ABSTRACT Introduction: Renal transplant recipients (RTR) with abnormal glucose tolerance (AGT) are at an increased risk of graft failure and cardiovascular disease (CVD). CVD is the major cause of death in RTR. Whilst there are numerous known risk factors for AGT in RTR, it is unknown whether lifestyle factors are found in the presence or play a role in the development of AGT in RTR. The nutritional status of RTR in an Australian population has also not been extensively investigated. Investigation into these areas could help identify modifiable areas for change in the RTR population. Multidisciplinary lifestyle modification, including diet and physical activity (PA) advice from a dietitian, may help reduce modifiable risk factors for CVD in RTR with AGT. Aims: The principle aims of this thesis are to; 1) assess the incidence of obesity and central obesity in RTR and compare to rates in the general Australian population, 2) investigate and compare modifiable lifestyle factors and adipokine levels in RTR with AGT and normal glucose tolerance (NGT) and 3) investigate the effect of a multidisciplinary lifestyle intervention (including dietetic advice) on modifiable CVD risk factors in RTR with AGT. Methods: Chapter 1 presents a review of the literature describing the main nutritional challenges in RTR, cardiovascular risk factors in RTR including adipokine profiles and the role of body composition, diet and PA in RTR. Chapter 2 details the clinical, biochemical, nutritional, body composition, PA and statistical methodologies used in this thesis. In Chapter 3 a descriptive analysis of the anthropometry and cardiovascular risk profile of RTR in an Australian setting is investigated. Chapter 4 investigates the nutritional status of RTR with NGT and AGT in more detail, assessing diet, PA, adipokines and body composition. In Chapter 5, the current literature on lifestyle intervention management (including nutritional management) for obesity and type 2 diabetes mellitus in the general population is discussed. Building on previous chapters, Chapter 6 investigates the effect of a multi-disciplinary lifestyle intervention (with dietetic input) on modifiable cardiovascular risk factors in RTR with AGT. Results: In Chapter 3 it was found that RTR are significantly more centrally obese than those in the general population, and this was particularly the case in younger RTR. Central obesity was associated with CVD risk factors in RTR. Chapter 4 found that a lower level of PA, obesity and central obesity are associated with AGT in RTR, whereas no difference in adipokines or dietary intake was found. In Chapter 6, multidisciplinary lifestyle intervention with dietetic input was found to improve certain risk factors for CVD in RTR with AGT, such as dietary factors (total fat and saturated fat intake) and lipid levels. Conclusions: Central obesity is a common problem in RTR, particularly in those with AGT. Higher levels of PA are associated with lower risk of AGT in RTR, and may help reduce the incidence of central obesity in RTR. Multidisciplinary lifestyle intervention, with dietetic input, can improve some modifiable CVD risk factors in RTR with AGT, however more intensive intervention is required to significantly reduce the incidence of obesity. Key Words: Renal Transplant; Abnormal Glucose Tolerance, Obesity; Cardiovascular Disease; Physical Activity Australian and New Zealand Standard Research Classifications (ANZSRC) 1111 Nutrition and Dietetics, 1102 Cardiovascular medicine and Haematology, 1199 Other Medicine and Health Sciences

Abstract Type 2 diabetes is one of the fastest increasing lifestyle diseases globally. Its cure is not yet possible, but there is firm evidence from scientific studies that it can effectively be prevented by lifestyle changes. There is limited evidence-based information on the prevention of diabetes in practice. This dissertation offers new desirable information on the issue. The aim of this dissertation study was to describe the prevalence of risk factors for type 2 diabetes and hidden glucose disorders predicting the development of diabetes in the Finnish adult population, and to analyse whether the risk for developing diabetes could be reduced by simple lifestyle counselling. Furthermore, the