Effect of a two-month detraining on glucose tolerance and insulin sensitivity in athletes--link to adrenal steroid hormones

Reduction in physical activity has been demonstrated to associate with the increased risk in insulin resistance and type 2 diabetes. To determine whether alteration in insulinemia, due to abstention from regular exercise training, is associated with changes in serum dehydroepiandrosterone sulfate (DHEA-S) and cortisol, 18 highly trained badminton players (21.2 +/- 0.3 years) were enrolled into a 2-month detraining study. Fasting serum insulin, glucose, DHEA-S, and cortisol were determined at trained state and at day 60 of detraining. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test (OGTT). The 2-month detraining increased fasting glucose and insulin concentrations and body weight slightly, but did not significantly affect glucose tolerance and insulin response curve, in which 10 subjects had increased and 8 subjects had slightly decreased in the area under curve for insulin (IAUC). In the subjects with increased IAUC, serum cortisol was also elevated (from 0.44 +/- 0.07 to 0.83 +/- 0.26 U/l, P < 0.05) in parallel, and serum creatine kinase (CK) was unaltered during detraining. Whereas in the subjects with decreased IAUC, serum cortisol (from 0.51 +/- 0.19 to 0.54 +/- 0.14 U/l, no significance) was not changed and serum creatine kinase (from 461 +/- 179 to 151 +/- 21 U/l) was decreased during detraining. Two groups of detrained subjects exhibited a similar reduction in serum DHEA-S levels and slight elevation in body weight. The novel finding of the study is that the changes in serum cortisol, but not DHEA-S, were associated with the change in insulin sensitivity during early phase of lifestyle change from physically active to sedentary, and this response appears to be varied individually among athletes.     

Interactive effect of an acute bout of resistance exercise and dehydroepiandrosterone administration on glucose tolerance and serum lipids in middle-aged women

The present study determined the interactive effect of an acute bout of resistance exercise and dehydroepiandrosterone (DHEA) administration on glucose tolerance and serum lipids. Twenty middle-aged female subjects performed an acute bout of resistance exercise and were subsequently divided into two groups: placebo (age 40.7 +/- 2.0) and DHEA administered (age 39.0 +/- 2.7). Ten subjects who received DHEA (age 41.5 +/- 4.6) participated in a non-exercise control. DHEA (25 mg twice daily) or placebo was orally supplemented for 48 hours. Before exercise and 48 hours after the last exercise bout (14 hours after the last DHEA intake), an oral glucose tolerance test and an insulin concentration were determined. Levels of fasting serum cholesterol and triglyceride, tumor necrosis factor-alpha (TNF-alpha), creatine kinase (CK) were also measured. The DHEA administration significantly elevated the fasting dehydroepiandrosterone sulfate (DHEA-S) level by approximately 3-fold. Both acute resistance exercise and DHEA administration improved glucose tolerance, but no addictive effect was found. Furthermore, exercise and DHEA administration did not affect serum triglyceride and cholesterol levels, but both lipids were significantly lowered when DHEA was given following exercise. Resistance exercise induced elevations in serum CK and TNFalpha levels, but these increases were attenuated by the DHEA administration. The new finding of this study was that post-exercise DHEA administration decreased serum triglycerides and cholesterol. This effect appeared to be associated with its TNF-alpha lowering action.     

Plasma insulin and C-peptide responses to oral glucose load after physical exercise in men with normal and impaired glucose tolerance

Blood glucose, plasma insulin and C-peptide responses to oral glucose tolerance test (OGTT) were studied under basal conditions and immediately after 90-min exercise (60% VO2 max) in nondiabetic subjects with normal or impaired glucose tolerance. During the postexercise recovery blood glucose response to OGTT was increased in normal subjects and markedly decreased in those with impaired glucose tolerance, while insulin and C-peptide responses were diminished in both subgroups. The ratio of blood glucose to insulin was similarly elevated in all subjects. Comparing with basal conditions no significant changes were found in C-peptide to insulin ratio in response to OGTT after exercise, although a tendency towards an elevation of this ratio was noted in the subjects with impaired glucose tolerance. The data indicate that the reduced insulin response to OGTT during postexercise recovery in healthy subjects is due to diminished insulin secretion without any substantial changes in the hormone removal from blood, whereas in the glucose intolerant men the latter process may be enhanced.     

