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...

The effects of oral carbohydrate on modulating counterregulatory responses in humans remain undecided. This study's specific aim was to determine the effects of oral carbohydrate on autonomic nervous system (ANS) and neuroendocrine responses during hyperinsulinemic hypoglycemia and euglycemia. Nineteen healthy volunteers were studied during paired, single blind experiments. Nine subjects underwent two-step glucose clamps consisting of 60 min of euglycemia (5.0 mmol/l) followed by either 15 g of oral carbohydrate (cal) as orange juice or a noncaloric control (nocal) and subsequent 90 min of clamped hypoglycemia (2.9 mmol/l). Ten other subjects underwent two randomized 150-min hyperinsulinemic-euglycemic clamps with cal or nocal control administered at 60 min. Oral carbohydrate initially blunted (P < 0.05) epinephrine, norepinephrine, cortisol, glucagon, pancreatic polypeptide, muscle sympathetic nerve activity (MSNA), symptom, and systolic blood pressure responses during hypoglycemia. However, by the end of 90 min of hypoglycemia, plasma epinephrine and norepinephrine responses had rebounded and were increased (P < 0.05) compared with control. MSNA and cortisol levels remained suppressed during hypoglycemia (P < 0.05) after cal, whereas pancreatic polypeptide, glucagon, symptom, and blood pressure responses increased similar to control following initial suppression. Oral carbohydrate had no effects on neuroendocrine or ANS responses during hyperinsulinemic euglycemia. These results demonstrate that oral carbohydrate can have differential effects on the time course of ANS and neuroendocrine responses during hypoglycemia. We conclude that gastro-splanchnic-portal sensing of an amount of carbohydrate recommended for use in clinical practice for correction of hypoglycemia can have widespread and significant effects on central nervous system mediated counterregulatory responses in healthy humans.

Western Australia's internal energy demand is projected to grow more than six times from 1975 until the year 2000. Demand has been divided into transport and non transport sectors in the context of existing known sources of supply (coal, oil, natural gas, natural gas liquids).Overall, comparing Western Australia's known energy reserves with estimated demand until the end of the century there is a surplus of total energy: natural gas and coal are in excess and there is a critical shortage of liquid fuels, and in particular fuel oil. The shortfall may be reduced by increasing gas production in order to recover the associated liquids.Known small oil reserves with doubtful economics could further reduce the deficit, but the most reliable method of filling the gap is, however, to find new oil reserves. Exploration prospects are thought to be sufficiently good in Western Australia to fill the gap provided incentive is given by government, but a period of shortage in the immediate future cannot be avoided. The crude expected to be discovered will be light and it is predicted that if large reserves are found it will be necessary to export light products to other States, and import heavy products from overseas to supply the necessary distillate for transportation and rising demand for duel oil in sectors where gas will not penetrate.