that differences in transient systemic inflammation and catabolic state between the intervention types could lead to differential effects on thyroid hormone physiology. We recruited 12 lean and 27 obese females with normal fasting glucose (normal glucose tolerant (NGT)) and 27 obese females with type 2 diabetes mellitus (T2DM) for this study. Weight loss was achieved by restrictive treatment (gastric banding or high-protein-low-calorie diet) or by RYGB. Fasting serum leptin, TSH, triiodothyronine (T₃), reverse T₃ (rT₃), and free thyroxine (fT₄) concentrations were measured at baseline and 3 weeks and 3 months after the start of the interventions. Obesity was associated with higher TSH, T₃, and rT₃ levels and normal fT₄ levels in all the subjects when compared with the controls. After 3 weeks, calorie restriction and RYGB induced a decline in TSH levels and a rise in rT₃ and fT₄ levels. The increase in rT₃ levels correlated with serum interleukin 8 (IL8) and IL6 levels. After 3 months, fT₄ and rT₃ levels returned to baseline levels, whereas TSH and T₃ levels were persistently decreased when compared with baseline levels. No differences in the effects on thyroid hormone parameters between the interventions or between NGT and T2DM subjects were observed at any time point. In summary, weight loss directly influences thyroid hormone regulation, independently of the weight loss strategy used. The effects may be explained by a combination of decreased leptin levels and transient changes in peripheral thyroid hormone metabolism.

Maternal serum leptin concentration in gestational diabetes

Objective The aim of this study was to evaluate fasting serum leptin concentration and its relation to insulin resistance in women with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (IGT). Materials and Methods This case-control study, at 28 weeks of gestation, measured serum concentration of fasting leptin, insulin, and homeostatic model assessment index in three groups, GDM, IGT, and normal control, and compared them with each other. Results The serum leptin level was significantly higher in women with GDM than in the two other groups ( p = 0.03). In women with GDM and IGT, leptin was significantly positively related with insulin and homeostatic model assessment index ( r = 0.221, p = 0.03) and ( r = 0.246, p = 0.03), respectively. In all of the participants, there was a significant correlation between leptin and body mass index before pregnancy ( r = 0.416, p = 0.001). Conclusion Our data showed that serum leptin level was higher in GDM and had a positive correlation with insulin resistance. Our findings suggest that high leptin levels might be a risk factor for GDM and IGT in pregnant women.

Hyperleptinaemia positively correlated with metabolic syndrome in hemodialysis patients

Objective To evaluate the relationship between metabolic syndrome (MetS) and the fasting serum leptin concentration in hemodialysis (HD) patients. Patients and methods Fasting blood samples were obtained from 101 HD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. Results Forty-eight patients (47.5%) had MetS. Serum leptin concentrations were positively correlated with MetS (p < 0.001). Serum leptin levels correlated with increasing numbers of MetS criteria in HD patients (p = 0.001). Univariate linear regression analysis showed that the pre-HD body weight (p < 0.001), waist circumference (p < 0.001), body mass index (p = 0.001), triglycerides (p = 0.003), insulin level (p = 0.043), and homeostasis model assessment of insulin resistance (p = 0.003) positively correlated with serum leptin levels in HD patients and high-density lipoprotein-cholesterol (p = 0.016) negatively correlated with serum leptin levels in HD patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that pre-HD body weight (R 2 = 0.175; p < 0.001) was the independent predictor of the fasting serum leptin concentration. Conclusion Fasting serum leptin levels positively correlated with MetS and the pre-HD body weight could influence serum leptin in HD patients.

