Belinda Lennerz

Effects of dietary glycemic index on brain regions related to reward and craving in men

BACKGROUND Qualitative aspects of diet influence eating behavior, but the physiologic mechanisms for these calorie-independent effects remain speculative. OBJECTIVE We examined effects of the glycemic index (GI) on brain activity in the late postprandial period after a typical intermeal interval. DESIGN With the use of a randomized, blinded, crossover design, 12 overweight or obese men aged 18-35 y consumed high- and low-GI meals controlled for calories, macronutrients, and palatability on 2 occasions. The primary outcome was cerebral blood flow as a measure of resting brain activity, which was assessed by using arterial spin-labeling functional magnetic resonance imaging 4 h after test meals. We hypothesized that brain activity would be greater after the high-GI meal in prespecified regions involved in eating behavior, reward, and craving. RESULTS Incremental venous plasma glucose (2-h area under the curve) was 2.4-fold greater after the high- than the low-GI meal (P = 0.0001). Plasma glucose was lower (mean ± SE: 4.7 ± 0.14 compared with 5.3 ± 0.16 mmol/L; P = 0.005) and reported hunger was greater (P = 0.04) 4 h after the high- than the low-GI meal. At this time, the high-GI meal elicited greater brain activity centered in the right nucleus accumbens (a prespecified area; P = 0.0006 with adjustment for multiple comparisons) that spread to other areas of the right striatum and to the olfactory area. CONCLUSIONS Compared with an isocaloric low-GI meal, a high-GI meal decreased plasma glucose, increased hunger, and selectively stimulated brain regions associated with reward and craving in the late postprandial period, which is a time with special significance to eating behavior at the next meal. This trial was registered at clinicaltrials.gov as NCT01064778.

Biologically Inactive Leptin and Early-Onset Extreme Obesity

Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss.

Bariatric surgery in adolescents and young adults—safety and effectiveness in a cohort of 345 patients

Objective:To examine the safety and effectiveness of adolescent bariatric surgery and to improve treatment recommendations for this age group.Design:Prospective longitudinal registry. Since January 2005, patients undergoing bariatric surgery in Germany are enlisted in an online registry called ‘study for quality assurance in obesity surgeries’.Subjects:Adolescents and young adults up to the age of 21 years, operated from January 2005 to December 2010.Measurements:Weight, BMI, comorbidities, complication rates.Results:N=345 primary procedures were recorded by 58 hospitals. N=51 patients were under the age of 18 years. Follow-up information was available for 48% (n=167) of patients, with an average observation period of 544±412 days (median: 388 days). The most common surgical techniques were gastric banding (n=118, 34.2%), gastric bypass (n=116, 33.6%) and sleeve gastrectomy (n=78, 22.6%). Short-term complications (intra-operative; general postoperative; specific postoperative) were slightly lower for gastric banding (0.8%; 2.5%; 0.8%) than for gastric bypass (2.6%; 5.2%; 1.7%) or sleeve gastrectomy (0%; 9.0%; 7.7%). In accordance with published findings, weight and BMI reduction were lower for gastric banding (−28 kg; −9.5 kg m−2) compared to gastric bypass (−50 kg; −16.4 kg m−2) P< 0.001 or sleeve gastrectomy (−46 kg; -15.4 kg m−2) P< 0.001. Outcomes did not differ between the <18 and ⩾18-year-old patients.Conclusion:Like in adults, bariatric surgery has low short-term complication rates and results in sustained weight loss in adolescents. However, the missing long-term observations prohibit a final conclusion about lasting effectiveness and safety. Clinical trials with structured follow-up programs and mechanisms to ascertain patient adherences are needed.

Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans

Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure.

Monogenic forms of childhood obesity due to mutations in the leptin gene

Congenital leptin deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the leptin gene. This review describes the molecular and cellular characteristics of the eight distinct mutations found so far in humans.

Plasma insulin levels in childhood are related to maternal factors – results of the Ulm Birth Cohort Study

The cardiovascular risk factor profile of a child as well as the development of body weight are influenced by genetic and childhood factors. Circulating insulin concentrations reflect the metabolic cardiovascular risk and may trigger weight gain. We aimed at identifying parental and childhood factors which may influence fasting plasma insulin concentrations in children.

