Effects of Apolipoprotein E polymorphism on carotid intima-media thickness, incident myocardial infarction and incident stroke.

The Apolipoprotein E (APOE) gene polymorphism (rs429358 and rs7412) shows a well-established association with lipid profiles, but its effect on cardiovascular disease is still conflicting. Therefore, we examined the association of different APOE alleles with common carotid artery intima-media thickness (CCA-IMT), carotid plaques, incident myocardial infarction (MI) and stroke. We analyzed data from 3327 participants aged 20-79 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 14.5 years. Linear, logistic, and Cox-regression models were used to assess the associations of the APOE polymorphism with CCA-IMT, carotid plaques, incident MI and stroke, respectively. In our study, the APOE E2 allele was associated with lower CCA-IMT at baseline compared to E3 homozygotes (ß: - 0.02 [95% CI - 0.04, - 0.004]). Over the follow-up, 244 MI events and 218 stroke events were observed. APOE E2 and E4 allele were not associated with incident MI (E2 HR: 1.06 [95% CI 0.68, 1.66]; E4 HR: 1.03 [95% CI 0.73, 1.45]) and incident stroke (E2 HR: 0.79 [95% CI 0.48, 1.30]; E4 HR: 0.96 [95% CI 0.66, 1.38]) in any of the models adjusting for potential confounders. However, the positive association between CCA-IMT and incident MI was more pronounced in E2 carriers than E3 homozygotes. Thus, our study suggests that while APOE E2 allele may predispose individuals to lower CCA-IMT, E2 carriers may be more prone to MI than E3 homozygotes as the CCA-IMT increases. APOE E4 allele had no effect on CCA-IMT, plaques, MI or stroke.

Longitudinal association of Apolipoprotein E polymorphism with lipid profile, type 2 diabetes and metabolic syndrome: Results from a 15 year follow-up study.

AIMS: To examine the association of different APOE alleles with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) as well as the influence of high-sensitive C-reactive protein (hs-CRP) on these associations. METHODS: We analyzed data from 3917 participants aged 20-81 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 10.8 years. Linear and logistic mixed models were performed to test the association of APOE alleles with T2DM and MetS. RESULTS: We observed 393 T2DM and 1411 MetS events at baseline, and 576 T2DM and 1342 MetS events over the follow-up. The E4 carriers had a lower odds of developing T2DM (OR: 0.47 [0.24, 0.94]) than E3 homozygotes even after adjustment for potential confounders. The E2 carriers showed no associations. The inverse association between E4 alleles and T2DM moderately attenuated after adjustment for hs-CRP levels. The lower odds of developing T2DM in E4 carriers was more pronounced in participants without obesity, hypertension or MetS. However, both E2 and E4 carriers had higher odds of developing MetS (E2 OR: 1.45 [1.03, 2.03]; E4 OR: 1.56 [1.17, 2.09]) than E3 homozygotes. CONCLUSIONS: While the presence of APOE E4 allele might increase the chance of MetS through its major action on lipids, E4 allele might offer a protection towards T2DM through its influence on inflammation.

Hepatic steatosis and hepatic iron overload modify the association of iron markers with glucose metabolism disorders and metabolic syndrome.

BACKGROUND: Iron status has been linked with impaired glucose metabolism (IGM), type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MetS), but the role of hepatic steatosis or iron overload on these associations remains uncertain. METHODS: We analysed data from 2310 participants without known T2DM of the population-based Study of Health in Pomerania (SHIP-TREND, Germany) through logistic regression models. We tested additive and multiplicative interactions between ferritin and hepatic steatosis or iron overload. RESULTS: Serum ferritin was positively associated with IGM (OR per 100 µg/L: 1.11 [1.01, 1.23]), T2DM (OR per 100 µg/L: 1.20 [1.06, 1.36]) and MetS (OR per 100 µg/L: 1.11 [1.02, 1.20]) in the total population as well as in participants without hepatic iron overload. However, the synergistic effect of higher ferritin concentrations and hepatic iron overload showed stronger associations with IGM and T2DM. Similarly, while ferritin was positively associated with T2DM and MetS even in the absence of hepatic steatosis, the synergistic effect of higher ferritin concentrations and hepatic steatosis showed stronger associations with IGM, T2DM and MetS. Transferrin was associated with isolated impaired glucose tolerance but not with T2DM and MetS. CONCLUSIONS: Our study suggests that ferritin may be associated with glucose metabolism disorders and MetS even in people without hepatic steatosis or iron overload. However, in individuals with higher ferritin concentrations, the presence of hepatic steatosis may indicate stronger risk for glucose metabolism disorders and MetS, while the presence of hepatic iron overload may indicate stronger risk only for glucose metabolism disorders.

Associations of iron markers with type 2 diabetes mellitus and metabolic syndrome: Results from the prospective SHIP study.

