Fuel and fluid homeostasis during long-term exercise in healthy subjects and type I diabetic patients.

OBJECTIVE--This study was designed to examine metabolic and hormonal effects of long-term exercise in healthy subjects and insulin-dependent (type I) diabetic patients. RESEARCH DESIGN AND METHODS--Two studies were performed. First, 16 healthy males (32 +/- 3 yr) were studied during a semitriathlon competition (2 km swimming, 90 km biking, and 21 km running). Second, 9 type I diabetic males (41 +/- 2 yr) and 17 healthy matched control subjects were studied during a 75 km cross-country skiing race. Blood samples were taken before and immediately after exercise, and also during the ski race. RESULTS--During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell. Apart from a fall in magnesium, serum electrolyte concentrations remained unchanged. Before long-term skiing, patients reduced their insulin dose by 30-40%. They were hyperglycemic during the initial part of the race, but near normoglycemic thereafter. There were large interindividual variations in the increments of counterregulatory hormones, whereas serum testosterone and luteinizing hormone fell quite uniformly. Plasma renin activity and aldosterone concentrations rose similarly in diabetic and healthy subjects, whereas the rise in antidiuretic hormone was slightly greater in diabetic patients. During the initial part of the race, serum atrial natriuretic peptide fell in both groups. CONCLUSIONS--Severalfold increments in hormone concentrations contribute to the maintenance of fuel and fluid homeostasis during long-term exercise. With an appropriate adjustment of insulin dose and diet, also type I diabetic patients can participate in competitive long-term exercise.     

Fluid homoeostasis during prolonged low-intensity walking on consecutive days

1. The effect on fluid homoeostasis of walking 37 km on each of 4 consecutive relatively cool days was studied in six male subjects. The daily exercise intensity was consistent and was equivalent to 17(1)% [mean (SE)] of maximum oxygen uptake for these subjects. 2. The diet during the study consisted of a mainly carbohydrate breakfast, consumed immediately before each day's exercise, and unrestricted access to a normal mixed diet after completion of each day's exercise. Water was allowed ad libitum during the walk. Food and fluid intake were recorded. 3. Body weight remained constant over the 4-day walk. The difference between total daily fluid intake and the corresponding 24 h urine output was 1684 (250) ml, 1621 (522) ml, 1107 (252) ml and 1406 (208) ml, respectively, on each of the 4 exercise days. 4. There was a calculated increase of 21.3(6.6)% in plasma volume over the 4-day walk; the largest daily change [11.3(2.9)%] occurred during the walk on day 1. The increase in plasma volume was maintained for at least 4 days after completion of the walk. 5. From day 2, serum sodium concentration tended to increase during the exercise period and fell to the pre-exercise concentration during the overnight rest periods. The concentration of the other measured serum constituents remained relatively constant, and serum osmolality did not alter over the study period.     

不同运动方式对心肌梗死大鼠心肌线粒体稳态的影响

目的 探讨中等强度持续运动(MCT)和高强度间歇运动(HIT)对急性心肌梗死(AMI)后心室重构及线粒体稳态的干预差异.方法 雄性SD大鼠制备AMI模型,随机(随机数字法)分为假手术组(Sham,n=10)、AMI对照组(AMI,n=9)、AMI+ MCT运动组(AMI+M,n=9)和AMI+ HIT运动组(AMI+H,n=10).AMI+M组和AMI+H组分别进行4周MCT或HIT运动训练.左心室导管法检测心功能,荧光探针法检测线粒体膜电位、ROS生成速率及ATP合成活力,Western blot法检测PINK1、Beclin1、Mfn2、Drp1、Tfam、COXⅣ和PGC-1α蛋白表达量.结果 与AMI组比较,AMI+M和AMI+H组Beclin1、PINK1、Mfn2和PGC-1α表达显著升高(P＜0.05或P＜0.01),ROS生成速率和Drp1表达显著降低(P＜0.05或P＜0.01);AMI+H组±dp/dt max绝对值、膜电位、ATP合成活力、Tfam和COXⅣ表达显著升高(P＜0.05).与AMI+M组比较,AMI+H组±dp/dt max绝对值、Tfam、COXⅣ和PGC-1α表达显著升高(P＜0.05).结论 HIT在干预AMI后心室重塑及线粒体稳态方面较MCT更具时效性.     

