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Diabetes is hallmarked by high blood glucose levels, which cause progressive generalised vascular damage, leading to microvascular and macrovascular complications. Diabetes-related complications cause severe and prolonged morbidity and are a major cause of mortality among people with diabetes. Despite increasing attention to risk factors of type 2 diabetes, existing evidence is scarce or inconclusive regarding vascular complications and research investigating both micro- and macrovascular complications is lacking. This thesis aims to contribute to current knowledge by identifying risk factors – mainly related to lifestyle – of vascular complications, addressing methodological limitations of previous literature and providing comparative data between micro- and macrovascular complications.
To address this overall aim, three specific objectives were set. The first was to investigate the effects of diabetes complication burden and lifestyle-related risk factors on the incidence of (further) complications. Studies suggest that diabetes complications are interrelated. However, they have been studied mainly independently of individuals’ complication burden. A five-state time-to-event model was constructed to examine the longitudinal patterns of micro- (kidney disease, neuropathy and retinopathy) and macrovascular complications (myocardial infarction and stroke) and their association with the occurrence of subsequent complications. Applying the same model, the effect of modifiable lifestyle factors, assessed alone and in combination with complication load, on the incidence of diabetes complications was studied. The selected lifestyle factors were body mass index (BMI), waist circumference, smoking status, physical activity, and intake of coffee, red meat, whole grains, and alcohol. Analyses were conducted in a cohort of 1199 participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, who were free of vascular complications at diabetes diagnosis. During a median follow-up time of 11.6 years, 96 cases of macrovascular complications (myocardial infarction and stroke) and 383 microvascular complications (kidney disease, neuropathy and retinopathy) were identified. In multivariable-adjusted models, the occurrence of a microvascular complication was associated with a higher incidence of further micro- (Hazard ratio [HR] 1.90; 95% Confidence interval [CI] 0.90, 3.98) and macrovascular complications (HR 4.72; 95% CI 1.25, 17.68), compared with persons without a complication burden. In addition, participants who developed a macrovascular event had a twofold higher risk of future microvascular complications (HR 2.26; 95% CI 1.05, 4.86). The models were adjusted for age, sex, state duration, education, lifestyle, glucose-lowering medication, and pre-existing conditions of hypertension and dyslipidaemia. Smoking was positively associated with macrovascular disease, while an inverse association was observed with higher coffee intake. Whole grain and alcohol intake were inversely associated with microvascular complications, and a U-shaped association was observed for red meat intake. BMI and waist circumference were positively associated with microvascular events. The associations between lifestyle factors and incidence of complications were not modified by concurrent complication burden, except for red meat intake and smoking status, where the associations were attenuated among individuals with a previous complication.
The second objective was to perform an in-depth investigation of the association between BMI and BMI change and risk of micro- and macrovascular complications. There is an ongoing debate on the association between obesity and risk of macrovascular and microvascular outcomes in type 2 diabetes, with studies suggesting a protective effect among people with overweight or obesity. These findings, however, might be limited due to suboptimal control for smoking, pre-existing chronic disease, or short-follow-up. After additional exclusion of persons with cancer history at diabetes onset, the associations between pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI and incidence of complications were evaluated in multivariable-adjusted Cox models. The analyses were adjusted for age, sex, education, smoking status and duration, physical activity, alcohol consumption, adherence to the Mediterranean diet, and family history of diabetes and cardiovascular disease (CVD). Among 1083 EPIC-Potsdam participants, 85 macrovascular and 347 microvascular complications were identified during a median follow-up period of 10.8 years. Higher pre-diagnosis BMI was associated with an increased risk of total microvascular complications (HR per 5 kg/m2 1.21; 95% CI 1.07, 1.36), kidney disease (HR 1.39; 95% CI 1.21, 1.60) and neuropathy (HR 1.12; 95% CI 0.96, 1.31); but no association was observed for macrovascular complications (HR 1.05; 95% CI 0.81, 1.36). Effect modification was not evident by sex, smoking status, or age groups. In analyses according to BMI change categories, BMI loss of more than 1% indicated a decreased risk of total microvascular complications (HR 0.62; 95% CI 0.47, 0.80), kidney disease (HR 0.57; 95% CI 0.40, 0.81) and neuropathy (HR 0.73; 95% CI 0.52, 1.03), compared with participants with a stable BMI. No clear association was observed for macrovascular complications (HR 1.04; 95% CI 0.62, 1.74). The impact of BMI gain on diabetes-related vascular disease was less evident. Associations were consistent across strata of age, sex, pre-diagnosis BMI, or medication but appeared stronger among never-smokers than current or former smokers.
