Scenario I: a 10%-unit increase in the Finnish population using at least one WGF serving a day, Scenario II: one or more additional whole grain servings a day among those who already use at least one whole grain serving a day, and Scenario III: the combination of Scenarios I and II. In all scenarios, the current situation was applied as a comparator. 95%CIs. Changing the discount rate from 0% to 5%, the savings varied from 629€ to 1140€ million, and the gained QALYs variated from 9551 to 19,821. Other studied model parameters had a modest or small effect on the potential population level savings in all the

**Figure 2.** Tornado diagrams showing the results of one-way sensitivity analyses in terms of (**a**) cost savings and (**b**) additional QALYs in Scenario I (i.e., 10%-unit increase in the proportion of Finnish adults with the daily use of whole grain foods) with the 20-year timeframe as an example. **Figure 2.** Tornado diagrams showing the results of one-way sensitivity analyses in terms of (**a**) cost savings and (**b**) additional QALYs in Scenario I (i.e., 10%-unit increase in the proportion of Finnish adults with the daily use of whole grain foods) with the 20-year timeframe as an example.

presented in Supplementary Figure S2A,B. As expected, the use of a longer time horizon increased the uncertainty related to the expected cost savings and QALY gains, leading to the wider joint distribution of cost savings and gained QALYs. However, regardless of this uncertainty, all plotted PSA iterations on an X–Y plane (Figure 3) constituted by cost savings and QALY gains remained in the southeast quadrant of the plane, where an intervention is expected to have greater effectiveness at lower costs. In addition, to take this parameter uncertainty into account, the probability of cost savings with and without T2D-related productivity loss costs conditional on the available data was estimated. Figure 4 illustrates the probabilities of cost savings in the modeled scenarios when applying the 20-year time horizon as an example. For example, as shown in Figure 4, there is around 97% probability at least for 1000 M€ savings in a case of Scenario III (when also considering the changes in productivity losses) conditional on the parameter uncertainty of the applied model. The results of other applied time horizons are presented in Sup-

*3.3. Results of Probabilistic Sensitivity Analysis* 

plementary Figure S3A,B.

#### *3.3. Results of Probabilistic Sensitivity Analysis*

The results of the PSA are shown in Figure 3 in terms of population-level cost savings and QALYs gained using Scenario I as an example. The results of other scenarios are presented in Supplementary Figure S2A,B. As expected, the use of a longer time horizon increased the uncertainty related to the expected cost savings and QALY gains, leading to the wider joint distribution of cost savings and gained QALYs. However, regardless of this uncertainty, all plotted PSA iterations on an X–Y plane (Figure 3) constituted by cost savings and QALY gains remained in the southeast quadrant of the plane, where an intervention is expected to have greater effectiveness at lower costs. In addition, to take this parameter uncertainty into account, the probability of cost savings with and without T2D-related productivity loss costs conditional on the available data was estimated. Figure 4 illustrates the probabilities of cost savings in the modeled scenarios when applying the 20-year time horizon as an example. For example, as shown in Figure 4, there is around 97% probability at least for 1000 M€ savings in a case of Scenario III (when also considering the changes in productivity losses) conditional on the parameter uncertainty of the applied model. The results of other applied time horizons are presented in Supplementary Figure S3A,B. *Nutrients* **2021**, *13*, x FOR PEER REVIEW 10 of 15

**Figure 3.** Results of the probabilistic sensitivity analysis showing the impact of applied time horizon on the distribution of expected population-level cost savings and gained QALYs on the X-Y-plane using Scenario I (current situation vs. a 10%-unit increase in the proportion of adult population using at least one whole grain servings a day) as an example. Blue, red, and green colors stand for 10-year, 20-year, and 30-year time horizons, respectively. **Figure 3.** Results of the probabilistic sensitivity analysis showing the impact of applied time horizon on the distribution of expected population-level cost savings and gained QALYs on the X-Y-plane using Scenario I (current situation vs. a 10%-unit increase in the proportion of adult population using at least one whole grain servings a day) as an example. Blue, red, and green colors stand for 10-year, 20-year, and 30-year time horizons, respectively.

**4. Discussion** 

**Figure 4.** Probability of cumulative savings (with and without T2D-related productivity losses) in the modeled scenarios when applying the 20-year time horizon (2017 as a baseline year). Scenario I: a 10%-unit increase in the Finnish population using at least one whole grain food serving a day, Scenario II: one or more additional whole grain servings a day among those who already use at

scenarios, the current situation was applied as a comparator. PL = productivity losses due to T2D.

