Vastine Klaus Mäkelälle

Vastine Sosiologia-lehden numerossa 1/2010 julkaistuun Klaus Mäkelän kirjoitukseen Pekka Sulkusen kirjasta The saturated society : governing risk and lifestyle in consumer culture.

A platform for anti-biofilm assays combining viability, biomass and matrix quantifications in susceptibility assessments of antimicrobials against Staphylococcus aureus biofilms

Bacteria can exist as planktonic, the lifestyle in which single cells exist in suspension, and as biofilms, which are surface-attached bacterial communities embedded in a selfproduced matrix. Most of the antibiotics and the methods for antimicrobial work have been developed for planktonic bacteria. However, the majority of the bacteria in natural habitats live as biofilms. Biofilms develop dauntingly fast high resistance towards conventional antibacterial treatments and thus, there is a great need to meet the demands of effective anti-biofilm therapy. In this thesis project it was attempted to fill the void of anti-biofilm screening methods by developing a platform of assays that evaluate the effect that screened compounds have on the total biomass, viability and the extracellular polysaccharide (EPS) layer of the biofilms. Additionally, a new method for studying biofilms and their interactions with compounds in a continuous flow system was developed using capillary electrochromatography (CEC). The screening platform was utilized with a screening campaign using a small library of cinchona alkaloids. The assays were optimized to be statistically robust enough for screening. The first assay, based on crystal violet staining, measures total biofilm biomass, and it was automated using a liquid handling workstation to decrease the manual workload and signal variation. The second assay, based on resazurin staining, measures viability of the biofilm, and it was thoroughly optimized for the strain used, but was then a very simple and fast method to be used for primary screening. The fluorescent resazurin probe is not toxic to the biofilms. In fact, it was also shown in this project that staining the biofilms with resazurin prior to staining with crystal violet had no effect on the latter and they can be used in sequence on the same screening plate. This sequential addition step was indeed a major improvement on the use of reagents and consumables and also shortened the work time. As a third assay in the platform a wheat germ agglutinin based assay was added to evaluate the effect a compound has on the EPS layer. Using this assay it was found that even if compounds might have clear effect on both biomass and viability, the EPS layer can be left untouched or even be increased. This is a clear implication of the importance of using several assays to be able to find “true hits” in a screening setting. In the pilot study of screening for antimicrobial and anti-biofilm effects using a cinchona alkaloid library, one compound was found to have antimicrobial effect against planktonic bacteria and prevent biofilm formation at low micromolar concentration. To eradicate biofilms, a higher concentration was needed. It was also shown that the chemical space occupied by the active compound was slightly different than the rest of the cinchona alkaloids as well as the rest of the compounds used for validatory screening during the optimization processes of the separate assays.

