Effect of differing antecedent hypoglycemia on counterregulatory responses to exercise in type 1 diabetes

Abstract

Hypoglycemia frequently occurs during or after exercise in intensively treated patients with type 1 diabetes mellitus (T1DM), but the underlying mechanisms are not clear. In both diabetic and nondiabetic subjects, moderate hypoglycemia blunts counterregulatory responses to subsequent exercise, but it is unknown whether milder levels of hypoglycemia can exert similar effects in a dose-dependent fashion. This study was designed to test the hypothesis that prior hypoglycemia of differing depths induces acute counterregulatory failure of proportionally greater magnitude during subsequent exercise in T1DM. Twenty-two T1DM patients (11 males/11 females, HbA1c 8.0 Ϯ 0.3%) were studied during 90 min of euglycemic cycling exercise after two 2-h periods of previous day euglycemia or hypoglycemia of 3.9, 3.3, or 2.8 mmol/l (HYPO-3.9, HYPO-3.3, HYPO-2.8, respectively). Patients' counterregulatory responses (circulating levels of neuroendocrine hormones, intermediary metabolites, substrate flux, tracer-determined glucose kinetics, and cardiovascular measurements) were 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 day 1 euglycemia, patients displayed normal counterregulatory responses to exercise. Conversely, when identical exercise was performed after day 1 hypoglycemia of increasing depth, a progressively greater blunting of glucagon, catecholamine, cortisol, endogenous glucose production, and lipolytic responses to exercise was observed. This was paralleled by a graduated increase in the amount of exogenous glucose needed to maintain euglycemia during exercise. Our results demonstrate that acute counterregulatory failure during prolonged, moderate-intensity exercise may be induced in a dose-dependent fashion by differing depths of antecedent hypoglycemia starting at only 3.9 mmol/l in patients with T1DM. dose response; glucagon; catecholamines; glucose clamp IN PATIENTS WITH TYPE 1 DIABETES MELLITUS (T1DM), hypoglycemia often occurs in association with physical exercise (10,19). This unfortunately limits the beneficial effects of exercise in type 1 diabetes, such as improving insulin sensitivity (4, 26) glycemic control (29, 42), blood pressure (35), and prevention of cardiovascular disease (2). Despite the many recent advances in diabetes management, the continued high prevalence of hypoglycemia, in general, and exercise-associated hypoglycemia, in particular, remain unresolved clinical challenges. Consequently, patients and physicians often choose suboptimal therapeutic regimens, including less effective insulin dosages and reduced physical activity to reduce the number of hypoglycemic episodes (43).Physical exercise elicits a complex pattern of adaptive neuroendocrine and metabolic responses (referred to as counterregulatory responses) aimed at maintaining glucose homeostasis in the face of increasing energy substrate needs. If adequately activated, these responses, includ...

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

“…The finding that antecedent hypoglycaemia has little or no effect on the glucoregulatory response to sprinting was unexpected considering the findings of Galassetti and colleagues [21,22], who reported that antecedent hypoglycaemia reduces the glucoregulatory response to moderate-intensity exercise in individuals with type 1 diabetes. In particular, they showed that although antecedent hypoglycaemia has no effect on growth hormone responses to moderate-intensity exercise it results in diminished adrenaline, noradrenaline, glucagon and cortisol responses [21,22].…”

“…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.…”

“…Following this, euglycaemia was restored once more by decreasing the insulin infusion rate and gradually reducing the glucose infusion rate. The depth and duration of this hypoglycaemic episode were chosen on the basis that they were expected to attenuate glucoregulatory hormone responses to a subsequent stimulus such as moderate-intensity exercise or hypoglycaemia [22,25,26]. At time intervals before and during euglycaemia and hypoglycaemia, blood samples were collected for the assessment of glucoregulatory hormone levels.…”

“…The insulin was titrated to achieve euglycaemia without any exogenous glucose. This procedure has been previously described by us and others and allows the determination of each participant's physiological basal insulin infusion rate [13,16,22]. At this point, the infusion of [6,6-2 H]glucose commenced with a priming bolus of 3 mg/kg and a constant infusion of 2.4 mg kg −1 h −1 that continued for the remainder of the experiment.…”

“…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.…”