Background: Real-time continuous glucose monitoring (CGM) devices help detect glycemic excursions associated with exercise, meals, and insulin dosing in patients with type 1 diabetes (T1D). However, the delay between interstitial and blood glucose may result in CGM underestimating the true change in glycemia during activity. The purpose of this study was to examine CGM discrepancies during exercise and the meal postexercise versus self-monitoring of blood glucose (SMBG). Methods: Seventeen adults with T1D using insulin pump therapy and CGM completed 60 min of aerobic exercise on three occasions. A standardized meal was given 30 min postexercise. SMBG was measured during exercise and in recovery using OmniPod Ò Personal Diabetes Manager (PDM; Insulet, Billerica, MA) with builtin glucose meter (FreeStyle; Abbott Laboratories, Abbott Park, IL), while CGM was measured with Dexcom G4 Ò with 505 algorithm (n = 4) or G5 Ò (n = 13), which were calibrated with subjects' own PDM. Results: SMBG showed a large drop in glycemia during exercise, while CGM showed a lag of 12-11 (meanstandard deviation) minutes and bias of-7-19 mg/dL/min during activity. Mean absolute relative difference (MARD) for CGM versus SMBG was 13 (6-22)% [median (interquartile range)] during exercise and 8 (5-14)% during mealtime. Clarke error grids showed CGM values were in zones A and B 94%-99% of the time for SMBG. Conclusion: In summary, the drop in CGM lags behind the drop in blood glucose during prolonged aerobic exercise by 12-11 min, and MARD increases to 13 (6-22)% during exercise as well. Therefore, if hypoglycemia is suspected during exercise, individuals should confirm glucose levels with a capillary glucose measurement.
To contend with the deleterious effects of accumulating misfolded protein aggregates or damaged organelles cells rely on a system of quality control processes, among them the autophagy-lysosome pathway. This pathway is itself controlled by a master regulator transcription factor termed transcription factor EB (TFEB). When TFEB localizes to the cell nucleus it promotes the expression of a number of genes involved in protein clearance. Here, we set out to determine (1) whether TFEB expression is altered in chronic kidney disease (CKD); (2) whether inhibition of the cytosolic deacetylase histone deacetylase 6 (HDAC6) affects TFEB acetylation and nuclear localization; and (3) whether HDAC6 inhibition, in turn, alters the natural history of experimental CKD. TFEB mRNA and protein levels were observed to be diminished in the kidneys of humans with diabetic kidney disease, accompanied by accumulation of the protein aggregate adaptor protein p62 in tubule epithelial cells. In cultured NRK-52E cells, HDAC6 inhibition with the small molecule inhibitor Tubastatin A acetylated TFEB, increasing TFEB localization to the nucleus and attenuating cell death. In a rat model of CKD, Tubastatin A prevented the accumulation of misfolded protein aggregates in tubule epithelial cells, attenuated proteinuria progression, limited tubule cell death and diminished tubulointerstitial collagenous matrix deposition. These findings point to the common occurrence of dysregulated quality control processes in CKD and they suggest that TFEB downregulation may contribute to tubule injury in CKD. They also identify a regulatory relationship between HDAC6 and TFEB. HDAC6 inhibitors and TFEB activators both warrant further investigation as treatments for CKD.
OBJECTIVE
To reduce exercise-associated hypoglycemia, individuals with type 1 diabetes on continuous subcutaneous insulin infusion typically perform basal rate reductions (BRRs) and/or carbohydrate feeding, although the timing and amount of BRRs necessary to prevent hypoglycemia are unclear. The goal of this study was to determine if BRRs set 90 min pre-exercise better attenuate hypoglycemia versus pump suspension (PS) at exercise onset.
RESEARCH DESIGN AND METHODS
Seventeen individuals completed three 60-min treadmill exercise (∼50% of VO2peak) visits in a randomized crossover design. The insulin strategies included 1) PS at exercise onset, 2) 80% BRR set 90 min pre-exercise, and 3) 50% BRR set 90 min pre-exercise.
RESULTS
Blood glucose level at exercise onset was higher with 50% BRR (191 ± 49 mg/dL) vs. 80% BRR (164 ± 41 mg/dL; P < 0.001) and PS (164 ± 45 mg/dL; P < 0.001). By exercise end, 80% BRR showed the smallest drop (−31 ± 58 mg/dL) vs. 50% BRR (−47 ± 50 mg/dL; P = 0.04) and PS (−67 ± 41 mg/dL; P < 0.001). With PS, 7 out of 17 participants developed hypoglycemia versus 1 out of 17 in both BRR conditions (P < 0.05). Following a standardized meal postexercise, glucose rose with PS and 50% BRR (both P < 0.05), but failed to rise with 80% BRR (P = 0.16). Based on interstitial glucose, overnight mean percent time in range was 83%, 83%, and 78%, and time in hypoglycemia was 2%, 1%, and 5% with 80% BRR, 50% BRR, and PS, respectively (all P > 0.05).
CONCLUSIONS
Overall, a 50–80% BRR set 90 min pre-exercise improves glucose control and decreases hypoglycemia risk during exercise better than PS at exercise onset, while not compromising the postexercise meal glucose control.
Exercising while fasted with type 1 diabetes facilitates weight loss; however, the best strategy to maintain glucose stability remains unclear.
RESEARCH DESIGN AND METHODSFifteen adults on continuous subcutaneous insulin infusion completed three sessions of fasted walking (120 min at 45% VO 2max ) in a randomized crossover design: 50% basal rate reduction, set 90 min pre-exercise (290 min 50% BRR ); usual basal rate with carbohydrate intake of 0.3 g/kg/h (CHO-only); and combined 50% basal rate reduction set at exercise onset with carbohydrate intake of 0.3 g/kg/h (Combo).
RESULTSCombo had a smaller change in glucose (5 6 47 mg/dL) versus CHO-only (249 6 61 mg/dL, P 5 0.03) or 290 min 50% BRR (234 6 45 mg/dL). The 290 min 50% BRR strategy produced higher b-hydroxybutyrate levels (0.4 6 0.3 vs. 0.1 6 0.1 mmol/ L) and greater fat oxidation (0.51 6 0.2 vs. 0.39 6 0.1 g/min) than CHO-only (both P < 0.05).
CONCLUSIONSAll strategies examined produced stable glycemia for fasted exercise, but a 50% basal rate reduction, set 90 min pre-exercise, eliminates carbohydrate needs and enhances fat oxidation better than carbohydrate feeding with or without a basal rate reduction set at exercise onset.Prolonged exercise in a fasted state may be preferable for people with diabetes since it increases lipid oxidation and is associated with better glucose stability than nonfasted exercise (1,2). On the basis of consensus, individuals with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) can attempt to prevent hypoglycemia during fasted exercise by supplementing with carbohydrates and/or by performing a temporary basal rate reduction (3). The objective of this study was to compare three common strategies used for fasted exercise in individuals on CSII.
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