Työterveyshuolto ikääntyvän työntekijän työkyvyn tukijana

Tutkimuksen tarkoituksena oli kuvata, miten työterveyshuolto tukee nykyisellä toiminnallaan ikääntyvien (45–54-vuotiaat) työntekijöiden työkykyä ja mitä työkyvyn tukemiseen liittyviä odotuksia ikääntyvillä työntekijöillä on työterveyshuollolle. Tutkimuskysymykset olivat ”Miten ikääntyvän työntekijän mielestä työterveyshuolto tukee ikääntyvän työntekijän työkykyä?” ja ”Millaista tukea työkyvyn ylläpitämiseksi ikääntyvät työntekijät odottavat työterveyshuollolta?”. Tutkimuksen kohderyhmänä olivat pääkaupunkiseudulla toimivan yksityisen lääkäriasemaketjun yli 10 hengen asiakasyritysten ikääntyvät työntekijät, jotka tekevät toimistotyöhön rinnastettavaa työtä. Tutkimusaineisto kerättiin sähköisellä kyselyllä kesäkuussa 2011. Tutkimukseen osallistui 21 yritystä, joissa oli ikääntyviä työntekijöitä yhteensä 422. Kyselyyn vastasi 93 työntekijää. Vastausprosentti oli 22. Aineisto analysoitiin tilastollisilla menetelmillä ja avoimien vastausten tuottama aineisto induktiivisella sisällön analyysillä. Työntekijöistä kaksi kolmasosaa oli samaa mieltä siitä, että työterveyshuollon palvelut yleisesti ottaen tukevat ikääntyvän työntekijän työkykyä. Kuitenkin työntekijöistä vain hieman yli yksi viidesosaa oli samaa mieltä siitä, että työterveyshuollon toimintatavat ikääntyvän työntekijän työkyvyn tukemiseksi ovat riittävät. Syitä sille, miksi työterveyshuollon toimintaa ei pidetty työkykyä tukevana, olivat riittämätön aktiivisuus ja seuranta, asiakasorganisaation tuntemuksen puute ja näkemys siitä, että työterveyshuollon vaikutusmahdollisuudet yrityksen sisäisissä asioissa ovat riittämättömät. Työterveyshuollon arvioitiin tukevan enemmän fyysistä kuin psyykkistä työkykyä. Työterveyshuollon eri toimintojen osa-alueista ikääntyvät työntekijät arvioivat työterveyshuollon ohjaus- ja neuvontatoiminnan ja sairaanhoidon tukevan eniten työkykyään. Työterveyshuollon yleisen toiminnan arvioitiin tukevan työkykyä toiseksi eniten. Jaksamisessa ja muutoksissa tukeminen ja kuntoutustoiminta arvioitiin työkykyä vähiten tukevaksi toiminnaksi. Työntekijät odottivat työterveyshuollon toiminnalta aktiivisuutta, toiminnan ja seurannan säännöllisyyttä ja yksilöllisyyden huomioimista. Keskeisinä osaalueina, joihin työterveyshuollon tulisi panostaa, pidettiin psyykkisen jaksamisen, terveellisten elämäntapojen ja fyysisen jaksamisen tukemista sekä terveystarkastuksia ja ryhmätoimintaa. Tutkimuksen tuloksia voidaan hyödyntää suunniteltaessa ja toteutettaessa työterveyshuollon ennaltaehkäisevää ikääntyville suunnattua pysyvän työkyvyn tukemiseen tähtäävää toimintaa. Tulokset auttavat suuntaamaan työterveyshuollon resurssit ja voimavarat oikeisiin kohteisiin.

Oxidized LDL and physical fitness in healthy young men: associations with body composition, smoking, metabolic syndrome and androgen status

Background: In the past, oxidized low density lipoprotein (ox-LDL) has been associated with an unbeneficial lipid profile. This atherogenic lipid profile increases the risk of atherosclerotic cardiovascular diseases. Physical fitness has substantial effect on serum lipoprotein concentration as well as body composition and humoral responses, however interrelationships between ox-LDL and physical fitness have not been widely examined in a nationally representative sample. Aims: This thesis evaluates how cardiorespiratory and muscular fitness associate with ox-LDL lipids and how the other known risk factors of atherosclerosis might alter these associations. Subjects and Methods: The study cohort consisted of 846 healthy young males (mean age 25.1, SD 4.6) who were gathered by voluntary nationwide recruitment. Each participant conducted a series of physical fitness tests (cardiorespiratory and muscular fitness) and answered a detailed questionnaire that included lifestyle habits (i.e. smoking and leisuretime physical activity). Venous blood samples including ox-LDL and serum lipids were also collected. Results: Higher levels of ox-LDL were found in overweight and obese men, however, high cardiorespiratory fitness seemed to protect the overweight from high levels of ox-LDL. Young men who smoked and had poor cardiorespiratory or muscular fitness possessed a higher concentration of ox-LDL lipids when compared to comparable levels of cardiorespiratory or muscular fitness non-smoking young men. Metabolic syndrome was associated with increased levels of ox-LDL and high levels of ox-LDL combined with poor cardiorespiratory and abdominal muscle fitness seems to predict metabolic syndrome in young men. Also, participants with poor cardiorespiratory fitness and low levels of testosterone had higher levels of ox-LDL when compared to participants with high cardiorespiratory fitness / low testosterone as well as those with poor cardiorespiratory fitness / high testosterone. Conclusions: Good cardiorespiratory and muscular fitness protects young men from increased levels of ox-LDL lipids. This association was discovered in young men who were categorized as being overweight, smokers, metabolic syndrome or with low levels of testosterone. Being fit seems to prevent higher levels of ox-LDL, even in young healthy