Glucose tolerance and insulin sensitivity following an one-week volleyball competition

The purpose of the study was to compare glucose tolerance and insulin sensitivity between trained (TR) and competition (CP) states, in relation to cortisol and testosterone levels. Sixteen highly trained volleyball players voluntarily participated in this study. The first testing session (TR state) occurred 1 week before the start of national level volleyball CP, and the second testing session (CP state) occurred next morning after the 1-week CP. Fasted serum sample was used for measuring cortisol and testosterone. Subjects were then orally challenged with 75 g of glucose solution for determinations of oral glucose tolerance test (OGTT) and insulin response. Under both fasted and glucose challenged conditions, glucose levels of CP were not different from TR state, whereas insulin levels of CP were significantly elevated above TR (50 min: from 78.8 +/- 8.7 to 96.6 +/- 8.1 microU/ml, P < 0.05; 80 min: from 62.8 +/- 7.0 to 82.0 +/- 7.3; P < 0.05). Muscle creatine kinase (CK) level in blood was significantly increased above TR, suggesting greater muscle damage by CP. Serum leptin level, percent fat mass, and body weight were not different between two states. CP significantly increased serum cortisol level without significantly change in testosterone level. The new finding of the study was that volleyball CP reduced the whole-body insulin sensitivity significantly compared to TR state. The greater level of insulin concentration under CP state appears to be associated with elevated serum cortisol level. Despites the benefit of increased physical activity on metabolic function is widely recognized, physiological stress associated with CP can result in attenuation of systemic insulin sensitivity compared TR state.     

Contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity of endurance athletes

The present study was designed to evaluate the contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity characterizing endurance athletes. Plasma glucose and insulin were measured during an oral glucose tolerance test (OGTT) in six endurance athletes. Glucose storage and lipid oxidation during this test were also determined using indirect calorimetry. These measurements were compared to those obtained in five non-trained subjects who were tested before and during the three days following a 90-min cycle ergometer exercise performed at 69% of their VO2max. As expected, preexercise values of non-trained subjects revealed a much higher insulin response to glucose, and a lower glucose storage and lipid oxidation compared to results obtained in endurance trained individuals. Glucose tolerance was comparable in both groups. The morning following the exercise test, i.e. about 16 h after exercise, glucose storage was significantly increased in non-trained subjects to a level similar to that found in trained subjects. Surprisingly, this was accompanied by higher values of glucose during the OGTT without significant changes in insulinaemia. This impairment in glucose homeostasis was transitory since glucose tolerance had returned to control level on day 2 after exercise. At that time, the increase in glucose storage was less pronounced than in day 1. On day 3 after exercise, glucose and insulin responses to glucose were similar to preexercise values. These results indicate that the increase in glucose storage by acute exercise is not systematically associated with an improved glucose homeostasis, suggesting that other adaptive mechanisms also contribute to the improvement of insulin sensitivity in endurance athletes.     

Retinol-binding protein 4 (RBP-4) levels do not change after oral glucose tolerance test and after dexamethasone, but correlate with some indices of insulin resistance in humans

Introduction: Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2. Material and methods: Both studies included 35 subjects (8 males), age (mean +/- SD) 39.1 +/- 15.6 years, BMI 35.8 +/- 8.7 kg/m(2). Twenty-four of those subjects (5 males), age 38.7 +/- 15.1 years, BMI 34.4 +/- 8.3 kg/m(2), had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 +/- 18.1 years, BMI 36.7 +/- 9.0 kg/m(2) underwent screening for Cushing's disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT. Results: Glucose administration resulted in significant increases in insulin and glucose (p < 0.0001). There was, however, no change in RBP-4 concentrations (124.1 +/- 32 mg/ml at 0 minutes, 123 +/- 35 mg/ml at 60 minutes and 126.5 +/- 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 +/- 6.8 to 17.1 +/- 7.2 muU/ml; p = 0.003), and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 +/- 26.8 vs. 117.5 +/- 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r(2) = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r(2) = 0.88]; p<0.00001). In subjects who received dexamethasone, a positive correlation between RBP-4 and HOMA (p = 0.01) was lost after two days of dexamethasone administration (p = 0.61). Conclusions: RBP-4 levels do not change during oral glucose tolerance test or after a dexamethasone-induced increase in insulin resistance. This implies that it is highly unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis in humans and that it responds to short-term changes in insulin resistance. A moderate correlation between RBP-4 and some insulin resistance indices (HOMA) does not exclude the fact that RBP-4 might be one of many factors that can influence insulin sensitivity in humans.     

