[Obesity treatment-legal and illegal drugs and the future]. / Adipositastherapie ­ legale und illegale Arzneimittel und die Zukunft.

Obesity and its comorbidities represent a worldwide growing health challenge. In Germany, at least 15 million people are suffering from this disease. To date, lifestyle modification is the most frequently used treatment modality, but offers only limited success concerning both the extent and the sustainability of weight loss, while surgical interventions are restricted to people with severe obesity (body mass index ≥40 kg/m2). For this reason, there are huge efforts to develop pharmacological options for better and clinically meaningful weight management. At present, only a few compounds (orlistat, liraglutide, amfepramon) are available for adjunct drug treatment of obesity in Germany. However, new principles and compounds that could revolutionize obesity management in the years to come are on the horizon. For alternative "slimming drugs", mainly dietary supplements, scientific evidence is lacking on efficacy or clinically meaningful weight loss.

Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial.

BACKGROUND/OBJECTIVES: Evidence regarding the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring's neurodevelopment is not conclusive. SUBJECTS/METHODS: In this analysis, the effect of a reduced n-6:n-3 LCPUFA ratio in the diet of pregnant/lactating women (1.2 g n-3 LCPUFA together with an arachidonic acid (AA)-balanced diet between 15th wk of gestation-4 months postpartum vs control diet) on child neurodevelopment at 4 and 5 years of age was assessed. A child development inventory (CDI) questionnaire and a hand movement test measuring mirror movements (MMs) were applied and the association with cord blood LCPUFA concentrations examined. RESULTS: CDI questionnaire data, which categorizes children as 'normal', 'borderline' or 'delayed' in different areas of development, showed no significant evidence between study groups at 4 (n=119) and 5 years (n=130) except for the area 'letters' at 5 years of age (P=0.043). Similarly, the results did not strongly support the hypothesis that the intervention has a beneficial effect on MMs (for example, at 5 years: dominant hand, fast: adjusted mean difference, -0.08 (-0.43, 0.26); P=0.631). Children exposed to higher cord blood concentrations of docosahexaenoic acid, eicosapentaenoic acid and AA, as well as a lower ratio of n-6:n-3 fatty acids appeared to show beneficial effects on MMs, but these results were largely not statistically significant. CONCLUSIONS: Our results do not show clear benefits or harms of a change in the n-6:n-3 LCPUFA ratio during pregnancy on offspring's neurodevelopment at preschool age. Findings on cord blood LCPUFAs point to a potential influence on offspring development.

Maternal insulin resistance, triglycerides and cord blood insulin in relation to post-natal weight trajectories and body composition in the offspring up to 2 years.

AIMS: The intrauterine metabolic environment might have a programming effect on offspring body composition. We aimed to explore associations of maternal variables of glucose and lipid metabolism during pregnancy, as well as cord blood insulin, with infant growth and body composition up to 2 years post-partum. METHODS: Data of pregnant women and their infants came from a randomized controlled trial designed to investigate the impact of nutritional fatty acids on adipose tissue development in the offspring. Of the 208 pregnant women enrolled, 118 infants were examined at 2 years. In the present analysis, maternal fasting plasma insulin, homeostasis model assessment of insulin resistance and serum triglycerides measured during pregnancy, as well as insulin in umbilical cord plasma, were related to infant growth and body composition assessed by skinfold thickness measurements and abdominal ultrasonography up to 2 years of age. RESULTS: Maternal homeostasis model assessment of insulin resistance at the 32nd week of gestation was significantly inversely associated with infant lean body mass at birth, whereas the change in serum triglycerides during pregnancy was positively associated with ponderal index at 4 months, but not at later time points. Cord plasma insulin correlated positively with birthweight and neonatal fat mass and was inversely associated with body weight gain up to 2 years after multiple adjustments. Subsequent stratification by gender revealed that this relationship with weight gain was stronger, and significant only in girls. CONCLUSIONS: Cord blood insulin is inversely associated with subsequent infant weight gain up to 2 years and this seems to be more pronounced in girls.

Effect of dietary intervention to reduce the n-6/n-3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age.

