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Objective. Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) commonly coexist and act synergistically to drive adverse clinical outcomes. This study is aimed at investigating the effects of exercise intervention and oral hypoglycaemic drug of metformin (MET) alone or combined on hepatic lipid accumulation. To investigate if oxidative stress and endoplasmic reticulum stress (ERS) are involved in lipotoxicity-induced hepatocyte apoptosis in diabetic mice and whether exercise and/or MET alleviated oxidative stress or ERS-apoptosis by AMPK-Nrf2-HO-1 signaling pathway. Methods. Forty db/db mice with diabetes ( random blood glucose ≥ 250 mg / dL ) were randomly allocated into four groups: control (CON), exercise training alone (EX), metformin treatment alone (MET), and exercise combined with metformin (EM) groups. Hematoxylin-eosin and oil red O staining were carried out to observe hepatic lipid accumulation. Immunohistochemical and TUNEL methods were used to detect the protein expression of the binding immunoglobulin protein (BiP) and superoxide dismutase-1 (SOD1) and the apoptosis level of hepatocytes. ERS-related gene expression and the AMPK-Nrf2-HO-1 signaling pathway were tested by western blotting. Results. Our data showed that db/db mice exhibited increased liver lipid accumulation, which induced oxidative and ER stress of the PERK-eIF2α-ATF4 pathway, and hepatocyte apoptosis. MET combined with exercise training significantly alleviated hepatic lipid accumulation by suppressing BiP expression, the central regulator of ER homeostasis, and its downstream PERK-eIF2α-ATF4 pathway, as well as upregulated the AMPK-Nrf2-HO-1 signaling pathway. Moreover, the combination of exercise and MET displayed protective effects on hepatocyte apoptosis by downregulating Bax expression and TUNEL-positive staining, restoring the balance of cleaved-caspase-3 and caspase-3, and improving the antioxidant defense system to prevent oxidative damage in db/db mice. Conclusion. Compared to MET or exercise intervention alone, the combined exercise and metformin exhibited significant effect on ameliorating hepatic steatosis, inhibiting oxidative and ER stress-induced hepatocyte apoptosis via improving the capacity of the antioxidant defense system and suppression of the PERK-eIF2α-ATF4 pathway. Furthermore, upregulation of AMPK-Nrf2-HO-1 signaling pathway might be a key crosstalk between MET and exercise, which may have additive effects on alleviating hepatic lipid accumulation.

Concurrent exercise and metformin administration may reduce the acute and chronic effects of exercise on glucose metabolism in patients with type 2 diabetes (T2D). However, several studies suggest that combing metformin and exercise treatment may have no additive effect and even cause adverse effects in T2D patients. This case report aimed to highlight the challenges associated with prescribing exercise to type 2 diabetes patients undergoing metformin treatment. A 67-years old woman was followed-up for 5 months, including assessment of the acute and chronic glucose and lactate metabolism induced by concomitant exercise and metformin. The findings were four-fold: 1) During a high-intensity interval training bout, blood glucose systematically decreased, while blood lactate concentrations fluctuated randomly; 2) Basal blood lactate levels were well above 2 mmol/L on days with medication only; 3) Combined exercise and metformin administration induced additive effects on the normalization of glucose and 4) high levels of physical activity had a positive impact on the continuous glucose fluctuations, while decreased levels of physical activity induced a large fluctuation of glucose due to home confinement of an infectious disease caused by the SARS-CoV-2 virus. Our findings showed that when combined with exercise and metformin treatment for T2D patients, exercise may contribute to improving glycemic control while metformin may elevate lactate levels in the long term. The observed results underline the need to prescribe exercise and monitor lactate levels for reducing possible risks associated with metformin treatment and reinforce the importance of tailoring exercise therapy. peerReviewed

Type 2 diabetes (T2D) is a common metabolic disorder characterized by elevated glucose levels. Recognizing people at high risk for T2D allows interventions that may delay or prevent the development of T2D and diabetes-related complications. The previously accepted methods for identifying these people are fasting plasma glucose (FPG), two-hour post-load glucose (2-h PG) in an oral glucose tolerance test (OGTT) and glycated hemoglobin A1c (HbA1c). However, one-hour post-load glucose (1-h PG) in an OGTT has risen in interest for its high predictive value for future T2D at an even earlier time point than the currently used methods. The aim of this thesis was to investigate the ability of 1-h PG to predict T2D and cardiovascular diseases as well as to evaluate the association between 1-h PG and other diabetic complications including retinopathy signs and albuminuria. The value of 1-h PG measurement was compared with current diagnostic methods. Four Finnish study populations were used for the analyses of the present thesis. The results revealed that 1-h PG was a better predictor of T2D and cardiovascular outcomes than FPG or 2-h PG, also improving the explanatory power of the traditional cardiovascular risk models. Elevated 1-h PG was related to retinopathy signs, while FPG, 2-h PG and HbA1c were not. Both prediabetic ( 8.6 mmol/L) and diabetic ( 11.6 mmol/L) 1-h PG levels were independently associated with albuminuria, but no such an association was seen in FPG, 2-h PG and HbA1c. Furthermore, the 2-h PG did not provide any benefit in addition to FPG and 1-h PG in the prediction of T2D and cardiovascular outcomes or in the detection of albuminuria. In conclusion, these findings indicate that the use of 1-h PG improves the predictability of T2D and cardiovascular diseases and the detection of retinopathy signs and albuminuria. Together with previous findings, these results indicate that the use of 1-h PG and shortened 1-h OGTT seems reasonable to consider in the future. Tiivistelmä Tyypin 2 diabetes on yleinen aineenvaihduntasairaus, johon liittyy kohonnut verensokeri. Suuressa sairastumisriskissä olevien potilaiden tunnistaminen on tärkeää, jotta tyypin 2 diabeteksen sekä siihen liittyvien komplikaatioiden kehittymistä voidaan ennaltaehkäistä. Aikaisemmin hyväksytyt menetelmät suuressa sairastumisriskissä olevien potilaiden tunnistamiseksi ovat paastoverensokeri, glukoosirasituskokeen 2 tunnin glukoosi ja glykohemoglobiini A1c (HbA1c). Glukoosirasituskokeen 1 tunnin glukoosi on herättänyt viime aikoina kiinnostusta, sillä sen on havaittu ennustavan hyvin tulevaa tyypin 2 diabetesta jopa varhaisemmassa vaiheessa kuin nykyisin käytössä olevat menetelmät. Tämän väitöskirjan tavoitteena oli tutkia 1 tunnin glukoosiarvon kykyä ennustaa tyypin 2 diabetesta ja sydän- ja verisuonitauteja sekä arvioida 1 tunnin glukoosiarvon yhteyttä retinopatiamuutoksiin ja albuminuriaan. Yhden tunnin glukoosiarvoa verrattiin nykyisiin käytössä oleviin diagnostisiin menetelmiin. Tässä väitöskirjassa hyödynnettiin neljää suomalaista väestöpohjaista aineistoa. Tutkimustulokset osoittivat, että 1 tunnin glukoosiarvo on parempi tyypin 2 diabeteksen sekä sydän- ja verisuonitapahtumien ennustaja kuin paastoglukoosi tai 2 tunnin glukoosi, ja se parantaa myös perinteisten sydän- ja verisuonitautien riskimallien selitysastetta. Retinopatiamuutokset olivat yhteydessä kohonneeseen 1 tunnin glukoosiarvoon, mutta eivät paastoarvoihin, 2 tunnin arvoihin tai HbA1c:hen. Sekä prediabeettinen ( 8.6 mmol/l) että diabeettinen ( 11.6 mmol/l) 1 tunnin glukoosiarvo olivat itsenäisesti yhteydessä albuminuriaan, mutta vastaavaa yhteyttä ei todettu paastoglukoosille, 2 tunnin glukoosille tai HbA1c:lle. Kahden tunnin glukoosiarvo ei myöskään parantanut paastoglukoosin ja 1 tunnin glukoosin lisänä tyypin 2 diabeteksen tai sydän- ja verisuonitapahtumien ennustettavuutta eikä albuminurian tunnistettavuutta. Tutkimustulosten perusteella 1 tunnin glukoosiarvon käyttö parantaa tyypin 2 diabeteksen ja sydän- ja verisuonitautien ennustettavuutta sekä niiden henkilöiden tunnistamista, joilla on retinopatiamuutoksia tai albuminuriaa. Näiden sekä aikaisempien tutkimustulosten perusteella 1 tunnin glukoosiarvon käyttöönottoa ja glukoosirasituskokeen lyhentämistä kahdesta tunnista yhteen tuntiin tulisi pohtia.