Longitudinal association between IGFBP-1 levels and parameters of the metabolic syndrome in obese children before and after weight loss

Insulin-like growth factor binding protein 1 (IGFBP-1) is a marker of insulin resistance. We hypothesized that IGFBP-1 is associated with the metabolic syndrome (MetS), which is related to insulin resistance. We examined 51 obese Caucasian children (mean age 12.1 ? 2.3, 55% male, mean body mass index [BMI] 31.8 ? 4.8 kg/m(2)). Anthropometrical markers, pubertal stage, hepatic ultrasound, waist circumference, blood pressure, fasting serum IGFBP-1, IGFBP-3, IGF-I, adiponectin, leptin, transaminases, glucose, insulin, triglycerides, and HDL-cholesterol concentrations were determined at onset and the end of the one-year lifestyle intervention. In contrast to IGF-I and IGFBP-3, IGFBP-1 correlated significantly to most parameters of the MetS in cross-sectional (waist circumference: r = -0.45, triglycerides: r = -0.29; insulin: r = -0.31; HOMA: r = -0.30) and longitudinal analyses (? triglycerides: r = ?0.22; ? Insulin: r = ?0.25; ? HOMA: r = ?0.62). The association between changes of HOMA and changes of IGFBP-1 was stronger than the associations between changes of leptin or adiponectin, and changes of HOMA. The risk for the MetS was inversely related to IGFBP-1 levels (odds ratio:-0.05 per additional IGFBP-1 unit; 95% confidence interval: -0.08 up to -0.02; p = 0.019) in a multiple logistic regression analyses adjusted to BMI, pubertal stage, age, and gender. The nine obese children with the MetS had significantly lower IGFBP-1 levels (1.6 ? 1.3 ngm/l) than the 42 obese children without the MetS (4.0 ? 3.8 ng/ml). The eleven obese children with fatty liver assessed by ultrasound had significantly lower IGFBP-1 levels (1.5 ? 1.3 ngm/l) than the 40 obese children without fatty liver (4.2 ? 4.1 ng/ml). The strong relationships between IGFBP-1, insulin resistance, and the MetS suggest that IGFBP-1 might be a promising marker for these entities in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Association of circulating visfatin concentrations with insulin resistance and low-grade inflammation after dietary energy restriction in Spanish obese non-diabetic women: Role of body composition changes

Background and AimsTo assess the influence of body composition changes on circulating serum visfatin after following 12 weeks of energy restricted diet intervention. We also examined the possible role of visfatin in glucose metabolism and in obesity-associated low-grade inflammation. Methods and ResultsA total of 78 obese (BMI 34.0 ± 2.8 kg/m2) women aged 36.7±7 y volunteered to participate in the study. We measured by DXA body fat mass (FM) and lean mass (LM). Fasting serum visfatin, glucose, insulin, adiponectin, leptin, IL-1β, IL-6, IL-8, TNF-α and CRP concentrations were analyzed before and after the intervention and HOMA and QUIKI indexes were calculated. Mean weight loss 7.7 ± 3.0 kg and HOMA decreased in 24 ± 35%. Serum visfatin concentration change was negatively associated with LM difference (P < 0.05), whereas no significant relationship was observed with FM changes after energy restricted diet intervention. Changes in circulating serum visfatin levels were significantly and inversely associated with HOMA-IR (P < 0.01) and positively with QUICKI index (P < 0.02) after energy restricted diet intervention, regardless of achieved body weight loss. We did not find any significant association between changes in visfatin levels and IL-1β, IL-6, IL-8, TNF-α and CRP levels after dietary intervention (all P > 0.2). ConclusionCirculating visfatin concentration is associated with sensitivity improvement achieved after energy restricted diet intervention induced weight loss. Furthermore, LM changes could be an influencing factor on visfatin concentrations and consequently, on the improvement of insulin sensitivity after weight loss in obese non-diabetic women. Our findings did not provide any evidence for a role of visfatin increase on low-grade inflammation after weight loss.

Hyperleptinemia positively correlated with metabolic syndrome in renal transplant recipients

Our aim was to evaluate the relationship between metabolic syndrome and fasting serum leptin concentration in renal transplant recipients. Fasting blood samples were obtained from 55 renal transplant recipients. Metabolic syndrome and its components were defined using the diagnostic criteria of the International Diabetes Federation. Thirteen patients (23.6%) had metabolic syndrome. Fasting leptin concentrations were positively correlated with metabolic syndrome (p=0.003). Univariate linear regression analysis indicated fasting serum leptin values were positively correlated with waist circumference (r=0.284; p=0.036), body mass index (r=0.358; p=0.007), body fat mass (r=0.610; p<0.001), triglycerides (r=0.268; p=0.048), high-sensitivity C-reactive protein (hs-CRP) (r=0.377; p=0.005), triceps skinfold (r=0.335; p=0.012), and mid-arm fat area (r=0.351; p=0.009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that body fat mass (R2 change=0.373; p<0.001) and hs-CRP (R2 change=0.045; p=0.049) were the independent predictors of fasting serum leptin concentration. Serum leptin concentration correlates positively with metabolic syndrome in renal transplant recipients.

