Fasting plasma lactate as a possible early clinical marker for metabolic disease risk.

BACKGROUND AND AIM: Elevated fasting plasma lactate concentrations are evident in individuals with metabolic diseases. However, it has yet to be determined if these associations exist in a young, healthy population as a possible early marker for metabolic disease risk. The purpose of this study was to determine if indices of the metabolic syndrome are related to plasma lactate concentrations in this population. METHODS: Fifty (29 ± 7 yr) men (n = 19) and women (n = 31) classified as overweight (26.4 ± 1.8 kg/m2) participated in this observational study. Blood pressure and blood metabolites were measured after an overnight fast. Lactate was also measured before and after a three-day eucaloric high-fat (70 %) diet. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Visceral adipose tissue mass was determined via dual X-ray absorptiometry. RESULTS: Triglycerides (r = 0.55, p=<0.0001), HOMA-IR (r = 0.53, p=<0.0001), and systolic and diastolic (both, r = 0.36, p = 0.01) blood pressures associated with fasting plasma lactate. No differences in visceral adipose tissue existed between the sexes (p = 0.41); however, the relationship between visceral adipose tissue and lactate existed only in females (r = 0.59, p = 0.02) but not in males (p = 0.53). Fasting lactate and HOMA-IR increased in males (p = 0.01 and p = 0.02, respectively), but not females, following a three-day high-fat diet. CONCLUSION: Indices of the metabolic syndrome associated with fasting plasma lactates in young relatively healthy individuals. Fasting lactate also increased in a sex-specific manner after a three-day high fat diet. Thus, lactate could become a clinical marker for metabolic disease risk.

Greater reliance on glycolysis is associated with lower mitochondrial substrate oxidation and insulin sensitivity in infant myogenic MSCs.

Individuals with insulin resistance and obesity display higher skeletal muscle production of nonoxidized glycolytic products (i.e., lactate), and lower complete mitochondrial substrate oxidation to CO2. These findings have also been observed in individuals without obesity and are associated with an increased risk for metabolic disease. The purpose of this study was to determine if substrate preference is evident at the earliest stage of life (birth) and to provide a clinical blood marker (lactate) that could be indicative of a predisposition for metabolic disease later. We used radiolabeled tracers to assess substrate oxidation and insulin sensitivity of myogenically differentiated mesenchymal stem cells (MSCs), a proxy of infant skeletal muscle tissue, derived from umbilical cords of full-term infants. We found that greater production of nonoxidized glycolytic products (lactate, pyruvate, alanine) is directly proportional to lower substrate oxidation and insulin sensitivity in MSCs. In addition, we found an inverse relationship between the ratio of complete glucose oxidation to CO2 and infant blood lactate at 1 mo of age. Collectively, considering that higher lactate was associated with lower MSC glucose oxidation and has been shown to be implicated with metabolic disease, it may be an early indicator of infant skeletal muscle phenotype.NEW & NOTEWORTHY In infant myogenically differentiated mesenchymal stem cells, greater production of nonoxidized glycolytic products was directly proportional to lower substrate oxidation and insulin resistance. Glucose oxidation was inversely correlated with infant blood lactate. This suggests that innate differences in infant substrate oxidation exist at birth and could be associated with the development of metabolic disease later in life. Clinical assessment of infant blood lactate could be used as an early indicator of skeletal muscle phenotype.

Prescribed exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P): Design, methods and rationale.

