For peer review only. BMJ Open. For peer review only -

Transcription

1 Increasing physical activity is associated with improved cardio-metabolic risk profile during lifestyle intervention in primary healthcare among individuals at high risk for type diabetes: the Finnish national diabetes prevention programme (FIN-DD) Journal: Manuscript ID: bmjopen Article Type: Research Date Submitted by the Author: 0-Aug-0 Complete List of Authors: Kujala, Urho; University of Jyväskylä, Department of Health Sciences Jokelainen, Jari Oksa, Heikki Saaristo, Timo Moilanen, Leena Korpi-Hyövälti, Eeva Saltevo, Juha Vanhala, Mauno Niskanen, Leo Peltonen, Markku Tuomilehto, Jaakko Uusitupa, Matti Keinänen-Kiukaanniemi, Sirkka <b>primary Subject Heading</b>: Endocrinology Keywords: Diabetes, lifestyle intervention, Physical activity : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

2 Page of Increasing physical activity is associated with improved cardio-metabolic risk profile during lifestyle intervention in primary healthcare among individuals at high risk for type diabetes: the Finnish national diabetes prevention programme (FIN-DD) Short title: Physical activity and cardio-metabolic risk profile Urho M. Kujala, professor, Jari Jokelainen, statistician,, Heikki Oksa, chief phycician, Timo Saaristo, project manager,, Leena Moilanen, specialist in internal medicine, Eeva Korpi-Hyövälti, specialist in internal medicine, Juha Saltevo, specialist in internal medicine, Mauno Vanhala, professor, Leo Niskanen, professor,,0 Markku Peltonen, associate professor, Jaakko Tuomilehto, professor, Matti Uusitupa, professor,, Sirkka Keinänen-Kiukaanniemi, professor,, Department of Health Sciences, FI-00 University of Jyväskylä, Jyväskylä, Finland Faculty of Medicine, Institute of Health Sciences, FI-00 University of Oulu, Finland Unit of General Practice, Oulu University Hospital, Finland Pirkanmaa Hospital District, FI- Tampere, Tampere, Finland Finnish Diabetes Association, FI-0 Tampere, Tampere, Finland Department of Medicine, Kuopio University Hospital, Northern Savo Hospital District, 0 Kuopio, Finland Department of Internal Medicine, Seinäjoki Central Hospital, FI-00 Seinäjoki, Finland Department of Internal Medicine, Central Finland Hospital District, FI-00 Jyväskylä, Jyväskylä, Finland Unit of Family Practice, Central Finland Hospital District, Jyväskylä, Kuopio University Hospital, and University of Eastern Finland, 0 Kuopio, Finland 0 Faculty of Health Sciences, University of Eastern Finland, 0 Kuopio, Finland National Institute for Health and Welfare, FI-00 Helsinki, Finland Hjelt Institute, Department of Public Health, University of Helsinki, 000 Helsinki, Finland Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio campus, 0 Kuopio, Finland Research Unit, Kuopio University Hospital, Finland Oulu University Hospital District Unit of General Practice, Finland Correspondence to: Urho M. Kujala, Department of Health Sciences, Sports and Health Laboratory, Rautpohjankatu, University of Jyväskylä, P.O. Box (LL), FI-00 University of Jyväskylä, Finland. Fax: , Telephone: +--0, urho.m.kujala@jyu.fi - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

3 Page of Abstract Objectives To investigate the association between increase in physical activity and changes in cardio-metabolic risk factors during a lifestyle intervention programme in routine clinical settings. Design Prospective lifestyle intervention among high-risk individuals implemented in daily routines in 00 primary health care centres and occupational health care outpatient clinics in Finland. Individuals at high risk for type diabetes were identified in the implementation project of the national diabetes prevention programme and participated in a baseline visit. Of the non-diabetic participants, responded at follow-up visit ( to months after their baseline examination) to a question on stability vs. increase of physical activity. Cardio-metabolic risk factors (body composition, blood pressure and those measured from fasting venous blood samples) were measured objectively at baseline and follow-up visits. Results Of the participants 0 (. % of all responders) reported at follow-up having clearly increased their physical activity during past year while,0 (.%) had been unable to increase their physical activity. Those who increased their activity decreased their weight by. kg (% CI. to.; age and sex adjusted P<0.00) and waist circumference by. cm (. to.; P<0.00) more than those who did not increase their activity. Similarly, those who increased their physical activity had greater reductions in total cholesterol (group difference in reduction 0. mmol/l; 0.0 to 0.; P=0.00), LDL cholesterol (0. mmol/l; 0.0 to 0.; P=0.00), LDL/HDL ratio (0.; 0.0 to 0.; P<0.00) as well as fasting glucose (0.0 mmol/l; 0.0 to 0.; P=0.00) and -h glucose levels (0. mmol/l; 0. to 0.; P=0.0) than those who did not increase their physical activity. Conclusions Increasing physical activity seems to be an important feature of cardio-metabolic risk reduction among individuals at high risk for type diabetes participating in preventive interventions in routine clinical settings. - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