Effects of amlodipine on serum levels of adrenal androgens and insulin in hypertensive men with obesity.

We investigated the effects of the calcium channel blocker amlodipine besilate on serum levels of adrenal androgens and insulin in 20 men with essential hypertension and obesity (age: 51.9+/-4.7 years, body mass index: 27.7+/-1.5 kg/m2). All were treated with amlodipine besilate (Norvasc) for 3 months. Blood pressure, fasting plasma glucose (FPG), HbA1c and serum levels of insulin, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and lipids were measured before and after a 3-month period. In 10 patients, 75 g oral glucose tolerance test (75 g-OGTT) was also performed. Amlodipine besilate treatment 1) lowered the fasting serum insulin level and total serum insulin level during 75 g-OGTT and 2) increased serum DHEA and DHEA-S levels. No changes in fasting plasma glucose, HbA1c and serum lipids were observed during treatment. We conclude that amlodipine besilate improves insulin resistance and consequently increases serum DHEA and DHEA-S levels.     

Dehydroepiandrosterone sulfate linked to physiologic response against hot spring immersion

The steroid dehydroepiandrosterone sulfate (DHEA-S) is associated with longevity and adaptation against external stress in humans. The aim of the study was to investigate the acute effect of a 30-min hot spring immersion at 41 °C on insulin resistance measures of 16 male subjects, in relation to DHEA-S level. To elucidate the role of DHEA-S in the coping against the heat stress, all subjects were evenly divided into lower and upper halves according to their baseline DHEA-S concentrations. The levels of glucose, insulin, blood pressure, and stress hormones (growth hormone, testosterone, and cortisol) in both groups were compared before and after hot spring immersion. The result shows that hot spring immersion significantly increased heart rate and reduced diastolic blood pressure, both of which were paralleled with a drop of DHEA-S concentration. Homeostasis model assessment for insulin resistance (HOMA-IR) and area under curve of glucose (GAUC) of oral glucose tolerance test were significantly increased by the hot spring immersion only in the Low DHEA-S group. Likewise, hot spring immersion caused an opposing effect on cortisol changes for the Low and High DHEA-S groups (+95% vs. −33%, p < 0.05), respectively. In conclusion, hot spring bathing induced insulin resistance confined only to those Low DHEA-S individuals. This response may be associated with a stress response such as increased cortisol levels.     

Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m2), sedentary (peak oxygen consumption, 23 ± 1 ml·kg?1·min?1) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, -7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively (P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under "free-living" conditions decreased during the final 3 days of exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.     

Serum and saliva adrenocortical hormones in obese diabetic men during submaximal exercise

The aim of this study was to evaluate serum and saliva adrenocortical hormones and their relationships at rest and during submaximal exercise and recovery in 9 obese diabetic middle-aged men (BMI: 35.2 ± 1.6 kg/m (2)). Blood and saliva samples were taken at rest, every 10 min of a 30-min cycling exercise at 70% of maximal heart rate, and after 10 min of recovery in order to analyze cortisol, dehydroepiandrosterone sulfate (DHEA-S) and dehydroepiandrosterone (DHEA). Serum and saliva cortisol increased significantly during recovery (p<0.05), but no significant difference was observed between the rest, exercise, and recovery DHEA-S and DHEA concentrations. A strong correlation was found at rest between both serum and saliva cortisol (r=0.72, p<0.001) and DHEA-S and DHEA (r=0.93, p<0.001). Serum DHEA-S and saliva DHEA remained strongly correlated during and after the submaximal exercise (r=0.81, p<0.001), whereas a weaker but still significant relationship was observed between serum and saliva cortisol during and after the exercise (r=0.52, p<0.001). In conclusion, these results suggest that saliva adrenocortical hormones, and especially saliva DHEA, may offer a practical surrogate for serum concentrations during both rest and exercise in obese diabetic men.     

