Dietary Modulation of Gene Expression and Metabolic Pathways in Glucose Metabolism (Sysdimet)

Systems Biology Approach to Understand Dietary Modulation of Gene Expression and Metabolic Pathways in Subjects With Abnormal Glucose Metabolism (Sysdimet)

Professor Matti Uusitupa, University of Kuopio, Department of Clinical Nutrition (www.uku.fi) Docent Matej Oresic, VTT (www.vtt.fi) Ursula Schwab, PhD, Docent, Marjukka Kolehmainen, PhD, Docent, Leena Pulkkinen, PhD, Docent, David Laaksonen, MD, PhD, MPH, Docent, Kaisa Poutanen, DSc (Tech), Research Professor ABSTRACT The metabolic syndrome (MS) and type 2 diabetes (T2DM) are the most important health problems worldwide. In Finland the prevalence of T2DM is 12-15% among middle-aged people. The prevalence of less marked disturbances in glucose metabolism and MS is 30-40%. Because MS and T2DM are important risk factors for cardiovascular diseases (CVD), the leading cause of death in western countries, all efforts to reverse the epidemic increase in the incidence of MS and T2DM are warranted. The investigators have focused for years on the prevention and non-pharmacological treatment of T2DM and its complications including studies on genetic regulation of glucose and lipid metabolism after dietary modifications. In the investigators' recent projects, the investigators have studied the effects of long-term dietary interventions on gene expression profiles of fat tissue in subjects who are at risk of T2DM. The ultimate goal of these projects has been to identify genes and gene clusters and their biological pathways that respond to dietary modification and modulate glucose and lipid metabolism, and to develop dietary strategies for prevention of T2DM. The main goal of this project is to find nutrition related early biomarkers for progression of MS to T2DM by using modern technologies of systems biology (transcriptomics, metabolomics) of carefully conducted dietary interventions involving subjects with MS. The data will be analysed by using bioinformatics. The investigators reflect these new data to well-known risk factors for T2DM and CVD, e.g., insulin sensitivity, insulin secretion, serum lipids and inflammatory factors among others. In addition to interventions conducted earlier, a new intervention with a whole grain-berry-fish diet and a whole grain diet compared to a control diet with refined foods will be performed. The aim is to increase the investigators' understanding on the synergistic effects of these foods, because the investigators' previous interventions have shown that these individual foods have beneficial effects on glucose and lipid metabolism. On the contrary, diets with refined foods may be harmful in long-term due to its high insulin response, which may through chronic stress lead to both insulin resistance and beta-cell damage. The significance of this project is to increase understanding of the pathophysiology of MS, T2DM and CVD in physiological, cellular and genetic systems, which may lead to more effective and individualised strategies for treatment and prevention, and better identification of high-risk individuals responsive to specific dietary modifications. Increasing knowledge of dietary factors involved in the progression of MS to T2DM and CVD offers new opportunities to individually tailored diets in the management and prevention of these disorders. The results will also be beneficial for the food industry in developing new functional foods. These results and actions may help delay or even stop the epidemic of MS and T2DM and their negative effect on public health currently seen in Finland and worldwide.

Systems biology, Nutrigenomics, Metabolomics, Gene expression, Fat tissue, Peripheral mononuclear cells, Gene clusters, Gene expression profiles, Personal diets, Metabolic syndrome, Type 2 Diabetes, Atherosclerosis

Inclusion Criteria: impaired glucose tolerance (oral glucose tolerance test with 2-h glucose concentration 7,8-11,0 mmol/l) OR impaired fasting glucose fasting plasma glucose concentration 5,6-6,9 mmol/l = IFG) and two of the criteria for metabolic syndrome: BMI 26-39 kg/m2 Waist circumference > 102 cm (men) or > 88 cm (women) hypertriglyceridemia (fasting serum triglyceride conc > 1,7 mmol/l), HDL-cholesterol (fasting serum HDL conc < 1,0 mmol/l for men and < 1,3 mmol/l for women) Blood pressure ≥ 130/≥ 85 mmHg Exclusion Criteria: BMI > 40 kg/m2 fasting serum triglyceride conc > 3.5 mmol/l fasting serum cholesterol > 8 mmol/l type 1 or 2 diabetes abnormal liver, kidney or thyroid function large alcohol intake (women >16, men > 24 doses (4cl liquor or equivalent) during week) inflammatory bowel disease disease that prevents participation neuroleptic neuroleptic cortisone medication

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