4 Page of Article summary Article focus There is evidence from randomized controlled trials that supervised exercise interventions improve cardio-metabolic risk factor levels. It is not known how knowledge from intensive interventions of randomized clinical trials can be applied in various real-life clinical settings with limited resources. In this paper we report the results of an analysis of physical activity changes and their association to cardio-metabolic risk factors among individual at high risk for type diabetes and participating in preventive lifestyle intervention in routine clinical settings of primary health care. Key messages Less than one fifth of the participants reported at one-year follow-up having clearly increased their physical activity during past year. Those who increased their activity improved clearly their cardio-metabolic risk profile including reductions of waist circumference and fasting LDL cholesterol and glucose levels. Increasing physical activity seems to be an important feature of cardio-metabolic risk reduction among individuals at high risk for type diabetes participating in preventive interventions in routine clinical settings. Strengths and limitations FIN-DD is the first national effort to implement the prevention of diabetes in a primary health care setting. Follow-up data on the changes in physical activity is available from a sub-group of participants. The limitations of this report include that physical activity changes are documented by a questionnaire and the association between physical activity and dietary changes has not been analyzed. - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

5 Page of Introduction Randomized clinical trials have shown that type diabetes can be prevented or at least postponed by lifestyle changes including changes in diet and physical activity. Prospective follow-up studies, one by clinic randomized controlled trial and one co-twin control study suggest that physical activity has an independent role in the prevention of type diabetes. Also, a post hoc analysis of the Finnish Diabetes Prevention Study participants suggested that increasing physical activity may substantially reduce the incidence of type diabetes in high-risk individuals. In addition, there is evidence that high leisure-time physical activity or high physical fitness is associated with less total and visceral fat and with a reduced prevalence of high cardio-metabolic risk factor levels, coronary heart disease as well as reduced mortality. There is accumulating evidence from hundreds of randomized controlled trials that physical exercise may help in improving health via different mechanisms including reduced body fat percent and improvement in many cardio-metabolic risk factor levels measured from blood. A major question is how knowledge from intensive interventions of randomized clinical trials can be applied in various real-life clinical settings with limited resources. Usually lifestyle interventions for patients at high risk of diabetes, delivered by a variety of healthcare providers in routine clinical settings, are feasible but appear to be of less clinical benefit than structured intensive trials. 0 In this paper we report the results of a post hoc analysis of physical activity changes and their association to cardio-metabolic risk factors in the high-risk cohort of the National Program for the Prevention of Type Diabetes, implemented through the FIN-DD program in five hospital districts in Finland covering a population of. million. - Methods Subjects The primary strategy of the FIN-DD was a high-risk strategy aiming at preventing diabetes and reducing cardiovascular risk factor levels among high-risk individuals in daily routines in health care centres and occupational health care outpatient clinics. The aim of the high-risk strategy was first to identify individuals at elevated risk of developing type diabetes and to support their life-style changes required to reduce their future risk. Altogether 00 primary health care centres or occupational health care clinics were involved in the programme. To identify high risk individuals for type diabetes, the modified Finnish Diabetes Risk Score (FINDRISC; scoring ) was used. FINDRISC test forms were available in primary health care and occupational health care centres, in public places and events and in the Internet. High-risk individuals were also identified by the history of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), cardiovascular events and gestational diabetes. After identification, consenting high-risk individuals for TD attended health check-ups conducted in the primary health care units as a part of the normal routine; therefore no informed consent was used, but individuals received written information on the FIN-DD. The Ministry of Social Affairs and Health in Finland gave the permission to collect the data from health care units for evaluation purposes to the National Public Health Institute. Of the high-risk cohort those individuals (age range - years) who were non-diabetic at baseline (no previous diabetes diagnosis or screen-detected diabetes) had one-year follow-up data and did not get diabetes during follow-up were included in the target group of this study (fig ). - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