ObjectiveType 2 diabetes mellitus (T2DM) is a high risk of cognitive decline and dementia, but the underlying mechanisms are not yet clearly understood. This study aimed to explore the functional connectivity (FC) and topological properties among whole brain networks and correlations with impaired cognition and distinguish T2DM from healthy controls (HC) to identify potential biomarkers for cognition abnormalities.MethodsA total of 80 T2DM and 55 well-matched HC were recruited in this study. Subjects’ clinical data, neuropsychological tests and resting-state functional magnetic resonance imaging data were acquired. Whole-brain network FC were mapped, the topological characteristics were analyzed using a graph-theoretic approach, the FC and topological characteristics of the network were compared between T2DM and HC using a general linear model, and correlations between networks and clinical and cognitive characteristics were identified. The support vector machine (SVM) model was used to identify differences between T2DM and HC.ResultsIn patients with T2DM, FC was higher in two core regions [precuneus/posterior cingulated cortex (PCC)_1 and later prefrontal cortex_1] in the default mode network and lower in bilateral superior parietal lobes (within dorsal attention network), and decreased between the right medial frontal cortex and left auditory cortex. The FC of the right frontal medial-left auditory cortex was positively correlated with the Montreal Cognitive Assessment scales and negatively correlated with the blood glucose levels. Long-range connectivity between bilateral auditory cortex was missing in the T2DM. The nodal degree centrality and efficiency of PCC were higher in T2DM than in HC (P < 0.005). The nodal degree centrality in the PCC in the SVM model was 97.56% accurate in distinguishing T2DM patients from HC, demonstrating the reliability of the prediction model.ConclusionFunctional abnormalities in the auditory cortex in T2DM may be related to cognitive impairment, such as memory and attention, and nodal degree centrality in the PCC might serve as a potential neuroimaging biomarker to predict and identify T2DM.

The amount of physical activity decreases and sedentary time increases with aging, predisposing older adults to increased risk of type 2 diabetes and cardiovascular diseases. The aims of this study were to evaluate the associations between accelerometer-measured physical activity and sedentary time with glucose metabolism, cardiovascular risk and mortality in older adults. In 2013–2015, population-based sample of older adults (n = 714) participated in the Oulu45 cohort study at age of 67–70 years. Physical activity and sedentary time were measured with wrist-worn Polar Active accelerometer based activity monitor for two weeks. Participants’ underwent an oral glucose tolerance test and risk of cardiovascular diseases was estimated with Framingham risk score. The data for all-cause mortality were identified from the Digital and Population Data Services Agency, Finland after an average of 6.2 years follow-up. Four physical activity profiles were identified. In more active profiles, prevalence of glucose metabolism disorders, 120 min glucose and insulin values in oral glucose tolerance test were lower compared with the less active profiles. In older adults with central obesity, even light physical activity and avoiding sedentary time were associated with improved glucose metabolism and decreased insulin resistance. Both light and moderate to vigorous physical activity were associated with lower risk of cardiovascular diseases. High sedentary time was associated with increased cardiovascular risk. Low sedentary time and high time spent in light physical activity were associated with lower mortality. Based on these results, a higher amount of physical activity, at any intensity level, and avoidance of sedentary time were associated with reduced risk of type 2 diabetes, cardiovascular diseases and mortality in older adults. Especially overweight older adults should be encouraged to increase their physical activity and to avoid being sedentary. Tiivistelmä Vähäinen fyysisen aktiivisuuden määrä ja runsas paikallaanoloaika lisäävät riskiä sairastua tyypin 2 diabetekseen sekä sydän- ja verisuonisairauksiin. Tämän tutkimuksen tavoitteina oli selvittää kiihtyvyysanturilla mitatun kevyen, kohtuukuormitteisen ja raskaan fyysisen aktiivisuuden sekä paikallaanolon yhteyttä iäkkäiden henkilöiden sokeriaineenvaihduntaan sekä sydän- ja verisuonisairauksien ja kuoleman riskiin. Väestöpohjaisen Oulu45-kohorttitutkimuksen aineisto (n = 714) kerättiin vuosina 2013–2015, ja tutkittavat olivat iältään 67–70-vuotiaita. Tutkittavien fyysinen aktiivisuus ja paikallaanolo mitattiin kahden viikon ajan ranteessa pidettävällä kiihtyvyysanturiin perustuvalla Polar Active -aktiivisuusmittarilla. Tutkittaville tehtiin sokerirasituskoe ja heidän sydän- ja verisuonisairauksien riskiään arvioitiin Framinghamin riskipisteillä. Kuolleisuustiedot kerättiin Digi- ja väestötietovirastosta keskimäärin 6,2 vuoden seuranta-ajan jälkeen. Tutkimuksessa tunnistettiin iäkkäistä neljä liikkujaprofiilia. Profiililtaan fyysisesti aktiivisilla oli harvemmin sokeriaineenvaihdunnan häiriöitä ja matalammat 120 minuutin glukoosi- ja insuliiniarvot sokerirasituskokeessa. Kevyt fyysinen aktiivisuus ja vähäisempi paikallaanoloaika tehostivat etenkin keskivartalolihavien iäkkäiden sokeriaineenvaihduntaa ja vähensivät insuliiniresistenssiä. Sekä kevyt, että kohtuukuormitteinen ja raskas fyysinen aktiivisuus vähensivät sydän- ja verisuonisairauksien riskiä, kun taas runsas paikallaanoloaika lisäsi riskiä. Runsaampi kevyt fyysinen aktiivisuus ja vähäinen paikallaanoloaika pienensivät kuoleman riskiä. Tämän väitöskirjan tulosten perusteella vähäinenkin fyysinen aktiivisuus on paikallaanoloa parempi vaihtoehto iäkkäiden henkilöiden sokeriaineenvaihdunnan ja sydänterveyden edistämiseksi. Erityisesti keskivartalolihavia iäkkäitä tulisi rohkaista lisäämään liikkumista ja vähentämään paikallaanoloa.

Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have been proven to share a role in lipid metabolism and hence in maintaining metabolic health. We have previously introduced a hypothesis suggesting that BCAA degradation mechanistically connects to lipid oxidation and storage in skeletal muscle. To test our hypothesis, the present study examined the effects of BCAA deprivation and supplementation on lipid oxidation, lipogenesis and lipid droplet characteristics in murine C2C12 myotubes. In addition, the role of myotube contractions on cell metabolism was studied by utilizing in vitro skeletal-muscle-specific exercise-like electrical pulse stimulation (EPS). Our results showed that the deprivation of BCAAs decreased both lipid oxidation and lipogenesis in C2C12 myotubes. BCAA deprivation further diminished the number of lipid droplets in the EPS-treated myotubes. EPS decreased lipid oxidation especially when combined with high BCAA supplementation. Similar to BCAA deprivation, high BCAA supplementation also decreased lipid oxidation. The present results highlight the role of an adequate level of BCAAs in healthy lipid metabolism.