Resistance and aerobic exercise: the influence of mode on the relationship between IL-6 and glucose tolerance in young men who are obese

Regular exercise lowers indicators of disease risk including some inflammatory cytokines; however, the relationship between different modes of acute exercise, cytokine levels, and subsequent glucose tolerance is unclear. The purpose was to determine the effects of resistance (RES) and aerobic (AER) exercises on interleukin-6 (IL-6) and its association with glucose tolerance 24 hours after exercise. After testing for 1 repetition maximum (1RM) and VO2peak, 10 obese (body mass index > 30 kg · m(-2)), untrained men aged 18-26 years completed 3 protocols: 60 minutes of RES, AER, and a resting (CON) condition. The RES was 2 sets of 8 repetitions and a third set to fatigue at 80% 1RM of 8 lifts using all major muscle groups. The AER was 60 minutes of cycling at 70% of VO2peak. On day 1, subjects completed the 60-minute exercise or resting protocol, and on day 2, they completed an oral glucose tolerance test (OGTT). Blood was collected before and after exercise, at 2 and 7 hour postexercise, and before and every 30 minutes during the OGTT and was analyzed for IL-6, glucose and insulin. Postexercise IL-6 was greater in RES (8.01 ± 2.08 pg · mL(-1)) vs. in AER (4.26 ± 0.27 pg · mL(-1)), and both were greater than in CON (1.61 ± 0.18 pg · mL(-1)). During the OGTT, there were no differences in glucose or insulin between conditions for single time points or as area under the curve. The RES caused greater IL-6 levels immediately after exercise that may be related to the greater active muscle mass compared to AER. Neither exercise produced enhanced glucose removal compared to control; thus, despite the greater elevation in IL-6 in RES, for these exercise conditions and this population, this cytokine did not influence glucose tolerance.     

Serum Chemerin Concentrations Associate with Beta-Cell Function,but Not with Insulin Resistance in Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)

The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P<0.004), but not with circulating glucose, insulin, lipids or liver enzymes (all P>0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P>0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI_cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI_ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD.     

Visfatin levels do not change after the oral glucose tolerance test and after a dexamethasone-induced increase in insulin resistance in humans

INTRODUCTION, MATERIAL AND METHODS: Visfatin is a cytokine, mainly expressed in visceral fat, that exerts insulin-mimicking effects in rodents through activation of an insulin receptor, although the binding-site is distinct from that of insulin. However, the mechanisms that regulate visfatin synthesis are still not fully understood. In particular, it is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as a glucocorticoid-induced increase in insulin resistance are reflected in appreciable alterations in serum visfatin levels in humans. In order to investigate this we measured serum visfatin, glucose and insulin concentrations during a 75.0 gram oral glucose tolerance test (OGTT) [Study 1], as well as before and after oral administration of dexamethasone [Study 2]. Study 1 included 17 subjects (2 males), aged 35.7 +/- 15.6 (mean +/- SD) years of BMI 35.2 +/- 9.3 kg/m(2). Blood samples were taken before (0 minutes) and at 60 and 120 minutes after glucose administration. Study 2 included 20 subjects (4 males, 5 subjects with type 2 diabetes), aged 42.1 +/- 17.2 years of BMI 36.7 +/- 8.38 kg/m(2) who underwent screening for Cushing's disease/syndrome. Dexamethasone was administered at a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of visfatin, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). Insulin resistance was assessed according to the HOMA method in non-diabetic individuals (n = 15). RESULTS: In Study 1 two subjects were found to have impaired glucose tolerance and one subject was found to have diabetes mellitus. Glucose administration resulted in a highly significant increase in insulin (from 11.4 +/- 7.2 microU/mL at 0 min to 98.9 +/- 68.6 microU/mL at 60 min and 72.6 +/- 45.1 microU/mL at 120 minute of OGTT, p < 0.001 for 60 and 120 minutes in comparison to baseline). However, there was no change in serum visfatin concentrations (84.6 +/- 11.6 ng/mL at 0 minutes, 82.6 +/- 12.7 ng/mL at 60 minutes and 81.1 +/- 14.5 ng/mL at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol concentrations below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.5 +/- 6.9 to 16.9 +/- 7.6 microU/mL; p = 0.011) and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), albeit without a significant change in serum visfatin concentrations (61.1 +/- 19.8 vs. 68.3 +/- 19.4 ng/mL, p = ns). In neither Study 1 nor Study 2 was there any significant correlation between serum visfatin and age, BMI or HOMA. CONCLUSIONS: There is a striking difference between the marked rise in insulin concentrations and the lack of change in visfatin concentrations during the oral glucose tolerance test. This implies that it is highly unlikely that visfatin is involved in the short-term regulation of glucose homeostasis in human subjects. Dexamethasone administration (4 mg/48 hours) induces an increase in insulin resistance, although without significant change in serum visfatin concentrations. Therefore in contrast to the in vitro data, short term glucocorticoid administration does not result in appreciable changes in serum levels of this adipocytokine. Furthermore, the results of our study do not support the notion that glucocorticoid-induced insulin resistance is likely to be related to changes in serum concentrations of visfatin.     