Effect of indomethacin on salt and water homeostasis.

The effects of indomethacin-induced prostaglandin inhibition on sodium and chloride homeostasis in normal man were assessed. Seven normal subjects were on a 150-mEq sodium diet for 3 days prior to receiving indomethacin or no drug. Indomethacin decreased fractional excretions of sodium and chloride without affecting fractional excretion of potassium, creatinine clearance, or percent fractional reabsorption of free water. Cumulative sodium excretion at 8 hr fell from 49.8 +/- 7.2 to 16.1 +/- 4.8 mEq (p less than 0.005) after indomethacin. Chloride fell at 8 hr from 49.7 +/- 6.4 to 21.3 +/- 5.1 mEq (p less than 0.005). Urinary volume and osmolal clearance decreased in similar magnitudes such that free water reabsorption was not changed by indomethacin. This study showed that indomethacin decreased renal sodium and chloride excretion, implying that endogenous prostaglandins may be modulators of renal sodium excretion.     

Interaction of sulfonylureas and exercise on glucose homeostasis in type 2 diabetic patients.

OBJECTIVE: To determine whether the plasma glucose-lowering effects of sulfonylureas and acute submaximal exercise are additive and, accordingly, to determine whether they may increase the risk of hypoglycemia when combined in fasting patients. RESEARCH DESIGN AND METHODS: Eight postabsorptive type 2 diabetic patients were examined at three occasions: after oral sulfonylurea (7 mg glibenclamide), during 60 min of ergometer cycle exercise at 57 +/- 3% of VO2max, and during exercise after glibenclamide. RESULTS: Heart rate, VO2, and lactate responses to exercise were comparable (P > 0.05) on days with and without glibenclamide. Plasma insulin concentrations were always increased by glibenclamide, and they were lowered identically by exercise with and without glibenclamide. However, throughout exercise, absolute concentrations of insulin were lower on days without glibenclamide compared with days with glibenclamide (34.5 +/- 4.7 vs. 47.4 +/- 5.5 pmol/l; P < 0.05). At the start of exercise, glucose concentrations were similar between experiments (P > 0.05). The rate of decrease in glucose during exercise was higher (P < 0.05) on days with both glibenclamide and exercise, compared with days with glibenclamide alone and days with exercise alone (-0.035 +/- 0.009 vs. -0.016 +/- 0.002 and -0.022 +/- 0.005 mmol.l-1.min-1, respectively). Consequently, the glucose nadir was lower on days with glibenclamide and exercise than on days with glibenclamide or exercise alone (6.7 +/- 1.1 vs. 8.1 +/- 0.9 and 7.6 +/- 1.0 mmol/l, respectively; P < 0.05). During exercise, the rate of appearance of plasma glucose determined by 3-[3H]glucose infusion was lower on days with glibenclamide than on days without glibenclamide (2.3 +/- 0.1 vs. 2.9 +/- 0.1 mg.min-1.kg-1; P < 0.05). In contrast, glucose clearance was identical (P > 0.05). CONCLUSIONS: In postabsorptive type 2 diabetic patients, the hypoglycemic action of glibenclamide and exercise is enhanced when the treatments are combined. The interaction reflects an increased inhibition by glibenclamide-enhanced insulin levels of hepatic glucose production when hepatic glucose production is accelerated by exercise.     

Effects of exercise training on glucose homeostasis: the HERITAGE Family Study

OBJECTIVE: To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (i.v.GTT). RESEARCH DESIGN AND METHODS: An i.v.GTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% VO2max for 30 min per session to 75% VO2max for 50 min per session. RESULTS: Mean insulin sensitivity increased by 10% (P < 0.001) following the intervention, but the variability in the changes was high. Men had larger improvements than women (P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P < 0.001), measures of glucose tolerance and of the capacity of glucose to mediate its own disposal, respectively. The acute insulin response to glucose, a measure of insulin secretion, increased by 7% in the quartile with the lowest baseline glucose tolerance and decreased by 14% in the quartile with the highest baseline glucose tolerance (P < 0.001). The glucose area below fasting levels during the i.v.GTT was reduced by 7% (P = 0.02). CONCLUSIONS: Although the effects of structured regular exercise were highly variable, there were improvements in virtually all i.v.GTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.     