The last objective was to evaluate whether individuals with a high-risk profile for diabetes and cardiovascular disease (CVD) also have a greater risk of complications. Within the EPIC-Potsdam study, two accurate prognostic tools were developed, the German Diabetes Risk Score (GDRS) and the CVD Risk Score (CVDRS), which predict the 5-year type 2 diabetes risk and 10-year CVD risk, respectively. Both scores provide a non-clinical and clinical version. Components of the risk scores include age, sex, waist circumference, prevalence of hypertension, family history of diabetes or CVD, lifestyle factors, and clinical factors (only in clinical versions). The association of the risk scores with diabetes complications and their discriminatory performance for complications were assessed. In crude Cox models, both versions of GDRS and CVDRS were positively associated with macrovascular complications and total microvascular complications, kidney disease and neuropathy. Higher GDRS was also associated with an elevated risk of retinopathy. The discrimination of the scores (clinical and non-clinical) was poor for all complications, with the C-index ranging from 0.58 to 0.66 for macrovascular complications and from 0.60 to 0.62 for microvascular complications.
In conclusion, this work illustrates that the risk of complication development among individuals with type 2 diabetes is related to the existing complication load, and attention should be given to regular monitoring for future complications. It underlines the importance of weight management and adherence to healthy lifestyle behaviours, including high intake of whole grains, moderation in red meat and alcohol consumption and avoidance of smoking to prevent major diabetes-associated complications, regardless of complication burden. Risk scores predictive for type 2 diabetes and CVD were related to elevated risks of complications. By optimising several lifestyle and clinical factors, the risk score can be improved and may assist in lowering complication risk.
Adipositas ist eine chronische Erkrankung mit erheblichen Komorbiditäten und Folgeschäden, die bereits im Kindes- und Jugendalter weit verbreitet ist. Unterschiedliche Faktoren sind an der Ätiologie dieser Störung beteiligt. Die Ernährung stellt dabei eine der Hauptsäulen dar, auf welche immer wieder Bezug genommen wird. Der Einfluss der Eltern auf die kindliche Ernährung spielt unbestritten eine zentrale Rolle – hinsichtlich genetischer Dispositionen, aber auch als Gestalter der Lebensumwelten und Vorbilder im Ernährungsbereich. Die vorliegende Arbeit hat zum Ziel, Übereinstimmungen elterlicher und kindlicher Ernährung zu untersuchen und dabei zu prüfen, inwiefern Prozesse des Modelllernens für die Zusammenhänge verantwortlich zeichnen. Grundlage ist die sozial-kognitive Theorie Albert Banduras mit dem Fokus auf seinen Ausführungen zum Beobachtungs- oder Modelllernen. Die Zusammenhänge elterlicher und kindlicher Ernährung wurden anhand einer Stichprobe 7 – 13-jähriger adipöser Kinder und ihrer Eltern in Beziehung gesetzt zu den Bedingungen des Modelllernens, die zuvor auch in anderen Studien gefunden worden waren. Eine hohe Ähnlichkeit oder gute Beziehung zwischen Modell (Mutter bzw. Vater) und Lernendem (Kind) sollte demnach moderierend auf die Stärke des Zusammenhangs wirken. Aus Banduras Ausführungen zu den Phasen des Modelllernens ergibt sich zudem ein dritter Aspekt, der in das Untersuchungsmodell einbezogen wurde. Die von Bandura postulierte Aneignungsphase setzt voraus, dass das zu lernende Verhalten auch beobachtet werden kann. Aus diesem Grund sollte die Analyse von Zusammenhängen im Verhalten nicht losgelöst von der Zeit betrachtet werden, die Modell und Beobachter miteinander verbringen bzw. verbracht haben. Zudem wurde die Wahrnehmung eines Elternteils als Vorbild beim Kind erfragt und als Moderator aufgenommen. In die Analysen eingeschlossen wurden vollständige Mutter-Vater-Kind-Triaden. Im Querschnitt der Fragebogenerhebung waren die Daten von 171 Mädchen und 176 Jungen, in einem 7 Monate darauf folgenden Längsschnitt insgesamt 75 Triaden (davon 38 Mädchen) enthalten. Es zeigte sich ein positiver Zusammenhang zwischen der kindlichen und mütterlichen Ernährung ebenso wie zwischen der kindlichen und väterlichen Ernährung. Die Übereinstimmungen zwischen Mutter und Kind waren größer als zwischen Vater und Kind. Überwiegend bestätigt werden konnten der moderierende Einfluss der Beziehungsqualität und der Vorbildwahrnehmung auf die Zusammenhänge elterlicher und kindlicher gesunder Ernährung und der Einfluss gemeinsam verbrachter Zeit vor allem in Bezug auf Vater-Kind-Zusammenhänge problematischer Ernährung. Der väterliche Einfluss, der sowohl in Studien als auch in präventiven oder therapeutischen Angeboten oft noch vernachlässigt wird und in vorliegender Arbeit besondere bzw. gleichberechtigte Beachtung fand, zeigte sich durch den Einbezug moderierender Variablen verstärkt. Eine Ansprache von Müttern und Vätern gleichermaßen ist somit unbedingtes Ziel bei der Prävention und Therapie kindlicher Adipositas. Auch jenseits des Adipositaskontextes sollten Eltern für die Bedeutung elterlicher Vorbildwirkung sensibilisiert werden, um eine gesunde Ernährungsweise ihrer Kinder zu fördern.