The invention relates to a method and device for determining physical activity thresholds exceeding of which reduce risks for diabetes, cardiovascular diseases, inflammations, cognitive impairments, cancers and mortality in subjects who have sedentary lifestyle. The use of motion sensors and transduction units to measure physical activity volume and intensity have been presented in US2008/0312560A1 and in US 2010/0137107 A1 .

The invention described here belongs to the medical discipline and includes the determination of physical activity thresholds that can be used in sedentary subjects for preventing risks for diabetes, cardiovascular diseases, inflammations, cognitive impairments, cancer and premature mortality by reducing glycoprotein acetylation (Glyc A) and very low density lipoprotein particles (VLDLs). The earlier invention related to physical activity reducing blood cholesterol (US 2010/0137107 A1 ) purposed for healthy subjects (Vainiopaa et al. Med Sci Sports Exerc 2007) is not sui- table to subjects who have sedentary lifestyle as they are not capable to perform prescribed physical activity previously shown to reduce blood cholesterol in healthy subjects (Herzig et al. Int J Obesity 2014). It should also be noted that subjects having sedentary ifestyle are unable to meet the current WHO guidelines for maintaining health and reducing health risks (Troiano et al. 2008).

The background of the invention

Sedentary lifestyle is increasingly common in industrialized countries in which energy rich diets are widely used and energy expenditure remains low. According to the WHO statistics over 1 ,400,000,000 of the world population are overweight or obese. Overweight and low physical activity result in an increase in the prevalence of several metabolic diseases mainly diabetes, cardiovascular diseases, inflammations, dementia, cancers, dementia and premature mortality. It is currently estimated that 500,000,000 of the population suffer from type 2 diabetes and the number will be doubled by the year 2030. In addition atherosclerosis, calcification of blood vessels, due to sedentary lifestyle exposes to deaths for cardiovascular diseases being the most frequent death causes in industrialized countries. The dead roll is presently 15,000,000 annually and is growing every year. Dementia relates also to sedentary lifestyle and according to WHO statistics we have today 40,000,000 people with dementia worldwide and the number is estimated to increase to 131 ,000,000 by the year 2050. Low levels of physical activity is also a dangerous risk factor disability- adjusted life years. According to the present WHO statistics it is annually responsi- ble for 1 ,000,000 death cases and loss of 8,000,000 disability-adjusted life years.

The current physical activity recommendations of WHO, American Diabetes Association and American Heart Association state that healthy adults should perform at least 150 min moderate intensity physical activity every week such as walking at the speed of 5 km/h. The two thresholds time and walking speeds given in the guidelines should imply walking daily 2 km or 2000-3000 steps (depending on step lengths) within 21 min. These recommendations have been developed by reviewing subjects about their physical activity levels and demonstrated that about 50% of the adult population met the guidelines. Later physical activity levels have been studied ob- jectively by accelerometers and the results showed that only less than 5 % of the adult population was able to meet the above-mentioned official guidelines of physical activity. Therefore all the previous studies about physical activity using personal reviews or questionnaires overestimate health status and do not reveal the large occurrence of sedentary lifestyle in the present populations.

Novel biomarkers have been identified in body fluids by nuclear magnetic techniques and measured in healthy and diseased populations. Elevated concentrations of glycoprotein acetylation (GlycA) and low density lipoprotein particles (VLDLs) have been observed to associate with chronic diseases and mortality. High blood GlycA was found to relate to cardiac events and to increase mortality risk by 300 % in healthy adult men (Engstrom et al. 2002) and to lead to premature death in patients suffering from lung cancer (Bruno et al 2013). In healthy elderly men and women high GlycA associated with early death (Carriere et al. 2008). High concentrations of GlycA in blood and urinary predict diabetes and mortality (Svendstrup et al. 2013). In a large population GlycA was measured and health status was followed for 5 years (Fischer et al. 2014). It was observed that high GlycA levels associated with cardiovascular diseases, cancer and mortality. High blood GlycA has also been found to be associated with bacterial sepsis, pneumonia and influenza (Rithchie et al. 2016). Many inflammatory markers were measured from young subjects and af- ter 13 years high GlycA levels were found to be associated with global cognitive impairment (Cohen Manheim et al. 2015). VLDL molecules carry blood lipids and their high concentrations have been found to relate to diabetes, cardiovascular disease and early deaths (Festa ey al. Garvey et al. 2003, Goff et al. 2005, Mora et al. 2010). High VLDL markers increase the diabetes risk by 400 % (Mora tm. 2010) and with GlycA mortality risk twofold Fischer et al. 2014).

Effects of exercise interventions on biomarkers have been observed to reduce concentrations of circulating VLDL molecules in healthy men and women (Kraus et al. 2002, Brown et al .2009) and in women suffering from polycystic ovarian disease (Halverstad et al. 2007). In corollary to this persistently physically active individuals had lower levels of VLDL molecules and GlycA than sedentary individuals (Kujala et al. 2013). Since high levels of GlycA and VLDLs present significant risks for diabetes, cardiovascular diseases, inflammation, dementia and cancer and predict early deaths and since regular exercises and physical activities reduce circulating levels of GlycA and VLDLs it is possible to tailor interventions for reducing the levels of these biomarkers.