Product placement on personal blogs: a multiple case study from companies’ perspective

As traditional advertising is losing its value in corporations’ marketing, new and growing social media marketing channels are increasing their importance. The growing interest in the media and the lack of research on the subject create a clear need for this study. The objectives are to increase understanding about product placement in personal blogs and examine the benefits as well as the downsides created by this marketing channel and present the requirements for success. The study also takes a stand on what kind of things a successful product placement strategy in personal blogs includes and what points should be considered when creating a strategy. The study’s empirical part consists of seven thematic interviews with case companies’ representatives and one agent. The study’s personal blogs were delimited to consist only lifestyle and fashion blogs. The results show that product placement on personal lifestyle and fashion blogs is a strongly growing marketing channel and it is best suited to reach young women. It is also a very good channel to change and improve brand image. Via personal blogs it is possible to reach a large number of consumers with a very cost-efficient manner. Thus utilizing the channel is suitable for all companies regardless of the size of the marketing budget. Of course, companies have to consider the suitability of their product to the themes of blogs. Executing a successful campaign in this media requires good relationship management skills and understanding of this particular media as the final content is not in advertiser’s hands. As a marketing channel, personal blogs differ highly from traditional marketing channels because of their constantly changing nature and multidirectional quality where several parties are in interaction.

Factors predicting mortality in type 2 diabetes. With special reference to physical exercise, blood pressure, proteinuria, inflammation and P wave duration

Background: Type 2 diabetes patients have a 2-4 fold risk of cardiovascular disease (CVD) compared to the general population. In type 2 diabetes, several CVD risk factors have been identified, including obesity, hypertension, hyperglycemia, proteinuria, sedentary lifestyle and dyslipidemia. Although much of the excess CVD risk can be attributed to these risk factors, a significant proportion is still unknown. Aims: To assess in middle-aged type 2 diabetic subjects the joint relations of several conventional and non-conventional CVD risk factors with respect to cardiovascular and total mortality. Subjects and methods: This thesis is part of a large prospective, population based East-West type 2 diabetes study that was launched in 1982-1984. It includes 1,059 middle-aged (45-64 years old) participants. At baseline, a thorough clinical examination and laboratory measurements were performed and an ECG was recorded. The latest follow-up study was performed 18 years later in January 2001 (when the subjects were 63-81 years old). The study endpoints were total mortality and mortality due to CVD, coronary heart disease (CHD) and stroke. Results: Physically more active patients had significantly reduced total, CVD and CHD mortality independent of high-sensitivity C-reactive protein (hs-CRP) levels unless proteinuria was present. Among physically active patients with a hs-CRP level >3 mg/L, the prognosis of CVD mortality was similar to patients with hs-CRP levels ≤3 mg/L. The worst prognosis was among physically inactive patients with hs-CRP levels >3 mg/L. Physically active patients with proteinuria had significantly increased total and CVD mortality by multivariate analyses. After adjustment for confounding factors, patients with proteinuria and a systolic BP <130 mmHg had a significant increase in total and CVD mortality compared to those with a systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with a systolic BP <130 mmHg and ≥160 mmHg. Among patients without proteinuria, a systolic BP <130 mmHg was associated with a non-significant reduction in mortality. A P wave duration ≥114 ms was associated with a 2.5-fold increase in stroke mortality among patients with prevalent CHD or claudication. This finding persisted in multivariable analyses. Among patients with no comorbidities, there was no relationship between P wave duration and stroke mortality. Conclusions: Physical activity reduces total and CVD mortality in patients with type 2 diabetes without proteinuria or with elevated levels of hs-CRP, suggesting that the anti-inflammatory effect of physical activity can counteract increased CVD morbidity and mortality associated with a high CRP level. In patients with proteinuria the protective effect was not, however, present. Among patients with proteinuria, systolic BP <130 mmHg may increase mortality due to CVD. These results demonstrate the importance of early intervention to prevent CVD and to control all-cause mortality among patients with type 2 diabetes. The presence of proteinuria should be taken into account when defining the target systolic BP level for prevention of CVD deaths. A prolongation of the duration of the P wave was associated with increased stroke mortality among high-risk patients with type 2 diabetes. P wave duration is easy to measure and merits further examination to evaluate its importance for estimation of the risk of stroke among patients with type 2 diabetes.