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Skeletal muscle physiology remains of paramount importance in understanding insulin resistance. Due to its high lipid turnover rates, regulation of intramyocellular lipid droplets (LDs) is a key factor. Perilipin 5 (PLIN5) is one of the most critical agents in such regulation, being often referred as a protector against lipotoxicity and consequent skeletal muscle insulin resistance. We examined area fraction, size, subcellular localization and PLIN5 association of LDs in two fiber types of type 2 diabetic (T2D), obese (OB) and healthy (HC) individuals by means of fluorescence microscopy and image analysis. We found that T2D type II fibers have a significant sub-population of large and internalized LDs, uncoated by PLIN5. Based on this novel result, additional hypotheses for the pathophysiology of skeletal muscle insulin resistance are formulated, together with future research directions. peerReviewed

Publisher Copyright: © Antti-Pekka E Rissanen, Mirva Rottensteiner, Urho M Kujala, Jari L O Kurkela, Jan Wikgren, Jari A Laukkanen. Originally published in JMIR Cardio (https://cardio.jmir.org), 25.10.2022. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Cardio, is properly cited. The complete bibliographic information, a link to the original publication on https://cardio.jmir.org, as well as this copyright and license information must be included. Background: Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. Adding CRF to conventional risk factors (eg, smoking, hypertension, impaired glucose metabolism, and dyslipidemia) improves the prediction of an individual's risk for adverse health outcomes such as those related to cardiovascular disease. Consequently, it is recommended to determine CRF as part of individualized risk prediction. However, CRF is not determined routinely in everyday clinical practice. Wearable technologies provide a potential strategy to estimate CRF on a daily basis, and such technologies, which provide CRF estimates based on heart rate and body acceleration, have been developed. However, the validity of such technologies in estimating individual CRF in clinically relevant populations is poorly known. Objective: The objective of this study is to evaluate the validity of a wearable technology, which provides estimated CRF based on heart rate and body acceleration, in working-aged adults with cardiovascular risk factors. Methods: In total, 74 adults (age range 35-64 years; n=56, 76% were women; mean BMI 28.7, SD 4.6 kg/m2) with frequent cardiovascular risk factors (eg, n=64, 86% hypertension; n=18, 24% prediabetes; n=14, 19% type 2 diabetes; and n=51, 69% metabolic syndrome) performed a 30-minute self-paced walk on an indoor track and a cardiopulmonary exercise test on a treadmill. CRF, quantified as peak O2 uptake, was both estimated (self-paced walk: a wearable single-lead electrocardiogram device worn to record continuous beat-to-beat R-R intervals and triaxial body acceleration) and measured (cardiopulmonary exercise test: ventilatory gas analysis). The accuracy of the estimated CRF was evaluated against that of the measured CRF. Results: Measured CRF averaged 30.6 (SD 6.3; range 20.1-49.6) mL/kg/min. In all participants (74/74, 100%), mean difference between estimated and measured CRF was −0.1 mL/kg/min (P = .90), mean absolute error was 3.1 mL/kg/min (95% CI 2.6-3.7), mean absolute percentage error was 10.4% (95% CI 8.5-12.5), and intraclass correlation coefficient was 0.88 (95% CI 0.80-0.92). Similar accuracy was observed in various subgroups (sexes, age, BMI categories, hypertension, prediabetes, and metabolic syndrome). However, mean absolute error was 4.2 mL/kg/min (95% CI 2.6-6.1) and mean absolute percentage error was 16.5% (95% CI 8.6-24.4) in the subgroup of patients with type 2 diabetes (14/74, 19%). Conclusions: The error of the CRF estimate, provided by the wearable technology, was likely below or at least very close to the clinically significant level of 3.5 mL/kg/min in working-aged adults with cardiovascular risk factors, but not in the relatively small subgroup of patients with type 2 diabetes. From a large-scale clinical perspective, the findings suggest that wearable technologies have the potential to estimate individual CRF with acceptable accuracy in clinically relevant populations.

Purpose: To assess the effect of chronic exercise training on blood lactate metabolism at rest (i.e., basal lactate concentrations) and during exercise (i.e., blood lactate concentration at a fixed load, load at a fixed blood lactate concentration, and load at the individual blood lactate threshold) among patients with type 2 diabetes mellitus (T2DM).Methods: PubMed (MedLine), Embase, Web of Science, and Scopus were searched. Randomized controlled trials, non-randomized controlled trials, and case-control studies using chronic exercise training (i.e., 4 weeks) and that assessed blood lactate concentrations at rest and during exercise in T2DM patients were included.Results: Thirteen studies were eligible for the systematic review, while 12 studies with 312 participants were included into the meta-analysis. In the pre-to-post intervention meta-analysis, chronic exercise training had no significant effect on changes in basal blood lactate concentrations (standardized mean difference (SMD) = −0.20; 95% CI, −0.55 to 0.16; p = 0.28), and the results were similar when comparing the effect of intervention and control groups. Furthermore, blood lactate concentration at a fixed load significantly decreased (SMD = −0.73; 95% CI, −1.17 to −0.29; p = 0.001), while load at a fixed blood lactate concentration increased (SMD = 0.40; 95% CI, 0.07 to 0.72; p = 0.02) after chronic exercise training. No change was observed in load at the individual blood lactate threshold (SMD = 0.28; 95% CI, −0.14 to 0.71; p = 0.20).Conclusion: Chronic exercise training does not statistically affect basal blood lactate concentrations; however, it may decrease the blood lactate concentrations during exercise, indicating improvements of physical performance capacity which is beneficial for T2DM patients' health in general. Why chronic exercise training did not affect basal blood lactate concentrations needs further investigation.

Lasten ylipaino on saavuttanut epidemian mittasuhteet maailmanlaajuisesti. Vaikka viime vuosina tilanne on hiukan parantunut, ylipaino on edelleen yksi merkittävimmistä kansanterveydellisistä ongelmista. Riskitekijöiden kasautumisen ehkäisy ja hoito tulisi aloittaa mahdollisimman varhain: mielellään jo sikiöaikana tai viimeistään varhaislapsuudessa. nonPeerReviewed

IntroductionThis study aims to investigate whether the associations between impaired glucose regulation and health-related quality of life are modified by severity or type of depressive symptoms.Research design and methodsFor this cross-sectional study, we included 1939 individuals (mean age 61.5 years) from the Helsinki Birth Cohort Study. Between 2001 and 2004, a standard 2-hour 75 g oral glucose tolerance test was applied to define normoglycemia, pre-diabetes, and newly diagnosed diabetes. Information on previously diagnosed diabetes was collected from national registers and questionnaires. Pre-diabetes was defined as having either impaired fasting glucose or impaired glucose tolerance. The Mental and Physical Component Scores of health-related quality of life were assessed with Short Form-36. Beck’s Depression Inventory was employed to investigate the severity of depressive symptoms and to define minimal (depression score ResultsGlucose regulation subgroups, especially previously known diabetes, were associated with lower Physical Component Score (p=0.001) and higher depression score (p=0.015), but not with the Mental Component Score (p=0.189). Non-melancholic depression was associated with lower Physical and Mental Component Scores compared with those with depression score 0.54).ConclusionsNon-melancholic type of depression and previously known diabetes are independently associated with lower health-related quality of life. This should be appraised in long-term treatment of diabetes and when treating non-melancholic depressive symptoms to maintain a higher health-related quality of life.

Introduction: Physical activity (PA) is important in the prevention and treatment of impaired glucose metabolism. However, association of physical inactivity during the transition between childhood and adulthood with glucose metabolism is unknown. Therefore, we studied the association of persistent physical inactivity since childhood with glucose metabolism in adulthood. Methods: Data were drawn from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow-ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol·L-1) or type 2 diabetes in adulthood. Leisure-time PA habits were repeatedly collected with a standardized questionnaire and expressed as a PA Index. Using PA Index, four groups were formed (n = 2000): 1) persistently low PA, 2) decreasingly active, 3) increasingly active, and 4) persistently active subjects. Poisson regression model was used to examine the association between PA groups and impaired glucose metabolism. Results: The proportion of the sample with impaired glucose metabolism was 16.1% in individuals with persistently low PA, 14.5% in decreasingly active, 6.8% in increasingly active, and 11.1% in persistently active. Compared with individuals with persistently low PA, age and sex-adjusted risk for impaired glucose metabolism were lower in those who increased PA (relative risk [RR], 0.47; 95% confidence interval [CI], 0.29-0.76) and in those who were persistently active (RR, 0.70; 95% CI, 0.51-0.97), but similar in those who decreased PA (RR, 0.93; 95% CI, 0.66-1.36). Conclusions: Persistently physically inactive lifestyle from youth to adulthood is associated with increased risk of impaired glucose metabolism in adulthood. Importantly, a moderate increase in PA lowered the risk. The results highlight the importance of avoiding physically inactive lifestyle at all stages of life.

