Kirsten Mehlig

Adipocyte size predicts incidence of type 2 diabetes in women

Enlarged subcutaneous abdominal adipocytes have been shown to predict incidence of type 2 diabetes (T2D) in the Pima population of Arizona (USA). We investigated the role of subcutaneous abdominal adipocyte size (AAS), as well as femoral adi‐pocyte size (FAS), as predictors of T2D in a population‐based Swedish cohort. In 1974–1975, a sample of 1302 middle‐aged women underwent a health examination, including anthropometry and evaluation of parental medical history. In addition, body composition (total body potassium and total body water), AAS and FAS (adipose tissue needle biopsy) were assessed in a sub‐sample of 245 women. Incidence of T2D was followed until 2001, with 36 cases eligible for inclusion in this analysis. Women developing T2D had larger AAS at baseline vs. women remaining healthy (age/heredity‐adjusted hazard ratio for increase of AAS by 1 sd [AAS‐HR] 1.91;P<0.001). Further adjustment for both body fat percentage and waist‐to‐height ratio (WHtR) indicated a robust association. For FAS, the corresponding associations were consistently weaker. WHtR retained a strong predictive association independent of AAS and FAS (WHtR‐HR 2.6 and 2.7, respectively; P<0.001). To conclude, in addition to the amount and distribution of body fat in women, subcutaneous adi‐pocyte size, particularly in the abdominal region, predicts incidence of T2D in later life.—Lönn, M., Mehlig, K., Bengtsson, C., Lissner, L. Adipocyte size predicts incidence of type 2 diabetes in women. FASEB J. 24, 326–331 (2010). www.fasebj.org

Alcoholic Beverages and Incidence of Dementia: 34-Year Follow-up of the Prospective Population Study of Women in Göteborg

The objective of this study was to assess the association between different types of alcoholic beverages and 34-year incidence of dementia. Among a random sample of 1,462 women aged 38-60 years and living in Göteborg, Sweden, in 1968-1969, 164 cases of dementia were diagnosed by 2002. At baseline as well as in 1974-1975, 1980-1981, and 1992-1993, the frequency of alcohol intake, as well as other lifestyle and health factors, was recorded and related to dementia with Cox proportional hazard regression, by use of both baseline and updated covariates. Wine was protective for dementia (hazard ratio (HR) = 0.6, 95% confidence interval (CI): 0.4, 0.8) in the updated model, and the association was strongest among women who consumed wine only (HR = 0.3, 95% CI: 0.1, 0.8). After stratification by smoking, the protective association of wine was stronger among smokers. In contrast, consumption of spirits at baseline was associated with slightly increased risk of dementia (HR = 1.5, 95% CI: 1.0, 2.2). Results show that wine and spirits displayed opposing associations with dementia. Because a protective effect was not seen for the other beverages, at least part of the association for wine may be explained by components other than ethanol.

Midlife homocysteine and late-life dementia in women. A prospective population study.

Elevated serum total homocysteine (tHcy) is an established risk factor for cardiovascular disease. Its role in dementia is still controversial, and no study has examined the role of midlife tHcy, or reports longer than 8 years of follow-up. We examined the relation between midlife tHcy and late-life dementia in women followed for 35 years. The Prospective Population Study of Women in Gothenburg began in 1968-1969, comprising a representative population of women aged 38-60 years. Four extensive follow-ups were conducted by 2003. Serum samples from 1968 to 1969 were analysed for tHcy in 1368 women. In total, 151 women developed dementia. The highest tHcy tertile was related to a hazard ratio of 1.7 (95% CI 1.1-2.6) for developing any dementia, 2.1 (95% CI 1.2-3.7, n=100) for AD and 2.4 (95% CI 1.3-4.7, n=68) for AD without cerebrovascular disease. Kaplan-Meier plots showed divergence with respect to dementia after 22 years of follow-up. In conclusion, high homocysteine in midlife is an independent risk factor for the development of late-life Alzheimer dementia in women.

Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women

OBJECTIVE Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary heart disease (CHD) risk. However, these associations may be modified by lifestyle factors. Therefore, we studied whether smoking, physical inactivity or overweight interact with APOE on cholesterol levels and CHD risk. METHODS Combining two Swedish case-control studies yielded 1735 CHD cases and 4654 population controls (3747 men, 2642 women). Self-reported questionnaire lifestyle data included smoking (ever [current or former regular] or never) and physical inactivity (mainly sitting leisure time). We obtained LDL cholesterol levels and APOE genotypes. CHD risk was modelled using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for relevant covariates. RESULTS Smoking interacted with APOE on CHD risk; adjusted ORs for ever versus never smoking were 1.45 (95% CI 1.00-2.10) in ɛ2 carriers, 2.25 (95% CI 1.90-2.68) in ɛ3 homozygotes and 2.37 (95% CI 1.85-3.04) in ɛ4 carriers. Female ɛ4 carriers had OR 3.62 (95% CI 2.32-5.63). The adjusted ORs for physical inactivity were 1.09 (95% CI 0.73-1.61), 1.34 (95% CI 1.12-1.61), and 1.79 (95% CI 1.38-2.30) in ɛ2, ɛ3ɛ3 and ɛ4 groups, respectively. No interaction was seen between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL cholesterol levels. CONCLUSION The APOE ɛ2 allele counteracted CHD risk from smoking in both genders, while the ɛ4 allele was seen to potentiate this risk mainly in women. Similar ɛ2 protection and ɛ4 potentiation was suggested for CHD risk from physical inactivity.