6 Page of Those individuals who got diabetes were excluded from this study as they are usually a focus of additional intensified lifestyle interventions. Finally, those non-diabetic individuals who responded to the structured question on the stability or increase of physical activity at follow-up (N=,) formed the final study group of this report. Follow-up visits were defined as visits occurring after - months of baseline visits (mean months). Visits between January, 00 and August, 00 were considered as baseline visits and one-year follow-up visits were between January, 00 and June, 00. Physical activity questions Leisure time physical activity (LTPA) was assessed at baseline and at follow-up by a selfadministered questionnaire, which included structured questions about general physical activity level ( alternatives) (see Appendix question ), frequency of at least moderate intensity LTPA (see Appendix question ), and a question on changes in physical activity during the past year (see Appendix question ). We primarily classified our participants according to responses to the structured question Have you increased your physical activity/exercise training during the past year? (the number of responders at follow-up being,) which included five options (Appendix). Participants at follow-up choosing one of the three first options (No, and I do not intend to increase it; No, but I intend to increase it in the near future; I have tried to increase it) were classified as those who had No increase in physical activity (n=,0). Those who chose option four (I have clearly increased it) were classified as those who Increased physical activity (n=0). Others (n=) were the group who chose the fifth alternative (I have already previously been highly physically active). Measurements at baseline and follow-up Height was measured to the nearest cm. Weight was measured to the nearest 0. kg in light clothing. Waist circumference was measured to the nearest cm. Body mass index (BMI) was calculated as weight (kg) divided by height (m ). Blood pressure was measured twice from the right arm in sitting position to the nearest mmhg and the mean reading was recorded. The examination also included an oral glucose tolerance test (OGTT) with a glucose load of g and fasting and -hour plasma samples. The test started in the morning after overnight fasting and 0% of the tests used capillary and 0% venous plasma samples at baseline and and % respectively, at one-year follow-up. Venous blood samples were drawn for fasting lipid and lipoprotein determinations. Plasma lipids and lipoproteins were determined locally using enzymatic methods. Identical examinations were performed at baseline and at one-year visit. Glucose tolerance was classified according to the WHO criteria. Individuals reporting at baseline that they had diabetes were not included in the OGTT, and those with fasting venous or capillary plasma glucose level >.0 mmol/l or h venous plasma glucose >. mmol/l or hour capillary plasma glucose >. mmol/l were classified as having diabetes. Intervention visits Intervention visits were either individual counselling visits or group sessions, at which the intervention visit form was filled. Counselling based on the intervention experiences in the DPS Study and applying different stages of change in behaviour was recommended. The focus of the visits was weight, meal frequency, fat intake, quality of fat, use of salt, fibre intake, alcohol consumption, exercise, or smoking taking into account the preferences of the individuals. Group sessions varied from weight maintenance groups to exercise groups and lectures on diabetes and - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

7 Page of lifestyle changes. The frequency of intervention visits varied between health centres depending on local circumstances and resources and the total number of intervention visits was recorded. Statistical methods Summary statistics are presented as frequencies and percentages for categorical variables and as means (SD) for continuous variables. Pearson s Chi-Square test was used to compare categorical variables between analysis groups and Student s t-test was used for continuous variables. Appropriate % confidence intervals (CI) were calculated for parameter estimates. A paired Student s t test or Bhapkar s test was used to examine the changes in self-reported physical activity at the baseline and one-year follow-up visits. Mixed models of repeated analyses were used to analyse changes during follow-up in risk factor levels according to self-reported changes in physical activity during follow-up. As physical activity is known to reduce intra-abdominal fat we also analysed the results adjusted for sex and age at baseline as well as change in weight or waist circumference. We also adjusted the results for the number of intervention visits. Statistical analyses and data management were performed using SAS (v..) for Windows. All significance tests were -tailed and values of P < 0.0 were considered statistically significant. Results Baseline characteristics of the participants show that the mean BMI was over 0 among both men and women and the mean waist circumference was 0 cm for men and cm for women. Mean levels of serum cardio-metabolic risk factor levels were near the upper limit of the recommended range (for details see table ). Of the participants, responded at follow-up to the question on increase in physical activity (see Appendix question ) of whom 0 (. % of all responders and. % of those who did not report having been highly physically active already previously) reported having clearly increased their physical activity during the past year (table ), while,0 were unable to increase their physical activity. Those who reported that they had increased physical activity during follow-up have also increased their physical activity level from baseline to follow-up according to the questions on general physical activity level (p<0.00) and the frequency of at least moderate intensity LTPA (P<0.00), which was not seen among those reporting no increase in physical activity (table ). Those who increased their activity decreased their weight by. kg (% CI. to.; sex and age-adjusted P for group difference <0.00), BMI by. kg/m (.0 to.; P<0.00) and waist circumference by. cm (. to.; P<0.00) more than those who did not increase their activity (table ). Similarly, compared to those who did not increase their physical activity, greater reductions during follow-up were seen among those who increased their physical activity in blood pressure values, the group difference in the reduction of systolic blood pressure being.0 mmhg (0. to.; P=0.0) and that of diastolic blood pressure being. mmhg (0. to.; P=0.00). Similarly, those who increased their physical activity had higher reductions in total cholesterol (group difference in the reduction 0. mmol/l; 0.0 to 0.; P=0.00), LDL cholesterol (0. mmol/l; 0.0 to 0.; P=0.00), LDL/HDL ratio (0.; 0.0 to 0.; P<0.00) as well as fasting glucose (0.0 mmol/l; 0.0 to 0.; P=0.00) and -h glucose levels (0. mmol/l; 0. to 0.; - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

