Impaired adrenergic response to prolonged exercise in type I diabetes

Schneider, Stephen H.; Vitug, Angelica C.; Ananthakrishnan, Radha; Khachadurian, Avedis K.

doi:10.1016/0026-0495(91)90219-m

Cited by 38 publications

(29 citation statements)

References 34 publications

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“…Although acute increases in insulin sensitivity caused by exercise, paralleled by the potential relative hyperinsulinemia resulting from the inability of diabetic patients to endogenously regulate insulin levels, have been hypothesized to play a role (34), this mechanism is likely to have only a modest impact (3). Additionally, both in well-controlled T1DM patients (i.e., exposed to frequent episodes of antecedent hypoglycemia) and in patients with classical diabetic autonomic neuropathy (32), reduced adrenergic adaptation to prolonged physical exercise has been reported (6). Furthermore, because of the many similarities existing between counterregulatory adaptation to hypoglycemia and exercise, it is possible that exercise also shares some of the mechanisms responsible for counterregulatory failure induced by repeated hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

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

Galassetti¹,

Tate²,

Neill³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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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...

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Section: Discussionmentioning

confidence: 99%

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

Galassetti¹,

Tate²,

Neill³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…Furthermore, if hypoglycemia occurs during exercise, neuroendocrine responses are in fact increased (39). Catecholamine responses to hypoglycemic exercise, on the other hand, are reduced in well-controlled type 1 diabetic patients (i.e., exposed to repeated antecedent hypoglycemia) (13). Furthermore, patients with classic diabetic autonomic neuropathy have blunted epinephrine responses during euglycemic exercise (12).…”

Section: Discussionmentioning

confidence: 99%

“…However, Bottini et al (12) reported that epinephrine responses to exercise can be reduced in patients with classic diabetic autonomic neuropathy. Furthermore, Schneider et al (13) have reported blunted neuroendocrine responses during exercise in metabolically well-controlled type 1 diabetic patients. Recently, a study from our laboratory in nondiabetic subjects demonstrated a significant reduction in counterregulatory responses to exercise after antecedent hypoglycemia (11).…”

mentioning

confidence: 99%

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

et al. 2003

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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.

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“…This level of insulin results in mild hypoglycemia of 3.9 mmol/L in the presence of functioning counterregulatory responses [19]. Therefore, this mild level of hyperinsulemia during exercise makes it unlikely that it is the only factor involved in severe exercise-related hypoglycemia [20], bearing in mind that neuroendocrine responses during exercise are usually increased in the presence of hypoglycemia [21].…”

Section: Hypoglycemia Related To Exercisementioning

confidence: 98%

Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitus

Ertl

2004

Diabetes Metabolism Res

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Exercise is a cornerstone of diabetes management as it aids in glycemic control, weight management, reducing blood pressure, and improving the quality of life of patients. Unfortunately, owing to the complexity and difficulties of regulating exogenous insulin in a physiologic manner during exercise, physical activity often results in hypoglycemia in patients with type 1 diabetes mellitus (type 1 DM). When glucose levels fall below threshold glycemic levels, neuroendocrine, autonomic nervous system (ANS), and metabolic glucose counterregulatory mechanisms are activated. These hypoglycemic counterregulatory mechanisms in type 1 DM can be blunted irreversibly by disease duration or by acute episodes of prior stress. These reduced (or absent) counterregulatory responses result in a threefold increase in severe hypoglycemia when intensive glycemic control is implemented in type 1 DM. Much recent work has been focused on determining the in vivo mechanisms responsible for causing the increased incidence of severe hypoglycemia in type 1 DM. Studies from several laboratories have demonstrated the role played by episodes of antecedent hypoglycemia in producing blunted glucose counterregulatory responses during subsequent exposures of hypoglycemia. Until recently, the mechanisms responsible for exercise related hypoglycemia in type 1 DM have been attributed to relative or absolute increases of insulin levels or incomplete glycogen repletion after physical activity. Owing to the qualitative similarity of neuroendocrine, ANS, and metabolic responses to hypoglycemia and exercise, we have hypothesized that neuroendocrine and ANS counterregulatory dysfunction may also play an important role in the pathogenesis of exercise-related hypoglycemia in type 1 DM. Vicious cycles can be created in type 1 DM, where an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and ANS responses to a subsequent episode of either stress, thereby creating further hypoglycemia. This article will review the recent work that has studied the contribution of counterregulatory dysfunction to exercise-induced hypoglycemia in type 1 DM.

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Impaired adrenergic response to prolonged exercise in type I diabetes

Cited by 38 publications

References 34 publications

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

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

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

Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitus

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