Role of changes in insulin and glucagon in glucose homeostasis in exercise.

This experiment was performed to determine if plasma glucose homeostasis is maintained in normal human volunteers during light exercise (40% maximal oxygen consumption [VO2 max]) when changes in insulin and glucagon are prevented. Hormonal control was achieved by the infusion of somatostatin, insulin, and glucagon. Glucose kinetics and oxidation rates were determined with stable isotopic tracers of glucose, and by indirect calorimetry. Two different rates of replacement of insulin and glucagon were used; in one group, insulin was clamped at 19.8 +/- 2.6 microU/ml (high-insulin group), and in the other group insulin was clamped at 9.2 +/- 1.3 microU/ml (low-insulin group). Glucagon was maintained at 261 +/- 16.2 and 124 +/- 6.4 pg/ml, respectively, in the high-insulin and low-insulin groups. Without hormonal control, plasma glucose homeostasis was maintained during exercise because the increase in glucose uptake was balanced by a corresponding increase in glucose production. When changes in insulin and glucagon were prevented, plasma glucose concentration fell, particularly in the high-insulin group. Glucose uptake increased to a greater extent than when hormones were not controlled, and glucose production did not increase sufficiently to compensate. The increase in glucose uptake in the hormonal control groups was associated with an increased rate of glucose oxidation. When euglycemia was maintained by glucose infusion in the hormonal control subjects, the modest increase in glucose production that otherwise occurred was prevented. It is concluded that during light exercise there must be a reduction in insulin concentration and/or an increase in glucagon concentration if plasma glucose homeostasis is to be maintained. If such changes do not occur, hypoglycemia, and hence exhaustion, may occur.     

A comprehensive analysis of the fluid and electrolytes system. An interactive exercise.

The fluid and electrolyte system is difficult to study because one cannot examine an organ in order to understand the anatomical and functional connection. This exercise was developed to emphasize the connection between different fluid and electrolyte situations.     

Comparison of blood-culture results after five and seven days of incubation using the BACTEC NR660

We compared 16,606 blood cultures for microbial growth on days 5, 6, and 7 of incubation using the BACTEC NR660. Only 20 potentially significant organisms (0.8% of positive cultures) were detected after day 5 and only one resulted in a change of patient management. We recommend users of the BACTEC NR660 consider a 5-day protocol for routine blood cultures.     

Effect of probenecid on cerebrospinal fluid methotrexate kinetics.

The effect of probenecid (PBC) on methotrexate (MTX) kinetics in the cerebrospinal fluid (CSF) and serum was studied in 4 patients on high-dose MTX with leucovorin rescue to determine whether addition of PBC could prolong effective CSF MTX levels. Each patient received 2 courses of MTX, 1 with and 1 without PBC. PBC caused a 2.8 to 4.2-fold increase in CSF MTX concentrations but failed to prolong the CSF half-life (1 1/2). PBC prolonged the initial MTX elimination t 1/2 in the blood from 2.7 to 4.1 hr, but had little effect on subsequent t 1/2s. No effect of MTX on PBC clearance was detected. Our data suggest that in man PBC in concentrations that were high enough to inhibit the renal clearance of MTX failed to alter the clearance of MTX from the CSF when both drugs were administered systemically.     

