Funding Acknowledgements Type of funding sources: None. Background Different intensive lifestyle interventions have been shown to be useful for effective control and even reversal of prediabetes and type 2 diabetes (T2D). Objectives Our heart institute cardiovascular prevention center started a comprehensive lifestyle clinic in 2019 to study the impact of 6 and 12-month non-pharmacological interventions on metabolic health and remission of these two conditions. Methods Between January 2019 and December 2020, 81 prediabetic (HbA1c ≥ 5.7%) and 184 T2D (HbA1c ≥ 6.5%) were recruited. All participants received regular nutritional counselling (therapeutic moderate carbohydrate restriction Mediterranean diet) and personalized physical exercise prescription (≥30 minutes of moderate aerobic training, 5 times a week, and strength training). Anthropometric measures and fasting blood analysis were measured at 0, 3, 6 and 12 months. Glucose-lowering therapies were not modified, unless necessary. Complete remission of prediabetes and T2D was defined as HbA1c <5.7%, whereas partial remission of T2D was defined as HbA1c <6.5% for at least 3 months, and it was calculated for all the participants that completed the 12-month program. Remission was further evaluated according to pharmacological status (drug-naïve or on glucose-lowering therapy). Results 231 participants completed the short-term program (87%) and 117 were followed-up to 12 months. Mean age was 67.1 (9.1) years, 67% male, 48.3% with CHD, 53.5% with glucose-lowering therapies. All metabolic health measures were improved, particularly among T2D participants (Table 1). Gains were achieved at 3 months and were maintained during the remainder of the program without significant change. Complete remission of prediabetes was achieved in 24% (95CI: 10.7 to 45.4%) of participants. Complete and partial remission of T2D were achieved in 5.4% (95CI: 2.2 to 12.5%) and 41.3% (95CI: 31.6 to 51.7%) of participants respectively and was observed in both with or without glucose-lowering therapies subgroups (Table 2). Conclusions Prioritizing lifestyle changes were shown to improve metabolic health measures even to the point of achieving remission among subjects with prediabetes or T2D. These metabolic changes were mostly achieved after 3 months and persisted throughout the intervention. Future research is required to better understand which non-pharmacological interventions work best among subjects with varying metabolic profiles and pharmacotherapy, how long should the interventions last and how partial or complete normalization of glucose impacts long-term outcomes.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Mirella and Lino Saputo Research Chair in Cardiovascular Diseases and the Prevention of Cognitive Decline from Université de Montréal at the Montreal Heart Institute. Montreal Heart Institute and the EPIC Center Foundations. FB are financially supported by a grant from the Fonds de Recherche du Québec – Santé (FRQ-S). Background/Introduction Cardiovascular and cerebrovascular disease are prevalent in type 2 diabetes (T2D) patient. Among people older than 70 years with T2D, up to 45% of might have cognitive dysfunction. Cardiorespiratory fitness (V̇O2peak) correlate with cognitive performances in healthy subjects, older adults, and people with CV diseases. The relationship between cognitive functions, V̇O2peak, cardiac output and cerebral oxygenation/perfusion responses during exercise has not been studied in patients with T2D. Studying cardiac and cerebrovascular hemodynamic responses during cardiopulmonary maximal exercise test (CPET) and its recovery phase and their relationship with cognition could be useful to detect patients at greater risk of future cognitive dysfunction. Purpose 1) To compare cerebral oxygenation/perfusion during a CPET and its post-exercise period (recovery), cognitive performances in T2D patients to those in healthy controls. 2) To examine if V̇O2peak, cardiac and cerebral hemodynamic are related to cognitive performances. Methods Nineteen T2D patients (61.9±7 years) and 22 healthy controls (HC) (61.8±10 years) were evaluated using a maximal CPET with impedance cardiography and cerebral oxygenation/perfusion (near-infrared spectroscopy) measure. The neuropsychological test battery evaluated short-term and working memory, processing speed, executive functions, and long-term verbal memory. Results T2D patients add a lower O2peak values compared to HC (34.5±5.6 vs 46.4±7.6 mL.kgFFM.min p<0.001). Peak cardiac index are also lowered compared to HC (p<0.05). Systemic vascular resistance index and systolic blood pressure at peak exercise were higher in T2D (p=0.005). Cerebral deoxyhemoglobin (HHb) during the 1st and 2nd min of the recovery remains significantly higher in HC compared to T2D (p<0.05). Executive functions were significantly lower in T2D patients compared to HC (p=0.016). Processing speed, working and verbal memory were similar in both groups. Total haemoglobin (tHb) during exercise and recovery, and oxyhemoglobin (O2Hb) during recovery only negatively correlated with executive function (p<0.05) in T2D patients (lower tHb values were associated with slower response times). Conclusion In addition to a reduced V̇O2peak and elevated vascular resistance, T2D patients showed a reduced cerebral O2Hb and HHb during early recovery (0 – 2 min) after peak exercise and a lower cognitive performance in executive function compared to healthy controls. Cerebrovascular responses with exercise and during the recovery phase could be a biological marker of cognitive impairment in T2D.

In older adults, executive functions are important for daily-life function and mobility. Evidence suggests that the relationship between cognition and mobility is dynamic and could vary according to individual factors, but whether cardiorespiratory fitness reduces the age-related increase of interdependence between mobility and cognition remains unexplored. One hundred eighty-nine participants (aged 50-87) were divided into three groups according to their age: middle-aged (MA; < 65), young older adults (YOA; 65-74), and old older adults (OOA; ≥75). Participants performed Timed Up and Go and executive functioning assessments (Oral Trail Making Test and Phonologic verbal fluency) remotely by videoconference. Participants completed the Matthews questionnaire to estimate their cardiorespiratory fitness (VO2 max in ml/min/kg). A three-way moderation was used to address whether cardiorespiratory fitness interacts with age to moderate the relationship between cognition and mobility. Results showed that the cardiorespiratory fitness x age interaction moderated the association between executive functioning and mobility (β = -.05, p = .047) (R2 = .18, p <.0001). At lower levels of physical fitness (< 19.16 ml/min/kg), executive functioning significantly influenced YOA’s mobility (β = -.48, p = .004) and to a greater extent OOA’s mobility (β = -.96, p = .002). Our results support the idea of a dynamic relationship between mobility and executive functioning during aging and suggest that physical fitness could play a significant role in reducing their interdependency.