0
selected
-
1.
Long-Term Effects of a Classic Ketogenic Diet on Ghrelin and Leptin Concentration: A 12-Month Prospective Study in a Cohort of Italian Children and Adults with GLUT1-Deficiency Syndrome and Drug Resistant Epilepsy.
De Amicis, R, Leone, A, Lessa, C, Foppiani, A, Ravella, S, Ravasenghi, S, Trentani, C, Ferraris, C, Veggiotti, P, De Giorgis, V, et al
Nutrients. 2019;(8)
Abstract
The classical ketogenic diet (cKD) is an isocaloric, high fat, very low-carbohydrate diet that induces ketosis, strongly influencing leptin and ghrelin regulation. However, not enough is known about the impact of a long-term cKD. This study evaluated the effects of a 12-month cKD on ghrelin and leptin concentrations in children, adolescents and adults affected by the GLUT1-Deficiency Syndrome or drug resistant epilepsy (DRE). We also investigated the relationship between the nutritional status, body composition and ghrelin and leptin variations. We carried out a longitudinal study on 30 patients: Twenty-five children and adolescents (15 females, 8 ± 4 years), and five adults (two females, 34 ± 16 years). After 12-monoths cKD, there were no significant changes in ghrelin and leptin, or in the nutritional status, body fat, glucose and lipid profiles. However, a slight height z-score reduction (from -0.603 ± 1.178 to -0.953 ± 1.354, p ≤ 0.001) and a drop in fasting insulin occurred. We found no correlations between ghrelin changes and nutritional status and body composition, whereas leptin changes correlated positively with variations in the weight z-score and body fat (ρ = 0.4534, p = 0.0341; ρ = 0.5901, p = 0.0135; respectively). These results suggest that a long-term cKD does not change ghrelin and leptin concentrations independently of age and neurological condition.
-
2.
Effects on metabolic variables after 12-month treatment with a new once-a-week sustained-release recombinant growth hormone (GH: LB03002) in patients with GH deficiency.
Roemmler, J, Gockel, A, Otto, B, Bidlingmaier, M, Schopohl, J
Clinical endocrinology. 2012;(1):88-95
Abstract
INTRODUCTION GH substitution in GH deficiency (GHD) must be subcutaneously administered daily. A new sustained-release formulation of GH (LB03002) has been developed, which has to be injected once a week. As a substudy to the phase III study, we performed this prospective study to evaluate the influence of LB03002 on metabolic variables and hormones. METHODS Eleven patients with GHD [four women/seven men, 58 years (29-69 years)] without GH therapy were included in the study. Eight patients were treated with LB03002 for 12 months and three patients received placebo for 6 months followed by LB03002 for 6 months. A 3-h oral glucose tolerance test (OGTT) was performed at study entry and at study end. Additionally, IGF-I, cholesterol, LDL, HDL, triglycerides, leptin, ghrelin, HbA1c and C-peptide were measured. Body composition was evaluated by dual-energy X-ray absorptiometry (DXA), and waist/hip ratio (WHR) and waist/height (WHtR) ratio were measured by tape and scale. RESULTS Multiple of upper limit of normal (xULN) of IGF-I (0·23 (0·09-0·4) vs 0·71 (0·4-1·04), P < 0·01), WHR (0·98 (0·86-1·04) vs 1·01 (0·86-1·05), P < 0·05) and ghrelin levels [119·8 ng/l (67·7-266·6) vs 137 ng/l (67-289·5), P < 0·05] were significantly higher, whereas fat mass (FM) [34·7% (20·4-49·2) vs 32·4% (16·7-48·5), P < 0·05] and leptin [11·2 μg/l (3·3-55·7) vs 7·05 μg/l (2·4-54·3), P < 0·05] were significantly lower at study end. Glucose, insulin, HOMA-IR, ISI, HOMA-β, C-peptide and HbA1c during OGTT were not significantly different before and after GH substitution, neither were BMI, WHtR, bone mineral density and lipid variables. CONCLUSION Substitution with LB03002 showed statistically significant reduction in FM, which reduces leptin levels and increases ghrelin levels but does not seem to influence glucose and lipid metabolism.
-
3.
Implantable gastric stimulator does not prevent the increase in plasma ghrelin levels that occurs with weight loss.
Korner, J, Nandi, A, Wright, SM, Waitman, J, McMahon, DJ, Bessler, M, Aronne, LJ
Obesity (Silver Spring, Md.). 2011;(10):1935-9
Abstract
UNLABELLED The SHAPE (Screened Health Assessment and Pacer Evaluation) trial was a 24 month randomized multicenter placebo-controlled study to determine the efficacy of an implantable gastric stimulator (IGS) for weight loss. This report is an investigator-initiated sub-study at one site designed to assess whether IGS affects plasma levels of ghrelin and peptide YY (PYY). The device was implanted in all subjects but was activated in the TREATMENT group (n = 7, BMI = 41.5 ± 2.0 kg/m2) and remained inactive in the CONTROL (n = 6, BMI = 39.5 ± 1.7 kg/m2) during the first 12 months. IGS was activated in both groups during months 12-24. Fasting venous blood was drawn at months 0, 12, and 24 and an oral glucose tolerance test (OGTT) was performed at month 12. Although there was no difference in weight loss at 6 months ( CONTROL -6.6 ± 1.5% vs. TREATMENT -6.2 ± 1.4%), at 24 months the CONTROL group exhibited weight gain from baseline (+2.2 ± 1.5%) that was significantly different from the weight loss in the TREATMENT group (-1.9 ± 1.4%; P < 0.05). At 12 months, fasting ghrelin was significantly increased (P < 0.05) in the TREATMENT group (285 ± 35 to 336 ± 35 pg/ml; weight change, -4.9 ± 1.4%), but not in the CONTROL (211 ± 36 to 208 ± 35 pg/ml; weight change, -3.4 ± 1.5%). No significant change was observed in postprandial suppression of plasma ghrelin or in fasting and postprandial PYY levels. In conclusion, IGS does not prevent the increase in fasting plasma ghrelin levels associated with weight loss. Further studies are needed to determine whether changes in technology can improve weight loss and maintenance, perhaps using gut hormones as biomarkers of possible efficacy.
-
4.
Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study.
Ejskjaer, N, Dimcevski, G, Wo, J, Hellström, PM, Gormsen, LC, Sarosiek, I, Søfteland, E, Nowak, T, Pezzullo, JC, Shaughnessy, L, et al
Neurogastroenterology and motility. 2010;(10):1069-e281
Abstract
BACKGROUND Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. METHODS Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 μg kg(-1) TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. KEY RESULTS The 80 μg kg(-1) dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 μg kg(-1) dose, the proportion of patients with at least 50% improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 μg kg(-1) TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 μg kg(-1) group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated. CONCLUSIONS & INFERENCES TZP-101 appears to be safe, well-tolerated, and effective at acutely addressing several gastroparesis symptoms.