AIMS: To assess the role of serum ferritin and transferrin with prevalent and incident type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and whether these associations are independent of inflammatory markers and hepatic enzymes. METHODS: We analyzed data from 3,232 participants aged 20-81 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 10.6 years. Logistic and Cox regression analyses were performed. RESULTS: Serum ferritin concentrations were associated with a higher prevalence of T2DM (total population OR: 1.16 [95% CI: 1.07, 1.26]; men OR: 1.18 [95% CI: 1.08, 1.30) and MetS (total population OR: 1.27 [95% CI: 1.16, 1.38]; men OR: 1.26 [95% CI: 1.15, 1.38]) in the total population and men independently of inflammatory markers and hepatic enzymes. In longitudinal analyses, baseline ferritin concentrations were associated with a higher risk of incident T2DM in women (HR: 1.38 [95% CI: 1.10, 1.71]), but not in men or in the total population and also with a higher risk of incident MetS (HR: 1.09 [95% CI: 1.01, 1.17]) in the total population. These longitudinal associations attenuated considerably after adjustment for hepatic enzymes but not inflammatory markers. Transferrin was not associated with any of the outcomes. CONCLUSIONS: Our results suggest a link between ferritin and T2DM and MetS, which might be partially explained by hepatic dysfunction.

Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring: Results from the Prospective TEDDY Study.

OBJECTIVE: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. METHODS: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross-sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. RESULTS: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes. CONCLUSIONS: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM.

Associations of maternal type 1 diabetes with childhood adiposity and metabolic health in the offspring: a prospective cohort study.

AIMS/HYPOTHESIS: Exposure to an intrauterine hyperglycaemic environment has been suggested to increase the offspring's later risk for being overweight or having metabolic abnormalities, but conclusive evidence for pregnancies affected by maternal type 1 diabetes is still lacking. This study aims to analyse the relationship between maternal type 1 diabetes and the offspring's metabolic health and investigate whether birthweight and/or changes in the offspring's metabolome are in the potential pathway. METHODS: We analysed data from 610 and 2169 offspring having a first-degree relative with type 1 diabetes from the TEENDIAB and BABYDIAB/BABYDIET cohorts, respectively. Anthropometric and metabolic outcomes, assessed longitudinally at 0.3-18 years of age, were compared between offspring of mothers with type 1 diabetes and offspring of non-diabetic mothers but with fathers or siblings with type 1 diabetes using mixed regression models. Non-targeted metabolomic measurements were carried out in 500 individuals from TEENDIAB and analysed with maternal type 1 diabetes and offspring overweight status. RESULTS: The offspring of mothers with type 1 diabetes had a higher BMI SD score (SDS) and an increased risk for being overweight than the offspring of non-diabetic mothers (e.g. OR for overweight status in TEENDIAB 2.40 [95% CI 1.41, 4.06]). Further, waist circumference SDS, fasting levels of glucose, insulin and C-peptide, and insulin resistance and abdominal obesity were significantly increased in the offspring of mothers with type 1 diabetes, even when adjusted for potential confounders and birthweight. Metabolite patterns related to androgenic steroids and branched-chain amino acids were found to be associated with offspring's overweight status, but no significant associations were observed between maternal type 1 diabetes and metabolite concentrations in the offspring. CONCLUSIONS/INTERPRETATION: Maternal type 1 diabetes is associated with offspring's overweight status and metabolic health in later life, but this is unlikely to be caused by alterations in the offspring's metabolome.

Long-term associations of modeled and self-reported measures of exposure to air pollution and noise at residence on prevalent hypertension and blood pressure.

Air pollution, traffic noise and noise annoyance are suggested to be associated with hypertension and blood pressure (BP); however, the evidence remains inconsistent. Our study examined the long-term associations of modeled and self-reported measures of air pollution and traffic noise on prevalent hypertension and BP. We analyzed cross-sectional data from 2552 participants aged 31-72years from the KORA F4 (2006-2008) study conducted in the region of Augsburg, Germany. Land-use regression models were used to estimate residential long-term exposure to particulate matter <2.5µm (PM2.5), soot content of PM2.5 (PM2.5abs) and nitrogen dioxide (NO2). Road traffic noise levels at the facade of the dwellings were estimated for the participants' residences. Participants filled-in a questionnaire on noise annoyance and heavy traffic passing their residence. Linear and logistic regression models adjusting for confounders were used to assess the association between exposure measures and hypertension and BP. An interquartile increase in annual mean PM2.5 (1µg/m3) was significantly associated with 15% higher prevalence of hypertension, without (95% CI: 2.5; 28.0%) and with (95% CI: 0.7; 30.8%) adjustment for traffic noise. Diastolic blood pressure (DBP) was associated with air pollutants and traffic noise with percent increases in mean of 0.7 (95% CI: 0.2; 1.2), 0.6 (95% CI: 0.1; 1.1) and 0.3 (95% CI: 0.0; 0.7) for an interquartile increase in PM2.5 (1µg/m3) and PM2.5abs (0.2∗10-5/m), and 5dB(A) increase in 24-hour road traffic noise, respectively. Associations of PM2.5abs and NO2 with hypertension or DBP were stronger in men and diabetic individuals. No clear associations were seen with systolic BP or noise annoyance. In conclusion, self-reported measures of air pollution or noise did not perform better than the objective measures. Our findings provide further evidence for a link between air pollution, noise and cardiovascular disease and indicate a stronger association for men and diabetic individuals.