Management of Type 1 Diabetes With a Very Low–Carbohydrate Diet

Among 316 participants with T1DM who follow a VLCD, the mean HbA1c was 5.67%, with low rates of hypoglycemia and other acute complications. OBJECTIVES: To evaluate glycemic control among children and adults with type 1 diabetes mellitus (T1DM) who consume a very low–carbohydrate diet (VLCD). METHODS: We conducted an online survey of an international social media group for people with T1DM who follow a VLCD. Respondents included adults and parents of children with T1DM. We assessed current hemoglobin A1c (HbA1c) (primary measure), change in HbA1c after the self-reported beginning of the VLCD, total daily insulin dose, and adverse events. We obtained confirmatory data from diabetes care providers and medical records. RESULTS: Of 316 respondents, 131 (42%) were parents of children with T1DM, and 57% were of female sex. Suggestive evidence of T1DM (based on a 3-tier scoring system in which researchers took into consideration age and weight at diagnosis, pancreatic autoimmunity, insulin requirement, and clinical presentation) was obtained for 273 (86%) respondents. The mean age at diagnosis was 16 ± 14 years, the duration of diabetes was 11 ± 13 years, and the time following a VLCD was 2.2 ± 3.9 years. Participants had a mean daily carbohydrate intake of 36 ± 15 g. Reported mean HbA1c was 5.67% ± 0.66%. Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia. CONCLUSIONS: Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD. The generalizability of these findings requires further studies, including high-quality randomized controlled trials.

A case of phace syndrome and acquired hypopituitarism

BackgroundPHACE is a neurocutaneous syndrome associated with: Posterior fossa brain malformations, large “segmental” facial hemangiomas, arterial cerebrovascular-, cardiovascular-, and eye anomalies.Case vignetteWe are reporting a girl with PHACE syndrome. The patient had a congenital right-sided facial hemangioma with plaque-morphology. At age 11 years and 2 months she presented with short stature, markedly decreased growth velocity and signs and symptoms suggestive of hypothyroidism. Magnetic Resonance Imaging (MRI) of the brain revealed complex structural and cerebrovascular arterial anomalies, including an empty sella. Testing of pituitary function revealed multiple pituitary dysfunctions, including absolute growth hormone deficiency, hypogonadotropic hypogonadism, central hypothyroidism, and secondary adrenal insufficiency.ConclusionsThis case suggests the necessity to screen all patients with PHACE syndrome and intracranial malformations for pituitary dysfunction at regular intervals.

Food Addiction, High-Glycemic-Index Carbohydrates, and Obesity

BACKGROUND Treatment success in obesity remains low, and recently food addiction has been delineated as an underlying etiologic factor with therapeutic relevance. Specifically, current treatment focuses on reduced food intake and increase of physical activity, whereas interventions for addiction encompass behavioral therapy, abstinence, and environmental interventions such as taxation, restrictions on advertising, and regulation of school menus. CONTENT Here, we reviewed the pertinent literature on food addiction with a specific focus on the role of high-glycemic-index carbohydrates in triggering addictive symptoms. Three lines of evidence support the concept of food addiction: (a) behavioral responses to certain foods are similar to substances of abuse; (b) food intake regulation and addiction rely on similar neurobiological circuits; (c) individuals suffering from obesity or addiction show similar neurochemical- and brain activation patterns.High-glycemic-index carbohydrates elicit a rapid shift in blood glucose and insulin levels, akin to the pharmacokinetics of addictive substances. Similar to drugs of abuse, glucose and insulin signal to the mesolimbic system to modify dopamine concentration. Sugar elicits addiction-like craving, and self-reported problem foods are rich in high-glycemic-index carbohydrates. These properties make high-glycemic-index carbohydrates plausible triggers for food addiction. SUMMARY We argue that food addiction is a plausible etiological factor contributing to the heterogeneous condition and phenotype of obesity. In at least a subset of vulnerable individuals, high-glycemic-index carbohydrates trigger addiction-like neurochemical and behavioral responses.

Fallserie zu BMI-Langzeitverläufen bei Patienten mit extremer juveniler Adipositas

