Dietary intervention studies in humans for the development of personalized nutritional recommendations

Contact persons: Prof. Dr. Andreas F. H. Pfeiffer, Dr. Stefan Kabisch, Dr. Margrit Kemper

Our working group investigates, to which extent different nutritional components affect the human metabolism and may induce or repair a dysregulation, as it is found in type 2 diabetes. Therefore, we are testing single nutrients, but also complex dietary patterns on their biological effect, in order to determine personalized nutritional recommendations for prevention and therapy of type 2 diabetes. Within this topic, weight reduction is considered to be a minor point of interest.

In previous studies (2013-2018) in elderly type 2 diabetes patients and subjects with severe obesity, a protein-rich, low-fat, plant-based diet turned out to positively affect glycemic metabolism and fatty liver disease. We could also show improved levels of uric acid, inflammatory parameters and lipids. These effects seem to be independent of the source of protein (animal vs. plant protein). Currently, we investigate the way of action of specific proteins.

Some of our smaller trials (2012-2016) were designed to detect the interaction between different sweeteners and hormone release in the gut. Plain sugar (sucrose) induces the secretion of the „incretins“: gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Isomaltulose, a less sweet sugar, which is slowly digested, preferably stimulates the metabolically beneficial GLP-1. It is still under debate, how non-caloric sweeteners – such as saccharin, sucralose or aspartame – affect the incretin system.

The Nutrigenomic Analysis in Twins (NUGAT) study (2011-2012) serves as a model experiment to determine, to which extent genetic factors contribute to metabolic responses and how these responses interact with specific nutrients. We could already determine an interaction between the ACE gene, high-fat diet and increasing blood pressure. Analyses of the NUGAT study will be continued for other genes and metabolic outcomes. We also intend to replicate our findings in larger trials within the next years.

Many studies have shown, that fat quality may be even more important than its mere quantity; some dietary fats are clearly a healthy part of our diet. In two smaller human intervention studies we examined, how canola oil, olive oil and sunflower oil affect glucose metabolism and fatty liver (2013-2017). Currently, we also investigate the impact of plant-derived fats (e.g. from walnuts and sunflowers) in larger RCTs on prediabetes and diabetes (DiNA-P, DiNA-D). Several recent trials have demonstrated, that a flexible diet with a sufficient amount of plant oils and nuts seems to be the healthies diet, irrespective of the amount of carbohydrates.

Dietary fiber – especially from whole grain – contribute to the prevention of type 2 diabetes and other disorders. In the Optimal Fiber Trial (OptiFiT; 2010-2014) we could show for the first time, that continuous intake of insoluble cereal fiber improves glucose tolerance in subjects with prediabetes, especially in the condition of impaired fasting glucose and independent of initial body weight. Diabetes risk could be reduced by about 40 %. We did not observe relevant side effects (such as bloating), as these fibers are poorly fermentable. Future studies with similar outcomes will be necessary, to replicate our findings.

These previous studies led to the development of two larger randomised controlled intervention studies in patients with prediabetes or overt type 2 diabetes (DiNA-P; DiNA-D). Both trials aim for a comparison of a low-carb and a low-fat diet over a period of one year. The projects assess the role of protein intake and quality, fat quality, fiber consumption as well as dynamics and interaction of weight loss and metabolic improvement in the intensive initiation phase and the long-term maintenance phase. We evaluate glucose and lipid metabolism, fatty liver disease, body composition and body fat distribution, inflammatory processes, functions of heart, arteries and small vessel as well as the peripheral nervous system. We also investigate aspects of dietary compliance and subgroup effects based on suitable stratification variables.

Our biobank is designed to provide long-term storage for biosamples, collected for later analyses of hormones, genetic factors and dietary markers even decades after completing the actual studies. Thus, we can assess the influence of endocrine, hereditary and environmental players on metabolic health whenever scientific progress provides new opportunities. Hopefully, we can identify biomarkers for the prediction of the clinical progression of type 2 diabetes and its individual responsiveness to preventive and therapeutic treatments.

Being a DZD facility, we also contribute to even larger clinical study projects, which as multicenter observational or interventional trials aim for the identification of specific phenotypes and treatment algorithms. The Prediabetes Lifestyle Intervention Study (PLIS) and the German Diabetes Study (DDS) serve as unique trials by themselves, but also as a platform for the development of new innovative studies, targeting the interaction of lifestyle and metabolic outcome.