The results of our study quantified the health economic significance of increased whole grain food consumption from the perspective of T2D prevention among the Finnish adult population. The inclusion of costs associated with T2D-related work absences and permanent work disabilities increased the savings potential, significantly highlighting the need for considering intervention consequences in a societal perspective in public health policy making. Our findings agree with the results of previous studies from Australia and Canada, showing a significant savings potential in the prevention of T2D among adult populations by increasing whole grain consumption [20–22]. However, our study demonstrated not only the significant savings potential but also significant gains in the number of QALYs (i.e., years lived in full health). This positive change in the number of years lived in full health is particularly important from the individual perspective,

**Figure 3.** Results of the probabilistic sensitivity analysis showing the impact of applied time horizon on the distribution of expected population-level cost savings and gained QALYs on the

population using at least one whole grain servings a day) as an example. Blue, red, and green col-

ors stand for 10-year, 20-year, and 30-year time horizons, respectively.

**Figure 4.** Probability of cumulative savings (with and without T2D-related productivity losses) in the modeled scenarios when applying the 20-year time horizon (2017 as a baseline year). Scenario I: a 10%-unit increase in the Finnish population using at least one whole grain food serving a day, Scenario II: one or more additional whole grain servings a day among those who already use at least one whole grain serving a day, and Scenario III: the combination of Scenarios I and II. In all scenarios, the current situation was applied as a comparator. PL = productivity losses due to T2D. **Figure 4.** Probability of cumulative savings (with and without T2D-related productivity losses) in the modeled scenarios when applying the 20-year time horizon (2017 as a baseline year). Scenario I: a 10%-unit increase in the Finnish population using at least one whole grain food serving a day, Scenario II: one or more additional whole grain servings a day among those who already use at least one whole grain serving a day, and Scenario III: the combination of Scenarios I and II. In all scenarios, the current situation was applied as a comparator. PL = productivity losses due to T2D.

#### **4. Discussion**

**4. Discussion** 

The results of our study quantified the health economic significance of increased whole grain food consumption from the perspective of T2D prevention among the Finnish adult population. The inclusion of costs associated with T2D-related work absences and permanent work disabilities increased the savings potential, significantly highlighting the need for considering intervention consequences in a societal perspective in public health policy making. Our findings agree with the results of previous studies from Australia and Canada, showing a significant savings potential in the prevention of T2D among adult populations by increasing whole grain consumption [20–22]. However, our study demonstrated not only the significant savings potential but also significant gains in the number of QALYs (i.e., years lived in full health). This positive change in the number of years lived in full health is particularly important from the individual perspective, The results of our study quantified the health economic significance of increased whole grain food consumption from the perspective of T2D prevention among the Finnish adult population. The inclusion of costs associated with T2D-related work absences and permanent work disabilities increased the savings potential, significantly highlighting the need for considering intervention consequences in a societal perspective in public health policy making. Our findings agree with the results of previous studies from Australia and Canada, showing a significant savings potential in the prevention of T2D among adult populations by increasing whole grain consumption [20–22]. However, our study demonstrated not only the significant savings potential but also significant gains in the number of QALYs (i.e., years lived in full health). This positive change in the number of years lived in full health is particularly important from the individual perspective, since the avoidance of T2D will provide life-years without T2D-related morbidity impacting negatively on an individual's health-related quality of life [40–44]. In addition, a previous Finnish study has shown the relationship between the future risk for T2D and current health-related quality of life [48]. Thus, the reduced future risk for T2D could also have an immediate positive impact on an individual's current quality of life mediated via changes in an individual's daily dietary habits and body weight. However, for simplicity, this positive immediate effect on health-related quality of life was not considered in the present study.

> In the present study, we focused on assessing the expected population-level impacts of the hypothetical scenarios, where the proportion of Finnish adults using whole grain foods daily (i.e., at least one whole grain serving a day) is increased by a 10%-unit or alternatively where the number of daily whole grain servings is increased by one serving (i.e., two or more additional whole grain servings a day) among those who already use at least one whole grain serving a day. Based on our results, the increased whole grain consumption will lead to a higher number of health benefits and greater savings when focused on those who currently already use at least one whole grain serving a day due to the bigger size of the existing subpopulation among the Finnish adults (i.e., the majority of the Finnish adults already use at least one serving of WGF a day). However, as shown in the third scenario, the largest benefits could be expected to occur by combining these two approaches. The realization of these expected health benefits and cost savings will naturally

require that public health policies supporting the increased consumption of whole grains, such as labeling, campaigns, and endorsement by manufacturers and catering services in schools, workplaces, health care, etc., can be implemented on a national level. Naturally, the implementation of such policies requires upfront investments, but these investments could be expected to be offset by the cost savings in the future with a potentially greater return on investment (ROI). However, the obtained level of ROI is conditional on an initial required investment as well as on the acceptable time horizon of that investment, since as in the case of all preventive policies, health benefits, and cost savings materialize beyond the present. Therefore, in the present study, we applied discounting to consider the fact that decisionmakers generally value future health benefits and cost savings less than current health effects and cost savings [49]. Thus, all results represent the present value of the future health and economic benefits of increased WGF consumption at the population level. Based on the conducted sensitivity analyses, the results of the study were sensitive among others to the applied annual discount rates, highlighting the need for the proper selection of discount rates to reflect societal preferences in public health policymaking.