8 Page of P=0.0) at OGTT than those who did not increase their physical activity (Table ). HDL cholesterol increased more (by 0.0 mmol/l; 0.0 to 0.0; P=0.0) among those who increased their physical activity compared to those who did not do so. As these results were similar for men and women (P for gender*group interaction >0. for all variables) the results are not shown separately. After further adjustment for sex and age at baseline as well as change in waist circumference, those who increased their physical activity during follow-up decreased their weight (P=<0.00, adjusted for sex, age and change in waist circumference), diastolic blood pressure (P=0.0), total cholesterol (P=0.00) and LDL cholesterol (P=0.00) more than those who did not increase their physical activity. The total number of intervention visits was higher among those who increased their physical activity than those who did not increase it (mean. vs.., P<0.000 by Kruskall-Wallis test). After adjustment for sex and age at baseline as well as the number of intervention visits the group differences in the changes of risk factors persisted either statistically significant or borderline significant (P<0., see Table ). Discussion Principal finding Our study shows that increases in leisure time physical activity among individuals at high risk for type diabetes and participating in lifestyle interventions in routine clinical settings of the primary health care system were associated with reductions in weight, waist, blood pressure, serum lipid risk factor levels and plasma glucose levels. This finding is in line with the findings of meta-analyses from randomized controlled trials on patients with chronic diseases. However, less than one fifth of those reporting not having been highly physically active already previously reported having increased their physical activity and thus the positive responses can be generalized only to the subgroup which really increased their physical activity during the life intervention programme. Strengths and weaknesses FIN-DD is the first national effort to implement the prevention of diabetes in a primary health care setting. Our study includes limitations related to the analysis of effects of real-life interventions concerning documentation time-points and standardization of different measurements. However, it is likely that these shortcomings do not cause biases which having a major effect on our results. Standardization of laboratory analyses in particular is a known challenge in large scale multi-centre intervention studies. During our study period there were some changes in the methodology of measuring fasting and -h glucose levels. We recorded the method used and did a sub-group analysis among those participants whose glucose levels had been measured with an identical method at baseline and follow-up. These results are not shown separately as the finding in the subgroup was similar to that presented in our results. Different individuals may report their physical activity levels different ways. However, we used as the main indicator the self-reported change in physical activity, which we consider very reliable despite the lack of objective measurements. All objective measurements of physical activity also have their own shortcomings. It is noteworthy that those who increased their physical activity had more intervention visits than those who did not increase, which may, in addition to leading to increased physical activity, be associated with increased motivation and also with more changes in diet. The main results remained either - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

9 Page of statistically significant or borderline significant after adjustment for the number of intervention visits. The association between physical activity and dietary changes is a topic for future analyses. Our study did not include fitness tests, which is a limitation, as a possible increase in aerobic fitness would have provided additional proof for the benefits of physical activity. Increase in physical fitness is one of the most direct and consistent effects of increasing physical activity and is important for future functioning and health. Comparisons to other studies Randomized controlled trials with structured, intensive lifestyle interventions promoting healthy eating and moderate physical activity and focusing on the prevention of diabetes in people at high risk have shown that clinically significant weight loss of. kg or more can be achieved. In our sub-group increasing their physical activity level, the mean reduction was. kg. It has been shown that physical activity maintains or may increase muscle mass but exercise interventions reduce visceral fat. In our study, too, waist circumference was reduced as an indirect indicator of intra-abdominal fat reduction. Further, as maintaining weight loss over time is a challenge 0 regular physical activity is an important way of maintaining both a healthy body weight and healthy body composition. The mean decreases in systolic (-. mmhg) and diastolic (-. mmhg) blood pressure levels among those who increased their physical activity are in line with those observed in randomized controlled trials. Our results are in line with the existing literature that exercise training is usually beneficial for the lipid risk factor levels, although there has been some variation in the results of different randomized controlled trials. - It is noteworthy that reduction in LDL levels was statistically significant also after adjustment for either change in body weight or change in waist circumference. Increased fat oxidation due to physical activity may also reduce LDL levels via other mechanisms than reduction of body fat. Reduced LDL levels are obviously associated with a reduced risk for cardio-vascular events, although longer follow-ups are needed to see whether this is true in our participants. Also, we found a small increase in HDL levels, which usually increases fairly consistently in response to long-term vigorous physical activity. Reduced LDL levels and increased HDL levels contributed to the reduced LDL/HDL ratio (table ). Predictably, fasting glucose levels and -hour glucose levels in the OGTT test also decreased in the sub-group who increased physical activity, which is a proof of increased insulin sensitivity usually seen in physically active individuals. The known independent effect of physical activity on insulin sensitivity was seen in particular in the -h glucose levels (table ). Meaning of the study and implications Increasing physical activity seems to be an important component in cardio-metabolic risk reduction among individuals at high risk for type diabetes participating in preventive interventions in routine clinical settings. This finding supports the idea that physical activity counselling should be one part of the preventive interventions of individuals at elevated risk for type diabetes. The finding concurs with the abundant observational evidence on the importance of increasing physical activity on health. Unanswered questions and future research The purpose of this analysis was not to investigate the factors which predict increases in leisure time physical activity. As only a small proportion of our target group increased their physical - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

