Effect of Antecedent Hypoglycemia on Counterregulatory Responses to Subsequent Euglycemic Exercise in Type 1 Diabetes

Abstract

Exercise-related hypoglycemia is common in intensively treated patients with type 1 diabetes. The underlying mechanisms are not clearly defined. In nondiabetic subjects, hypoglycemia blunts counterregulatory responses to subsequent exercise. It is unknown whether this also occurs in type 1 diabetes. Therefore, the goal of this study was to test the hypothesis that prior hypoglycemia could result in acute counterregulatory failure during subsequent exercise in type 1 diabetes. A total of 16 type 1 diabetic patients (8 men and 8 women, HbA 1c 7.8 ؎ 0.3%) were investigated during 90 min of euglycemic cycling exercise, following either two 2-h periods of previous-day hypoglycemia (2.9 mmol/l) or previous-day euglycemia. Patients' counterregulatory responses (circulating levels of counterregulatory hormones, intermediary metabolites, substrate flux via indirect calorimetry, tracer-determined glucose kinetics, and cardiovascular measurements) were comprehensively assessed during exercise. Identical euglycemia and basal insulin levels were successfully maintained during all exercise studies, regardless of blood glucose levels during the previous day. After resting euglycemia, patients displayed normal counterregulatory responses to exercise. Conversely, when identical exercise was repeated after hypoglycemia, the glucagon response to exercise was abolished, and the epinephrine, norepinephrine, cortisol, endogenous glucose production, and lipolytic responses were reduced by 40 -80%. This resulted in a threefold increase in the amount of exogenous glucose needed to maintain euglycemia during exercise. Our results demonstrate that antecedent hypoglycemia, in type 1 diabetes, can produce acute counterregulatory failure during a subsequent episode of prolonged moderate-intensity exercise. The metabolic consequence of the blunted neuroendocrine and autonomic nervous system counterregulatory responses was an acute failure of endogenous glucose production to match the increased glucose requirements during exercise. These data indicate that counterregulatory failure may be a significant in vivo mechanism responsible for exercise-associated hypoglycemia in type 1 diabetes.

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study

“…It is plausible that a preserved exercise-induced increase in circulating catecholamines rather than the glucagon response enabled continuous substrate mobilisation from the liver in this patient cohort [14,30,[36][37][38]. It is known that pre-exercise hypoglycaemia is associated with blunted counter-regulation and impaired hepatic glycogenolysis [23,39]. Since in the present study, patients were admitted overnight and hypoglycaemia was avoided prior to the experiment, counter-regulatory mechanisms were likely to have been preserved.…”

A 10-s sprint performed prior to moderate-intensity exercise prevents early post-exercise fall in glycaemia in individuals with type 1 diabetes

“…In the 48 h prior to the experimental trial, participants were not allowed to exercise as antecedent exercise could have affected the endocrine response to exercise [6]. In addition, testing was rescheduled if participants had experienced a hypoglycaemic episode during the 48 h pre-trial phase.…”

Antecedent hypoglycaemia does not diminish the glycaemia-increasing effect and glucoregulatory responses of a 10 s sprint in people with type 1 diabetes

“…Since an episode of hypoglycaemia can reduce the glucoregulatory response to a subsequent bout of moderate-intensity exercise [21,22], the purpose of this study was to investigate the possibility that antecedent hypoglycaemia impairs both the glucoregulatory and glycaemia-increasing responses to a 10 s sprint. This study shows that morning hypoglycaemia does not attenuate the glycaemia-increasing effect of a 10 s sprint performed in the afternoon and has little or no effect on the glucoregulatory response to this type of exercise in young adults with type 1 diabetes.…”

“…Before each of the following two testing sessions, participants were required to visit the research unit to be fitted with a continuous glucose monitoring system (CGMS) (Guardian REAL-Time CGM System; Medtronic, Northridge, CA, USA) and an accelerometer (Activity Monitor GT1M; ActiGraph, Pensacola, FL, USA) to continuously monitor interstitial fluid glucose levels and physical activity levels, respectively. The CGMS and accelerometer were worn for 3 days prior to each testing session to ensure that the participants did not experience any episodes of hypoglycaemia and were not engaging in any vigorous activity prior to testing; both being important precautions to take, since the glucoregulatory response to exercise is affected by antecedent hypoglycaemia and antecedent exercise [21,23]. All CGMS readings ≤3.5 mmol/l were confirmed with a blood glucose measurement; testing was rescheduled if blood glucose levels were ≤3.5 mmol/l or if the participants experienced any symptoms of hypoglycaemia at any stage over this 3 day period.…”

“…Antecedent hypoglycaemia has been shown to attenuate the glucoregulatory responses to subsequent moderate-intensity exercise, with a marked dampening of the rise in catecholamine, glucagon and cortisol levels [20][21][22]. If an episode of hypoglycaemia were also to reduce the glucoregulatory response to a subsequent sprint, the glycaemia-increasing effect of a 10 s sprint may be diminished, thus reducing the efficacy of sprinting in hypoglycaemia prevention.…”