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

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

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

Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3</jats:p

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Peer reviewe

Assessment of risk and prevention of type 2 diabetes in primary health care

Abstract Type 2 diabetes is one of the fastest increasing lifestyle diseases globally. Its cure is not yet possible, but there is firm evidence from scientific studies that it can effectively be prevented by lifestyle changes. There is limited evidence-based information on the prevention of diabetes in practice. This dissertation offers new desirable information on the issue. The aim of this dissertation study was to describe the prevalence of risk factors for type 2 diabetes and hidden glucose disorders predicting the development of diabetes in the Finnish adult population, and to analyse whether the risk for developing diabetes could be reduced by simple lifestyle counselling. Furthermore, the ability of the Finnish Diabetes Risk Score (FINDRISC) to detect glucose disorders leading to diabetes and undiagnosed diabetes was analysed. In the dissertation data from large Finnish population surveys (the FINRISK 2002 glucose tolerance survey and the FIN-D2D 2004−2005 survey) were analysed. In addition, a prospective design and large-scale intervention were included. We found that obesity and glucose disorders are very common in the Finnish middle-aged population. Prevalence of obesity was 24% for men and 28% for women, that of abnormal glucose metabolism 42% for men and 33% for women, and that of undiagnosed diabetes 9% for men and 7% for men. One quarter of individuals aged 45−64 years were at high risk for diabetes. Lifestyle interventions were offered to more than 10,000 high-risk individuals, 3,379 men and 6,770 women. Of the men, 43% were also at high risk for cardiovascular morbidity and 42% at high risk for cardiovascular mortality estimated through the FRAMINGHAM and SCORE risk engines, respectively. The FINDRISC, originally developed for predicting the risk of development of type 2 diabetes, also predicted the prevalence of diabetes in the population. The effect of lifestyle interventions on weight and its association with glucose tolerance was evaluated in individuals at high risk for diabetes in a one-year follow-up. In total 17.5% of them lost ≥&#160;5% weight. Their relative risk for diabetes decreased 69% compared with the group that maintained their weight. This study shows that FINDRISC predicts prevalent type 2 diabetes. A significant proportion of middle-aged Finnish population has a glucose disorder including undiagnosed type 2 diabetes. Lifestyle interventions in primary health care may promote weight loss, which decreases the risk of diabetes.Tiivistelmä Diabetes on yksi nopeimmin lisääntyvistä elintapasairauksista maailmassa. Sitä ei vielä voida parantaa, mutta tieteellisissä tutkimuksissa on kiistattomasti osoitettu, että sitä voidaan tehokkaasti ehkäistä elintapamuutoksilla. Diabeteksen ehkäisystä käytännössä on hyvin niukasti tutkimustietoa. Tämä väitöskirja tuo kaivattua lisätietoa aiheesta. Väitöstutkimuksen päätavoitteena oli selvittää diabeteksen riskitekijöiden ja piilevien diabetesta ennakoivien sokerihäiriöiden yleisyyttä suomalaisessa aikuisväestössä. Tämän ohella tavoitteena oli selvittää voidaanko yksinkertaisella elintapaneuvonnalla vähentää sellaisten henkilöiden sairastumisvaaraa, joilla oli suuri riski sairastua diabetekseen. Lisäksi arvioitiin diabetesriskitestin kykyä tunnistaa ennakoivat sokerihäiriöt ja aiemmin tunnistamaton diabetes. Tutkimuksessa käytettiin laajoja suomalaisia väestötutkimusaineistoja: FINRISKI-2002 -tutkimusta, sen alaotosta ja D2D-väestötutkimusta 2004–2005. Mukana oli myös pitkittäisasetelma ja laajamittainen interventio. Tutkimuksen perusteella huomasimme, että lihavuus ja sokerihäiriöt ovat hyvin yleisiä keski-ikäisillä suomalaisilla. Merkittävästi lihavia (BMI&#160;≥&#160;30 kg/m2) oli 24&#160;% miehistä ja 28&#160;% naisista ja poikkeava sokeriaineenvaihdunta oli 42&#160;%:lla miehistä ja 33&#160;%:lla naisista. Tunnistamaton diabetes oli 9&#160;%:lla miehistä ja 7&#160;%:lla naisista. Suuressa diabetekseen sairastumisvaarassa oli neljäsosa 45−64-vuotiaista. Interventioon otettiin yli 10&#160;000 suuressa diabeteksen sairastumisriskissä olevaa henkilöä, 3&#160;379 miestä ja 6&#160;770 naista. Miehistä 43&#160;% oli suuressa sairastumisvaarassa myös sydän- ja verisuonisairauteen ja 42&#160;% suuressa kuolemanvaarassa Framingham- ja SCORE-riskilaskureilla arvioituna. Tyypin 2 diabeteksen sairastumisriskin arviointiin kehitetty Riskitesti ennusti hyvin myös diabeteksen esiintymistä väestössä. Elintapainterventioiden vaikutusta painoon ja sokeriaineenvaihduntaan analysoitiin vuoden seurannassa sellaisilla henkilöillä, joilla oli suuri diabetesriski. Paino laski 5&#160;% tai enemmän 17,5&#160;%:lla, jolloin sairastumisriski diabetekseen väheni 69&#160;% verrattuna ryhmään, jonka paino ei muuttunut. Tutkimuksen perusteella lihavuus, sokerihäiriöt ja tunnistamaton diabetes ovat yleisiä keski-ikäisessä väestössä. Riskitesti on hyvä työkalu myös diabeteksen seulonnassa. Perusterveydenhuollossa tarjottavalla elintapaneuvonnalla voidaan saada aikaan laihtuminen, joka vähentää sairastumisvaaraa diabetekseen

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