The Serial Changes of Ghrelin and Leptin Levels and Their Relations to Weight Loss After Laparoscopic Minigastric Bypass Surgery

The ghrelin and leptin levels have been reported to be correlated with weight loss after bariatric surgery. However, the serial changes of ghrelin and leptin levels after laparoscopic minigastric bypass surgery (LMGBP) have not been reported yet. Therefore, we aimed to evaluate their serial changes and to analyze their relations to weight reduction after LMGBP. Serial fasting serum leptin and ghrelin concentrations were measured in 68 morbidly obese patients before (M0) and 1 (M1), 3 (M3), 6 (M6), and 12 (M12) months after LMGBP surgery. The correlations between ghrelin, insulin, and leptin concentrations and weight reduction were analyzed. Leptin levels were significantly reduced at 1, 3, 6, and 12 months after surgery, respectively (vs M0, p < 0.001), whereas the ghrelin concentrations were not significantly changed after surgery. The percent of excess BMI lost (%EBL) 12 months after surgery was negatively correlated with higher preoperative ghrelin concentrations (p = 0.004) and larger preoperative BMI (p = 0.002) in the multivariate analysis. Higher preoperative ghrelin concentrations and larger BMI are predictive of less %EBL at 12 months after LMGBP surgery.

Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight

Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal-weight children and to analyse the effect of weight loss on obestatin and ghrelin levels. We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11.2 years) before and after participating in a 1-year outpatient obesity intervention programme based on a high-carbohydrate, fat-reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal-weight healthy children of similar age, gender and pubertal stage. Obestatin and leptin concentrations were significantly (P < 0.001) higher and ghrelin concentrations were significantly (P < 0.001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0.007) increase in obestatin and to a significant (P < 0.05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0.009) lower obestatin and a tendency (P = 0.064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin. The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long-term lifestyle intervention resulted in an increase in obestatin levels.

Association of Nonalcoholic Fatty Liver Disease With Abnormal Aminotransferase and Postprandial Hyperglycemia

This study was conducted to explore the association between nonalcoholic fatty liver disease and glucose metabolism as well as insulin resistance using the homeostasis model assessment method (HOMA). From July 2003 to June 2004, 23 patients with ultrasound-proved fatty liver and either normal (10 patients) or abnormal (13 patients) serum aminotransferase levels were enrolled. Blood tests included a routine biochemistry, a 75-g glucose oral glucose tolerance test (OGTT) with blood sampled at 30-minute intervals during a 120-minute period. Fasting and 120-minute serum leptin, insulin, and C-peptide concentrations were also measured. Using the Mann-Whitney U test, significant differences were found in gamma glutamyl transpeptidase (28.6+/-7.9 vs. 65.1+/-65.9 U/L, P=0.008), fasting insulin (FI) (13.11+/-7.53 vs. 31.76+/-42.95 muU/mL, P=0.02), fasting C-peptide (3.82+/-3.00 vs. 2.17+/-0.43 ng/mL, P=0.01), fasting leptin (10.34+/-4.05 vs. 24.27+/-24.97 ng/mL, P=0.01), HOMA-IR (3.34+/-1.06 vs. 8.81+/-13.18, P=0.02), and HOMA beta-cell function (120.32+/-52.50 vs. 242.20+/-247.29, P=0.02) between normal and abnormal ALT/AST function groups. From the 75-g OGTT, no significant difference of plasma glucose was noted at 0, 30, 60, and 90 minutes but significant change was noted in 120-minute plasma glucose (99.3+/-21.5 vs. 131.4+/-27.3 mg/dL, P=0.004) of 2 groups. In conclusion, patients with fatty liver proved by ultrasound sonography might be at high risk of developing type 2 diabetes, especially when they had elevated liver enzymes. OGTT is warranted for the early diagnosis of these high risk patients.