A particular strength of the present modeling study is that we applied nationally representative data to estimate the long-term incidence of T2D in the target subpopulations [23,28]. Furthermore, we also applied the recent results by Hu et al. [10] providing the non-linear marginal effects of an increased number of whole grain servings a day, reducing the risk for T2D. In addition, we applied Finnish estimates for the incidence of complications in patients with newly diagnosed T2D and T2D-related additional health care costs as well as nationally representative estimates for productivity losses associated with T2D and its complications. As mentioned above, the inclusion of T2D-related productivity losses had a significant impact on the obtained results. This finding agrees with recent studies highlighting the significant role of productivity losses in T2D-related economic burden [50,51].

As in all modeling-based studies requiring assumptions, there are also several limitations that need to be considered when interpreting the results of the present study. First, in the present study, we defined the national level of daily whole grain consumption based on a self-reported daily use of rye bread, porridge, or mixed bread observed in FinHealth 2017 [23]. We did not have information on the consumption of other whole grain products e.g., whole grain cereals or brown rice, which may have led to the underestimation of WGF consumption in the Finnish adult population at the baseline of the study. Therefore, the obtained results may be too optimistic, assuming a lower baseline population-level whole grain consumption than there really is in practice. Second, we focused on the adult population aged 30–79 years without T2D at baseline, since the risk for T2D elevates gradually after the age of 30, ignoring the long-term health and economic benefits of increased whole grain consumption in the younger Finnish population (i.e., <30 years). Third, our present study considers only a partial savings and QALY gain potential produced by increasing daily whole grain consumption, since there is well-established evidence for the benefits of whole grains, for example, in the prevention of cardiovascular diseases and various types of cancers [52–54]. For example, a recent study from the US showed substantial cardiovascular health care savings potential associated with increased whole grains consumption among the US adults [55]. However, since cardiovascular complications are common in the patients with T2D, the benefits obtained by reducing cardiovascular morbidity are partly considered also in the present study. Fourth, in the present study, risk factor levels for T2D were assumed to stay at the same level as they were in year 2017. This may lead to an underestimation of expected benefits due to the current unfavorable increasing trends of obesity among the Finnish adult population [56]. Finally, in the present study, we did not consider the costs of different public policies promoting the daily use of whole grain products, thus not allowing the cost-effective considerations of different policy approaches. However, we believe that the results of the present study support the development of such policies, promoting whole grain consumption and providing possibilities to assess the cost-effectiveness of such policies in the future.

As a summary, the findings from this modeling study suggest that increased whole grain consumption could lead to significant health gains and societal savings by preventing the incidence of T2D in the Finnish adult population, even when its current daily whole grain consumption is already at relatively high level in a global context.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/ 10.3390/nu13103583/s1, Figure S1: Graphical scheme of the study design, Figure S2: Results of the probabilistic sensitivity analysis using Scenario II and III. Figure S3: Probability of cumulative savings in 10 and 20-year time horizons, Table S1: The FINDRISC score distribution in the general population [23], Table S2: Coefficients of the Weibull regression for incidence of T2D, Table S3: The complications considered to be T2D-related in the Weibull regression model, Table S4: Weibull regression coefficients for the incidence of T2D-related complications, Table S5: The correlations between the Weibull regression coefficients.

**Author Contributions:** Conceptualization, J.M.; Data curation, P.L. and M.P.; Formal analysis, K.J. and J.H.; Methodology, J.M.; Project administration, J.M.; Software, K.J.; Supervision, J.M.; Validation, P.L., M.P., T.L. and J.L.; Visualization, K.J. and J.H.; Writing—original draft, J.M. and K.J.; Writing review and editing, J.H., P.L., M.P., T.L. and J.L. All authors will be informed about each step of manuscript processing including submission, revision, revision reminder, etc. via emails from our system or assigned Assistant Editor. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was financially supported by the International Association for Cereal Science and Technology Service GmbH, Vienna, Austria.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data that support the findings of this study are available from the Finnish Institute for National Institute of Health and Welfare and Joint Municipal Authority for North Karelia Social and Health Services, but restrictions apply to the availability of these data, which were used under license for the current study, and so, they are not publicly available. However, data are available from the authors upon reasonable request and with the permission of the Joint Municipal Authority for North Karelia Social and Health Services and the Finnish Institute for National Institute of Health and Welfare.

**Conflicts of Interest:** J.M. is a founding partner of ESiOR Oy and a board member of Siltana Oy. These companies were not involved in carrying out this research. Other authors declare no competing interests. The funder of this study had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

#### **References**

