| 331. |
- Mehlig, Kirsten, 1964, et al.
(author)
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Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children's cohort.
- 2023
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In: Diabetologia. - 1432-0428. ; 66:10, s. 1914-24
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Journal article (peer-reviewed)abstract
- There is increasing evidence for the existence of shared genetic predictors of metabolic traits and neurodegenerative disease. We previously observed a U-shaped association between fasting insulin in middle-aged women and dementia up to 34 years later. In the present study, we performed genome-wide association (GWA) analyses for fasting serum insulin in European children with a focus on variants associated with the tails of the insulin distribution.Genotyping was successful in 2825 children aged 2-14 years at the time of insulin measurement. Because insulin levels vary during childhood, GWA analyses were based on age- and sex-specific z scores. Five percentile ranks of z-insulin were selected and modelled using logistic regression, i.e. the 15th, 25th, 50th, 75th and 85th percentile ranks (P15-P85). Additive genetic models were adjusted for age, sex, BMI, survey year, survey country and principal components derived from genetic data to account for ethnic heterogeneity. Quantile regression was used to determine whether associations with variants identified by GWA analyses differed across quantiles of log-insulin.A variant in the SLC28A1 gene (rs2122859) was associated with the 85th percentile rank of the insulin z score (P85, p value=3×10-8). Two variants associated with low z-insulin (P15, p value <5×10-6) were located on the RBFOX1 and SH3RF3 genes. These genes have previously been associated with both metabolic traits and dementia phenotypes. While variants associated with P50 showed stable associations across the insulin spectrum, we found that associations with variants identified through GWA analyses of P15 and P85 varied across quantiles of log-insulin.The above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker-disease associations.
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| 332. |
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| 333. |
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| 334. |
- Mehlig, Kirsten, 1964, et al.
(author)
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Low fasting serum insulin and dementia in nondiabetic women followed for 34 years.
- 2018
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In: Neurology. - 1526-632X. ; 91:5, s. e427-e435
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Journal article (peer-reviewed)abstract
- In a representative population of women followed over 34 years, we investigated the prospective association between fasting serum insulin and dementia, taking into account the incidence of diabetes mellitus.Fasting values for serum insulin and blood glucose were obtained in 1,212 nondiabetic women 38 to 60 years of age at the 1968 baseline. Risk of dementia was assessed by Cox proportional hazard regression with adjustment for insulin, glucose, and other covariates and, in a second model, after censoring for incident cases of diabetes mellitus. Incident diabetes mellitus was considered as a third endpoint for comparison with dementia.Over 34 years, we observed 142 incident cases of dementia. The low tertile of insulin displayed excess risk for dementia (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.52-3.58) compared to the medium tertile, but the high tertile of insulin did not (HR 1.28, 95% CI 0.81-2.03). These associations were also seen for dementia without diabetes comorbidity. In contrast, high but not low insulin predicted incident diabetes mellitus (115 cases) (HR 1.70, 95% CI 1.08-2.68 and HR 0.76, 95% CI 0.43-1.37, respectively).A previous study reported a U-shaped association between fasting insulin and dementia in a 5-year follow-up of elderly men. Our results confirmed a nonlinear association in a female population, with high risk at low insulin values that was not attributable to preclinical dementia or impaired insulin secretion. This condition suggests a new pathway to dementia, which differs from the metabolic pathway involving diabetes mellitus.
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| 335. |
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| 336. |
- Mehlig, Kirsten, 1964, et al.
(author)
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Negative life events predict weight gain in a 13-year follow-up of an adult Swedish population.
- 2020
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In: Journal of psychosomatic research. - : Elsevier BV. - 1879-1360 .- 0022-3999. ; 132
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Journal article (peer-reviewed)abstract
- Increasing psychosocial stress may underlie contemporary obesity trends. We investigate cross-sectional and prospective associations between negative life events (NLEs) and anthropometric indicators, and whether these are explained by lifestyle, depression and sleeping problems.Participants in the Swedish INTERGENE cohort answered questions about ten types of NLE, and indicated whether they occurred during the last year or earlier (2001-04, n = 2706). Body mass index (BMI) and waist-to-hip ratio (WHR) were measured at baseline, and at follow-up (2014-16, n = 974). Numbers of recent and distant NLE were related to anthropometric variables using linear models including age, sex, and education, and further adjusted for lifestyle, and psychological problems. Prospective models were adjusted for baseline anthropometric values.Participants reported on average 3.6 types of NLEs, of which 70% were experienced more than one year ago. At baseline, distant but not recent NLEs were associated with higher values of both BMI and WHR. These associations were explained in part by lifestyle and depression assessed at baseline. Recent but not distant NLEs predicted gain in BMI, 0.19 (0.07, 0.30) kg/m2, and WHR, 0.005 (0.002, 0.007), per event and independent of baseline covariates. The largest associations were seen for job insecurity and financial worries, with 0.35 (0.17, 0.52) kg/m2 increase in BMI corresponding to approximately 1.2 kg per event, in both sexes.We observed positive associations between NLEs and weight gain over 13 years including signs of latency and recovery regarding adverse weight development.
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| 337. |
- Mehlig, Kirsten, 1964, et al.