Clinically significant weight loss is associated with health benefits for overweight and obese adults. Participation in adequate amounts of physical activity is critical for weight maintenance. However, the recommended amount of physical activity needed to promote weight maintenance is based primarily on retrospective studies that quantified physical activity levels through questionnaires which tend to overestimate physical activity levels. In addition, the present literature has provided little data on the impact of these physical activity levels on cardiovascular and diabetes risk factors, which may have equal or more clinical importance than weight changes. The Prescribed Exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P) study will evaluate the effect of aerobic exercise training amount on weight maintenance following clinically significant weight loss in overweight and obese adults (BMI 25-40 kg/m2) age 30-65 years. Participants (N = 39) will complete a 10-week OPTIFAST® weight loss program with supervised aerobic exercise training. Individuals who achieve ≥7% weight loss from baseline will be subsequently randomized to levels of aerobic training consistent with physical activity recommendations (PA-REC) or weight maintenance recommendations (WM-REC) for 18 additional weeks. The primary outcome of the PREVAIL-P study will be change in weight from the completion of OPTIFAST® program to the end of the study. Notable secondary measures include changes in clinically relevant cardiometabolic risk factors between study groups (e.g. blood lipids concentrations, oral glucose tolerance, arterial stiffness). This pilot study will be used to estimate the effect sizes needed for a randomized controlled trial on this topic.

The association between lactate and muscle aerobic substrate oxidation: Is lactate an early marker for metabolic disease in healthy subjects?

Fasting plasma lactate concentrations are elevated in individuals with metabolic disease. The aim of this study was to determine if the variance in fasting lactate concentrations were associated with factors linked with cardiometabolic health even in a young, lean cohort. Young (age 22 ± 0.5; N = 30) lean (BMI (22.4 ± 0.4 kg/m2 ) women were assessed for waist-to-hip ratio, aerobic capacity (VO2 peak), skeletal muscle oxidative capacity (near infrared spectroscopy; fat oxidation from muscle biopsies), and fasting glucose and insulin (HOMA-IR). Subjects had a mean fasting lactate of 0.9 ± 0.1 mmol/L. The rate of deoxygenation of hemoglobin/myoglobin (R2  = .23, p = .03) in resting muscle and skeletal muscle homogenate fatty acid oxidation (R2  = .72, p = .004) were inversely associated with fasting lactate. Likewise, cardiorespiratory fitness (time to exhaustion during the VO2 peak test) was inversely associated with lactate (R2  = .20, p = .05). Lactate concentration was inversely correlated with HDL:LDL (R2  = .57, p = .02) and positively correlated with the waist to hip ratio (R2  = .52, p = .02). Plasma lactate was associated with various indices of cardiometabolic health. Thus, early determination of fasting lactate concentration could become a common biomarker used for identifying individuals at early risk for metabolic diseases.

Plasma lactate as a marker of metabolic health: Implications of elevated lactate for impairment of aerobic metabolism in the metabolic syndrome.

BACKGROUND: Fasting lactate is elevated in metabolic diseases and could possibly be predictive of the risk of developing the metabolic syndrome. METHODS: Plasma samples were analyzed for fasting lactate to compare lean subjects, nondiabetic subjects with severe obesity, and metabolically impaired subjects. Subjects with severe obesity were studied 1 week before and 1 week to 9 months after gastric bypass surgery. Subjects with components of the metabolic syndrome were studied before and after 6 months of an exercise intervention. RESULTS: Metabolically impaired subjects had higher fasting lactate concentrations (P < .0001) and respond to a glucose or insulin challenge with higher lactates than non-obese subjects (P < .004). Lactate was significantly reduced a week after gastric bypass surgery (P < .05) and further reduced 1 to 9 months after surgery (0.95 ± 0.04 mM in non-obese, 1.26 ± 0.12 mM in subjects with severe obesity, and 0.68 ± 0.03 mM 1-3 months after gastric bypass). Six months of chronic exercise resulted in a 16% reduction (P = .028) in fasting lactate. CONCLUSION: Fasting plasma lactate was elevated in obese subjects with the metabolic syndrome compared with healthy lean individuals. Lactate was reduced by exercise and bariatric surgery, interventions that improve metabolic health and risk for subsequent disease. The results of this study and those previously published by our research group suggest that elevated lactate may be caused by an impairment in aerobic metabolism and may offer a metric assessing the severity of the metabolic syndrome.

Electrical pulse stimulation induces differential responses in insulin action in myotubes from severely obese individuals.