金耳菌丝体多糖对实验性2型糖尿病大鼠的降血糖作用研究

本文研究了金耳菌丝体多糖(TMP)对实验性2型糖尿病大鼠血糖、血脂、胰岛素敏感性和抗氧化能力的影响。采用烟酰胺,链脲佐菌素和高脂饲料诱导2型糖尿病大鼠模型,以50和100mg/(kg.d)剂量的TMP连续灌胃48d,监测血糖,测定血清胰岛素、体重、脂代谢及抗氧化系统部分相关指标,并进行口服糖耐量实验。结果显示,TMP可明显降低2型糖尿病大鼠的血清葡萄糖、总胆固醇、甘油三酯和丙二醛水平,并极显著提高受试模型鼠的胰岛素敏感指数,血清超氧化物歧化酶活性和肝脏过氧化氢酶活性。此外,TMP能显著降低糖耐量实验中糖负荷后120min时糖尿病大鼠的血糖含量。上述结果表明TMP可有效降低实验性2型糖尿病大鼠的血糖水平,纠正脂代谢紊乱,改善胰岛素抵抗,增强抗氧化能力。     

Caffeine ingestion elevates plasma insulin response in humans during an oral glucose tolerance test

We tested the hypothesis that caffeine ingestion results in an exaggerated response in blood glucose and (or) insulin during an oral glucose tolerance test (OGTT). Young, fit adult males (n = 18) underwent 2 OGTT. The subjects ingested caffeine (5 mg/kg) or placebo (double blind) and 1 h later ingested 75 g of dextrose. There were no differences between the fasted levels of serum insulin, C peptide, blood glucose, or lactate and there were no differences within or between trials in these measures prior to the OGTT. Following the OGTT, all of these parameters increased (P < or = 0.05) for the duration of the OGTT. Caffeine ingestion resulted in an increase (P < or = 0.05) in serum fatty acids, glycerol, and plasma epinephrine prior to the OGTT. During the OGTT, these parameters decreased to match those of the placebo trial. In the caffeine trial the serum insulin and C peptide concentrations were significantly greater (P < or = 0.001) than for placebo for the last 90 min of the OGTT and the area under the curve (AUC) for both measures were 60 and 37% greater (P < or = 0.001), respectively. This prolonged, increased elevation in insulin did not result in a lower blood glucose level; in fact, the AUC for blood glucose was 24% greater (P = 0.20) in the caffeine treatment group. The data support our hypothesis that caffeine ingestion results in a greater increase in insulin concentration during an OGTT. This, together with a trend towards a greater rather than a more modest response in blood glucose, suggests that caffeine ingestion may have resulted in insulin resistance.     

Effects of age and anesthetic on plasma glucose and insulin levels and insulin sensitivity in spontaneously hypertensive and Wistar rats

We examined the effects of anesthetic, age, and strain on oral glucose tolerance tests (OGTT, 1 g/kg body weight) and intraperitoneal glucose tolerance tests (IPGTT, 2 g/kg body weight) in spontaneously hypertensive (SH) and Wistar rats. Pentobarbital anesthesia caused an elevation in basal glucose and insulin levels in Wistar rats at 9 and 16 weeks of age and in SH rats at 9 weeks. Anesthesia increased the insulin output during an OGTT in both strains of rats while glucose was unchanged. Anesthesia reduced the insulin sensitivity index calculated from the OGTT but not from the IPGTT data. The age of the rats (9-11 vs. 16-18 weeks) had no effect on the basal glucose or insulin levels, but older Wistar rats had a greater insulin output following oral glucose and older SH rats had a greater insulin output following intraperitoneal glucose. On the basis of the insulin sensitivity index, SH rats were clearly more insulin resistant than age-matched Wistar rats. The SH rats also had higher basal insulin levels, as well as higher insulin output, following both glucose challenges. In summary, SH rats are more insulin resistant than Wistar rats, and anesthesia, which elevated basal glucose and insulin levels and increased the insulin output in response to a glucose challenge, may increase insulin resistance.     

