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Objective: Impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D) is a major risk factor for severe hypoglycemia (SH) and is associated with atypical responses to hypoglycemia in brain regions involved in arousal, decision making, and memory. Whether restoration of hypoglycemia awareness alters these responses is unknown. We sought to investigate the impact of awareness restoration on brain responses to hypoglycemia.Research Design and Methods: Twelve adults with T1D and IAH underwent pseudocontinuous arterial spin labeling functional MRI during a hypoglycemic clamp (5-2.6 mmol/L) before and after a hypoglycemia avoidance program of structured education (Dose Adjustment for Normal Eating), specialist support, and sensor-augmented pump therapy (Medtronic MiniMed 640G). Hypoglycemic cerebral blood flow (CBF) responses were compared pre- and postintervention using predefined region-of-interest analysis of the thalamus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and hippocampus.Results: Postintervention, Gold and Clarke scores fell (6.0 ± 1.0 to 4.0 ± 1.6, P = 0.0002, and 5.7 ± 1.7 to 3.4 ± 1.8, P = 0.0008, respectively), SH rates reduced (1.5 ± 2 to 0.3 ± 0.5 episodes per year, P = 0.03), hypoglycemic symptom scores increased (18.8 ± 6.3 to 27.3 ± 12.7, P = 0.02), and epinephrine responses did not change (P = 0.2). Postintervention, hypoglycemia induced greater increases in ACC CBF (P = 0.01, peak voxel coordinates [6, 40, -2]), while thalamic and OFC activity did not change.Conclusions: Increased blood flow is seen within brain pathways involved in internal self-awareness and decision making (ACC) after restoration of hypoglycemia awareness, suggesting partial recovery of brain responses lost in IAH. Resistance of frontothalamic networks, involved in arousal and emotion processing, may explain why not all individuals with IAH achieve awareness restoration with education and technology alone. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present cross-sectional study was to examine the association among physical activity (PA), sedentary time (ST), and cardiometabolic risk in adults with prediabetes.Research Design and Methods: Participants (n = 2,326; 25-70 years old, 67% female) from eight countries, with a BMI >25 kg ⋅ m-2 and impaired fasting glucose (5.6-6.9 mmol ⋅ L-1) or impaired glucose tolerance (7.8-11.0 mmol ⋅ L-1 at 2 h), participated. Seven-day accelerometry objectively assessed PA levels and ST.Results: Multiple linear regression revealed that moderate-to-vigorous PA (MVPA) was negatively associated with HOMA of insulin resistance (HOMA-IR) (standardized β = -0.078 [95% CI -0.128, -0.027]), waist circumference (WC) (β = -0.177 [-0.122, -0.134]), fasting insulin (β = -0.115 [-0.158, -0.072]), 2-h glucose (β = -0.069 [-0.112, -0.025]), triglycerides (β = -0.091 [-0.138, -0.044]), and CRP (β = -0.086 [-0.127, -0.045]). ST was positively associated with HOMA-IR (β = 0.175 [0.114, 0.236]), WC (β = 0.215 [0.026, 0.131]), fasting insulin (β = 0.155 [0.092, 0.219]), triglycerides (β = 0.106 [0.052, 0.16]), CRP (β = 0.106 [0.39, 0.172]), systolic blood pressure (BP) (β = 0.078 [0.026, 0.131]), and diastolic BP (β = 0.106 [0.39, -0.172]). Associations reported between total PA (counts ⋅ min-1), and all risk factors were comparable or stronger than for MVPA: HOMA-IR (β = -0.151 [-0.194, -0.107]), WC (β = -0.179 [-0.224, -0.134]), fasting insulin (β = -0.139 [-0.183, -0.096]), 2-h glucose (β = -0.088 [-0.131, -0.045]), triglycerides (β = -0.117 [-0.162, -0.071]), and CRP (β = -0.104 [-0.146, -0.062]).Conclusions: In adults with prediabetes, objectively measured PA and ST were associated with cardiometabolic risk markers. Total PA was at least as strongly associated with cardiometabolic risk markers as MVPA, which may imply that the accumulation of total PA over the day is as important as achieving the intensity of MVPA. [ABSTRACT FROM AUTHOR]