Aims. Cross‐country skiing is associated with reduction in risk of adverse vascular outcomes, but its association with type 2 diabetes is uncertain. We aimed to assess the associations between leisure‐time cross‐country skiing habits and incident type 2 diabetes. Methods. We analyzed data of 2,483 middle‐aged men with no history of diabetes at baseline in the KIHD prospective study. The frequency, average duration, and intensity of leisure cross‐country skiing were assessed at baseline using a 12‐month physical activity questionnaire. Hazard ratios (HRs) (95% CIs) for type 2 diabetes were estimated. Results. During a median follow‐up of 21.6 years, 539 men developed type 2 diabetes. Type 2 diabetes risk decreased with increasing total volume of cross‐country skiing up to 1,215 MET hours/year. In analyses adjusted for several established risk factors, when compared to men with no cross‐country skiing activity, the HRs (95% CIs) for type 2 diabetes were 0.75 (0.62‐0.92) and 0.59 (0.46‐0.76) for men who did 1‐200 and >200 MET hours/year of cross‐country skiing respectively. Compared to men with no cross‐country skiing activity, the corresponding adjusted HRs (95% CIs) for type 2 diabetes were 0.73 (0.60‐0.89) and 0.64 (0.50‐0.82) for men who did 1‐60 and >60 mins/week of cross‐country skiing respectively. The associations remained consistent following further adjustment for prevalent comorbidities. Conclusion. Total volume and duration of leisure‐time cross‐country skiing are each inversely and independently associated with future type 2 diabetes risk in a male population. Cross‐country skiing undertaken as a leisure activity has the potential to promote public health. peerReviewed

Background: Physical activity (PA) is a key component in management of type 2 diabetes (T2D). Pain might be a barrier to PA especially among older adults with T2D, but surprisingly few studies have investigated the association between chronic pain and PA. Our aim was to evaluate the prevalence of chronic pain among older adults with T2D and to examine the association between chronic pain and PA while taking important life-contextual factors into account. Methods: Data of this register-based, cross-sectional study were collected in a survey among adults with T2D (n=2866). In the current study, only respondents aged 65–75 years were included (response rate 63%, n=1386). Data were analysed by means of descriptive statistics and multivariate logistic regression analysis. Results: In total, 64% reported chronic pain. In specific groups, e.g. women and those who were obese, the prevalence was even higher. Among respondents experiencing chronic pain, frequent pain among women and severe pain among both genders were independently associated with decreased likelihood of being physically active. Moreover, the likelihood of being physically active decreased with higher age and BMI, whereas it increased with higher autonomous motivation and feelings of energy. Among physically active respondents suffering from chronic pain, neither intensity nor frequency of pain explained engagement in exercise (as compared with incidental PA). Instead, men were more likely to exercise regularly as were those with good perceived health and higher autonomous motivation. Conclusions: The prevalence of chronic pain is high among older adults with T2D. This study shows that among those suffering from chronic pain, severe pain is independently and inversely associated with being physically active, as is frequent pain, but only among women. Moreover, the findings show the importance of autonomous motivation and health variables for both incidental PA and exercise among older adults with T2D experiencing chronic pain. peerReviewed

Obesity and dyslipidemia are major risk factors for type 2 diabetes, cardiovascular diseases (CVD), cancer, and musculoskeletal disorders. In prevention, the major goal is to limit calorie consumption and to reduce LDL-C and triglyceride. Dietary fiber (DF) intake is inversely related to body weight gain, insulin resistance, dyslipidemia, and CVD. This thesis investigated the effects of the DFs polydextrose (PDX) and lignin-rich insoluble residue (INS) from brewer’s spent grain (BSG) on lipid metabolism and obesity in diet-induced obese mice. In study 1, PDX was investigated on lipid metabolism in Western-diet-fed mice. We found that PDX reduced fasting plasma cholesterol and triglyceride, food intake, and increased bacteria such as Allobaculum, Bifidobacterium and Coriobacteriaceae in the gut. These changes in the gut microbiota with PDX were associated with downregulation of the genes Fiaf, Dgat1 and Cd36, and upregulation of Fxr in the intestine. We suggest that the hypolipidemic effect of PDX is exerted via diet-induced modification of gut microbiota and gene expression. In study II, INS from BSG was studied for its degradation products in mice fed with a fiber-deficient diet. We found that INS was partially degraded by gut microbiota and contributed to the phenolic pool. The major metabolite in mouse urine was 4-methylcatechol, a degradation product of lignin. In study III, the effects of INS from BSG were studied on lipid metabolism and obesity in high-fat diet-fed mice. INS showed hypocholesterolemic effects, reduced body weight and hepatic steatosis, and increased bacterial diversity, Clostridium leptum, and Bacteroides. INS increased bile acid excretion in the feces and upregulated the genes Srebp2, Hmgcr, Ldlr, Cyp7a1, Pparα, Fxr and Pxr in the liver. The present results suggest that INS from BSG induced beneficial systemic changes via bile acid and gut microbiota. In study IV, PDX was investigated for food intake and appetite-related parameters in healthy and overweight females in an acute study. A midmorning preload of 12.5 g PDX reduced hunger by 31.4% during satiation period while there was no significant change in energy intake compared to placebo. In addition, PDX lowered plasma insulin significantly, by 15.7%, and increased GLP-1 by 39.9%. PDX may reduce appetite, but a larger trial would be needed. Tiivistelmä Liikalihavuus ja rasvatasapainon häiriöt ovat riskitekijöitä sydän- ja verisuonisairauksien, tyypin 2 diabeteksen, syövän sekä luuston ja lihaksiston sairauksien kehittymiseen. Näiden sairauksien ehkäisyssä pääasiallisena tavoitteena on vähentää energiansaantia, LDL-kolesterolia ja triglyseridejä. Ruoan ravintokuitujen saannin on osoitettu olevan yhteydessä painon ja plasman rasvatasojen laskuun sekä sydän- ja verisuonisairauksien vähenemiseen. Tässä tutkimuksessa selvitettiin ravintokuitu polydekstroosin (PDX) ja viljanjyvien prosessoinnista ylijäävän (BSG, brewer’s spent grain) ligniinipitoisen liukenemattoman sivutuotteen (INS) merkitystä rasva-aineenvaihduntaan ja aineenvaihduntasairauksiin liikalihavilla hiirillä. Tutkimuksessa I tarkasteltiin ravintokuitu PDX:n vaikutusta rasvojen aineenvaihduntaan länsimaisella ruokavaliolla ruokituilla hiirillä. Tutkimus osoitti, että ruokavalioon lisätty PDX alensi plasman kolesteroli- ja triglyseriditasoja paastossa sekä hillitsi ravinnonottoa ja lisäsi Allobaculum-, Bifidobacterium- ja Coriobacteriaceae-suolistobaktereja. Nämä suolistomikrobiston muutokset ovat yhteydessä Fiaf, Dgat1 ja Cd36 -geenien ilmentymistasojen laskuun ja Fxr -geenin ilmentymistason nousuun PDX-lisäruokittujen hiirien suolistossa. PDX:n hypolipideeminen vaikutus näyttäisi välittyvän ruokavaliosta johtuvan suoliston geenien ilmentymisen ja suolistomikrobiston muuttumisen kautta. Tutkimuksessa II tarkasteltiin runsaasti ligniiniä sisältävän INS:n hajoamistuotteiden vaikutusta aineenvaihduntaan hiirillä, joiden ruokavaliossa on vähemmän kuitua. Tutkimuksessa havaittiin, että suolistomikrobit hajottivat ravintokuitu INS:n osittain fenoliyhdisteiksi verenkiertoon. INS lisäsi virtsassa 4-metyylikatekolin määrää, joka on ligniinin hajoamistuote. Tutkimuksessa III tarkasteltiin INS-lisäyksen vaikutusta rasva-aineenvaihduntaan ja liikalihavuuteen korkearasvapitoisella ruokavaliolla ruokituilla hiirillä. Tulokset osoittivat, että INS-lisäys ruokavalioon alensi kolesterolia ja eläimen painoa sekä vähensi maksan rasvoittumista ja lisäsi vallitsevien bakteerien monimuotoisuutta, Clostridium leptum- ja Bacteroides -bakteereja. INS lisäsi sappihappojen erittymistä ulosteeseen ja Srebp2, Hmgcr, Ldlr, Cyp7a1, Pparα, Fxr ja Pxr -geenien ilmentymistä maksassa. Tuloksemme osoittivat, että BSG-ylijäämätuotteesta saatu ligniinipitoinen INS sai aikaan hyödyllisiä systeemisiä vaikutuksia suoliston mikrobiston ja sappihappojen muutosten kautta. Tutkimuksessa IV tarkasteltiin PDX:n vaikutusta ravinnonottoon ja ruokahaluun vaikuttaviin muuttujiin normaalipainoisilla ja liikalihavilla naisilla akuutissa tutkimuksessa. Tulosten mukaan ravintokuitu PDX:n nauttiminen aamiaisella vähensi näläntunnetta (31,4 %) seuraavalla aterioinnilla, kun taas plasebolla ei ollut vaikutusta. Lisäksi PDX alensi merkitsevästi insuliinitasoa (15,7 %) ja nosti GLP-1-tasoa (39,9 %). PDX vaikuttaisi vähentävän ruokahalua, mutta lisätutkimuksia tarvitaan.