ability of the Finnish Diabetes Risk Score (FINDRISC) to detect glucose disorders leading to diabetes and undiagnosed diabetes was analysed. In the dissertation data from large Finnish population surveys (the FINRISK 2002 glucose tolerance survey and the FIN-D2D 2004−2005 survey) were analysed. In addition, a prospective design and large-scale intervention were included. We found that obesity and glucose disorders are very common in the Finnish middle-aged population. Prevalence of obesity was 24% for men and 28% for women, that of abnormal glucose metabolism 42% for men and 33% for women, and that of undiagnosed diabetes 9% for men and 7% for men. One quarter of individuals aged 45−64 years were at high risk for diabetes. Lifestyle interventions were offered to more than 10,000 high-risk individuals, 3,379 men and 6,770 women. Of the men, 43% were also at high risk for cardiovascular morbidity and 42% at high risk for cardiovascular mortality estimated through the FRAMINGHAM and SCORE risk engines, respectively. The FINDRISC, originally developed for predicting the risk of development of type 2 diabetes, also predicted the prevalence of diabetes in the population. The effect of lifestyle interventions on weight and its association with glucose tolerance was evaluated in individuals at high risk for diabetes in a one-year follow-up. In total 17.5% of them lost ≥ 5% weight. Their relative risk for diabetes decreased 69% compared with the group that maintained their weight. This study shows that FINDRISC predicts prevalent type 2 diabetes. A significant proportion of middle-aged Finnish population has a glucose disorder including undiagnosed type 2 diabetes. Lifestyle interventions in primary health care may promote weight loss, which decreases the risk of diabetes. / Tiivistelmä Diabetes on yksi nopeimmin lisääntyvistä elintapasairauksista maailmassa. Sitä ei vielä voida parantaa, mutta tieteellisissä tutkimuksissa on kiistattomasti osoitettu, että sitä voidaan tehokkaasti ehkäistä elintapamuutoksilla. Diabeteksen ehkäisystä käytännössä on hyvin niukasti tutkimustietoa. Tämä väitöskirja tuo kaivattua lisätietoa aiheesta. Väitöstutkimuksen päätavoitteena oli selvittää diabeteksen riskitekijöiden ja piilevien diabetesta ennakoivien sokerihäiriöiden yleisyyttä suomalaisessa aikuisväestössä. Tämän ohella tavoitteena oli selvittää voidaanko yksinkertaisella elintapaneuvonnalla vähentää sellaisten henkilöiden sairastumisvaaraa, joilla oli suuri riski sairastua diabetekseen. Lisäksi arvioitiin diabetesriskitestin kykyä tunnistaa ennakoivat sokerihäiriöt ja aiemmin tunnistamaton diabetes. Tutkimuksessa käytettiin laajoja suomalaisia väestötutkimusaineistoja: FINRISKI-2002 -tutkimusta, sen alaotosta ja D2D-väestötutkimusta 2004–2005. Mukana oli myös pitkittäisasetelma ja laajamittainen interventio. Tutkimuksen perusteella huomasimme, että lihavuus ja sokerihäiriöt ovat hyvin yleisiä keski-ikäisillä suomalaisilla. Merkittävästi lihavia (BMI ≥ 30 kg/m2) oli 24 % miehistä ja 28 % naisista ja poikkeava sokeriaineenvaihdunta oli 42 %:lla miehistä ja 33 %:lla naisista. Tunnistamaton diabetes oli 9 %:lla miehistä ja 7 %:lla naisista. Suuressa diabetekseen sairastumisvaarassa oli neljäsosa 45−64-vuotiaista. Interventioon otettiin yli 10 000 suuressa diabeteksen sairastumisriskissä olevaa henkilöä, 3 379 miestä ja 6 770 naista. Miehistä 43 % oli suuressa sairastumisvaarassa myös sydän- ja verisuonisairauteen ja 42 % suuressa kuolemanvaarassa Framingham- ja SCORE-riskilaskureilla arvioituna. Tyypin 2 diabeteksen sairastumisriskin arviointiin kehitetty Riskitesti ennusti hyvin myös diabeteksen esiintymistä väestössä. Elintapainterventioiden vaikutusta painoon ja sokeriaineenvaihduntaan analysoitiin vuoden seurannassa sellaisilla henkilöillä, joilla oli suuri diabetesriski. Paino laski 5 % tai enemmän 17,5 %:lla, jolloin sairastumisriski diabetekseen väheni 69 % verrattuna ryhmään, jonka paino ei muuttunut. Tutkimuksen perusteella lihavuus, sokerihäiriöt ja tunnistamaton diabetes ovat yleisiä keski-ikäisessä väestössä. Riskitesti on hyvä työkalu myös diabeteksen seulonnassa. Perusterveydenhuollossa tarjottavalla elintapaneuvonnalla voidaan saada aikaan laihtuminen, joka vähentää sairastumisvaaraa diabetekseen.