10 Page of activity there is a need to investigate how to identify those individuals able to increase their physical activity levels and also to study the most effective ways of implementing physical activity recommendations in real life, possibly taking into account individuals self-efficacy, psychological flexibility and other factors. Conclusions Increasing physical activity seems to be an important feature of cardio-metabolic risk reduction among individuals at high risk for type diabetes participating in preventive interventions in routine clinical settings. - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

11 Page 0 of Footnotes Contributors: UMK designed this post hoc sub-study, drafted the manuscript, and is the guarantor. JJ analyzed the data. All authors contributed to the study design, collection and interpretation of data, and writing of the manuscript. All authors declare that they accept full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. Copyright: The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its licensees, to permit this article (if accepted) to be published in BMJ editions and any other BMJPG products and to exploit all subsidiary rights, as set out in the licence ( Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any company for the submitted work; no financial relationships with any organizations other than the hospital districts that might have an interest in the submitted work in the previous years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: Ministry of Social Affairs and Health in Finland gave the permission to collect the data from health care units for evaluation purposes to National Public Health Institute. Funding: FIN-DD was supported by hospital districts of Pirkanmaa, Southern Ostrobothnia, Northern Ostrobothnia, Central Finland and Northern Savo, the Finnish National Public Health Institute, the Finnish Diabetes Association, the Ministry of Social Affairs and Health in Finland, Finland s Slottery Machine Association, the Academy of Finland (grant number ), and Commission of the European Communities, Directorate CPublic Health (grant agreement number 000) in cooperation with the FIN-DD Study Group, and the Steering Committee: Huttunen J, Kesäniemi A, Kiuru S, Niskanen L, Oksa H, Pihlajamäki J, Puolakka J, Puska P, Saaristo T, Vanhala M, and Uusitupa M. Role of study sponsors: The funding organizations (except for the hospital districts) had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of data; the writing of the manuscript for publication. Data sharing: No additional data available

12 Page of References. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, et al. Prevention of Type diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 00;:-0.. Knowler WC, Barret-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type diabetes with lifestyle intervention or metformin. N Engl J Med 00;:-0.. Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Krolewski AS, et al. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet ;:-.. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS,Jr. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med ;:-.. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care ;0:-.. Waller K, Kaprio J, Lehtovirta M, Silventoinen K, Koskenvuo M, Kujala UM. Leisure-time physical activity and type diabetes during a -year follow-up in twins. Diabetologia 00;:-.. Laaksonen DE, Lindström J, Lakka TA, Eriksson JG, Niskanen L, Wikström K, et al. Physical activity in the prevention of type diabetes. The Finnish Diabetes Prevention Study. Diabetes 00;:-.. Physical Activity Guidelines Advisory Committee. Physica Activity Guidelines Advisory Committee Report, 00. Washington, DC: U.S. Department of Health and Human Services, 00.. Kujala UM. Evidence of the effects of exercise therapy in the treatment of chronic disease. Br J Sports Med 00;: Cardona-Morrell M, Rychetnik L, Morrell SL, Espinel PT, Bauman A. Reduction of diabetes risk in routine clinical practice: are physical activity and nutrition interventions feasible and are the outcomes from reference trials replicable? A systematic review and meta-analysis. BMC Public Health 00;0:, /0/. Finnish Diabetes Association. Implementation of type diabetes prevention plan. Project plan 00-00, FIN-DD project, Tampere, 00. ( Diabetes_Prevention._Proje ct_plan_00-00.pdf).. Saaristo T, Peltonen M, Keinänen-Kiukaanniemi S, Vanhala M, Saltevo J, Niskanen L, et al. National Type diabetes prevention programme in Finland: FIN-DD. Int J Circumpolar Health 00;:0-.. Saaristo T, Moilanen L, Korpi-Hyövälti E, Vanhala M, Saltevo J, Niskanen L. et al. Lifestyle intervention for prevention of type diabetes in primary health care: one-year follow-up of the Finnish national diabetes prevention program (FIN-DD). Diabetes Care 00;:-.. Lindström J, Tuomilehto J. The Diabetes Risk Score. A practical tool to predict type diabetes risk. Diabetes Care 00; :-.. Saaristo T, Moilanen L, Jokelainen J, Korpi-Hyövälti E, Vanhala M, Saltevo J, et al. Cardiometabolic profile of people screened for high risk of type diabetes in a national prevention programme (FIN-DD). Prim Care Diabetes 00; :-. -