KEY POINTS: Exercise/exercise training can enhance insulin sensitivity through adaptations in skeletal muscle, the primary site of insulin-mediated glucose disposal; however, in humans the range of improvement can vary substantially. The purpose of this study was to determine if obesity influences the magnitude of the exercise response in relation to improving insulin sensitivity in human skeletal muscle. Electrical pulse stimulation (EPS; 24 h) of primary human skeletal muscle myotubes improved insulin action in tissue from both lean and severely obese individuals, but responses to EPS were blunted with obesity. EPS improved insulin signal transduction in myotubes from lean but not severely obese subjects and increased AMP accumulation and AMPK Thr172 phosphorylation, but to a lesser degree in myotubes from the severely obese. These data reveal that myotubes of severely obese individuals enhance insulin action and stimulate exercise-responsive molecules with contraction, but in a manner and magnitude that differs from lean subjects. ABSTRACT: Exercise/muscle contraction can enhance whole-body insulin sensitivity; however, in humans the range of improvements can vary substantially. In order, to determine if obesity influences the magnitude of the exercise response, this study compared the effects of electrical pulse stimulation (EPS)-induced contractile activity upon primary myotubes derived from lean and severely obese (BMI ≥ 40 kg/m2 ) women. Prior to muscle contraction, insulin action was compromised in myotubes from the severely obese as was evident from reduced insulin-stimulated glycogen synthesis, glucose oxidation, glucose uptake, insulin signal transduction (IRS1, Akt, TBC1D4), and insulin-stimulated GLUT4 translocation. EPS (24 h) increased AMP, IMP, AMPK Thr172 phosphorylation, PGC1α content, and insulin action in myotubes of both the lean and severely obese subjects. However, despite normalizing indices of insulin action to levels seen in the lean control (non-EPS) condition, responses to EPS were blunted with obesity. EPS improved insulin signal transduction in myotubes from lean but not severely obese subjects and EPS increased AMP accumulation and AMPK Thr172 phosphorylation, but to a lesser degree in myotubes from the severely obese. These data reveal that myotubes of severely obese individuals enhance insulin action and stimulate exercise-responsive molecules with contraction, but in a manner and magnitude that differs from lean subjects.

Exercise Effects on Adipose Tissue Postprandial Lipolysis and Blood Flow in Children.

Poor suppression of lipolysis and blunted increase in blood flow after meal ingestion in obese adults may indicate resistance to the antilipolytic action of insulin. Exercise may be used to normalize lipolytic responses to food intake by increasing insulin sensitivity. PURPOSE: To determine if acute bouts of aerobic exercise and/or excise training alter lipolytic and blood flow responses to food intake in lean (LN) and obese (OB) children. METHODS: Sixty-five children (9-11 yr) were randomized into acute exercise (EX: 16 LN and 28 OB) or control (CON: 9 LN and 12 OB) groups that exercised (EX), or rested (CON) between standardized breakfast and lunch. Microdialysis probes were inserted into the subcutaneous abdominal adipose tissue to monitor interstitial glycerol (lipolysis) and blood flow. Changes in interstitial glycerol and nutritive flow were calculated from dialysate samples before and after each meal. A subgroup (OB = 15 and LN = 9) from the acute exercise group underwent 16 wk of aerobic exercise training. RESULTS: Poor suppression of lipolysis and a blunted increase in adipose tissue nutritive blood flow in response to breakfast was associated with BMI percentile (r = 0.3, P < 0.05). These responses were normalized at lunch in the OB in the EX (P < 0.05), but not in OB in the CON. Sixteen weeks of exercise training did not improve meal-induced blood flow and marginally altered the antilipolytic response to the two meals (P = 0.06). CONCLUSIONS: Daily bouts of acute aerobic exercise should be used to improve the antilipolytic and nutritive blood flow response to a subsequent meal in obese children.

Intellectual development is positively related to intrinsic motivation and course grades for female but not male students.