Beauty for Sale - An Empirical Study of Appearance-Related Consumption in Finland

This study examines appearance-related consumption in Finland. The theoretical portion discusses appearance-related consumption, on one hand from a consumer culture perspective, as both a possibility and responsibility for everyone; and on the other hand, from the point of view of behaviour and attitudes associated with sociodemographic and lifestyle-related factors. The empirical part of the study concentrates on the following aspects: 1) Finns’ appearance-related consumption patterns, attitudes towards appearance-related consumption and attending to one’s looks through consumption, as well as general changes in consumption patterns and attitudes; 2) gender differences in attitudes and consumption patterns, and their possible changes over time, and; 3) other differences among population groups in attitudes and consumption patterns, and their possible changes over time. The following dissertation utilises data from seven different nationally representative surveys. Data include Finnish Household Budget surveys from 1998 (N=4 359), 2001 (N=5 495) and 2006 (N=4 007), as well as, The Everyday Life and Well-being Survey (N=908) collected in 2011, and Finland 1999 (N=2 417), Finland 2004 (N=3 574) and Finland 2009 (N=1 202) surveys. The study indicates that Finns’ relationship to appearance-related consumption is, generally, somewhat inconsistent. In Finland, a significant share of a household’s total spending, around the EU average, is allocated to products and services related to appearance. In addition, at an attitudinal level, physical appearance is important to most Finnish consumers. However, in many respects, these attitudes reflect a certain reservation towards appearance-related consumption practices. The number of those consumers who see themselves as truly dedicated to attending to their looks through consumption is quite small, whereas the amount of those willing to take a reserved or even negative attitude towards appearance-related consumption is clearly higher. Attitudes towards attending to one’s looks and the importance of appearance-related consumption had not changed during the past decade. Study shows that at present, appearance-related consumption is a form of consumption that is particularly important to women, younger consumers, people with middle or higher income, and those with normal weight. Gender is in the key role when explaining appearance-related consumption and contrary to common belief, gender differences seem to have stayed quite stable. The results also indicate that, to some extent, differences between younger and older age groups might be diminishing.

Millaiset psykososiaaliset prosessit johtavat elämäntapamuutoksen onnistumiseen?

Nelli Hankosen väitöskirja Psychosocial processes of health behaviour change in a lifestyle intervention : influences of gender, socioeconomic status and personality (Helsingin yliopisto 2011).

Virulence properties of Aggregatibacter actinomycetemcomitans biofilm and characterisation of its putative cytokine exploitation

