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Title: Physical inactivity and sedentary time : impact on metabolic health and development of type 2 diabetes
Author: Bowden Davies, K. A.
ISNI:       0000 0004 7658 0785
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Physical inactivity is a major risk factor for global mortality; it is associated with the development of obesity, metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and cardiovascular disease (CVD). Despite the worldwide recommendations and health guidelines recommending an active lifestyle, low levels of physical activity (PA) and sedentary behaviour are increasingly prevalent in modern society. The primary aim of this thesis is to examine the role of sedentary time and physical inactivity with a specific emphasis on the development of multiorgan insulin resistance as precursor for the development of T2D. The initial data within this thesis provided evidence for the importance of a physically active lifestyle irrespective of obesity. Ninety-eight individuals were recruited, screened, identified as free from disease and subsequently categorised according to obesity status and MetS (termed herein unhealthy). Seventy-three individuals were non-obese, of which 11 were unhealthy, and 25 individuals were obese, of which 13 were unhealthy. PA did not fully explain metabolic health status but sedentary time was higher in obese individuals. Secondary data in this cohort revealed an independent association between sedentary time and liver fat, which is a proxy for poor metabolic health and clinical manifestations related to T2D. Of note, moderate-vigorous physical activity, which is the cornerstone of PA recommendations, did not significantly influence metabolic health, obesity or liver fat. Research examining the consequences of a physically inactive lifestyle (i.e. sedentary behaviour) is warranted. The major data detailed within this thesis were derived from inducing short-term physical inactivity in first-degree relatives (FDR) of patients with T2D, compared with healthy controls (CON). Forty-five habitually active participants (16 FDR, 29 CON) were assessed at baseline, after 14 days of inactivity and after 14 days of resuming normal activity. Sedentary time increased in parallel with a decrease in PA during the period of inactivity. Cardiorespiratory fitness reduced, lower limb lean mass decreased, while gynoid fat increased and significantly more android fat was accumulated in FDR. Significant increases in liver fat were accompanied by increased plasma triglycerides, which were increased to a greater extent in FDR. Whole body insulin sensitivity significantly with no difference between the groups. Resumption of normal activity reversed all observed changes. FDR seem susceptible to some of the the risks of physical inactivity. Taken together, these data support the importance of reducing physical inactivity and sedentary time. FDR have an increased risk of developing T2D compared with CON and therefore these data must be used as a platform to develop guidelines and strategies aimed at preventing chronic physical inactivity and sedentary behaviour, particularly in these individuals. Considering linked epidemics of T2D and physical inactivity, innovative strategies must be developed to promote the importance of a habitually active lifestyle, either as a minimum or in addition to current guidelines.
Supervisor: Cuthbertson, Daniel ; Sprung, Victoria ; Kemp, Graham Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral