Refine
Document Type
- Doctoral Thesis (3)
Language
- English (3) (remove)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- Epidemiologie (3) (remove)
Institute
- Institut für Community Medicine (3) (remove)
Obesity and diabetes have reached epidemic proportions and have emerged as massive public health problems globally. The etiology of both obesity and diabetes are related, multifactorial, highly complex, and involves interplay of genetic, environmental, socio-economic and physiological factors, which calls for a more extensive research in understanding the risk factors and biological pathways. Hence, this dissertation contributed in part to understanding the role of iron markers in the development of type 2 diabetes mellitus and the role of intrauterine hyperglycemia in influencing the risk of offspring obesity along with investigating potential pathways.
In the first part of my dissertation, the associations of iron markers (ferritin and transferrin) with type 2 diabetes mellitus and metabolic syndrome were investigated using the population-based Study of Health in Pomerania. The present analyses were based on 3,232 participants aged 20-81 years with a follow-up time of nearly 11 years. The results suggest that serum ferritin concentrations were associated with a higher prevalence of type 2 diabetes mellitus and metabolic syndrome in the total population as well as in men. However, the effects of serum ferritin on incident type 2 diabetes mellitus were observed only in women, while the effects on incident metabolic syndrome were seen in the total population. Serum ferritin is also known to reflect systemic inflammation or hepatic dysfunction in addition to increased iron stores. Hence, upon further analyses, the associations were found to be attenuated after adjustment for hepatic enzymes but not after adjustment for inflammation. Transferrin was not associated with any of the outcomes. Thus, our study provides evidence for a link between the iron marker ferritin and type 2 diabetes mellitus and metabolic syndrome, although the association seemed to vary by sex. Moreover, hepatic dysfunction seems likely to be in the pathway between ferritin and type 2 diabetes mellitus and metabolic syndrome.
In the second part of my dissertation, the association between maternal hyperglycemia and the risk of offspring overweight and obesity were investigated using three different cohorts: TEDDY, TEENDIAB and BABYDIAB/BABYDIET. The present analyses were based on a total of 8,103 children who were followed until 6 years of age in TEDDY study and until 18 years of age in TEENDIAB and BABYDIAB/BABYDIET studies. The dissertation revealed that maternal hyperglycemia in general may be associated with increased risk for childhood overweight and obesity, and that the association gets stronger as children grow older, with the risk being clearly evident at late childhood and adolescence. Moreover, this dissertation adds that this association can be driven by different pathways based on the type of maternal diabetes to which the offspring was exposed. The association of maternal gestational diabetes mellitus with offspring overweight can be largely explained by the confounding influence of maternal BMI, whereas the association of maternal type 1 diabetes mellitus with offspring overweight can be substantially explained by birthweight in all three studies. In our attempt to understand biological pathways at a cellular level, we found that the offspring metabolome was unlikely to be in the causal pathway between maternal type 1 diabetes mellitus and overweight, because this association could not be explained by any of the potentially relevant metabolites.
To conclude, this dissertation acknowledges the fact that prevention and early intervention of obesity and diabetes is of paramount importance to lessen the impact of these public health problems. Thus, our findings of the role of ferritin in increasing the risk of type 2 diabetes mellitus/ metabolic syndrome and the role of intrauterine hyperglycemia in increasing the risk of offspring overweight helped to identify particular risk groups who may need closer attention with respect to prevention of obesity and diabetes.
Type 2 diabetes mellitus is one of the most challenging health problems for the next decades. The impact of type 2 diabetes mellitus on health care systems is largely driven by the increasing prevalence, the management of the disease and subsequent comorbidities, even in people with prediabetes or undiagnosed type 2 diabetes mellitus. An early detection of high risk groups is necessary to identify and modify risk factors such as obesity, physical inactivity or cigarette smoking which showed regional disparities in their distribution within a country. This leads to the assumption that there might be regional disparities regarding the prevalence and incidence of type 2 diabetes mellitus as well. For Germany as for other countries, comparable data on possible regional disparities in the prevalence and incidence of type 2 diabetes mellitus are missing. The aim of the present dissertation is to estimate the prevalence and incidence of type 2 diabetes mellitus on regional level within Germany, and to estimate the smoking prevalence as a modifiable risk factor in individuals with type 2 diabetes mellitus using data from the Diabetes Collaborative Research of Epidemiologic Studies consortium (DIAB CORE) within the Competence Net Diabetes in Germany. Well comparable data of five regional studies and one nationwide reference study are included: the Study of Health in Pomerania (SHIP); the Cardiovascular Disease, Living and Ageing in Halle Study (CARLA); the Dortmund Health Study (DHS); the Heinz Nixdorf Recall Study (HNR); the Cooperative Health Research in the Region of Augsburg Study (KORA); and the German National Health Interview and Examination Survey 1998 (GNHIES 98). First, the prevalence of type 2 diabetes mellitus was estimated. Data from five regional