13 Page of WHO. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO Consultation. Part : diagnosis and classification of diabetes mellitus. World Health Organization;, Report No... Lindström J, Louheranta A, Mannelin M, Rastas M, Salminen V, Eriksson J, et al. The Finnish Diabetes Prevention Study (DPS). Lifestyle intervention and -year results on diet and physical activity. Diabetes Care 00;:0-.. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V, et al. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-). Diabetologia 00;:-.. Ohkawara K, Tanaka S, Miyachi M, Ishikawa-Takata K, Tabata I. A dose-response relation between aerobic exercise and visceral fat reduction: systematic review of clinical trials. Int J Obesity 00;:-. 0. Svetkey LP, Stevens VJ, Brantley PJ, Appel LJ, Hollis JF, Loria CM, et al. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA 00;:-.. Cornelissen VA, Fagard RH. Effect of endurance training on blood pressure, blood pressureregulating mechanisms, and cardiovascular risk factors. J Hypertens 00;:-.. Leon AS, Sanchez OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Med Sci Sports Exerc 00;:0-.. Kelley GA, Kelley KS, Z Vu Tran. Aerobic exercise, lipids and lipoproteins in overweight and obese adults: a meta-analysis of randomized controlled trials. Int J Obesity 00;:-.. Kelley GA, Kelley KS. Effects of aerobic exercise on lipids and lipoproteins in adults with type diabetes: A meta-analysis of randomized-controlled trials. Public Health 00;:-.. Vartiainen E, Puska P, Pekkanen J, Tuomilehto J, Jousilahti P. Changes in risk factors explain changes in mortality from ischaemic heart disease in Finland. BMJ ;0:-.. Vartiainen E, Sarti C, Tuomilehto J, Kuulasmaa K. Do changes in cardiovascular risk factors explain changes in mortality from stroke in Finland? BMJ ;0:0-.. Byberg L, Melhus H, Gedeborg R, Sundström J, Ahlbom A, Zethelius B, Berglund LG, Wolk A, Michaëlsson K. Total mortality after changes in leisure time physical activity in 0 year old men: year follow-up of population based cohort. BMJ 00;:b doi:0./bmj.b. Weiler R, Stamatakis E, Blair S. Should health policy focus on physical activity rather than obesity? Yes. BMJ 00;0:c0 doi:0./bmj.c0 - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

14 Page of Tables Table. Baseline characteristics of the participants (N=). Men Women (N=) (N=) Variable N Mean (SD) N Mean (SD) Age, years. (.). (0.) Weight, kg. (.). (.) BMI, kg/m 0. (.). (.) Waist, cm 0. (.).0 (.0) Systolic BP, mmhg 0. (.).0 (.) Diastolic BP, mmhg. (.). (.) Total Cholesterol (mmol/l). (.0) 0. (.0) HDL Cholesterol (mmol/l) 0. (0.) 0. (0.) LDL Cholesterol (mmol/l).0 (0.) 0. (0.) LDL/HDL ratio. (0.) 00. (0.) Triglycerides (mmol/l) 0. (.) 0. (0.) Fasting glucose (mmol/l ). (0.). (0.) -h glucose (mmol/l).0 (.). (.) -

15 Page of Table. Self-reported general physical activity level* and frequency of at least moderate intensity leisure time physical activity at baseline and follow-up according to self-reported changes in physical activity at follow-up. Self-reported changes in physical activity No increase in physical activity Increase in physical activity Baseline Follow-up P Value Baseline Follow-up P Value General physical activity level*, N (%) (.%) (.0%) 0. (.0%) (.%) <0.00 (.%) (.%) 0 (0.%) (.%) (.%) 0 (.%) (.%) 0 (.%) 0 (0.%) 0 (0.%) Frequency of at least moderate. (.). (.) 0.0. (.). (.) <0.00 intensity LTPA, mean (SD) *Question in Appendix. Question in Appendix. Question in Appendix. Differences in frequency distributions (cross-tab marginal homogeneity) were checked for significance using Bhapkar's test for multiple categories By paired t-test -