Metabolic syndrome is a constellation of metabolic abnormalities predisposing to cardiovascular diseases (CVD), type 2 diabetes, and increased mortality. Due to the high prevalence and severe co-morbidities, metabolic syndrome constitutes a major burden for both public health and the global economy. Improved understanding of the detailed molecular mechanisms could provide novel strategies for the treatment and preferably prevention of the metabolic syndrome-related health issues. Recent advancements in ‘omics’ technologies have facilitated the development of novel tools to examine the links between genetic variation and human health. The new techniques allow determination of millions of genotypes or quantification of hundreds of metabolic measures from a single blood sample. In this thesis, genomics and metabolomics approaches are coupled to improve our understanding of the metabolic syndrome-related health issues. More precisely, my projects evaluate the metabolic effects of two lipid-lowering therapies and non-alcoholic fatty liver, as well as assess genetic determinants of chronic inflammation. The present results indicate generally consistent metabolic effects of statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) genetic inhibition. The subtle discrepancies observed could potentially contribute to differences in the efficacy to lower CVD risk between statins and PCSK9 inhibitors. The dissimilar metabolic effects of the four genetic variants that increase the risk of non-alcoholic fatty liver disease (NAFLD) highlight the heterogeneity of the molecular mechanisms involved in NAFLD pathogenesis. The results further suggest that fatty liver by itself might not promote unfavourable metabolic aberrations associated with fatty liver on a population level. The newly identified loci associating with inflammatory phenotypes elucidate the genetic mechanisms contributing to the inflammatory load. In particular, the present results suggest the important role of the locus determining the ABO blood types in the regulation of the soluble adhesion molecule levels. To conclude, this thesis successfully complements the knowledge of the molecular mechanisms involved in metabolic syndrome-related traits and provides examples of how to couple omics technologies in the study of complex traits or in the evaluation of drug effects. Tiivistelmä Metabolinen oireyhtymä on tila, jossa useiden aineenvaihdunnallisten riskitekijöiden kasautuminen suurentaa riskiä sairastua tyypin 2 diabetekseen ja sydän- ja verisuonitauteihin sekä lisää kokonaiskuolleisuutta. Vakavista liitännäissairauksista ja suuresta esiintyvyydestä johtuen metabolinen oireyhtymä kuormittaa merkittävästi sekä terveydenhuoltoa että kansantaloutta. Jotta metabolisen oireyhtymän hoitoon ja ennaltaehkäisyyn voitaisiin kehittää uusia keinoja, on tärkeää ymmärtää paremmin oireyhtymän syntyyn vaikuttavat täsmälliset molekyylimekanismit. Niin sanottujen ’omiikka-tekniikoiden’ viimeaikainen kehitys tarjoaa uusia mahdollisuuksia tutkia geenimuutosten vaikutuksia terveyteen. Uusien tekniikoiden avulla voidaan määrittää miljoonia genotyyppejä tai satoja aineenvaihdunnan merkkiaineita yhdestä verinäytteestä. Tässä väitöskirjatyössä yhdistetään genomiikan ja metabolomiikan menetelmiä metaboliseen oireyhtymään liittyvien terveysongelmien tutkimiseksi. Väitöskirjani osatöissä arvioin kahden lipidilääkkeen sekä ei-alkoholiperäisen rasvamaksan aineenvaihdunnallisia vaikutuksia sekä pyrin tunnistamaan krooniseen tulehdukseen vaikuttavia geneettisiä tekijöitä. Tulosten mukaan statiinien ja PCSK9:n (engl. proprotein convertase subtilisin/kexin type 9) geneettisen eston aineenvaihduntavaikutukset ovat hyvin samankaltaiset. Kuitenkin havaitut pienet poikkeavuudet tietyissä merkkiaineissa voivat vaikuttaa eroavaisuuksiin siinä, kuinka tehokkaasti lääkeaineet alentavat sydäntautiriskiä. Suuret erot rasvamaksan riskiä lisäävien geenimuutosten vaikutuksissa aineenvaihduntaan korostavat rasvamaksaan liittyvien molekyylimekanismien monimuotoisuutta. Tulosten perusteella vaikuttaa siltä, että rasvan kertyminen maksaan ei luultavasti itsessään aiheuta suuria muutoksia verenkierron aineenvaihduntatuotteiden pitoisuuksiin. Tulehdusmerkkiaineisiin assosioituvat uudet geenialueet täydentävät tulehduksen molekyylimekanismeihin liittyvää tietoa. Tulokset korostavat ABO-veriryhmän määräävän geenin vaikutusta liukoisten adheesiomolekyylien pitoisuuksiin. Kaiken kaikkiaan väitöskirjan osatyöt tuovat uutta tietoa metaboliseen oireyhtymään liittyvien terveysongelmien molekyylimekanismeihin. Projektit havainnollistavat, miten omiikka-tekniikoita voidaan hyödyntää monitekijäisten fenotyyppien tutkimuksessa sekä lääkeaineiden aineenvaihduntavaikutusten arvioinnissa.

This study investigated the impact of Nordic walking on bone properties in postmenopausal women with pre-diabetes and non-alcohol fatty liver disease (NAFLD). A total of 63 eligible women randomly participated in the Nordic walking training (AEx, n = 33), or maintained their daily lifestyle (Con, n = 30) during intervention. Bone mineral content (BMC) and density (BMD) of whole body (WB), total femur (TF), femoral neck (FN), and lumbar spine (L2-4) were assessed by dual-energy X-ray absorptiometry. Serum osteocalcin, pentosidine, receptor activator of nuclear factor kappa-B ligand (RANKL) levels were analyzed by ELISA assay. After an 8.6-month intervention, the AEx group maintained their BMCTF, BMDTF, BMCL2−4, and BMDL2−4, and increased their BMCFN (p = 0.016), while the Con group decreased their BMCTF (p = 0.008), BMDTF (p = 0.001), and BMDL2−4 (p = 0.002). However, no significant group × time interaction was observed, except for BMDL2−4 (p = 0.013). Decreased pentosidine was correlated with increased BMCWB(r = −0.352, p = 0.019). The intervention has no significant effect on osteocalcin and RANKL. Changing of bone mass was associated with changing of pentosidine, but not with osteocalcin and RANKL. Our results suggest that Nordic walking is effective in preventing bone loss among postmenopausal women with pre-diabetes and NAFLD.

Type 2 diabetes (T2D) is one of the most rapidly increasing non-communicable diseases worldwide. Lifestyle interventions are effective in preventing T2D but also resource intensive. This study evaluated with discrete event simulation (DES) the relative budget impacts of three hypothetical diabetes prevention programs (DPP), including group-based contact intervention, digital program with human coaching and fully automated program. The data for simulation were derived from research literature and national health and population statistics. The model was constructed using the iGrafx Process for Six Sigma software and simulations were carried out for 10 years. All simulated interventions produced cost savings compared to the situation without any intervention. However, this was a modeling study and future studies are needed to verify the results in real-life. Decision makers could benefit the predictive models regarding the long-term effects of diabetes prevention interventions, but more data is needed in particular on the usage, acceptability, effectiveness and costs of digital intervention tools. peerReviewed

nonPeerReviewed

INTRODUCTION: Physical activity (PA) is important in the prevention and treatment of impaired glucose metabolism. However, association of physical inactivity during the transition between childhood and adulthood with glucose metabolism is unknown. Therefore, we studied the association of persistent physical inactivity since childhood with glucose metabolism in adulthood. METHODS: Data were drawn from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow-ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol·L) or type 2 diabetes in adulthood. Leisure-time PA habits were repeatedly collected with a standardized questionnaire and expressed as a PA Index. Using PA Index, four groups were formed (n = 2000): 1) persistently low PA, 2) decreasingly active, 3) increasingly active, and 4) persistently active subjects. Poisson regression model was used to examine the association between PA groups and impaired glucose metabolism. RESULTS: The proportion of the sample with impaired glucose metabolism was 16.1% in individuals with persistently low PA, 14.5% in decreasingly active, 6.8% in increasingly active, and 11.1% in persistently active. Compared with individuals with persistently low PA, age and sex-adjusted risk for impaired glucose metabolism were lower in those who increased PA (relative risk [RR], 0.47; 95% confidence interval [CI], 0.29-0.76) and in those who were persistently active (RR, 0.70; 95% CI, 0.51-0.97), but similar in those who decreased PA (RR, 0.93; 95% CI, 0.66-1.36). CONCLUSIONS: Persistently physically inactive lifestyle from youth to adulthood is associated with increased risk of impaired glucose metabolism in adulthood. Importantly, a moderate increase in PA lowered the risk. The results highlight the importance of avoiding physically inactive lifestyle at all stages of life. peerReviewed