Biofilms are surface-attached multispecies microbial communities that are embedded by their self-produced extracellular polymeric substances. This lifestyle enhances the survival of the bacteria and plays a major role in many chronic bacterial infections. For instance, periodontitis is initiated by multispecies biofilms. The phases of active periodontal tissue destruction and notably increased levels of proinflammatory mediators, such as the key inflammatory mediator interleukin (IL)-1beta, are typical of the disease. The opportunistic periodontal pathogen Aggregatibacter actinomycetemcomitans is usually abundant at sites of aggressive periodontitis. Despite potent host immune system responses to subgingival invaders, A. actinomycetemcomitans is able to resist clearance attempts. Moreover, some strains of A. actinomycetemcomitans can generate genetic diversity through natural transformation, which may improve the species’ adjustment tothe subgingival environment in the long term. Some biofilm forming species are known to bind and sense human cytokines. As a response to cytokines, bacteria may increase biofilm formation and alter their expression of virulence genes. Specific outer membrane receptors for interferon-γ or IL-1β have been characterised in two Gram-negative pathogens. Because little is known about periodontal pathogens’ ability to sense cytokines, we used A. actinomycetemcomitans as a model organism to investigate how the species responds to IL-1beta. The main aims of this thesis were to explore cytokine binding on single-species A. actinomycetemcomitans biofilms and to determine the effects of cytokines on the biofilm formation and metabolic activity of the species. Additionally, the cytokine’s putative internalisation and interaction with A. actinomycetemcomitans proteins were studied. The possible impact of biofilm IL-1beta sequestering on the proliferation and apoptosis of gingival keratinocyte cells was evaluated in an organotypic mucosa co-culture model. Finally, the role of the extramembranous domain of the outer membrane protein HofQ (emHofQ) in DNA binding linked to DNA uptake in A. actinomycetemcomitans was examined. Our main finding revealed that viable A. actinomycetemcomitans biofilms can bind and take up the IL-1β produced by gingival cells. At the sites of pathogen-host interaction, the proliferation and apoptosis of gingival keratinocytes decreased slightly. Notably, the exposure of biofilms to IL-1beta caused their metabolic activity to drop, which may be linked to the observed interaction of IL-1beta with the conserved intracellular proteins DNA binding protein HU and the trimeric form of ATP synthase subunit beta. A Pasteurellaceaespecific lipoprotein, which had no previously determined function, was characterized as an IL-1beta interacting membrane protein that was expressed in the biofilm cultures of all tested A. actinomycetemcomitans strains. The use of a subcellular localisation tool combined with experimental analyses suggested that the identified lipoprotein, bacterial interleukin receptor I (BilRI), may be associated with the outer membrane with a portion of the protein oriented towards the external milieu. The results of the emHofQ study indicated that emHofQ has both the structural and functional capability to bind DNA. This result implies that emHofQ plays a role in DNA assimilation. The results from the current study also demonstrate that the Gram-negative oral species appears to sense the central proinflammatory mediator IL-1beta.

Export Tire Entry to Chinese Market

After the economic reform, China has undergone fast economic growth, urbanization and adopted the western lifestyle. Global enterprises are investing in China and Finnish companies began to enter the Chinese market after the 1980s. Fast economic growth has downside effects like pollution and thus more cleantech solutions are needed. There are different kinds of entry modes that companies are using when entering the Chinese market. This thesis focuses on export tire entry mode. The purpose of this study is to examine cleantech companies’ opinions about the export tire operations. The background of this study is built by combining the written knowledge about the history of the Chinese industry and market entry modes. The empirical part of the study is a semi-structured, qualitative analysis of five case companies that are operating together in a particular export tire and represent the highest Finnish cleantech knowledge. The results of this study indicate that the export tire entry is an easy and cost effective way to enter new markets or market segment. Export tire is really dependent on the leader who in this particular case succeeded well.

Waste Management in Commercial Activity: State-of-the-Art and the Potential Innovation in the Urban Areas of Hanoi, Vietnam

As the rapid development of the society as well as the lifestyle, the generation of commercial waste is getting more complicated to control. The situation of packaging waste and food waste – the main fractions of commercial waste in different countries in Europe and Asia is analyzed in order to evaluate and suggest necessary improvements for the existing waste management system in the city of Hanoi, Vietnam. From all waste generation sources of the city, a total amount of approximately 4000 tons of mixed waste is transported to the composting facility and the disposal site, which emits a huge amount of 1,6Mt of GHG emission to the environment. Recycling activity is taking place spontaneously by the informal pickers, leads to the difficulty in managing the whole system and uncertainty of the overall data. With a relative calculation, resulting in only approximately 0,17Mt CO2 equivalent emission, incinerator is suggested to be the solution of the problem with overloaded landfill and raising energy demand within the inhabitants.