(author)
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Physical Activity, Weight Status, Diabetes and Dementia: A 34-Year Follow-Up of the Population Study of Women in Gothenburg
- 2014
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In: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 42:4, s. 252-259
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Journal article (peer-reviewed)abstract
- Background: There is evidence of a synergistic interaction between obesity and sedentary lifestyle with respect to diabetes. Although diabetes is a known risk factor for dementia, it is unclear if both diseases have common aetiologies. Methods: A community-based sample of 1,448 Swedish women, aged 38-60 years and free of diabetes and dementia in 1968, was followed by means of up to 5 examinations spread over 34 years. 9.6% of all women developed diabetes and 11.4% developed dementia (over 40,000 person-years of follow-up for each disease). Cox proportional hazard regression was used to assess the influence of selected risk factors on both diseases, and the relation between diabetes and dementia. Results: Comparing risk factors for incident diabetes and dementia, both diseases showed a synergistic association with obesity combined with a low level of leisure time physical activity [hazard ratio (HR) for interaction = 2.7, 95% confidence interval (Cl) = 1.2-6.3 for diabetes and HR = 3.3, 95% Cl = 1.1-9.9 for dementia]. Development of diabetes doubled the risk for subsequent dementia (HR = 2.2, 95% Cl = 1.1-4.4), which was slightly reduced upon adjustment for common risk factors. Conclusions: Shared risk factors suggest a similar aetiology for diabetes and dementia and partially explain the association between diseases. (C) 2014 S. Karger AG, Basel
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| 338. |
- Mehlig, Kirsten, 1964, et al.
(author)
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Secular trends in diet-related greenhouse gas emission estimates since 2000 - a shift towards sustainable diets in Sweden
- 2021
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In: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 24:12, s. 3916-
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Journal article (peer-reviewed)abstract
- Objective: This study examines secular changes in diet-related greenhouse gas emissions (GHGE) in younger and older Swedish adults, since the turn of this century. Setting: The municipality of Gothenburg, in western Sweden. Design: Two cross-sectional health examination surveys were conducted in 2001-04 (T1) and 2014-18 (T2). At both times, an 86-item food frequency questionnaire was embedded in the survey. From the food frequencies and age-standardized portion sizes, GHGE estimates (kg CO2e/year) were calculated. GHGE was modeled as a function of time period and covariates, for five distinct age groups. Participants: Women and men aged 25-34, 35-44, 45-54, 55-64 and 65-75 were randomly selected from the population registry and recruited for examinations. After exclusion of participants with incomplete dietary data, the analytic sample consisted of 2569 individuals at T1 and 2119 at T2. Results: Lower dietary GHGE scores were observed at T2 compared to T1, in each age group, adjusting for sex, body mass index, and education. The largest differences in GHGE were observed in the youngest age group (circa 30% reduction). Decreasing trends in GHGE from animal-based foods were observed at all ages and were accompanied by smaller increases from plant-based sources in younger groups only. At all ages, GHGE from discretionary foods decreased, and prevalence of overweight remained stable. Conclusions: Optimal dietary trends should support both human health and planetary health. Our results suggest that Swedish adults have moved in this direction, e.g. through less intake of red meat products and stable weight status.
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| 339. |
- Mehlig, Kirsten, 1964, et al.
(author)
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The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.
- 2013
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In: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 99:23, s. 1761-1765
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Journal article (peer-reviewed)abstract
- An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism.
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| 340. |
- Mehlig, Kirsten, 1964, et al.
(author)
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Weight status and BMI-related traits in adolescent friendship groups and role of sociodemographic factors: The european IDEFICS/I.family cohort
- 2021
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In: Obesity Facts. - : S. Karger AG. - 1662-4025 .- 1662-4033. ; 14:1, s. 121-130
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Journal article (peer-reviewed)abstract
- © 2020 Background: During adolescence, health behaviors and weight status are increasingly influenced by friendship and peer networks. This paper examines resemblances in weight-related characteristics and how they differ by sociodemographic factors. Methods: Over 3,000 friendships were reported by 1,603 adolescents, aged 11-16 years, who participated in the school-based I.Family study in 6 European countries. Each "source child"named 1-10 friends for whom standardized weight-related traits were available in the same survey. The mean value of the friends' traits weighted by time spent together was calculated, and related to the source child's trait. Country, age and sex of the source child, parental education, and immigrant background were considered for confounding and moderation. Results: Source children's z-scores of body fat percent and BMI were positively associated with their friends' characteristics, in particular if they had highly educated parents. Positive associations were also found regarding the frequency of fast-food consumption, impulsivity, screen time, preference for sugar-sweetened foods, and hours spent in sports clubs, in increasing order of effect size. Additionally, correlations were observed between friends' cognitive and school functioning and being bullied. No associations were seen for a preference for high-fat foods, weight concerns, and health-related quality of life. Finally, parental education and immigrant background were associated between friends in all countries except Sweden, where no associations were observed. Conclusion: Adolescent friends shared a number of weight-related characteristics. For weight measures per se, positive associations with friends' characteristics were only observed in adolescents with high parental education. Associations regarding energy-balance behaviors and indicators of school-related well-being did not differ by parental education. Parental education and immigrant background correlated positively in friends in most countries showing that social aggregation is already occurring in adolescence. The wide spectrum of friendship associations in weight-related traits and behaviors suggests that health promotion initiatives in adolescents should be directed towards peer groups in both school-related and leisure-time environments.
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