population-based studies and one nationwide study conducted between 1997 and 2006 with participants aged 45 to 74 years were analyzed. Type 2 diabetes mellitus prevalence estimates based on self-reports (standardized to the German population for the regional studies, reference date 2007/12/31) were compared. Of 11,688 participants of the regional studies, 1,008 had a known type 2 diabetes mellitus, corresponding to a prevalence of 8.6% (95% confidence interval [CI] 8.1% 9.1%). The standardized prevalence was highest in the East with 12.0% (95% CI 10.3% 13.7%) and lowest in the South of Germany with 5.8% (95% CI 4.9% 6.7%).Second, the incidence of type 2 diabetes mellitus was estimated. Data from participants (baseline age 45 to 74 years) from five regional population-based studies were included. The incidence rates per 1,000 person-years (95% CI) and the cumulative incidence (95% CI) from regional studies were directly standardized to the German population (reference date 2007/12/31) and weighted by inverse probability weights for losses to follow-up. Of 8,787 participants, 521 (5.9%) developed type 2 diabetes mellitus corresponding to an incidence rate of 11.8 per 1,000 person-years (95% CI 10.8 12.9). The incidence of known type 2 diabetes mellitus showed regional disparities within Germany. The incidence was highest in the East and lowest in the South of Germany with 16.9 (95% CI 13.3 21.8) vs. 9.0 (95% CI 7.4 11.1) per 1,000 person-years, respectively. Third, the smoking prevalence in participants aged 20 to 79 years with type 2 diabetes mellitus in the regional SHIP and the nationwide GNHIES 98 was estimated. Prevalence estimates of cigarette smoking were calculated using weights reflecting the European adult population (reference date 2005/12/31). The overall prevalence of current smoking was lower among participants with type 2 diabetes mellitus than among participants without type 2 diabetes mellitus (17.3% vs. 38.0% in SHIP and 24.7% vs. 32.1% in GNHIES 98). In both studies, the prevalence of current smoking was highest in men aged 20 to 39 years, in particular among men with type 2 diabetes mellitus. To conclude, considerable disparities in prevalence and incidence of type 2 diabetes mellitus indicate the need for interventions on the regional level within Germany. Former smoking was more prevalent among both men and women with type 2 diabetes mellitus in comparison to current and non-smoking. This finding probably reflects behavioural changes secondary to the disease onset and medical counselling. The finding that men aged 20 to 39 years with type 2 diabetes mellitus were more often current smokers than men without type 2 diabetes mellitus underpins the importance of smoking as one of the main modifiable risk factors for type 2 diabetes mellitus.
Background: Cardiovascular diseases are the leading cause of death worldwide. Subclinical alterations of the cardiovascular system, such as increased exercise blood pressure or an endothelial dysfunction confer a higher risk of manifest cardiovascular diseases and incident events. Detecting associations between circulating markers of the endocrine-metabolic system and the subclinical cardiovascular phenotypes could be useful to better understand cardiovascular disease progression and to improve risk prediction for manifest cardiovascular diseases. Methods: The associations between (a) serum thyroid-stimulating hormone and increased exercise blood pressure, (b) serum hemoglobin A1c and endothelial dysfunction as well as (c) serum insulin-like growth factor I and endothelial dysfunction were studied using cross-sectional data from around 1400 subjects aged 25 to 85 years collected during the 5-year follow-up of the population-based Study of Health in Pomerania (SHIP-1). Increased exercise blood pressure was defined as a value above the sex- and age-specific 80th percentile measured at the 100 W stage of a symptom-limited bicycle ergometry test. Endothelial dysfunction was defined as an impaired flow-mediated dilation measured as a continuous decrease or below the median of sex-specific distribution. Non-fasting blood samples were drawn from the cubital vein in the supine position. Results: The odds for increased systolic exercise blood pressure (odds ratio 1.24, 95% confidence interval 0.88; 1.76) and diastolic exercise blood pressure (odds ratio 0.98, 95% confidence interval 0.70; 1.39) as well as for exercise-induced increase of systolic and diastolic blood pressure were not significantly different between subjects with high and low serum thyroid-stimulating hormone levels within the reference range. In women without current use of antihypertensive medication, increasing serum hemoglobin A1c levels were associated with decreasing flow-mediated dilation levels (ß = -1.17, 95% confidence interval -2.03; -0.30). Such an association was not found in men. In men, logistic regression analysis revealed an odds ratio of 1.27 (95% confidence interval 1.07; 1.51) for decreased flow-mediated dilation for each decrement of serum insulin-like growth factor I standard deviation. In women, no significant association between serum insulin-like growth factor I levels and flow-mediated dilation was observed (odds ratio 0.88, 95% confidence interval 0.74; 1.05). Conclusions: Based on the presented results it is concluded that (a) serum thyroid-stimulating hormone levels are not associated with exercise blood pressure in the general population, (b) higher serum hemoglobin A1c levels in non-diabetic subjects are inversely associated with flow-mediated dilation in women without antihypertensive medication, but not in men, and (c) lower serum insulin-like growth factor I levels are associated with impaired endothelial function in men, but not in women. Therefore the metabolic marker hemoglobin A1c and the endocrine marker insulin-like growth factor I might be markers facilitating the identification of subjects at high risk of subclinical cardiovascular alterations.