Quantitative Analysis of Novel Prostate Cancer Markers in Tissue

Prostate cancer is a heterogeneous disease affecting an increasing number of men all over the world, but particularly in the countries with the Western lifestyle. The best biomarker assay currently available for the diagnosis of the disease, the measurement of prostate specific antigen (PSA) levels from blood, lacks specificity, and even when combined with invasive tests such as digital rectal exam and prostate tissue biopsies, these methods can both miss cancers, and lead to overdiagnosis and subsequent overtreatment of cancers. Moreover, they cannot provide an accurate prognosis for the disease. Due to the high prevalence of indolent prostate cancers, the majority of men affected by prostate cancer would be able to live without any medical intervention. Their latent prostate tumors would not cause any clinical symptoms during their lifetime, but few are willing to take the risk, as currently there are no methods or biomarkers to reliably differentiate the indolent cancers from the aggressive, lethal cases that really are in need of immediate medical treatment. This doctoral work concentrated on validating 12 novel candidate genes for use as biomarkers for prostate cancer by measuring their mRNA expression levels in prostate tissue and peripheral blood of men with cancer as well as unaffected individuals. The panel of genes included the most prominent markers in the current literature: PCA3 and the fusion gene TMPRSS2-ERG, in addition to BMP-6, FGF-8b, MSMB, PSCA, SPINK1, and TRPM8; and the kallikrein-related peptidase genes 2, 3, 4, and 15. Truly quantitative reverse-transcription PCR assays were developed for each of the genes for the purpose, time-resolved fluorometry was applied in the real-time detection of the amplification products, and the gene expression data were normalized by using artificial internal RNA standards. Cancer-related, statistically significant differences in gene transcript levels were found for TMPRSS2-ERG, PCA3, and in a more modest scale, for KLK15, PSCA, and SPINK1. PCA3 RNA was found in the blood of men with metastatic prostate cancer, but not in localized cases of cancer, suggesting limitations for using this method for early cancer detection in blood. TMPRSS2-ERG mRNA transcripts were found more frequently in cancerous than in benign prostate tissues, but they were present also in 51% of the histologically benign prostate tissues of men with prostate cancer, while being absent in specimens from men without any signs of prostate cancer. PCA3 was shown to be 5.8 times overexpressed in cancerous tissue, but similarly to the fusion gene mRNA, its levels were upregulated also in the histologically benign regions of the tissue if the corresponding prostate was harboring carcinoma. These results indicate a possibility to utilize these molecular assays to assist in prostate cancer risk evaluation especially in men with initially histologically negative biopsies.

Pre- and postnatal nutrition – target for allergy risk reduction

A rapid increase in allergic diseases in Western societies has led to the conclusion that our modern lifestyle is a risk factor for immune dysregulation. Potential culprits and benefactors are searched among early dietary and microbial exposures, which may act to program later allergic disease. The aim of this thesis was to investigate the role of early maternal and child nutrition in reducing the risk of child allergy. The study population comprised of 256 mother – child pairs from families with a history of allergy participating in a randomized controlled dietary counseling and probiotic intervention (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12) study from early pregnancy onwards. The dietary counseling aimed for a diet complying with dietary recommendations for pregnant and lactating women, with special attention to fat quality. Maternal dietary counseling was reflected in cord blood fatty acids suggesting better essential fatty acid status in infants in the counseling group. Dietary counseling with probiotics or placebo had no effect on child allergy risk, but associations between maternal diet during pregnancy and breastfeeding and child allergic outcomes were found in secondary analyses. During pregnancy, milk intake was related to decreased and cheese intake to increased risk of child atopic eczema. During breastfeeding, intake of vitamin C was related to increased risk of asthma and intake of egg was related to decreased risk of atopic eczema. The timing of introduction of complementary foods to infant’s diet was not associated with risk of atopic eczema, when adjusted with parental opinion of child allergic symptoms (i.e., potential reverse causality). In conclusion, the results demonstrate that infant fatty acid supply can be modified via maternal dietary changes. In addition, interesting associations of maternal diet with child allergy risk were discovered. However, no difference in the incidence of allergic diseases with dietary counseling was observed. This suggests that more potent dietary interventions might be necessitated to induce clinical risk reduction of allergy. Highrisk families can safely adhere to dietary recommendations for pregnant and lactating women, and the results support the current conception that no additional benefit is gained with delaying introduction of complementary feeding.