We hypothesized that the intellectual development of students, i.e., their beliefs about the nature of knowledge and learning, affects their intrinsic motivation and class performance. Specifically, we hypothesized that students with low intellectual development (i.e., the naive beliefs that knowledge is simple, absolute, and certain) have low intrinsic motivation and low class performance, whereas students with high intellectual development (i.e., more sophisticated beliefs that knowledge is complex, tentative, and evolving) have high intrinsic motivation and class performance. To test this hypothesis, we administered the Learning Context Questionnaire to measure intellectual development. In addition, we administered the Intrinsic Motivation Inventory to assess our students' intrinsic motivation. Furthermore, we performed regression analyses between intellectual development with both intrinsic motivation and class performance. The results document a positive relationship among intellectual development, intrinsic motivation, and class performance for female students only. In sharp contrast, there was a negative relationship between intellectual development, intrinsic motivation, and class performance for male students. The slope comparisons documented significant differences in the slopes relating intellectual development, intrinsic motivation, and class performance between female and male students. Thus, female students with more sophisticated beliefs that knowledge is personally constructed, complex, and evolving had higher intrinsic motivation and class performance. In contrast, male students with the naive beliefs that the structure of knowledge is simple, absolute, and certain had higher levels of intrinsic motivation and class performance. The results suggest that sex influences intellectual development, which has an effect on intrinsic motivation for learning a specific topic.

Exercise and Weight Loss Improve Muscle Mitochondrial Respiration, Lipid Partitioning, and Insulin Sensitivity After Gastric Bypass Surgery.

Both Roux-en-Y gastric bypass (RYGB) surgery and exercise can improve insulin sensitivity in individuals with severe obesity. However, the impact of RYGB with or without exercise on skeletal muscle mitochondria, intramyocellular lipids, and insulin sensitivity index (SI) is unknown. We conducted a randomized exercise trial in patients (n = 101) who underwent RYGB surgery and completed either a 6-month moderate exercise (EX) or a health education control (CON) intervention. SI was determined by intravenous glucose tolerance test. Mitochondrial respiration and intramyocellular triglyceride, sphingolipid, and diacylglycerol content were measured in vastus lateralis biopsy specimens. We found that EX provided additional improvements in SI and that only EX improved cardiorespiratory fitness, mitochondrial respiration and enzyme activities, and cardiolipin profile with no change in mitochondrial content. Muscle triglycerides were reduced in type I fibers in CON, and sphingolipids decreased in both groups, with EX showing a further reduction in a number of ceramide species. In conclusion, exercise superimposed on bariatric surgery-induced weight loss enhances mitochondrial respiration, induces cardiolipin remodeling, reduces specific sphingolipids, and provides additional improvements in insulin sensitivity.

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, ß-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

Clinical trial demonstrates exercise following bariatric surgery improves insulin sensitivity.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S(I)) in obese patients. Regular exercise can also improve S(I) in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S(I) and other cardiometabolic factors. METHODS: We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1-3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included S(I) and glucose effectiveness (S(G)), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week). RESULTS: 119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). S(I) improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min⁻¹/µU/ml, P = 0.18 for Δ, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive S(I) improvement (PP: CON vs. EX; +1.57 vs. +2.69 min⁻¹/µU/ml, P = 0.019) above that of surgery. Exercise also improved S(G) (ITT: CON vs. EX; +0.0023 vs. +0.0063 min⁻¹, P = 0.009) compared with the CON group. Exercise improved cardiorespiratory fitness (VO2 peak) compared with the CON group. CONCLUSION: Moderate exercise following RYGB surgery provides additional improvements in S(I), S(G), and cardiorespiratory fitness compared with a sedentary lifestyle during similar weight loss. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00692367. FUNDING: This study was funded by the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK078192) and an NIH/National Center for Research Resources/Clinical and Translational Science Award (UL1 RR024153).

Cortisol as a biomarker of stress in term human labor: physiological and methodological issues.

Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation, the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal well-being and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol, and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology.

Impairments in site-specific AS160 phosphorylation and effects of exercise training.

The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18-84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18-84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751. Twelve weeks of endurance- or strength-oriented exercise training increased whole-body insulin action and reversed impairments in AS160 phosphorylation evident in insulin-resistant aged individuals. These findings suggest that a dampening of insulin-induced phosphorylation of AS160 on specific sites in skeletal muscle contributes to the insulin resistance evident in a sedentary aging population and that exercise training is an effective intervention for treating these impairments.