BACKGROUND/OBJECTIVE: Evidence is accumulating that the long-chain PUFA (LCPUFA) are associated with offspring growth and body composition. We investigated the relationship between LCPUFAs in red blood cells (RBCs) of pregnant women/breastfeeding mothers and umbilical cord RBCs of their neonates with infant growth and body composition ≤ 1 year of age. SUBJECTS/METHODS: In an open-label randomized, controlled trial, 208 healthy pregnant women received a dietary intervention (daily supplementation with 1200 mg n-3 LCPUFAs and dietary counseling to reduce arachidonic acid (AA) intake) from the 15th week of gestation until 4 months of lactation or followed their habitual diet. Fatty acids of plasma phospholipids (PLs) and RBCs from maternal and cord blood were determined and associated with infant body weight, body mass index (BMI), lean body mass and fat mass assessed by skinfold thickness measurements and ultrasonography. RESULTS: Dietary intervention significantly reduced the n-6/n-3 LCPUFA ratio in maternal and cord-blood plasma PLs and RBCs. Maternal RBCs docosahexaenoic acid (DHA), n-3 LCPUFAs and n-6 LCPUFAs at the 32nd week of gestation were positively related to birth weight. Maternal n-3 LCPUFAs, n-6 LCPUFAs and AA were positively associated with birth length. Maternal RBCs AA and n-6 LCPUFAs were significantly negatively related to BMI and Ponderal Index at 1 year postpartum, but not to fat mass. CONCLUSION: Maternal DHA, AA, total n-3 LCPUFAs and n-6 LCPUFAs might serve as prenatal growth factors, while n-6 LCPUFAs also seems to regulate postnatal growth. The maternal n-6/n-3 LCPUFA ratio does not appear to have a role in adipose tissue development during early postnatal life.

[Carbohydrate intake and prevention of nutrition-related diseases]. / Kohlenhydratzufuhr und Prävention ausgewählter ernährungsmitbedingter Krankheiten.

The relative contribution of nutrition-related chronic diseases to the total disease burden of the society and the healthcare costs have risen continuously over the last decades. This challenge requires to explore and use the potential of dietary prevention of diseases such as obesity, type 2 diabetes, dyslipidaemia, cardiovascular disease and cancer. This evidence-based guideline systematically assessed the potential role of carbohydrates in the primary prevention of these diseases. The major findings were: a high consumption of sugar-sweetened beverages increases the risk of obesity and type 2 diabetes (strength of evidence: probable), whereas a high dietary fibre intake, mainly from whole-grain products, reduces the risk of obesity, type 2 diabetes, dyslipidaemia, hypertension, coronary heart disease and colorectal cancer (strength of evidence: probable and convincing, respectively). The practical consequences for current dietary recommendations are presented.

The impact of nutritional fatty acids during pregnancy and lactation on early human adipose tissue development. Rationale and design of the INFAT study.

Recent observational studies suggest that mean birth weight and body fat growth in the first year of life have increased continuously over the last decades. Both elevated birth weight and early fat mass are potential risk factors for childhood obesity. Experimental and limited clinical data suggest that the dietary ratio of n-6 to n-3 fatty acids (FAs) during pregnancy is critical for early adipose tissue growth. The aim of this randomized controlled study is to examine the effect of the supplementation with n-3 long-chain polyunsaturated FAs and reduction in the n-6/n-3 ratio in the diet of pregnant women/breast-feeding mothers on adipose tissue growth in their newborns using various methods for the assessment of body fat mass. Measurement of skinfold thickness in the newborn is the primary outcome parameter. Two hundred and four pregnant women will be recruited before the 15th week of gestation and randomly assigned to either active intervention or an isocaloric control diet. This upcoming study will explore the potential of this dietary approach to limit early adipose tissue growth and may contribute to the development of a new strategy for the primary prevention of childhood obesity.

[Nutritional and psychosomatic aspects of morbid obesity]. / Ernährungsmedizinische und psychosomatische Aspekte der Adipositas.

Obesity results from a complex interaction of genetic and environmental factors and has reached epidemic dimensions in Germany. In addition to chronic overnutrition and lack of physical activity, psychosomatic aspects considerably contribute to the etiology, risk of complications, and extent of excess weight, at least in subgroups of obese patients. The basis of every treatment programme should be a combination of a moderately hypocaloric diet, increased physical activity, and behaviour modification. Although this programme is potentially effective for patients with severe or class III obesity, there is increasing use of surgical interventions. Although bariatric surgery produces substantial weight loss and is increasingly recommended, it should be offered only in centers providing multiprofessional care and psychosomatic expertise.

[Nutrition therapy for gestational diabetes]. / Ernährungstherapie bei Gestationsdiabetes.