Vitamin D binding protein, bone status and body composition in community-dwelling elderly men

The vitamin D binding protein (DBP) is the major carrier protein for vitamin D metabolites in plasma. Polymorphisms in DBP have been described to be associated with an increased bone fracture risk and diabetes. The present study investigates the influence of both phenotypic and (TAAA) n-Alu repeat DBP-polymorphism and DBP-concentration on bone mineral density, body composition, bone turnover- and metabolic markers in a cohort of ambulatory elderly men. We included 211 men (>70 years) in this study. Bone mineral density (BMD) was determined by dual energy X-ray absorptiometry. Bone turnover was assessed by measurement of serum osteocalcin, serum and urinary C-terminal telopeptides of type I collagen and urinary deoxypyridinoline, together with 25(OH)-vitamin D and 1,25(OH) 2-vitamin D concentrations. DBP-phenotypes were determined electrophoretically and the (TAAA) n-Alu repeat polymorphism was determined by polymerase chain reaction. Body composition was estimated using bioelectrical impedance analysis, together with handgrip and arm strength, fasting serum glucose and leptin concentrations. No differences in BMD or bone turnover markers among DBP-phenotypes or (TAAA) n-genotypes were observed in this study. Serum 25(OH)-vitamin D was comparable among DBP-variants and did not relate to DBP-concentrations, whereas 1,25(OH) 2-vitamin D was different among DBP-phenotypes and was correlated positively with DBP-concentrations. DBP-concentrations related positively to body mass index, fat mass, leptin and glucose concentration. The correlation with leptin remained significant after correction for fat mass. Fasting glucose concentrations were different among DBP-phenotypes, whereas no difference was observed between (TAAA) n-genotypes. In conclusion, serum 1,25(OH) 2-vitamin D concentrations are codetermined by DBP-phenotypes and DBP-concentrations. No major effect of DBP-polymorphism was demonstrated on BMD, bone turnover markers or body composition.

Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet

Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite. A total of 44 healthy adult men (aged: 43 +/- 5 years; BMI: 27.3 +/- 3.2 kg/m(2)). Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite. After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% CI: -43.6; -34.9%). This decline was associated with an increase in fasting hunger (r = -0.42; P < 0.01), desire to eat (r = -0.39; P < 0.05) and total appetite (r = -0.38; P < 0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period (for total appetite: day 0 r = -0.15, P = 0.32; day 2 r = -0.31, P =< 0.05; day 4 r = -0.41, P < 0.01). The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite.

Serum leptin in the development of insulin resistance and other disorders in the metabolic syndrome.

The metabolic syndrome mostly represented by obesity and hyperinsulinaemia connected with insulin resistance, presents the main mechanism in the pathogenesis of cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including leptin) and factors related to insulin resistance in groups of both normal and non-diabetic hyperlipemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. Two groups of patients (20 men, 20 women) with hypertriglyceridemia were compared with 30 individuals (10 men, 20 women) with normal serum triacylglycerols. Fasting serum leptin concentration, lipid parameters (triacylglycerols, HDL cholesterol, LDL cholesterol) and BMI were measured and compared with changes in insulin parameters influencing insulin resistance (HOMA IR, insulin, intact proinsulin, C-peptide). Statistical analysis was performed using SAS/STAT software including unpaired Student's t-test, Kolmogorov-Smirnov's test, Spearman's rank-order correlation and multiple regression analysis. In men, the insulin sensitivity correlates with leptin only. In women insulin sensitivity is markedly influenced by a complex of factors: leptin and lipid parameters. Increased insulin resistance in men is followed mainly by the increased correlations between leptin, HOMA IR and insulin parameters. In women correlations between leptin, HOMA IR and insulin parameters were smaller, but the inverse correlation with HDL cholesterol was stronger. In postmenopausal women and also in men, serum leptin concentration contributes to insulin resistance. However in women the effect of increase in serum triacylglycerols in contribution of insulin resistance seems to be more dominant.