Obesity, insulin resistance, and skeletal muscle nitric oxide synthase.

The molecular mechanisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means ± SE: nonobese, body mass index = 25.5 ± 0.3 kg/m(2), n = 13; obese, body mass index = 36.6 ± 0.4 kg/m(2), n = 14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensitivity index (S(I)). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. S(I) was significantly lower in the obese compared with the nonobese group (~43%; P < 0.05), yet skeletal muscle iNOS protein expression was not different between nonobese and obese groups. Skeletal muscle eNOS protein was significantly higher in the nonobese than the obese group, and skeletal muscle nNOS protein tended to be higher (P = 0.054) in the obese compared with the nonobese group. Alternative analysis based on S(I) (high and low tertile) indicated that the most insulin-resistant group did not have significantly more skeletal muscle iNOS protein than the most insulin-sensitive group. In conclusion, human insulin resistance does not appear to be associated with an elevation in skeletal muscle iNOS protein in middle-aged individuals under fasting conditions.

Effect of short-term exercise training on intramyocellular lipid content.

The purpose of this study was to investigate the influence of exercise training on intramyocellular lipid (IMCL) content and test the hypothesis that the effect of endurance-oriented exercise training on IMCL is dependent on characteristics of the population studied. Lean (N = 11, body mass index (BMI) = 22.2 ± 0.7 kg·m⁻²), obese (N = 14, BMI = 38.8 ± 1.7 kg·m⁻²), and type 2 diabetic (N = 9, BMI = 35.5 ± 2.5 kg·m⁻²) participants were examined before and after 10 consecutive days of endurance-oriented (60 min·day⁻¹ at ~70% [Formula: see text]O(2peak)) exercise training. IMCL and muscle glycogen were measured by Oil-Red-O and periodic acid - Schiff staining, respectively. The results indicated that IMCL was elevated (p < 0.05) in the obese and diabetic groups compared with the lean subjects prior to training. After training, IMCL content decreased (-35%) in the participants with type 2 diabetes; there were no changes in IMCL in the lean or obese groups. Muscle glycogen content was lower in the diabetic subjects than in the lean subjects both before and after training. These data indicate that changes in IMCL with exercise training do not exhibit a universal response but rather depend on the metabolic status of the population studied.

Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT.

While the benefits of exercise are clear, many unresolved issues surround the optimal exercise prescription. Many organizations recommend aerobic training (AT) and resistance training (RT), yet few studies have compared their effects alone or in combination. The purpose of this study, part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and/or Resistance Training (STRRIDE/AT/RT), was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]. In a randomized trial, 249 subjects [18-70 yr old, overweight, sedentary, with moderate dyslipidemia (LDL cholesterol 130-190 mg/dl or HDL cholesterol ≤ 40 mg/dl for men or ≤ 45 mg/dl for women)] performed an initial 4-mo run-in period. Of these, 196 finished the run-in and were randomized into one of the following 8-mo exercise-training groups: 1) RT, which comprised 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set, 2) AT, which was equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O(2) uptake, and 3) full AT + full RT (AT/RT), with 155 subjects completing the intervention. The primary outcome variables were as follows: visceral and liver fat via CT, plasma liver enzymes, and HOMA. AT led to significant reductions in liver fat, visceral fat, alanine aminotransferase, HOMA, and total and subcutaneous abdominal fat (all P < 0.05). RT resulted in a decrease in subcutaneous abdominal fat (P < 0.05) but did not significantly improve the other variables. AT was more effective than RT at improving visceral fat, liver-to-spleen ratio, and total abdominal fat (all P < 0.05) and trended toward a greater reduction in liver fat score (P < 0.10). The effects of AT/RT were statistically indistinguishable from the effects of AT. These data show that, for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase, a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode.

The effects of hydrotherapy on anxiety, pain, neuroendocrine responses, and contraction dynamics during labor.