Physical activity, weight status, diabetes and dementia: a 34-year follow-up of the population study of women in Gothenburg.

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 (CI) = 1.2-6.3 for diabetes and HR = 3.3, 95% CI = 1.1-9.9 for dementia]. Development of diabetes doubled the risk for subsequent dementia (HR = 2.2, 95% CI = 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.

The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism

Objective 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. Design and setting Data from two case-control studies of first-time myocardial infarction (MI), Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina, INTERGENE, were analysed in parallel. Patients THcy was determined in a total of 1150 cases and 1753 controls. Interventions None. Main outcome measures The outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic regression was used to investigate the association between tHcy and CHD, and its modification by genotype. Results High tHcy was confirmed to be a risk factor for CHD in both studies. In SHEEP, the association between tHcy and MI was observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in T-homozygotes, independent of smoking, physical activity and obesity. An effect modification of similar magnitude was observed but not statistically significant in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies. Conclusions Two Swedish case-control studies showed that the association between elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which could have implications for the efficiency of tHcy-lowering treatment.

Secular trends in weight, height and BMI in young Swedes: The ‘Grow up Gothenburg’ Studies

This study aims to document secular differences in anthropometry (level and variability of weight, height, BMI) in two cohorts born around 1990 and 1974 and examined as young adults.

Perceived mental stress in women associated with psychosomatic symptoms, but not mortality: observations from the Population Study of Women in Gothenburg, Sweden.

Purpose To investigate possible association between mental stress and psychosomatic symptoms, socioeconomic status, lifestyle, as well as incident mortality in a middle-aged female population followed over 37 years. Methods A prospective observational study initiated in 1968–1969, including 1462 women aged 60, 54, 50, 46, and 38 years, with follow-ups in 1974–1975, 1980–1981, and 2000–2001, was performed. Measures included self-reported mental stress as well as psychosomatic symptoms and smoking, physical activity, total cholesterol, S-triglycerides, body mass index, waist–hip ratio, blood pressure, socioeconomic status and mortality. Results Smoking, not being single, and not working outside home were strongly associated with reported mental stress at baseline. Women who reported high mental stress in 1968–1969 were more likely to report presence of abdominal symptoms (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.39–2.46), headache/migraine (OR = 2.04, 95% CI: 1.53–2.72), frequent infections (OR = 1.75, 95% CI: 1.14–2.70), and musculoskeletal symptoms (OR = 1.70, 95% CI: 1.30–2.23) than women who did not report mental stress. Women without these symptoms at baseline 1968–1969, but with perceived mental stress were more likely to subsequently report incident abdominal symptoms (OR = 2.15, 95% CI: 1.39–3.34), headache/migraine (OR = 2.27, 95% CI: 1.48–3.48) and frequent infections (OR = 2.21, 95% CI: 1.12–4.36) in 1974–1975 than women without mental stress in 1968–1969. There was no association between perceived mental stress at baseline and mortality over 37 years of follow-up. Conclusion Women reporting mental stress had a higher frequency of psychosomatic symptoms than women who did not report these symptoms. Not working outside home and smoking rather than low socioeconomic status per se was associated with higher stress levels. Perception of high mental stress was not associated with increased mortality.

Socioeconomic inequalities in childhood overweight: heterogeneity across five countries in the WHO European Childhood Obesity Surveillance Initiative (COSI–2008)

Background:Excess risk of childhood overweight and obesity occurring in socioeconomically disadvantaged families has been demonstrated in numerous studies from high-income regions, including Europe. It is well known that socioeconomic characteristics such as parental education, income and occupation are etiologically relevant to childhood obesity. However, in the pan-European setting, there is reason to believe that inequalities in childhood weight status may vary among countries as a function of differing degrees of socioeconomic development and equity.Subjects and Methods:In this cross-sectional study, we have examined socioeconomic differences in childhood obesity in different parts of the European region using nationally representative data from Bulgaria, the Czech Republic, Lithuania, Portugal and Sweden that were collected in 2008 during the first round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative.Results:Heterogeneity in the association between parental socioeconomic indicators and childhood overweight or obesity was clearly observed across the five countries studied. Positive as well as negative associations were observed between parental socioeconomic indicators and childhood overweight, with statistically significant interactions between country and parental indicators.Conclusions:These findings have public health implications for the WHO European Region and underscore the necessity to continue documenting socioeconomic inequalities in obesity in all countries through international surveillance efforts in countries with diverse geographic, social and economic environments. This is a prerequisite for universal as well as targeted preventive actions.

Differential outcome of the IDEFICS intervention in overweight versus non-overweight children: Did we achieve 'primary' or 'secondary' prevention?

The aim of this study was to explore whether the IDEFICS intervention had a differential effect on 11,041 childrens weight trajectories depending on their baseline body mass index status.