16 Page of Table. Changes from baseline to follow-up in cardio-metabolic risk factors according to selfreported changes in physical activity during follow-up. No increase in physical activity Increase in physical activity Variable N Mean (SD) N Mean (SD) P P P P Value* Value Value Value Weight, kg 0-0. (.0) 0 -. (.0) <.00 <.00 <.00 BMI, kg/m -0. (.) 0 -. (.) < <.00 <.00 Waist, cm -0. (.) (.) <.00 <.00 <.00 Systolic BP, mmhg -. (.) 0 -. (.) Diastolic BP, mmhg -. (.) 0 -. (.0) Total Cholesterol (mmol/l) -0. (0.) -0. (0.) HDL Cholesterol (mmol/l) 0.0 (0.) 0.0 (0.0) LDL Cholesterol (mmol/l) -0. (0.) -0. (0.) LDL/HDL ratio -0. (0.) -0. (0.) <0.00 < Triglycerides (mmol/l) -0.0 (0.0) -0. (0.) Fasting glucose (mmol/l) (0.) 0-0. (0.) h glucose (mmol/l) -0.0 (.) 0-0. (.) *P Values for difference between group I and II adjusted for sex and age at baseline (ANOVA) P Values adjusted for sex, age at baseline and change in weight during follow-up (ANOVA). P Values adjusted for sex, age at baseline and change in waist circumference during follow-up (ANOVA). P Values adjusted for sex and age at baseline and number of intervention visits (ANOVA) -

17 Page of High-risk cohort of the FIN-DD; N=0, (, men,,0 women) Baseline visit including OGTT; N=, (,0 men,,0 women) Follow-up visit - months; N=,0 (, men,, women) of whom non-diabetic at the baseline; N=, ( men,, women) OGTT at follow-up N=, ( men,, women) of whom had screen-detected TD at follow-up; N= ( men, women) Non-diabetic at follow-up; N = (0 men,, women) of whom had missing data for physical activity question; N= (0 men, 0 women) Final study group; N= ( men, women) Fig. Flow chart of the study participants. OGTT= oral glucose tolerance test. - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

18 Page of Appendix: Question on leisure physical activity. How much do you exercise and exert yourself physically in your leisure time? If it varies greatly according to the season mark the alternative which best describes the average situation. In my leisure time I read, watch TV, and do household tasks which does not make me move much and which does not physically tax me. In my leisure time I walk, cycle or exercise otherwise at least hours per week. This includes walking, fishing and hunting, light gardening etc. but excludes travel to work. In my leisure time I exercise to maintain my physical condition, e.g. running, jogging, skiing, gymnastics, swimming, playing ball games or I do heavy gardening or the like for at least hours per week. In my leisure time I regularly engage in competitive sports such as running, orienteering, skiing, swimming, playing ball games or other heavy sports several times a week.. How many times per week do you exercise in your leisure time so that you are at least mildly out of breath and sweaty? (if not at all, mark 0.) times per week. Have you increased your physical activity/exercise training during the past year? No, and I do not intend to increase No, but I intend to increase in near future I have tried to increase I have clearly increased I have already previously been highly physically active - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

19 Page of x0mm (00 x 00 DPI) - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

20 Page of STROBE 00 (v) checklist of items to be included in reports of observational studies in epidemiology* Checklist for cohort, case-control, and cross-sectional studies (combined) Section/Topic Item # Recommendation Reported on page # Title and abstract (a) Indicate the study s design with a commonly used term in the title or the abstract, (b) Provide in the abstract an informative and balanced summary of what was done and what was found, Introduction Background/rationale Explain the scientific background and rationale for the investigation being reported Objectives State specific objectives, including any pre-specified hypotheses Methods Study design Present key elements of study design early in the paper - Setting Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection - Participants (a) Cohort study Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up -, Fig. Case-control study Give the eligibility criteria, and the sources and methods of case ascertainment and control selection. Give the rationale for the choice of cases and controls Cross-sectional study Give the eligibility criteria, and the sources and methods of selection of participants (b) Cohort study For matched studies, give matching criteria and number of exposed and unexposed Case-control study For matched studies, give matching criteria and the number of controls per case Variables Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable Data sources/ measurement * For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe - comparability of assessment methods if there is more than one group Bias Describe any efforts to address potential sources of bias -, - Study size 0 Explain how the study size was arrived at -, Fig. Quantitative variables Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen - and why Statistical methods (a) Describe all statistical methods, including those used to control for confounding (b) Describe any methods used to examine subgroups and interactions (c) Explain how missing data were addressed - (d) Cohort study If applicable, explain how loss to follow-up was addressed Case-control study If applicable, explain how matching of cases and controls was addressed -, Fig

