Estudios de suelos para el diseño de fundaciones de puentes

BETWEEN WEIGHT LOSS AND TYPE 2 DIABETES INCIDENCE

Several intervention studies addressing weight loss as means of preventing T2D have proven successful weight loss to reduce the risk of T2D incidence (Peirson et al. 2014, Haw et al. 2017, LeBlanc et al. 2018). In most of these studies, the differences between the weight lost in the lifestyle intervention groups and the control groups have only been a few kilograms. Despite these small differences, in a meta-analysis by Haw et al. (2017), the risk of developing T2D decreased by 39% in the intervention groups compared to the control groups during the active intervention periods. Moreover, intervention studies with long follow-ups after the actual intervention periods have shown the preventive effects of the interventions to last compared to the long-term outcomes of the control groups (Diabetes Prevention Program Research Group et al. 2009, Lindström et al. 2013).

However, as in most cases, the intervention study participants have had overweight or obesity or have been at an elevated risk of T2D, as the follow- up periods in most of the studies have been relatively short (mostly between 0.5-6.3 years), and as the participants have received support to lose and maintain weight, the results of these studies cannot be directly generalized to the population level. Results of many observational studies with WLW as an exposure, however, have also agreed with the intervention studies (Chan et al. 1994, Colditz et al. 1995, Resnick et al. 2000, Koh-Banerjee et al. 2004, Wannamethee et al. 2005, Kim et al. 2018, Stokes et al. 2018), although in some studies, the association has remained absent (Ford et al. 1997, Moore et

al. 2000, Oguma et al. 2005, Mishra et al. 2007, Waring et al. 2010, Nanri et al. 2011).

Three studies predicting T2D incidence or T2D-related mortality with IWL, all conducted using extensive (n=approximately 43 000–181 000) American Cancer Society's Cancer Prevention Study data with individuals with overweight or obesity, have shown IWL to be associated with a lowered risk (Williamson et al. 1995, Williamson et al. 1999, Will et al. 2002). Moreover, a study conducted using the San Antonio Heart Study data indicated that self-report dieting predicted a decreased risk of T2D among women (Monterrosa et al. 1995). Among men, when BMI was not included in the model, a tentatively elevated risk emerged. This association, however, attenuated to non-existent when BMI was adjusted for in the final model. Hence, apart from this one indicative finding, the results found in this study are rather conflicting compared to the existing literature.

Potential explanations for this discrepancy between studies include issues related to the validity and/or reliability of the IWL variable in this study or between-study differences in weight loss variables, the decades of the data collection, the study populations, the lengths of follow-ups, control for confounding, and the definition of T2D. The questions related to the validity and reliability of the IWL variable are discussed in section 6.6.2. Other potential reasons are scrutinized in detail in the appendix of original Article IV. In summary, it can be interpreted that in spite of some methodological differences between studies, none of these differences appears to solely be accounted for the discrepancy. Hence, it seems that the direct association between IWL and the risk of T2D derives from other reasons.

6.5.2 POTENTIAL MECHANISMS EXPLAINING THE DIRECT

ASSOCIATION BETWEEN INTENTIONAL WEIGHT LOSS AND TYPE 2 DIABETES INCIDENCE

Despite the inverse associations found in the literature on weight loss and T2D incidence, and despite even a relatively small weight loss with healthy lifestyle changes effectively preventing T2D incidence in intervention studies (Haw et al. 2017), long-term weight maintenance appears to be difficult and rare (Melby et al. 2017). The direct association between self-report dieting attempts and IWL and subsequent weight gain found in many observational studies is further described in section 2.2.6. Weight gain and obesity, in turn, increase the risk of developing T2D. In addition to the potential linear weight gain after dieting, weight cycling itself may possibly increase the risk of T2D. Suggested potential metabolic pathways by which weight cycling may promote the development of T2D include general weight gain and the accumulation of abdominal obesity (Mackie et al. 2017). Abdominal obesity in particular has been indicated to contribute to the development of insulin resistance (Tchernof & Despres 2013). Additionally, weight gain and weight

Discussion

cycling may induce unfavorable alterations in metabolic factors such as MetS components (Montani et al. 2015, Rhee 2017). MetS, in turn, is a considerable risk factor of T2D, increasing the risk fivefold (O'Neill & O'Driscoll 2015). However, in a review by Mackie et al. (2017), only a little more than half of the studies found weight cycling to increase the risk of future weight gain or to alter body composition into more unfavorable, and the majority of the studies failed to find an association between weight cycling and impairment in metabolic markers. Despite this uncertainty, the evidence suggesting that weight cycling is associated with T2D occurrence is relatively consistent (Kodama et al. 2017, Rhee et al. 2018).

In addition, one meta-analysis on weight loss and mortality risk concluded that IWL is associated with increased mortality among initially healthy individuals, but with decreased mortality among unhealthy individuals (Harrington et al. 2009). Hence, it is possible that also in this general population the adverse consequences of IWL may reverse the potential beneficial effects of weight loss in the long term (Sørensen et al. 2005).

It is possible that self-initiated weight loss is insufficient to reduce the risk of T2D. However, in this study, the magnitude of the risk of T2D appeared to grow in parallel with the amount of intentionally lost weight. This is in disagreement with the findings of some of the previous observational studies suggesting that greater weight loss would result in a greater reduction of risk (Colditz et al. 1995, Resnick et al. 2000, Koh-Banerjee et al. 2004, Kim et al. 2018), although not all studies have supported this. The present finding may derive from greater amounts of weight loss during only one year, resulting in greater potential subsequent weight gain or weight cycling, and thus a greater risk of developing T2D.

Alternatively, it is possible that individuals with IWL may initially be at a greater risk of T2D or they may be more health conscious, and thus their T2D may become diagnosed more frequently. In order to understand the findings more thoroughly, the associations were further studied in subgroups of several background variables.