EXERCISE AND NON-PHARMACOLOGICAL INTERVENTIONS TO IMPROVE METABOLIC HEALTH AND WELL-BEING IN CHRONIC CONDITIONS

Physical activity is known to improve metabolic profile and mental well-being in the general population and in individuals affected by various chronic conditions. Type, timing, intensity and frequency of exercise are important to warrant adherence and to optimize results in subjects affected by metabolic and other chronic diseases. Cryostimulation is currently seen as a potential adjuvant strategy to tackle obesity and metabolic conditions by triggering cold-induced thermogenesis; although suggestive, the effectiveness and mechanisms of cryostimulation are still poorly elucidated. The aim of this work was to assess the effectiveness and applicability of physical exercise adapted on subjects’ age and disease and partial body cryostimulation as adjunctive therapeutic strategies to help improving metabolic- and global-health status in obese, diabetics and subjects living with substance use disorder. Four studies have been carried out to ascertain the effect of exercise and cryotherapy on such chronic conditions. The first study was aimed to assess the effect of Nordic Walking (NW) on cardio-metabolic health, physical performance, and well-being, in sedentary older adults with type-2 diabetes (T2D). Fifteen subjects with T2D were enrolled in a 6-month NW training program. Fasting glycemia, glycosylated hemoglobin (HbA1c), lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides), systolic and diastolic blood pressure were measured pre- and post-intervention. Participants’ quality of life (Short Form Health Survey) and physical fitness (6-minute-walking test; 6MWT) were also evaluated. Compared to baseline, NW significantly improved fasting glycemia (103.5±18.5 vs 168.7±37.7 mg/dl; p =0.01), systolic blood pressure (121.8±12.2 vs 133±14.4 mmHg; p =0.02), physical fitness (759.88 ±69 vs 615.5±62.6 m; p <0.001) and both mental (54.5±4.4 vs 45.7±5.6; p <0.01) and physical health (49.8±4.7 vs 40.3±5.9; p<0.01). HbA1c (6.15±0.8 vs 6.4±1%; p=0.46), total cholesterol (162.2± 31.2 vs 175.5±28.8 mg/dl P=0.13), LDL-C (95.2±24.2 vs 106.3± 32.3 mg/dl; p=0.43) and triglycerides (135.5 ±60.8 vs 127.6±57.4 mg/dl; p=0.26) improved without reaching significance. The second study was aimed to assess the effect of recreational sport-based physical activity (SBA) on depression, anxiety, and other parameters that measure mental wellness in a cohort of community-dwelling individuals living with substance use disorder. Twenty subjects (age: 26.1±3.2 years, mean±SD) participated in an 8-week training program. These subjects were randomly assigned to two groups: a) a group practicing sport-based physical activity; and b) a non-exercising group, performing as control. Depression and anxiety levels were assessed using the Beck Depression Inventory (BDI) and the PROMIS Anxiety Short Form, respectively. Additionally, insomnia and perceived stress were evaluated using the Insomnia Severity Index (ISI) and the Perceived Stress Scale (PSS). The PROMIS score significantly improved after 8 weeks of SBA in the treated group compared to controls (group × time; F1,29 = 5.58; p = 0.025), indicating that anxiety improved significantly following the intervention. The BDI score improved in the intervention group (-24,4; CI,11.5-37.4; p<0,0018), but no interaction was detected (group × time F1,29 = 5.58; p=0.23). No significant difference at 8 week was found also in the PSS and ISI score (PSS: F1,4.= 1.21; p = 0.35. ISI: F1,4 = 1.21; p=0.21). The third study was aimed to assess the effect of single or repeated applications of partial-body cryostimulation (PBC) on resting energy expenditure (REE) in exposed individuals. Sixteen middle-aged obese (BMI 34±1.7 kg/m2) and paired lean (BMI 22 ±4 kg/m2) women underwent a daily PBC (-130°C x 150s) for five consecutive days. Resting energy metabolism (REE) was assessed by indirect calorimetry pre- and post-PBC on day 1 and day 5. As concerns REE, the repeated measures three-way ANOVA revealed a significant interaction of the session*time (F1,30=5.299; P=0.02) but not for the session*time*group (F1,30=3.349; P=0.07). On day 5, REE pre-PBC resulted higher than baseline of day 1 either in leans (by 8.2 %, 1665±106 vs 1538±111kcal/day) or in obese women (by 5.5%, 1755±265 vs 1664±241 kcal/day). As to RQ, there was a significant interaction for the time (F1,30=50.146; P<0.000001), with RQ_post > RQ_pre, suggesting a shift in substrate oxidation. The fourth study was aimed to determine the association of exercise timing with differences in glycemic control in young subjects with type-1 diabetes. Hundred well-compensated participants affected by diabetes type-1 (DM1; 55 females, 45 males; mean age: 16±6 years) undergoing continuous glucose monitoring (CGM) were recruited. Physical activity performed over seven days was recorded for each subject. Timing, duration, intensity, and volume of physical activity were derived from a 7-day training log. Daily parameters related to glycemic control were derived from the device in the same time span. Glucose control was assessed through the evaluation of the following variables: time in range (TIR; 70- 180mg/dL), time below range (TBR; <70 mg/dL), time below extreme hypoglycemia range (TBER; <54 mg/dL); time above range (TAR; 180-250mg/dL), TIME >250mg/dL, mean glucose (MGLU) and total daily dose (TDD). Subjects were divided in three groups, according to the prevalent timing of exercise: morning (6-12 am), afternoon (12am-6pm) and night (6-12 pm). Subjects’ glycemic profiles were grouped according to same criteria. A comparison between groups has been assessed. The mixed model analysis for fixed effects demonstrated that TIR, TAR, TBER and MGLU were significantly influenced by the timing of exercise (p<0.05). The post-hoc analysis revealed that this difference was present only when NO activity vs afternoon exercise was considered, suggesting a positive effect of exercise, in general. In the pairwise comparisons, TIR, TAR, TBER and MGLU did not present any difference when timing (morning vs afternoon vs evening/night) was considered. While timing of exercise seems to have scarce relevance for glycemic control in DM1 subjects, exercise optimized on subjects’ age and disease and partial body cryostimulation are effective in improving clinical outcomes and physical variables in obese/dysmetabolic subjects and people living with substance use disorder. Therefore, our results suggest that these treatment strategies can be implemented as adjuvating strategies in people affected by metabolic diseases and conditions characterized by mood unbalance and psychic distress. While the effect of sport activity is backed up by large evidence, research on cryostimulation is in its infancy and more studies are warranted to sustain these and other preliminary results on obesity and obesity-associated metabolic conditions. Tailoring exercise to maximize benefits and minimize dropouts and side effects is critical for the improvement of metabolic and mental condition in a variety of different chronic disease. To reach this target, a tighter interplay between clinicians and physical trainers is highly warranted. Further efforts are required to exercise scientists, who are asked to provide solid evidence on tailored/optimized exercise for specific classes of diseased subjects, with specific attention to indicating the optimal type, intensity, frequency and timing.