Objective. The purpose of the study was to examine the acute effects of the timing of exercise on the glycemic control during and after exercise in T2D. Methods. This study included 26 T2D patients (14 women and 12 men) who were treated with metformin. All patients were tested on four occasions: metformin administration alone (Metf), high-intensity interval training (HIIT) performed at 30 minutes (EX30), 60 minutes (EX60), and 90 minutes (EX90) postbreakfast, respectively. Glucose, insulin, and superoxide dismutase (SOD) activity were examined. Results. Glucose decreased significantly after the exercise in EX30, EX60, and EX90. Compared with Metf, the decline in glucose immediately after the exercise was larger in EX30 (−2.58 mmol/L; 95% CI, −3.36 to −1.79 mmol/L; p<0.001), EX60 (−2.13 mmol/L; 95% CI, −2.91 to −1.34 mmol/L; p<0.001), and EX90 (−1.87 mmol/L; 95% CI, −2.65 to −1.08 mmol/L; p<0.001), respectively. Compared with Metf, the decrease in insulin was larger in EX30 and EX60 (both p<0.001). Conclusions. Timing of exercise is a factor to consider when prescribing exercise for T2D patients treated with metformin. This trial is registered with ChiCTR-IOR-16008469 on 13 May 2016.

Forskningens bakgrund och syfte: Fysisk aktivitet är en central del i vården av typ 2-diabetes. Trots påvisade positiva effekter av regelbunden fysisk aktivitet verkar en liten andel diabetiker vara fysiskt aktiva. Smärta har i tidigare studier identifierats som ett hinder till fysisk aktivitet bland diabetiker och man har kunnat se samband mellan kronisk smärta och svårigheter att utföra fysisk aktivitet. Det finns dock endast ett fåtal studier som undersöker detta samband. Syftet med denna avhandling var att kartlägga förekomsten av kronisk smärta bland äldre personer med typ 2-diabetes och att undersöka sambandet mellan kronisk smärta och fysisk aktivitet. Forskningsmaterial och –metoder: Datamaterialet som användes i avhandlingen är en del av forskningsprojektet God vård vid diabetes, som genomfördes av Folkhälsans forskningscentrum och avdelningen för folkhälsovetenskap vid Helsingfors universitet. Materialet samlades in som en enkätstudie år 2011. I avhandlingen avgränsades samplet till respondenterna i åldern 65–75 år (N = 1386). Forskningsvariablerna skapades utifrån frågor som kartlade smärta och fysisk aktivitet. Som huvudsakliga analysmetoder användes korstabulering, X2-test och logistisk regressionsanalys. Resultat: Kronisk smärta förekom hos 64,3 % av respondenterna i det undersökta samplet. Av dem som hade kronisk smärta utförde 74,0 % åtminstone vardagsmotion, jämfört med 81,6 % av dem som inte hade kronisk smärta. Den kroniska smärtan i sig hade inte ett samband med fysisk aktivitet, då sambandet testades under kontroll för utvalda kontrollvariabler. Då frekvensen respektive intensiteten av smärtan beaktades hade smärtan däremot betydelse. Ofta förekommande smärta, liksom också stark smärta, minskade sannolikheten för fysisk aktivitet bland dem som hade kronisk smärta, också under kontroll för kontrollvariablerna. Sannolikheten för fysisk aktivitet minskade också med högre ålder och BMI, men ökade med högre grad av autonom motivation och energi. Frekvensen respektive intensiteten av smärtan var inte relaterad till vilken typ av fysisk aktivitet (vardagsmotion eller hälsomotion) respondenterna utförde. Slutsatser: Kronisk smärta verkar vara vanligt förekommande bland äldre personer med typ 2-diabetes och värd att beakta i samband med rådgivning om fysisk aktivitet i denna patientgrupp. En noggrann bedömning av smärta rekommenderas för att identifiera dem som har ofta förekommande och stark smärta. Background and purpose: Physical activity is a key component in the management of type 2 diabetes. Although health benefits of regular physical activity, adherence to physical activity among people with type 2 diabetes seems to be low. In previous studies, pain has been identified as a barrier to physical activity among people with diabetes and a relationship between chronic pain and difficulties following an exercise plan has been seen. However, there are only a few studies investigating this relationship. The aim of this thesis was to evaluate the prevalence of chronic pain among elderly people with type 2 diabetes and to examine the relationship between chronic pain and physical activity. Methods: The data was a part of the research project Good care in diabetes, carried out by Folkhälsan Research Center and the Department of Public Health at the University of Helsinki. The data was collected through a mail survey in 2011. Only respondents aged 65–75 years were included in the present analysis (n = 1386). The primary study variables were created from questions measuring pain and physical activity. In data analysis cross tabulation, X2-test and logistic regression analysis were used. Results: Chronic pain was reported by 64.3% of respondents. Of respondents with chronic pain, 74.0% performed at least incidental physical activity, compared to 81.6% of respondents without chronic pain. After adjusting for several control variables, chronic pain in itself was not related to physical activity. When frequency and intensity of pain were taken into account, however, there was a significant relationship. Frequent pain, as well as severe pain, was related to decreased likelihood of being physically active among respondents with chronic pain, even after adjusting for the control variables. The likelihood of being physically active also decreased with higher age and BMI, but increased with higher autonomous motivation and energy. Frequency and intensity of pain were not related to what type of physical activity (incidental physical activity or health exercise) respondents performed. Conclusions: Chronic pain seems to be prevalent among elderly people with type 2 diabetes and should be taken into account when giving physical activity guidance in diabetes care. A comprehensive assessment of pain is recommended to identify individuals with frequent and severe pain.

The purpose of this study was to describe the contents of type 2 diabetes patient self-management counselling documentation, how counselling of self- management appeared in various content areas and how patients’ self- management competence developed during the counselling. The research data consisted of nurses’ documentations from type 2 diabetes patient self- management counselling situations (N = 60) in primary health care. The data was collected in 2014 from the period between the years 2005 and 2014. Data were analyzed using content analysis as well as a case study approach. The documentation of self-management counselling included entries from content areas on nutrition, exercise, weight control, substance abuse, medication, self-monitoring, foot care, mood, and follow-up treatment. There were no entries related to sleep and rest content areas. The main focus of the self-management counselling documentation was descriptive entries related to nutritional discipline and change as well as planning and following medication care. In the descriptions, patients’ knowledge and skills were described briefly while their attitudes were described in a number of ways. The support offered by nurses consisted mainly of giving information. In addition, only in scattered instances did the patients’ own experiences, understanding, and the application of their knowledge to practice appear in the entries. Entries made on the guidance offered in self-management counselling situations consisted of short references to issues that were handled. They resembled notes more than they did considerations of patients’ progress in their need to change or evaluations of changes or competence development from the previous meeting. The overall guidance of the treatment path seemed illogical and in places even contradictory because early entries were not returned to. The same issues were repeated while others remained open. These findings suggest that self-management documentation should include the patient`s point of view more often than is currently the case. Findings are useful for the development of self-management counselling documentation.

The purpose of the study was to describe the supervisors’ action in the support of changing one’s living habits in two weight management groups in the type 2 diabetes prevention program. The data consists of 17 video-recorded 90-minute “Small decision a day” weight management group counselling sessions of two groups with 10 and 20 participants in the years 2004-2005. The supervisors’ talk was analyzed with the deductive analysis from five teaching perspectives including theirs beliefs, intentions and actions. The transtheoretical change model and the participants’ talk were analyzed with the inductive analysis. Quantitative methods were used to give more information about the counselling sessions. The results show that the transmission perspective was the most dominating followed by the apprenticeship perspective. The developmental perspective consisted of self-assessment and was nearly as dominating as the apprenticeship perspective. The supervisors changed the emphasis from the lesson- focused type to the participant-centered counselling. The need for the change and the objectives were continually connected to new information. The apprenticeship perspective consisted of physical exercise where the participants were also given individual advice. The self-assessment was supported with focused questions, comments, advice, positive feedback, encouragement, comfort and other linguistic methods by the supervisors. The supervisors adapted to the challenge of the change according to the participants’ resources. Mostly, the supervisors supported the awareness of participants and their self-assessment, the re-assessment of the environment and follow-up. The time used in the sessions and participation in the groups were quantified. Further research could concentrate on participants’ experiences in group counseling, the outcome expectations, the objectives and the role of peers, and also the factors of physical and psychosocial environment in the change, physical exercise intervention and web counseling.

