Please select the eligibility criteria that correspond to the clinical trial below.
Title: Systems Biology Approach to Understand Dietary Modulation of Gene Expression and Metabolic Pathways in Subjects With Abnormal Glucose Metabolism (Sysdimet)
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* those permanently assigned to one of the 45 IFD stations
* with a fire department-provided medical exam in the last two years
* at least 18 years of age
* full duty status at the time of consent

Exclusion Criteria:

* those without a recorded fire department exam in the last two years
* less than 18 years of age
* restrictions on duty at the time of consent.
B: Inclusion Criteria:

* Any coronary artery disease evidence in the past 10 years; or any ischemic stroke or TIA evidence in the past 10 years; or peripheral arterial disease in the past 10 years; or at least one of the following additional risk factors:
* Diabetes Mellitus; Hypertension; Dyslipidemia; Coronary artery disease family history;
* Asymptomatic carotid artery disease;
* Body mass index\> 25 kg/m2 for adults and\> 28 kg/m2 for seniors

Exclusion Criteria:

* Neurocognitive or psychiatric condition;
* Life expectancy less than 6 months (eg, metastatic malignancy or other defined as clinical trial investigators).
* Pregnancy or breast feeding.
* Hepatic impairment defined as elevated liver enzymes above three times the upper limit of normal
* Renal impairment defined as creatinine values higher than 1.5 mg/dL.
C: Inclusion Criteria:

* Any evidence of coronary artery disease (CAD) over the preceding 10 years, as defined by any of the following criteria:

  * defined by previous myocardial infarction,
  * stable or unstable angina,
  * history of atherosclerotic stenosis ≥70% of the diameter of any coronary artery on conventional or computed tomographic (CT) coronary angiography,
  * history of angioplasty, stenting, or coronary artery bypass surgery)
* Any evidence of stroke in the preceding 10 years
* Peripheral Arterial Disease over the preceding 10 years, as defined by any of the following criteria:

  * ankle/arm ratio \<0.9 of systolic blood pressure in either leg at rest, angiography or Doppler demonstrating \>70% stenosis in a cardiac artery,
  * intermittent claudication,
  * vascular surgery for atherosclerotic disease,
  * amputation due to atherosclerotic disease,
  * aortic aneurysm

Exclusion Criteria:

* Refusal to provide Informed Consent Statement
* neurocognitive or psychiatric condition that may hinder collection of reliable clinical data (defined at the trial investigator's discretion)
* Life expectancy less than 6 months
* Pregnancy or lactation
* Liver failure with a history of encephalopathy or anasarca
* Renal Failure with indication for dialysis
* Congestive heart failure
* Previous organ transplantation
* Wheelchair use
* Any restrictions to receiving an oral diet.
D: 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

Answer: D