The results of scientific studies demonstrate that increased physical activity is effective in preventing risk factors of diabetes, cardiovascular diseases, inflammations, dementia, cancers and early death in healthy and sedentary subjects. However, in none of these above-cited or other previous studies the exact amounts and intensities of physical activity preventing diabetes, cardiovascular diseases, inflammations, cancer or premature mortality have been described. Purpose of the intervention

High occurrence of chronic diseases and early deaths in the sedentary populations are major health problems and associate with high levels of GlycA and VLDLs. Regular physical activities are known to reduce high GlycA and VLDLs, but presently no physical activity guidelines are available to reduce these risk factors. It is our purpose to offer exact information about amounts and intensities of physical activity reducing blood GlyA and VLDLs and risks of diabetes, cardiovascular diseases inflammations, dementia, cancers and premature deaths. In order to achieve our purpose we registered physical activities and measured blood biomarkers in sedentary and active subjects and determined amounts and intensities of physical activities reducing GlycA and VLDLs concentrations. Our invention determines for the first time in sedentary subjects the thresholds of the amount and intensity of the physical activity reducing blood GlycA and VLDLs and risks of diabetes, cardiovascular diseases, inflannnnations, cancers and premature deaths.

The methods of the invention

Sixty-eight sedentary men and women aged 30-70 years participated in supervised exercise carrying accelerometers during wake-full time on their waist for 3 months. Walking induced steps and accelerations were continuously registered reaching totally 50,000,000 data points. Exercises increased significantly number of steps or impacts in the acceleration classes 1 .3 - 1 .7 g (1 g is standing).

Blood samples were taken at the beginning and end of the trial to measure blood GlycA and VLDLs by an NMR method. The VLDLs measured in this invention are VLDL triglycerides (VLDL TG), medium size VLDL particles (M VLDL P), extra large VLDL particles (XL VLDL P), extremely large VLDL triglycerides (XXL VLDL TG, see figure 1 ). The steps in the acceleration class 1 .3 - 1 .7 were divided by their magnitudes to quartiles. The changes during 3 months in GlycA and VLDLs concentrations within each quartile were analyzed and were in first quartile (below 2890 daily steps) significantly higher than in the other quartiles. Therefore 2890 daily steps at 1 .3 - 1 .7 g are the thresholds for physical activity, the exceeding of which significantly reduces blood GlycA and VLDLs. This finding relates significantly to beneficial health effects of reduced levels of GlycA and VLDLs (Herzig et al. 2017 accepted for publication). Corresponding results in subjects with sedentary lifestyle have not been able to obtain by using previous methods.

The invention described herein essentially differs from the previously known methods by which exercises have been used for prevention of risk factors of diabetes, cardiovascular diseases, inflammations, cancers, dementia and premature deaths. Physicians have generally been aware about the beneficial effects of regular exer- cise, but the volume, intensity and duration of the exercises have remained unknown. It was novel and unexpected in our invention that in sedentary subjects physical activity of very low amount and intensity (> 2890 daily steps and accelerations 1 .3 - 1 .7 g) reduced concentrations of the major risk factors of diabetes, cardiovascular diseases inflammations, cancers and early deaths. Therefore, the contents of our invention is different from those in other publications, patents and recommendations, since they do not provide information about the exact thresholds of the amounts and intensities of physical activity reducing elevated concentrations of GlycA and VLDLs known to be associated with chronic diseases and early death.

The threshold levels for daily steps and accelerations were collected from 50,000,000 data points and did not show statistically different changes during the 3 months ^' trial. Hence, it is not possible that new threshold levels will be needed. E.g. the WHO guidelines for physical activity were published in 2008 and the present guidelines are still similar as 19 years before. For a skilled person it is not evident to load new threshold values. High amounts of data points will make the random chance extremely low. Also the threshold levels depend on patients ^' physical condition, the biomarker studied and the disease to be prevented. E.g. for preventing osteoporosis appr. 50 daily steps at > 4.1 g are needed but for cholesterol reduction appr. 2000 daily steps at > 2.1 g are needed in healthy subjects (Vainionpaa et al. 2006, Osteoporosis Int and 2007 Med Sci Sports Exerc). In sedentary subjects appr. 6500 daily steps at 1.3 - 1 .7 g are needed to reduce cholesterol and visceral fat (Herzig et al. In J Obesity) and now 2890 daily steps at 1.3 - 1 .7 g to reduce GlycA and VLDLs (Herzig et al. 2017 accepted for publication). It is well known that regular physical activities protects from many diseases and premature deaths but no exact biomarker threshold values for beneficial physical activities than ours presently exist.