21 Page 0 of Results Participants Descriptive data Cross-sectional study If applicable, describe analytical methods taking account of sampling strategy (e) Describe any sensitivity analyses - * (a) Report numbers of individuals at each stage of study eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed -, Fig. (b) Give reasons for non-participation at each stage Fig. (c) Consider use of a flow diagram * (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders (b) Indicate number of participants with missing data for each variable of interest (c) Cohort study Summarise follow-up time (eg, average and total amount) Table. Fig., Tables Outcome data * Cohort study Report numbers of outcome events or summary measures over time -, Tables Case-control study Report numbers in each exposure category, or summary measures of exposure - Cross-sectional study Report numbers of outcome events or summary measures - Main results (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, % confidence interval). Make clear which confounders were adjusted for and why they were included -, Table. (b) Report category boundaries when continuous variables were categorized - (c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period - Other analyses Report other analyses done eg analyses of subgroups and interactions, and sensitivity analyses - Discussion Key results Summarise key results with reference to study objectives Limitations Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias - Interpretation 0 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence - Generalisability Discuss the generalisability (external validity) of the study results Other information Funding Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based *Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies. Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at Annals of Internal Medicine at and Epidemiology at Information on the STROBE Initiative is available at

22 Increase in physical activity and cardio-metabolic risk profile change during lifestyle intervention in primary healthcare: one-year follow-up study among individuals at high risk for type diabetes Journal: Manuscript ID: bmjopen r Article Type: Research Date Submitted by the Author: -Oct-0 Complete List of Authors: Kujala, Urho; University of Jyväskylä, Department of Health Sciences Jokelainen, Jari Oksa, Heikki Saaristo, Timo Rautio, Nina Moilanen, Leena Korpi-Hyövälti, Eeva Saltevo, Juha Vanhala, Mauno Niskanen, Leo Peltonen, Markku Tuomilehto, Jaakko Uusitupa, Matti Keinänen-Kiukaanniemi, Sirkka <b>primary Subject Heading</b>: Secondary Subject Heading: Diabetes and endocrinology General practice & Family practice, Health services research, Public health, Sports & exercise medicine Keywords: Diabetes, lifestyle intervention, Physical activity : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.

23 Page of Increase in physical activity and cardio-metabolic risk profile change during lifestyle intervention in primary healthcare: one-year follow-up study among individuals at high risk for type diabetes Short title: Physical activity and cardio-metabolic risk profile Urho M. Kujala, professor, Jari Jokelainen, statistician,, Heikki Oksa, chief phycician, Timo Saaristo, project manager,, Nina Rautio, researcher, Leena Moilanen, specialist in internal medicine, Eeva Korpi-Hyövälti, specialist in internal medicine, Juha Saltevo, specialist in internal medicine, Mauno Vanhala, professor, Leo Niskanen, professor,,0 Markku Peltonen, associate professor, Jaakko Tuomilehto, professor, Matti Uusitupa, professor,, Sirkka Keinänen- Kiukaanniemi, professor,, Department of Health Sciences, FI-00 University of Jyväskylä, Jyväskylä, Finland Faculty of Medicine, Institute of Health Sciences, FI-00 University of Oulu, Finland Unit of General Practice, Oulu University Hospital, Finland Pirkanmaa Hospital District, FI- Tampere, Tampere, Finland Finnish Diabetes Association, FI-0 Tampere, Tampere, Finland Department of Medicine, Kuopio University Hospital, Northern Savo Hospital District, 0 Kuopio, Finland Department of Internal Medicine, Seinäjoki Central Hospital, FI-00 Seinäjoki, Finland Department of Internal Medicine, Central Finland Hospital District, FI-00 Jyväskylä, Jyväskylä, Finland Unit of Family Practice, Central Finland Hospital District, Jyväskylä, Kuopio University Hospital, and University of Eastern Finland, 0 Kuopio, Finland 0 Faculty of Health Sciences, University of Eastern Finland, 0 Kuopio, Finland National Institute for Health and Welfare, FI-00 Helsinki, Finland Hjelt Institute, Department of Public Health, University of Helsinki, 000 Helsinki, Finland Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio campus, 0 Kuopio, Finland Research Unit, Kuopio University Hospital, Finland Oulu University Hospital District Unit of General Practice, Finland Correspondence to: Urho M. Kujala, Department of Health Sciences, Sports and Health Laboratory, Rautpohjankatu, University of Jyväskylä, P.O. Box (LL), FI-00 University of Jyväskylä, Finland. Fax: , Telephone: +-0-0, urho.m.kujala@jyu.fi - : first published as 0./bmjopen on December 0. Downloaded from on April 0 by guest. Protected by copyright.