Effect of exercise on pharmacokinetics

The increasing popularity of sporting events, even for people on drug treatment, has raised the question of the interaction of exercise and pharmacokinetics. Exercise reduces splanchnic blood flow, but possible changes in the absorption of orally given drugs seem to be of minor clinical significance. Absorption from intramuscular, subcutaneou and transdermal application sites may be accelerated by exercise, possibly causing harmful consequences, e.g. in diabetics treated with insulin. Exercise or physical work increases the rate and depth of respiration thus increasing alveolar exchange of gases and vapours. Physical activity increases muscular blood flow and the binding of digoxin to muscular structures, with a simultaneous fall in the concentration of serum digoxin. Reduction in blood flow to adipose and other inactive tissues may delay the distribution of some drugs that are stored or removed by these tissues. The change from supine to upright position can affect the distribution of a drug. Exercise reduces the blood flow in the liver and deactivation of drugs with flow-limited (high clearance) hepatic metabolism such as nitrates and lidocaine. Metabolism of capacity-limited (low clearance) drugs, e.g. antipyrine, diazepam and amobarbital, is not influenced by exercise. Renal plasma flow, urine excretion rate and urine pH are also reduced by exercise. This is an important reason why the serum levels of drugs eliminated through the kidneys increase during physical stress. The changes in parenteral absorption and distribution volume of some drugs caused by exercise, as well as the short half-life of drugs, are properties resulting in altered therapeutic/toxic response in those drugs with a narrow therapeutic range.     

Effect of marihuana on cardiorespiratory responses to submaximal exercise.

Six male chronic marihuana (MH) users exercised on a bicycle ergometer for 15 min at approximately 50% VO2max under 3 conditions: (1) not smoking (control), (2) after smoking MH containing 7.5 mg (-) delta-9-tetrahydrocannabinol, and (3) after smoking placebo marihuana (PL). The MH was administered double-blind in a counterbalanced repeated-measures design. Heart rates (HRs), arterial blood pressures (BPs), pulmonary ventilation (VE), and oxygen uptake (VO2) were measured during exercise and 15 min recovery. PL had no effect on any of the physiologic variables. Smoking MH had no effect on systolic blood pressure (SBP), diastolic blood pressure (DBP), VE, or VO2, but did induce a marked increase in heart rate which persisted throughout exercise and recovery periods, averaging 34% higher than control values at rest, 18% higher during exercise, and up to 50% higher during recovery. MH smoking increased the product of HR x SBP in all circumstances.     

Reproducibility of insulin dosage on consecutive days of blood glucose control by an artificial beta-cell in brittle diabetic patients

The profiles of blood glucose and of insulin dosage were compared between the first and second of 2 consecutive days of Biostator administration under constant conditions in 12 brittle type I diabetic inpatients. All blood glucose criteria and the daily insulin doses were reproducible between these 2 days for the entire group of patients. In nearly all patients, however, there were distinct but unsystematic differences between the 2 days in the diurnal patterns of insulin dose distribution. These differences could be ascribed to some stress reaction or inherent metabolic lability. It is concluded that, in these extremely labile diabetic patients, due to the insufficient short-term reproducibility of the outcome of an extracorporal artificial beta-cell, caution must be used when constant profiles are to be predicted from these doses for open-loop insulin delivery systems or for conventional subcutaneous injection therapy.     

运动对红细胞功能的影响

目的:总结运动时红细胞在细胞水平上出现各种功能的变化。资料来源:应用计算机检索Medline1991-01/2004-12关于运动对红细胞的影响的文章,检索词:“sports;redbloodcell,immunefunctiondeformability”,限定语言种类为英文;同时检索中国期刊网1991-01/2004-12关于运动对红细胞的影响的文章,检索词:“运动,红细胞,免疫功能;抗氧化酶”。限定语言种类为中文。同时阅读相关内容的书籍。资料选择:对资料进行初审,选择与运动引起的红细胞变形,红细胞免疫机能的改变;红细胞抗氧化酶活性的变化;红细胞生成与老化的相关文章,然后筛除与以上要求无明显联系的文章。纳入标准:详细阐述运动对红细胞的影响的文献。排除重复性研究。资料提炼:收集69篇关于运动、红细胞及其运动对红细胞的影响的文献,排除55篇,选用14篇文献和1本书籍内容用以综述。资料综合:红细胞是机体重要的免疫活性细胞之一,运动时红细胞流变性受运动强度、持续时间和训练水平等因素影响。高强度、长时间的运动训练可抑制红细胞免疫功能。在运动中红细胞超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性明显增高,能快速消除自由基对红细胞的损伤,改善红细胞的运氧功能,延缓运动性疲劳的发生。运动增加了红细胞的更新。但高强度、大运动量训练引起的红细胞和血红蛋白破坏速度超过生成速度,则可能导致红细胞的减少和血红蛋白下降,可严重影响运动员的运动能力和恢复能力。结论:了解运动中红细胞的变形性、免疫功能的变化及其恢复特点、抗氧化酶活性、生成与老化的影响,对科学地指导大众健身运动、运动训练与体育教学具有重要的意义。     

