METSIM (METabolic Syndrome In Men) Study
The cross-sectional METSIM Study includes 10,197 men, aged from 45 to 73 years, randomly selected from the population register of the Kuopio town, Eastern Finland, and examined in 2005-2010 (Stancakova A, et al. Diabetes 2009A). The aim of the study is to investigate genetic and non-genetic factors associated with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and insulin resistance –related traits in a cross-sectional and longitudinal setting. Study protocol includes e.g. collection of data on CVD risk factors (smoking, exercise, diet, history of chronic diseases including coronary heart disease, stroke, cardiac failure, medication, history of diabetes or early onset coronary heart disease in the family), questionnaire on the FINDISC Score, measurement of height, weight, waist, hip, blood pressure (3 times), and bioimpedance for the evaluation of fat percentage.
Department of Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Principal Investigator and Contact Person:
Markku Laakso, firstname.lastname (at) kuh.fi
Stancakova A, Javorsky M, Kuulasmaa T, Haffner SM, Kuusisto J, Laakso M: Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6416 Finnish men. Diabetes 58:1212-1221, 2009 (A).
Stancakova A, Kuulasmaa T, Paananen J, Jackson AU, Bonnycastle LL, Collins FS, Boehnke M, Kuusisto J, Laakso M: Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5 327 non-diabetic Finnish men. Diabetes 58:2129-2136, 2009 (B).
Stancáková A, Paananen J, Soininen P, Kangas AJ, Bonnycastle LL, Morken MA, Collins FS, Jackson AU, Boehnke ML, Kuusisto J, Ala-Korpela M, Laakso M: Effects of 34 Risk Loci for Type 2 Diabetes or Hyperglycemia on Lipoprotein Subclasses and Their Composition in 6,580 Nondiabetic Finnish Men. Diabetes. 60;1608-1616, 2011.
METSIM Study - Additional Information
Laboratory determinations: Laboratory studies include an oral glucose tolerance test to evaluate glucose tolerance (samples for glucose, insulin, proinsulin and free fatty acids at 0, 30, and 120 minutes), as well as fasting laboratory measurements (lipids, lipoproteins, apolipoproteins, adiponectin, bilirubin, ALT, bile acids, hs-CRP, IL1-RA, IL-1beta, HbA1c, proton NMR metabonomics data [Stancakova A, et al. Diabetes 2011] including lipids and lipoproteins, low molecular weight molecules (including e.g. amino acids), and fatty acids of different lengths (total number of different measurements about 150).
Adipose tissue biopsies: In 1410 subjects a subcutaneous adipose tissue biopsy and a sample for peripheral blood mononuclear cells for gene expression studies have been taken, and RNA has been isolated. From these samples RNA expression analysis, sequencing (includes splicing variants, coding variants, microRNAs) and 1M GWAS (Affymetrix) is currently performed (data on the first 600 participants available). In these same 1410 subjects 13 fatty acids of different lengths from erythrocyte membranes have been measured (replications data from about 600 additional participants) which reflect dietary fatty acid intake during the last 3 months. These data make it possible to evaluate the gene-diet interaction in a large number of subjects for the risk of hyperglycaemia and insulin resistance related CVD risk factors.
Cardiovascular endpoints: Diagnoses of myocardial infarction, stroke and peripheral vascular disease have been verified on the basis of medical records (baseline study). We also have data on coronary angiograms, balloon angioplasty and bypass surgery. Data on all diabetes complications have also been collected from medical records.
Follow-up study: The protocol for 5-year follow-up study is identical to that of the baseline study. So far we have re-examined ~ 3000 participants, and for example identified 300 new individuals with T2D. We will re-examine about 2000 participants/year, and therefore we estimate that the follow-up study will be finished around the end of 2013 assuming that the participation rate is about 70%.
Other sources of follow-up data: All participants have signed a consent form which allows the use of several Finnish registries: hospital discharge registry, drug reimbursement registry, cancer registry, mortality registry etc. Therefore, the coverage of the follow-up data of the participants will be about 100% with respect to diagnoses of different diseases.
DNA analyses: We have genotyped about 7000 participants of the METSIM Study for all common variants which have been associated with weight, BMI, waist circumference, the waist-to-hip ratio, and fat percentage, LDL and HDL cholesterol, total triglycerides, glucose, insulin, elevated blood pressure, and type 2 diabetes (Stancakova A, et al. Diabetes 2010B). Additionally MetaboChip analysis from about 2000 participants has been finished and the results will be reported in 2012. Currently 1040 participants of the METSIM Study (520 patients with type 2 diabetes and 520 controls) will be exome-sequenced in the US and the results should be available in the first part of 2012. Low-frequency (<5%) and rare variants (<1%) will be determined in all > 10,000 participants using the Illumina Exome Chip which includes > 200,000 SNPs. These data should be available in March 2012 and make it possible to evaluate the role of common and low frequency/rare variants as determinants of obesity, central obesity, type 2 diabetes, dyslipidemia, and elevated blood pressure.