Background GLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans. Methods and Results Healthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R 2 *), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%, P <0.001) and cortical perfusion (13±4%, P <0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (−5±2%, P =0.007), whereas cortical perfusion remained unchanged. R 2 * values increased by 3±2% ( P =0.025) in the medulla and 4±1% ( P =0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP‐1. Blood flow in the renal artery was not altered significantly by either intervention. Conclusions GLP‐1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP‐1 may account for the increase in regional perfusion. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04337268.

Sustaining a weight loss after a lifestyle intervention is challenging. The objective of the present study was to investigate if mitochondrial function is associated with the ability to maintain a weight loss. Sixty-eight former participants in an 11–12-week lifestyle intervention were recruited into 2 groups; weight loss maintenance (WLM; body mass index (BMI): 32 ± 1 kg/m2) and weight regain (WR; BMI: 43 ± 2 kg/m2) based on weight loss measured at a follow-up visit (WLM: 4.8 ± 0.4; WR: 7.6 ± 0.8 years after lifestyle intervention). Maximal oxygen consumption rate, physical activity level, and blood and muscle samples were obtained at the follow-up experiment. Mitochondrial respiratory capacity and reactive oxygen species (ROS) production were measured. Fasting blood samples were used to calculate glucose homeostasis index. WR had impaired glucose homeostasis and decreased maximal oxygen uptake and physical activity level compared with WLM. The decreased physical activity in WR was due to a lower activity level at vigorous and moderate intensities. Mitochondrial respiratory capacity and citrate synthase (CS) activity was higher in WLM, but intrinsic mitochondrial respiratory capacity (mitochondrial respiratory capacity corrected for mitochondrial content (CS activity)) was similar. ROS production was higher in WR compared with WLM, which was accompanied by a decreased content of antioxidant proteins in WR. Intrinsic mitochondrial respiratory capacity in skeletal muscle is not associated with the ability to maintain a long-term weight loss. WLM had a higher maximal oxygen uptake, physical activity level, mitochondrial respiratory capacity and CS activity compared with WR. The reduced glucose tolerance was concurrent with increased ROS production per mitochondria in WR, and could also be associated with the lower physical activity level in this group.

Context Current guidelines for exercise-related glucose management focus on reducing bolus and/or basal insulin doses and considering carbohydrate intake. Yet far less attention has been paid to the potential role of other macronutrients alongside carbohydrates on glucose dynamics around exercise. Objective To investigate the effects of a low-carbohydrate-high-protein (LCHP) compared to a high-carbohydrate-low-protein (HCLP) pre-exercise meal on the metabolic, hormonal, and physiological responses to exercise in adults with insulin pump-treated type 1 diabetes. Methods Fourteen adults with insulin pump-treated type 1 diabetes (11 females with a median [range] HbA1c of 50 [43-59] mmol/mol (6.7 [6.1-7.5] %), age of 49 [25-65] years, and BMI of 24.0 [19.3-27.1] kg/m2) completed an unblinded, two-arm, randomised, crossover study. Participants ingested isocaloric meals that were either LCHP (carbohydrate 21%, protein 52%, fat 27%) or HCLP (carbohydrate 52%, protein 21%, fat 27%) 90 min prior to undertaking 45 min of cycling at moderate intensity. Meal insulin bolus was dosed according to meal carbohydrate content but reduced by 25%. Basal insulin rates were reduced by 35% from meal ingestion to end of exercise. Results Around exercise the coefficient of variability was lower during LCHP (LCHP:14.5±5.3 vs. HCLP: 24.9±7.7%, p=0.001). Over exercise, LCHP was associated with a lesser drop (LCHP: Δ-1.49±1.89 vs. HCLP: Δ-3.78±1.95 mmol/L, p=0.001). Mean insulin concentration was 30% lower during exercise for LCHP compared to HCLP (LCHP: 25.5±11.0 vs. HCLP: 36.5±15.9 mU/L, p&lt;0.001). Conclusions Ingesting a LCHP pre-exercise meal lowered plasma glucose variability around exercise and diminished the drop in plasma glucose over exercise.

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