Fyysinen aktiivisuus on yksi tyypin 2 diabeteksen hoidon ja ennaltaehkäisyn kulmakivistä. Fyysisellä aktiivisuudella on myös osoitettu olevan yhteys vähentyneisiin masennusoireisiin. Tämän pro gradu-tutkielman tarkoituksena oli selvittää fyysisen aktiivisuuden, masennusoireiden ja tyypin 2 diabeteksen välistä yhteyttä sekä kartoittaa sosiodemografisten ja kliinisten tekijöiden yhteyttä tyypin 2 diabetekseen. Poikkileikkaustutkimukseen kutsuttiin yhteensä 4500 tutkittavaa, joista 2745 iältään 45-74 –vuotiasta osallistui mukaan D2D-masennustutkimukseen. Tutkittavat rekrytoitiin kolmen eri sairaanhoitopiirin alueelta: Keski-Suomesta, Pirkanmaalta ja Etelä-Pohjanmaalta. Tutkittaville suoritettiin terveystarkastus, jonka aikana he täyttivät kyselylomakkeita. Tutkittavilla todettiin olevan tyypin 2 diabetes, jos sairaus oli itse raportoitu ja lääkärin aikaisemmin toteama tai terveystarkastuksen yhteydessä todettu. Masennusoireita kartoitettiin Beckin kyselylomakkeella ja fyysistä aktiivisuutta International Physical Activity Questionnaire (IPAQ) kyselylomakkeen lyhyellä versiolla. Fyysisen aktiivisuuden, masennusoireiden ja tyypin 2 diabeteksen välistä yhteyttä kartoitettiin Pearson Chi-Square testillä ja sosiodemografisten ja kliinisten muuttujien yhteyttä tyypin 2 diabetekseen tarkasteltiin logistisella regressioanalyysilla. Tyypin 2 diabeteksen esiintyvyys oli 23 % alhaisessa, 17 % kohtalaisessa ja 13% korkeassa fyysisen aktiivisuuden luokassa (p

Sydämen ympärille kertyvä intratorakaalirasva jaetaan epikardiaaliseen ja perikardiaaliseen rasvaan. Intratorakaalirasvan ja sydänlihakseen kerääntyvän rasvan on havaittu olevan yhteydessä mm. insuliiniresistenssiin, ateroskleroosiin ja dyslipidemiohin. Säännöllisen liikunnan on osoitettu vähentävän tehokkaasti sisäelinten ympärille ja vatsanalueelle kertyviä viskeraalirasvoja. Tämän tutkimuksen tarkoituksena oli tutkia kahden eri liikuntaharjoittelumenetelmän vaikutusta intratorakaalirasvojen määrään, sydämen rasvapitoisuuteen ja insuliiniherkkyyteen terveillä sekä tyypin 2 diabeetikoilla (T2D) tietokonetomografiaa ja magneettispektroskopiaa hyödyntäen. Tutkimukseen osallistui yhteensä 49 henkilöä (T2D, n=21 ja terveet koehenkilöt, n=28). Diabetesluokittelun lisäksi ryhmät satunnaistettiin kahteen harjoittelultaan eroavaan ryhmään, lyhytkestoiseen kovatehoiseen (HIT, high intensity training, n=24) ja pitkäkestoiseen kohtuukuormitteiseen (MIT, moderate intensity training, n=25) harjoitteluryhmään. Harjoittelun kesto kummassakin tutkimusryhmässä oli kaksi viikkoa ja sisälsi kuusi harjoituskertaa. Kahden viikon harjoittelu paransi kestävyyskuntoa 3 % (p=0.04) ja koko kehon insuliiniherkkyyttä keskimäärin 25 % (p

Metabolic syndrome is a constellation of metabolic abnormalities including abdominal obesity, glucose intolerance, insulin resistance, hypertension and dyslipidemia. Metabolic syndrome increases the risk of cardiovascular diseases and type 2 diabetes mellitus. A unifying pathophysiological mechanism behind these abnormalities has not been detected. The prevalence of cardiovascular diseases and type 2 diabetes mellitus is increasing all over the world. It is important to identify the factors contributing to these diseases. The aim of this thesis was to study how the peptide hormone resistin is associated with metabolic syndrome and find out whether intrauterine growth restriction predisposes to adverse changes in lipid and glucose metabolism and peptide hormones in a rat model. Resistin is secreted mainly from macrophages in humans. It possesses proinflammatory properties. Controversial results about its role on obesity, insulin resistance and metabolic syndrome have been reported. In the first study of this thesis, resistin levels were measured from 1500 Finnish subjects in the cross-sectional Health 2000 study. Higher resistin levels were detected in subjects fulfilling the criteria for metabolic syndrome compared to subjects without metabolic syndrome. Resistin was associated with several components of metabolic syndrome. Data derived from epidemiological studies show that low birth weight is associated with an increased risk for chronic diseases in adulthood. A rat model of intrauterine growth restriction was created. In the second study, unfavorable changes in the peptide hormones resistin and adiponectin were detected that may predispose rats to subsequent insulin resistance. In addition to intrauterine growth restriction, the effect of postnatal fructose-rich diet was explored in the third study. Intrauterine growth restriction and postnatal fructose diet decreased body weight and induced adverse changes in lipid and glucose metabolism in offspring. However, fetally growth-restricted rats were not more susceptible to the adverse effect of fructose diet. In conclusion, this study demonstrates that resistin is associated with metabolic syndrome and is increased by intrauterine growth restriction. Restricted maternal diet during pregnancy influences weight and lipid metabolism in rat offspring. Tiivistelmä Metaboliseksi oireyhtymäksi kutsutaan sydän- ja verisuonitautien sekä tyypin 2 diabeteksen riskitekijöiden kasaumaa. Näitä riskitekijöitä ovat keskivartalolihavuus, heikentynyt glukoosin sieto, insuliiniresistenssi, korkea verenpaine sekä rasva-aineenvaihdunnan häiriöt, erityisesti korkea triglyseridipitoisuus ja matala HDL-taso. Näiden tekijöiden taustalta ei ole löydetty selkeää yhdistävää mekanismia. Tämän väitöskirjan tavoitteena oli tutkia resistiinin yhteyttä metaboliseen oireyhtymään sekä selvittää, altistaako raskauden aikainen aliravitsemus ja siihen liittyvä alhainen syntymäpaino häiriöille rasva- ja glukoosiaineenvaihdunnassa sekä peptidihormoneissa rotalla. Resistiini erittyy ihmisellä pääasiassa tulehdussoluista, erityisesti makrofageista. Sillä on todettu olevan tulehdusta edistäviä vaikutuksia. Resistiinin yhteydestä lihavuuteen, insuliiniresistenssiin ja metaboliseen oireyhtymään on julkaistu ristiriitaisia tuloksia. Väitöskirjan ensimmäisessä osatyössä plasman resistiinipitoisuudet määritettiin 1500 suomalaiselta poikkitieteellisessä Terveys 2000 -tutkimuksessa. Havaittiin, että resistiinipitoisuudet olivat korkeammat niillä tutkimushenkilöillä, joilla oli metabolinen oireyhtymä verrattuna henkilöihin, joilta oireyhtymä puuttui. Epidemiologisissa tutkimuksissa on havaittu, että alhainen syntymäpaino on yhteydessä korkeampaan riskiin sairastua moniin kroonisiin sairauksiin, kuten sydän- ja verisuonitauteihin aikuisiässä. Toisessa ja kolmannessa osatyössä tutkittiin rottamallissa raskauden aikaisen ravintorajoituksen vaikutusta jälkeläisten kasvuun, rasva- ja sokerimetaboliaan sekä peptidihormoneihin. Toisessa osatyössä todettiin, että rajoitettu ravinto raskauden aikana aiheutti haitallisia muutoksia resistiini- ja adiponektiinipitoisuuksissa altistaen jälkeläiset insuliiniresistenssille. Kolmannessa osatyössä tutkittiin lisäksi syntymänjälkeisen fruktoosipitoisen ravinnon vaikutuksia. Raskauden aikaisen aliravitsemuksen ja fruktoosiravinnon vaikutuksesta rotat olivat aikuisena pienempiä ja niillä havaittiin häiriöitä rasva- ja sokeriaineenvaihdunnassa. Tutkimus osoittaa, että korkea plasman resistiini-pitoisuus liittyy metaboliseen oireyhtymään. Lisäksi voidaan todeta, että rajoitettu ravinto raskauden aikana aiheuttaa rotalla korkeamman resistiini-pitoisuuden lisäksi muutoksia painossa ja rasva-aineenvaihdunnassa.