运动对红细胞功能的影响

目的：总结运动时红细胞在细胞水平上出现各种功能的变化。 资料来源：应用计算机检索Medlinel991—01／2004-12关于运动对红细胞的影响的文章，检索词：“sports；redbloodcell，immunefunctiondeformability”，限定语言种类为英文；同时检索中国期刊网1991-01／2004—12关于运动对红细胞的影响的文章，检索词：“运动，红细胞，免疫功能；抗氧化酶”。限定语言种类为中文。同时阅读相关内容的书籍。资料选择：对资料进行初审，选择与运动引起的红细胞变形，红细胞免疫机能的改变；红细胞抗氧化酶活性的变化；红细胞生成与老化的相关文章，然后筛除与以上要求无明显联系的文章。纳入标准：详细阐述运动对红细胞的影响的文献。排除重复性研究。 资料提炼：收集69篇关于运动、红细胞及其运动对红细胞的影响的文献，排除55篇，选用14篇文献和1本书籍内容用以综述。 资料综合：红细胞是机体重要的免疫活性细胞之一，运动时红细胞流变性受运动强度、持续时间和训练水平等因素影响。高强度、长时间的运动训练可抑制红细胞免疫功能。在运动中红细胞超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性明显增高，能快速消除自由基对红细胞的损伤，改善红细胞的运氧功能，延缓运动性疲劳的发生。运动增加了红细胞的更新。但高强度、大运动量训练引起的红细胞和血红蛋白破坏速度超过生成速度，则可能导致红细胞的减少和血红蛋白下降，可严重影响运动员的运动能力和恢复能力。 结论：了解运动中红细胞的变形性、免疫功能的变化及其恢复特点、抗氧化酶活性、生成与老化的影响，对科学地指导大众健身运动、运动训练与体育教学具有重要的意义。     

Comparison of carbohydrate-containing and carbohydrate-restricted hypocaloric diets in the treatment of obesity. Endurance and metabolic fuel homeostasis during strenuous exercise.

Eight untrained, obese females (greater than 30% body fat), ages 25-33 yr, were studied before, at 1 wk, and after 6 wk while taking either of two 830-kcal/d diets: carbohydrate-containing (CC) group (n = 4): 35% protein, 29% fat, 36% carbohydrate-restricted (CR) group (n = 4): 35% protein, 64% fat, 1% carbohydrate. Endurance, at approximately 75% of VO2max (maximum oxygen uptake) on a cycle decreased from base line by 50% at 1 and 6 wk in the CR group, but there was no change in the CC group. Preexercise muscle glycogen (vastus lateralis) did not change significantly in the CC group, but was decreased by 49% in the CR group after 1 wk, and by 51% after 6 wk. There was a close correlation between percent decrease in resting muscle glycogen and percent decrease in endurance (r = 0.79, P less than 0.01). The mean fasting and exercise plasma glucose concentration was lower in the CR group than in the CC group after 6 wk, but no subject became hypoglycemic during exercise. Serum FFA, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon changed similarly in the two groups during exercise at base line, 1 and 6 wk. Glycerol concentration was higher in the CR group during exercise only after 6 wk. Increases in serum lactate concentrations, and a mean exercise respiratory quotient of 0.93 suggested that cycle exercise at approximately 75% VO2max used predominantly glucose as a fuel. Conclusions: Resting muscle glycogen and endurance, during cycle exercise at approximately 75% VO2max, were maintained during a 36% carbohydrate, 830-kcal/d diet. In contrast, significant decreases, occurred in resting muscle glycogen and endurance, during similar exercise, after 6 wk of a 1% carbohydrate, 830-kcal/d diet.