Overweight and increased energy intake before conception are powerful risk factors in the development of gestational diabetes mellitus (GDM) and may also represent important determinants of the so-called fetal (mal-)programming, which may have long-term consequences for the health of the newborn. Thus, an adequate intake of energy and nutrients is of fundamental significance in the treatment of GDM, along with regular self-monitoring of blood glucose. This concept suffices in most cases to achieve the strict therapeutic goal of normoglycemia. However, because of a lack of data from interventional studies, there is uncertainty about the optimal macronutrient composition of the diet (carbohydrates, fat, protein) and meal distribution, as well as of the mode of calorie restriction in overweight and obese women with GDM. Varying the carbohydrate intake between 40 and 55 % of total energy intake appears to be acceptable and may be distributed across main meals and snacks. Thus, individualized nutritional treatment together with other specific lifestyle interventions are the principal components in the management of GDM.

The importance and effect of dietary fiber in diabetes prevention with particular consideration of whole grain products.

The state of prediabetes is characterized by an increase in insulin resistance and a decrease in pancreatic beta cell function. The prestage of type 2 diabetes mellitus can be identified by an impaired glucose tolerance and/or by an impaired fasting blood sugar. Apart from weight loss and increase in physical activity, the development of type 2 diabetes mellitus can also be prevented by dietary changes. A low-fat diet with a dietary fiber intake of more than 30g/d was shown to represent an effective preventive approach. A high-fiber diet has many positive effects on the physical health status. In addition to positive effects in the gastrointestinal tract it has an obvious potential to support weight reduction and to improve disturbances of carbohydrate and fat metabolism. At the present state of knowledge, insoluble dietary fibers as found in whole grain cereal products are considered to be especially effective in the prevention of type 2 diabetes mellitus. A high intake of fruits and vegetables as well as pulses also exerts health-promoting properties. A high-fiber diet also plays an important role in the prevention of obesity and coronary heart diseases.

Effect of acarbose on weight maintenance after dietary weight loss in obese subjects.

AIMS: Acarbose is a well established antidiabetic drug and is known to exert a modest weight-lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects. DESIGN: Randomised, double-blind, placebo-controlled trial of the effect of acarbose on weight change over a 6-month follow-up period. PATIENTS AND METHODS: One hundred and ten obese subjects with a BMI > or = 32 and < or = 38 kg/m2 were included in the study and underwent a 10-16-week very-low-calorie diet programme to initiate weight loss. Then, subjects were randomised to receive either acarbose or placebo for 26 +/- 2 weeks. The primary variable was body weight. The primary efficacy analysis was performed in the per-protocol population (n = 75). RESULTS: After an initial mean weight loss of 10.0 +/- 3.4 kg, 54 subjects received acarbose at increasing dosage and 56 subjects received placebo treatment. After 14 weeks of follow-up, there was no change in body weight in the two groups. After 26 weeks, completed by 37 subjects in the acarbose group and by 38 subjects in the placebo group, a small weight regain of 0.6 kg was documented in the latter, whereas no weight increase was observed under acarbose treatment (p = 0.38, analysis of covariance with initial body weight as covariable). CONCLUSION: In obese individuals who undergo a hypocaloric diet and achieve a substantial loss of body weight, acarbose treatment provides only a very modest, not significant benefit to stabilise weight reduction. Thus, acarbose is not a useful adjunct to improve weight maintenance in obese subjects after weight loss.

[Does long-term blood pressure reduction in patients with essential hypertension improve concomitant metabolic disorders?]. / Führt eine langfristige Blutdrucksenkung bei essentiellen Hypertonikern zu einer Verbesserung begleitender Stoffwechselstörungen?

AIM: Aim of this study was to investigate the occurrence of metabolic abnormalities in patients with newly diagnosed essential hypertension and to assess the effects of a blood pressure lowering drug therapy on the respective variables. PATIENTS AND RESULTS: Twenty-six hypertensive subjects (12 female, 14 male) were included in the study. Twenty-one normotensive subjects (9 female, 12 male) served as a control group. During an oral glucose tolerance test the hypertensive subjects had higher blood glucose and serum insulin levels than the controls. The hypertensive patients also showed higher triglyceride concentrations and a more abdominal pattern of body fat distribution. In addition, the women with essential hypertension exhibited a higher free androgen index (32.2 +/- 14.8 vs 20.1 +/- 15.0%, p < 0.05) than the women of the control group. After a 3 to 6 month treatment period with nifedipine or nitrendipine the elevated blood pressure of the hypertensives was significantly reduced. In a second glucose tolerance test carried out in 13 patients blood glucose, serum insulin and triglyceride concentrations were significantly lower compared to the pretreatment period. The other metabolic and hormonal variables remained unchanged. CONCLUSION: This observation raises the question, whether a long-term vasodilatating antihypertensive therapy can improve the metabolic abnormalities found in patients with essential hypertension.