Effects of Moderate Cycling Exercise on Blood Glucose Regulation Following Successful Clinical Islet Transplantation.

Context: Islet transplantation is effective in preventing hypoglycemia in patients with type 1 diabetes (T1D). However, it is unknown whether transplanted islets regulate plasma glucose concentrations appropriately during and after exercise in human islet transplant recipient (ITxs). Objective: To determine the effect of exercise on plasma glucose, insulin, and glucagon concentrations in ITxs compared with control subjects (CONs) without diabetes. Intervention: Participants completed two conditions in random order: 45 minutes of aerobic exercise (60% VO2peak) and 45 minutes of seated rest. Blood samples were drawn at baseline, immediately after exercise or rest, and every 15 minutes throughout a 60-minute recovery period. Postexercise (24 hours) interstitial glucose was monitored with continuous glucose monitoring (CGM). Results: Twenty-four participants (12 ITxs, 12 CONs) completed the protocol. Plasma glucose decreased more over time with exercise in ITxs compared with CONs [main effects of treatment (P = 0.019), time (P = 0.001), and group (P = 0.012)]. Plasma glucose was lower during exercise vs rest in ITxs but not CONs [treatment by group interaction (P = 0.028)]. Plasma glucose decreased more during exercise than during rest [treatment by time interaction (P = 0.001)]. One ITx and one CON experienced plasma glucose concentrations <3.5 mmol/L at the end of exercise, both of whom returned above that threshold within 15 minutes. Nocturnal CGM glucose <3.5 mmol/L was detected in two CONs but no ITxs. Conclusion: Despite a greater plasma glucose decline during exercise in ITxs, hypoglycemia risk was similar during and after exercise in ITxs compared with CONs.

Peripheral chemoreceptor deactivation attenuates the sympathetic response to glucose ingestion.

Acute increases in blood glucose are associated with heightened muscle sympathetic nerve activity (MSNA). Animal studies have implicated a role for peripheral chemoreceptors in this response, but this has not been examined in humans. Heart rate, cardiac output (CO), mean arterial pressure, total peripheral conductance, and blood glucose concentrations were collected in 11 participants. MSNA was recorded in a subset of 5 participants via microneurography. Participants came to the lab on 2 separate days (i.e., 1 control and 1 experimental day). On both days, participants ingested 75 g of glucose following baseline measurements. On the experimental day, participants breathed 100% oxygen for 3 min at baseline and again at 20, 40, and 60 min after glucose ingestion to deactivate peripheral chemoreceptors. Supplemental oxygen was not given to participants on the control day. There was a main effect of time on blood glucose (P < 0.001), heart rate (P < 0.001), CO (P < 0.001), sympathetic burst frequency (P < 0.001), burst incidence (P = 0.01), and total MSNA (P = 0.001) for both days. Blood glucose concentrations and burst frequency were positively correlated on the control day (r = 0.42; P = 0.03) and experimental day (r = 0.62; P = 0.003). There was a time × condition interaction (i.e., normoxia vs. hyperoxia) on burst frequency, in which hyperoxia significantly blunted burst frequency at 20 and 60 min after glucose ingestion only. Given that hyperoxia blunted burst frequency only during hyperglycemia, our results suggest that the peripheral chemoreceptors are involved in activating MSNA after glucose ingestion.

Minimal effect of walking before dinner on glycemic responses in type 2 diabetes: outcomes from the multi-site E-PAraDiGM study.

AIM: To examine the effect of walking before dinner on 24-h glycemic control in individuals with type 2 diabetes using the standardized multi-site Exercise-Physical Activity and Diabetes Glucose Monitoring (E-PAraDiGM) Protocol. METHODS: Eighty participants were studied under two conditions (exercise vs. non-exercise control) separated by 72 h in a randomized crossover design. Each condition lasted 2 days during which standardized meals were provided. Exercise consisted of 50 min of treadmill walking at 5.0 km/h before the evening meal, while control involved 50 min of sitting. The primary outcome measure was mean glucose during the 24-h period following exercise (or sitting) measured by continuous glucose monitoring. RESULTS: Of the 80 participants who were initially randomized, 73 completed both exercise and control. Sixty-three participants [29 males, 34 females; age = 64 ± 8 years, body mass index = 30.5 ± 6.5 kg/m2 and HbA1c = 51 ± 8 mmol/mol (6.8 ± 0.7%), mean ± SD] complied with the standardized diets and had complete continuous glucose monitoring data. Exercise did not affect mean 24-h glucose compared to control (0.03 mmol/L; 95% CI - 0.17, 0.22, P = 0.778) but individual differences between conditions ranged from - 2.8 to +1.8 mmol/L. Exercise did not affect fasting glucose, postprandial glucose or glucose variability. Glucose concentrations measured by continuous glucose monitoring were reduced during the 50 min of walking in exercise compared to sitting in control (- 1.56 mmol/L; 95% CI - 2.18, - 0.95, p < 0.001). CONCLUSION: Contrary to previous acute exercise studies, 50 min of walking before dinner in the E-PAraDiGM protocol did not affect 24-h glucose profiles. However, highly heterogeneous responses to exercise were observed. TRIAL REGISTRATION: NCT02834689.

Does exercise pose a challenge to glucoregulation after clinical islet transplantation?

Islet transplantation (ITx) is effective in preventing severe hypoglycemia by restoring glucose-dependent insulin secretion in type 1 diabetes (T1D), but may not normalize glucose regulation. Studies suggest that physical activity plays a role in maintaining ß-cell mass and function in individuals with type 2 diabetes and animal models of diabetes. This could indicate that physical activity plays a role in graft survival in ITx recipients. This review's objective is to assess current knowledge related to physical activity in ITx recipients. Responses to other challenges in blood glucose control (i.e., hypoglycemia) in human ITx recipients were examined to provide in-depth background information. To identify studies involving exercise in ITx recipients, a systematic search was performed using PubMed, Medline, and Embase, which revealed 277 English language publications. Publications were excluded if they did not involve ITx recipients; did not involve physical activity or hypoglycemia; or did not report on glucose, insulin, or counterregulatory hormones. During induced hypoglycemia, studies indicate normal suppression of insulin in ITx individuals compared with healthy non-T1D controls. Studies involving exercise in ITx animals have conflicting results, with time since transplantation and transplantation site (spleen, liver, kidney, peritoneal cavity) as possible confounders. No study examining blood glucose responses to physical activity in human ITx recipients was identified. A small number of induced-hypoglycemia studies in humans, and exercise studies in animals, would suggest that glucoregulation is greatly improved yet is still imperfect in this population and that ITx does not fully restore counterregulatory responses to challenges in blood glucose homeostasis.