BACKGROUND Extreme obesity in adolescents is considered largely resistant to therapy. The aim of this study was to demonstrate the short- and long-term BMI histories of patients who have successfully participated in an inpatient weight loss program, and to look for factors influencing the very good success. METHODS For the case series 10 youths were selected, who participated in an inpatient weight reduction program for 6-12 months and who succeeded in reducing BMI for the short and for the long term. The inpatient weight reduction program was based on a lifestyle intervention. Information on BMI (kg/m(2)) per patient are available for time of baseline examination (T0, admission), final examination (T1, end of inpatient treatment) and follow-up (T2, 3-18 years after the beginning of the intervention). Socio-demographic data were collected within the first consultation (T0). RESULTS Mean BMI was 41.9 kg/m(2) (BMI-SDS: 3.22) at time of admission. It clearly decreased under therapy and continued decreasing after the end of inpatient treatment. At time of follow-up (T2) 9 patients had a BMI < 30 kg/m(2) and were not any longer rated as obese, 4 patients had normal weight (BMI: 18.5-24.9 g/m(2)). The majority of patients had at least one normal-weight parent, all families had an average or high socioeconomic status (SES) and the majority of young people attended school for at least 10 years. Occurrence of binge eating before the inpatient treatment was rejected by two thirds of patients. CONCLUSIONS The case series shows that there is a group of patients who have a clear and lasting decrease of BMI and thus benefit for the long term from an inpatient weight reduction program. In literature discussed predictors of long-term weight reduction such as normal weight of parents, high SES of parents and a high school education of the patients were observed in this selective group. In individual cases, a long-term inpatient therapy leading to lasting lifestyle changes should firstly be preferred to bariatric surgery.ZusammenfassungHintergrund:Die extreme Adipositas bei Jugendlichen gilt als weitgehend therapieresistent. Ziel dieser Studie war es, die kurz- und langfristigen BMI-Verläufe von Patienten darzustellen, die erfolgreich an einer stationären Gewichtsreduktion teilgenommen haben, und nach Einflussfaktoren für den sehr guten Erfolg zu suchen.Methode:Für die Fallserie wurden 10 Jugendliche ausgewählt, die für 6–12 Monate an einem stationären Gewichtsreduktionsprogramm teilgenommen haben und ihren BMI kurz- und langfristig reduzieren konnten. Das stationäre Gewichtsreduktionsprogramm erfolgte auf Basis einer Lebensstilintervention. Angaben zum BMI (kg/m2) pro Patient liegen für die Zeitpunkte Basisuntersuchung (T0, Aufnahme), Abschlussuntersuchung (T1, Ende der stationären Therapie) und Nachuntersuchung (T2, 3–18 Jahre nach dem Beginn der Intervention) vor. Familiäre und soziodemographische Daten wurden im Rahmen der Erstanamnese (T0) erhoben.Ergebnisse:Der mittlere BMI betrug bei der Aufnahme 41,9 kg/m2 (BMI-SDS: 3,22). Er ging unter der Intervention deutlich zurück und reduzierte sich auch danach weiter. Zum Zeitpunkt der Nachuntersuchung (T2) wiesen 9 Patienten einen BMI < 30 kg/m2 auf und galten nicht mehr als adipös, 4 Patienten waren normalgewichtig (BMI: 18,5–24,9 kg/m2). Bei der Mehrheit der Patienten war mindestens ein Elternteil normalgewichtig, alle Familien wiesen einen mittleren oder hohen sozioökonomischen Status (SES) auf und die Mehrheit der Jugendlichen hat die Schule für mindestens 10 Jahre besucht. Das Auftreten von Essattacken vor Beginn der stationären Therapie wurden von zwei Dritteln der Patienten verneint.Schlussfolgerungen:Die Fallserie zeigt, dass es eine Gruppe von Patienten gibt, die langfristig von einem stationären Gewichtsreduktionsprogramm in Bezug auf eine deutlich nachhaltige Reduktion des BMI profitieren. In der Literatur diskutierte Prädiktoren für eine langfristige Gewichtsreduktion wie Normalgewicht und hoher SES der Eltern sowie eine hohe Schulbildung des Patienten wurden in dieser selektiven Gruppe beobachtet. Eine stationäre Langzeittherapie zur nachhaltigen Lebensstiländerung sollte in Einzelfällen einem Adipositas-chirurgischen Eingriff zunächst vorgezogen werden.AbstractBackground:Extreme obesity in adolescents is considered largely resistant to therapy. The aim of this study was to demonstrate the short- and long-term BMI histories of patients who have successfully participated in an inpatient weight loss program, and to look for factors influencing the very good success.Methods:For the case series 10 youths were selected, who participated in an inpatient weight reduction program for 6–12 months and who succeeded in reducing BMI for the short and for the long term. The inpatient weight reduction program was based on a lifestyle intervention. Information on BMI (kg/m2) per patient are available for time of baseline examination (T0, admission), final examination (T1, end of inpatient treatment) and follow-up (T2, 3–18 years after the beginning of the intervention). Socio-demographic data were collected within the first consultation (T0).Results:Mean BMI was 41.9 kg/m2 (BMI-SDS: 3.22) at time of admission. It clearly decreased under therapy and continued decreasing after the end of inpatient treatment. At time of follow-up (T2) 9 patients had a BMI < 30 kg/m2 and were not any longer rated as obese, 4 patients had normal weight (BMI: 18.5–24.9 g/m2). The majority of patients had at least one normal-weight parent, all families had an average or high socioeconomic status (SES) and the majority of young people attended school for at least 10 years. Occurrence of binge eating before the inpatient treatment was rejected by two thirds of patients.Conclusions:The case series shows that there is a group of patients who have a clear and lasting decrease of BMI and thus benefit for the long term from an inpatient weight reduction program. In literature discussed predictors of long-term weight reduction such as normal weight of parents, high SES of parents and a high school education of the patients were observed in this selective group. In individual cases, a long-term inpatient therapy leading to lasting lifestyle changes should firstly be preferred to bariatric surgery.