The preservation of mobility is essential for maintaining an independent and active lifestyle in old age. However, diabetes greatly increases older people’s susceptibility to mobility loss, leading to an increased risk of dependence. Given the increased prevalence of diabetes with age, and the increasing incidence of the disease worldwide, public health initiatives for preventing mobility loss with age must also prove effective for diabetics. The screening and counseling for physical activity among older people (SCAMOB) study examines the effectiveness of physical activity counseling for the prevention of mobility loss in an older population. Although the cohort as a whole has shown positive results, the effectiveness of the intervention among diabetics, particularly type 2 diabetics, is still unknown. For this reason, I proposed a secondary analysis of the SCAMOB study and 2-year follow-up data, which will evaluate the effectiveness of the SCAMOB intervention for the prevention of mobility loss in older type 2 diabetics versus non-diabetics. The primary findings of this study were as follows: (1) Physical activity counseling does not improve diabetics’ habitual physical activity level or mobility; however, it can help diabetics maintain current levels of mobility, by preventing decline in 2 km walking ability. (2) Physical activity counseling influences more change among non-diabetics than it does among diabetics, in regards to both habitual physical activity level and mobility outcomes. Directions for future research include similar analyses in a more suitable sample, as well as the investigation of supplementary intervention strategies for the reversal of mobility loss in older type 2 diabetics.

Vähäinen fyysinen aktiivisuus lisää tyyppi 2 diabeteksen esiintyvyyttä ja mikä tahansa fyysinen aktiivisuus ehkäisee diabeteksen syntyä. Tarkoituksena oli selvittää aiemmin tunnistamattomien tyypin 2 diabeetikoiden, henkilöiden, joilla oli kohonneet glukoosiarvot ja normaalien verrokkien vapaa-ajan liikunta-aktiivisuuden ja tietämyksen tyyppi 2 riskitekijöistä muutokset viiden vuoden seurantatutkimuksessa. Tämän lisäksi tarkoituksena oli selvittää, ovatko tietämyksen muutokset yhteydessä muutoksiin vapaa-ajan liikunnassa. Tutkimus on osa Kansanterveyslaitoksen FINRISKI–väestötutkimusta, jonka yhteydessä toteutettiin erillinen glukoosirasitusalaotos, jonka tarkoituksena oli selvittää diabeteksen ja muiden glukoosiaineenvaihdunnan häiriöiden esiintyvyys väestössä. FINRISKI-perustutkimukseen osallistui vuonna 2002 13 500 henkilöä, jotka olivat 45-74-vuotiaita. Glukoosirasitusalaotos tehtiin 3700 henkilölle. Vuonna 2007 tehtiin seurantatutkimus 1200 henkilölle. Tutkimusaineistoksi valikoitui 909 henkilöä, jotka osallistuivat sekä 2002 että 2007. Fyysinen aktiivisuus ja tietämys diabeteksen riskitekijöistä arvioitiin kyselylomakkeen avulla. Fyysisestä aktiivisuudesta haluttiin tietää liikunnan kestoa, intensiteettiä ja useutta. Diabeteksen riskitekijöistä kysyttiin kehon painoon, fyysiseen aktiivisuuteen ja ravitsemukseen liittyviä kysymyksiä. Tulokset analysoitiin käyttämällä ristiintaulukointia ja Pearsonin korrelaatiokerrointa. Vapaa-ajan liikunnan muutokset eivät eronneet tilastollisesti normaalien verrokkien ja niiden välillä, joilla oli poikkeavat glukoosiarvot. Tietämys diabeteksen riskitekijöistä lisääntyi (p < 0,001) kaikissa kolmessa tutkittavassa ryhmässä. Tietämyksen muutoksen ja vapaa-ajan fyysisen aktiivisuuden muutoksen välillä oli tilastollisesti merkitsevä yhteys terveillä, mutta ei muissa tutkittavien ryhmissä. Johtopäätöksenä todetaan, että vapaa-ajan fyysinen aktiivisuus ei ole lisääntynyt missään tutkittavassa ryhmässä tutkimusaikana. Tietämyksen lisääntyminen diabeteksen riskitekijöistä oli yhteydessä vapaa-ajan fyysiseen aktiivisuuteen ainoastaan terveillä. Tietämyksen parantuminen kaikissa tutkittavissa ryhmissä, tukee väestöneuvonnan onnistumista, mitä Suomessa on toteutettu Dehko-hankkeen myötä. Physical inactivity increases occurrence of type 2 diabetes and any physical activity can prevent type 2 diabetes. The aim of the study was to investigate leisure-time physical activity and awareness of type 2 diabetes risk factors in a five year follow up study with type 2 diabetics, normal control group and people, who had high glucose levels. Also the aim of the study was to investigate if there is an association between the changes in the awareness of type 2 diabetes risk factors and changes in physical activity. This study is a part of a larger FINRISKI-survey. A random sample of 3700 subjects 45-74 years of age was selected in 2002 and included in the oral glucose tolerance test sample. 1200 of them were invited to a follow up study in 2007. In this study the population was 909 persons, who participated both in 2002 and 2007. Physical activity and awareness of type 2 diabetes risk factors were assessed by a self-administered questionnaire. Results were analyzed using cross-tabulation and Wilcoxon signed ranks- test. Leisure time physical activity did not differ between study groups according to glucose levels. The awareness of type 2 diabetes risk factors increased in every glucose group (p < 0.001) from 2002 to 2008. There was an association between the change in the awareness of type 2 diabetes risk factors and change in leisure time physical activity among healthy participants, but this trend was not statistically significant in the other study groups. This study supports that Finnish Dehko-project succeeded well in increasing the awareness of type 2 diabetes risk factors.

Tämän tutkimuksen tarkoituksena oli selvittää soveltuuko kuuden minuutin kävelytesti mittaamaan työikäisten tyypin 2 diabeetikoiden fyysistä kuntoa. Lisäksi tutkimuksessa selvitettiin kuntoutujien mielikuvia kuuden minuutin kävelytestistä fyysisen kunnon mittarina ja liikuntamuutosten tukijana. Tutkimus toteutettiin vuonna 2009 kuudella Suomen Diabetesliiton järjestämällä työikäisten, tyypin 2 diabeetikoiden kuntoutuskurssilla. Yhteensä tutkimukseen osallistui 78 koehenkilöä, joista oli 42 naista ja 36 miestä. Tutkimusaineisto muodostui työikäisten, tyypin 2 diabeetikoiden kuuden minuutin kävelytesteistä sekä demografisista mittauksista ensimmäisellä ja toisella kuntoutusjaksolla. Mittauksiin liittyi kyselylomake kuntoutujien mielikuvista kuuden minuutin kävelytestistä loppumittauksen jälkeen, joita palautui 74 kappaletta. Kuuden minuutin kävelytestit ja kyselylomakkeet analysoitiin ristiintaulukoimalla, t-testillä sekä testaamalla tilastollinen merkitsevyys 2 -testillä. MANOVA:lla testattiin iän, sukupuolen ja kävelymatkojen keskiarvoerojen välistä merkittävyyttä. Varianssien yhtäsuuruutta testattiin Levenen testillä. Kyselylomakkeen kaksi avointa kysymystä analysoitiin induktiivisella sisällönanalyysilla. Kuntoutujien(n=67) kävelymatka erosi alkumittauksen 525,2 m:stä (SD±81,6) loppumittauksen 570,6 m:iin (SD±101,5), erotus 45,1 m (SD±78,3) oli tilastollisesti merkitsevä (p