Oxidized LDL lipids as a risk factor for atherosclerosis

University of Turku, Faculty of Medicine, Department of Clinical Medicine, Department of Physical Activity and Health, Paavo Nurmi Centre, Doctoral Programme of Clinical Investigation, University of Turku, Turku, Finland. Annales Universitatis Turkuensis. Medica – Odontologica, Turku, Finland, 2014. Background: Atherosclerosis progression spans an entire lifetime and has a wide pool of risk factors. Oxidized LDL (oxLDL) is a crucial element in the progression of atherosclerosis. As a rather new member in the atherosclerosis risk factor family, its interaction with the traditional pro-atherogenic contributors that occur at different ages is poorly known. Aims: The aim of this study was to investigate oxLDL and its relation to major contributing risk factors in estimating atherosclerosis risk in data consisting mostly of adult men. The study subjects of this study consisted of four different sets of data, one of which contained also women. The age range of participants was 18-100 years and totaled 2337 participants (of whom 69% were men). Data on anthropometric and hormonal parameters, laboratory measures and medical records were assessed during 1998-2009. Results: Obesity was paralleled with high concentrations of oxLDL, which consequentially was reduced by weight reduction. Importantly, successful weight maintenance preserveed this benefit. A shift from insulin sensitivity to insulin resistance increased oxLDL. Smokers had more oxLDL than non-smokers. A combination of obesity and smoking, or smoking and low serum total testosterone,resulted in even higher levels of oxLDL than any of the three conditions alone. Proportioning oxLDL to HDL-c or apoA1 stood out as a risk factor of all-cause mortality in the elderly. Conclusions: OxLDL was associated with aging, androgens, smoking, obesity, insulin metabolism, weight balance and other circulating lipid classes. Through this variety of metabolic environments containing both constant conditions (aging and gender) as well as lifestyle issues, these findings supported an essential and multidimensional role that oxLDL plays in atherosclerosis pathogenesis.

Starting Insulin Treatment in Type 2 Diabetes

Type 2 diabetes is a disorder of glucose metabolism characterized by chronic hyperglycemia. Initially type 2 diabetes is characterized by insulin resistance and impaired function of beta cells, leading progressively to insulin deficiency. Type 2 diabetes is treated with diet and other lifestyle changes, and with medication modulating e.g. insulin resistance, liver glucose production and insulin secretion. Injectable insulin is added to the treatment when lifestyle changes and other medication are insufficient to maintain adequate control of hyperglycemia. The aim of the treatment is to remove the symptoms of diabetes and to prevent late complications of diabetes. Insulin was traditionally started at hospital wards, but from the early 1990’s also in outpatient care. The first substudy of this thesis examined retrospectively initiation practices and how successfully insulin treatment was introduced in 1990 – 1996 in Southwestern Finland. This study aimed also at identifying the best methods of controlling plasma glucose. It showed that in the 1990’s the incidence of insulin treatment increased and was initiated more often in outpatient care than previously. The use of combination treatment also increased, first with sulfonylureas and later with metformin as the oral drug. In combination therapy the insulin dose was smaller than with insulin monotherapy. HbA1c improved similarly in middle-aged and older age groups. Weight increase associated with insulin initiation was smaller when combined with oral agents. A prospective insulin initiation study (1994 – 1998) tested the hypothesis that hyperglycemia (fasting and postprandial hyperglycemia) may affect the outcome of insulin initiation. The type of hyperglycemia was determined by the relation of fasting plasma glucose to HbA1c. Treatment was initiated with insulin Lente or human NPH insulin. In patients treated with insulin monotherapy twice daily the decline in HbA1c was markedly greater for postprandial than fasting hyperglycemia patients suggesting that hyperglycemia type has significance in the selection of the insulin regimen. Another insulin initiation study showed that patients with fasting hyperglycemia starting on insulin (2004-2005) were significantly more prone to overweight than patients with postprandial hyperglycemia. Irrespective of the insulin preparation (insulin NPH or insulin glargine), patients with fasting hyperglycemia had a greater weight increase compared to patients with postprandial hyperglycemia. Special attention should be paid to prevention of weight increase in these patients.