Metabolically healthy and unhealthy obesity phenotypes in the general population : the FIN-D2D Survey

Peer reviewe

High prevalence of obesity, central obesity and abnormal glucose tolerance in the middle-aged Finnish population

<p>Abstract</p> <p>Background</p> <p>There is a worldwide increase in the prevalence of obesity and disturbances in glucose metabolism. The aim of this study was to assess the current prevalence of obesity, central obesity and abnormal glucose tolerance in Finnish population, and to investigate the associations between body mass index (BMI), waist circumference and abnormal glucose tolerance.</p> <p>Methods</p> <p>A cross-sectional population-based survey was conducted in Finland during October 2004 and January 2005. A total of 4500 randomly selected individuals aged 45–74 years were invited to a health examination that included an oral glucose tolerance test. The participation rate was 62% in men and 67% in women.</p> <p>Results</p> <p>The prevalence of obesity was 23.5% (95% Confidence Interval (CI) 21.1–25.9) in men, and 28.0% (95% CI 25.5–30.5) in women. The overall prevalence of abnormal glucose tolerance (including type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose) was 42.0% (95% CI 39.2–44.8) in men and 33.4% (95% CI 30.9–36.0) in women. The prevalence of previously unknown, screen-detected type 2 diabetes was 9.3% (95% CI 7.7–11.0) in men and 7.3% (95% CI 5.9–8.7) in women. Central obesity was associated with abnormal glucose tolerance within each of the three BMI categories normal (< 25 kg/m²), overweight (25–29 kg/m²), and obese (≥ 30 kg/m²).</p> <p>Conclusion</p> <p>In a population-based random sample of Finnish population, prevalences of obesity, central obesity and abnormal glucose tolerance were found to be high. A remarkably high number of previously undetected cases of type 2 diabetes was detected. Waist circumference is a predictor of abnormal glucose tolerance in all categories of obesity.</p

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis

Gender differences in thyroid function and obesity among finnish women and men:the FIN-D2D-study

Abstract Background: Our aim was to study the relationship between thyroid function and body weight in a large Finnish adult population, taking into account the effect of gender, because the results of previous studies are conflicting. Methods: A random sample of 4500 Finnish subjects aged 45–74 years old was selected from the National Population Register. The participation rate was 64%. Height, weight, waist circumference, and blood pressure were measured. Medications used, current smoking, the use of alcohol, and leisure-time physical activity (LTPA) wereas queried. Thyroid values (free T4, free T3, and TSH) were measured in 1307 men and 1434 women. Subjects receiving thyroid hormone (N=92) were excluded. Results: The mean age of the subjects was 59.7 years and their mean body mass index (BMI) was 27.4 kg/m². After adjustment for age, LTPA, and current smoking, TSH showed no linearity (p=0.09) across increasing BMI; in women TSH ranged from 1.85 ± 1.15 to 2.02 ± 1.29 IU/L and in men, from 1.79 ± 1.19 to 2.04 ± 1.33 IU/L (p=0.13). FT3 -values increased from 3.85 ± 0.67 to 3.97 ± 0.59 pmol/L in women (p=0.004), but not in men, with increasing BMI. FT4 -values decreased from 13.78 ± 2.07 to 13.31 ± 1.91 pmol/L with increasing BMI in men (p&lt;0.001 for linearity), but not in women. Conclusions: TSH values did not increase along with BMI in men and women with BMI, but FfT3 levels increased in women, and FfT4 levels decreased in men along with increasing BMI. The reasons for these gender differences need further research

A population-based study on the prevalence of NASH using scores validated against liver histology

Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology

Diabeteksen kansallisen ehkäisyhankkeen pitkäaikaiset vaikutukset ja merkitys

Tiivistelmä Tyypin 2 diabeteksen ilmaantuvuus perustuen erityiskorvattavien lääkkeiden käyttöön on laskenut Suomessa koko 2010-luvun, mutta D2D-alueen sairaanhoitopiirien väliset erot ovat säilyneet. Kolmasosa D2D-hankkeessa vuosina 2003–2007 tunnistetuista suuren sairastumisriskin henkilöistä osallistui tarjottuun hoito- ja seurantaohjelmaan. Perusterveydenhuollossa ja myös työterveyshuollossa on herätty torjumaan diabetesta. Väestön diabetestietoisuus on lisääntynyt koko maassa DEHKO-ohjelman, D2D-hankkeen ja FINDRISC-diabeteksen riskitestin laajan käytön myötä. Tuloksellinen tyypin 2 diabeteksen ehkäisy edellyttää sekä korkean riskin että väestötason strategiaan perustuvia toimia ja monialaista yhteistyötä terveyttä edistävien elintapojen edistämiseksi ja omaksumiseksi