BACKGROUND: Hydrotherapy (immersion or bathing) is used worldwide to promote relaxation and decrease parturient anxiety and pain in labor, but the psychophysiological effects of this intervention remain obscure. DESIGN: A pretest-posttest design with repeated measures was used to examine the effects of hydrotherapy on maternal anxiety and pain, neuroendocrine responses, plasma volume shift (PVS), and uterine contractions (CXs) during labor. Correlations among variables were examined at three time points (preimmersion and twice during hydrotherapy). METHODS: Eleven term women (mean age 24.5 years) in spontaneous labor were immersed to the xiphoid in 37 degrees C water for 1 hr. Blood samples and measures of anxiety and pain were obtained under dry baseline conditions and repeated at 15 and 45 min of hydrotherapy. Uterine contractions were monitored telemetrically. RESULTS: Hydrotherapy was associated with decreases in anxiety, vasopressin (V), and oxytocin (O) levels at 15 and 45 min (all ps < .05). There were no significant differences between preimmersion and immersion pain or cortisol (C) levels. Pain decreased more for women with high baseline pain than for women with low baseline levels at 15 and 45 min. Cortisol levels decreased twice as much at 15 min of hydrotherapy for women with high baseline pain as for those with low baseline pain. beta-endorphin (betaE) levels increased at 15 min but did not differ between baseline and 45 min. During immersion, CX frequency decreased. A positive PVS at 15 min was correlated with contraction duration. CONCLUSIONS: Hydrotherapy during labor affects neuroendocrine responses that modify psychophysiological processes.

Effects of exercise training intensity on pancreatic beta-cell function.

OBJECTIVE: Insulin resistance and beta-cell dysfunction both are important contributors to the pathogenesis of type 2 diabetes. Exercise training improves insulin sensitivity, but its effects on beta-cell function are less well studied. RESEARCH DESIGN AND METHODS: Sedentary, overweight adults were randomized to control or one of three 8-month exercise programs: 1) low amount/moderate intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous intensity. Of 387 randomized, 260 completed the study and 237 had complete data. Insulin sensitivity (S(i)), acute insulin response to glucose (AIRg), and the disposition index (DI = S(i) x AIRg) were modeled from an intravenous glucose tolerance test. RESULTS: Compared with control subjects, all three training programs led to increases in DI. However, the moderate-intensity group experienced a significantly larger increase in DI than either of the vigorous-intensity groups and through a different mechanism. The high-amount/vigorous-intensity group improved S(i) and had a compensatory reduction in AIRg, whereas the moderate-intensity group had a similar improvement in S(i) but almost no reduction in AIRg. Importantly, the inactive control group experienced a significant increase in fasting glucose. CONCLUSIONS: To the extent that the DI accurately reflects beta-cell function, we observed that both moderate- and vigorous-intensity exercise training improved beta-cell function, albeit through distinct mechanisms. It is not clear which of these mechanisms is preferable for maintenance of metabolic health. While moderate-intensity exercise led to a larger improvement in DI, which may reflect a transition toward a more normal DI, longer-term investigations would be necessary to determine which was more effective at reducing diabetes risk.

Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women.

OBJECTIVE: To determine whether circulating metabolic intermediates are related to insulin resistance and beta-cell dysfunction in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: In 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry-based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates. RESULTS: The 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (S(I)) (R(2) = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R(2) = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R(2) = 0.39). Sex differences were found for metabolic predictors of S(I) and DI. CONCLUSIONS: In addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation.

The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of approximately 12 miles/wk, 1,200 kcal/wk at 40-55% peak O(2) consumption (Vo(2peak)), 200 min exercise/wk], 2) low volume/vigorous intensity ( approximately 12 miles/wk, 1,200 kcal/wk at 65-80% Vo(2peak), 125 min/wk), and 3) high volume/vigorous intensity ( approximately 20 miles/wk, 2,000 kcal/wk at 65-80% Vo(2peak), 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, S(I)) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. S(I) increased with training compared with the sedentary condition (P < or = 0.05) at 16-24 h with all of the exercise prescriptions. S(I) decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days S(I) was significantly elevated compared with sedentary (P < or = 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.