Assessing Impaired Glucose Tolerance and Insulin Resistance in Polycystic Ovarian Syndrome with A Muffin Test: An Alternative to the Glucose Tolerance Test

ObjectiveTo determine the sensitivity of a high-glucose load in a meal as an alternative to the standard oral glucose tolerance test (OGTT) in detecting impaired glucose tolerance and insulin resistance in women with polycystic ovarian syndrome (PCOS) and the relationship of body composition to insulin resistance in the PCOS cohort.MethodsIn this prospective, single-center study, women with PCOS who were being followed up as outpatients were recruited. The study was performed between November 2007 and March 2008. All participants underwent OGTT before study enrollment. Participants were given a meal including carbohydrates, fat, and protein. Glucose and insulin levels were measured every 30 minutes for 2 hours after completing the meal. Body composition was measured by dual-energy x-ray absorptiometry.ResultsThirteen of the 15 participants completed the meal tolerance test and the body composition study. Four of 13 participants (31%) had abnormal glucose tolerance with the meal test compared with 2 of 8 participants (25%) who completed the OGTT. Those who had insulin resistance on OGTT were detected with the meal test. The 2-hour insulin levels following the meal were 38% higher than with the OGTT. Of 10 participants with insulin resistance, 9 had a total body fat mass greater than the 90th percentile, whereas 1 of 3 participants (33%) with normal body composition was insulin resistant.ConclusionAdministration of oral glucose load via a meal is an effective alternative to the OGTT in diagnosing impaired glucose tolerance and insulin resistance and may be more sensitive, without the adverse effects of the oral glucose load in the OGTT. PCOS is an independent risk factor for impaired glucose tolerance and insulin resistance, regardless of body composition. (Endocr Pract. 2010;16:810-817)     

Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle

Physiological stress associated with muscle damage results in systemic insulin resistance. However, the mechanisms responsible for the insulin resistance are not known; therefore, the present study was conducted to elucidate the molecular mechanisms associated with insulin resistance after muscle damage. Muscle biopsies were obtained before (base) and at 1 h during a hyperinsulinemic-euglycemic clamp (40 mU x kg(-1) x min(-1)) in eight young (age 24+/-1 yr) healthy sedentary (maximal O(2) consumption, 49.7+/-2.4 ml x kg(-1) x min(-1)) males before and 24 h after eccentric exercise (ECC)-induced muscle damage. To determine the role of cytokines in ECC-induced insulin resistance, venous blood samples were obtained before (control) and 24 h after ECC to evaluate ex vivo endotoxin-induced mononuclear cell secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta. Glucose disposal was 19% lower after ECC (P<0.05). Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation was 45% lower after ECC (P<0.05). Insulin-stimulated phosphatidylinositol (PI) 3-kinase, Akt (protein kinase B) serine phosphorylation, and Akt activity were reduced 34, 65, and 20%, respectively, after ECC (P < 0.05). TNF-alpha, but not IL-6 or IL-1beta production, increased 2.4-fold 24 h after ECC (P<0.05). TNF-alpha production was positively correlated with reduced insulin action on PI 3-kinase (r = 0.77, P = 0.04). In summary, the physiological stress associated with muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase, presumably leading to decreased insulin-mediated glucose uptake. Although more research is needed on the potential role for TNF-alpha inhibition of insulin action, elevated TNF-alpha production after muscle damage may impair insulin signal transduction.     

Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART

The protease inhibitor (PI) ritonavir (RTV) has been associated with elevated resting lipolytic rate, hyperlipidemia, and insulin resistance/glucose intolerance. The purpose of this study was to examine relationships between lipolysis and fatty acid (FA) oxidation during rest, moderate exercise and recovery, and measures of insulin sensitivity/glucose tolerance and fat redistribution in HIV-positive subjects taking RTV (n=12), HAART but no PI (n=10), and HIV-seronegative controls (n=10). Stable isotope tracers [1-(13)C]palmitate and [1,1,2,3,3-(2)H5]glycerol were continuously infused with blood and breath collection during 1-h rest, 70-min submaximal exercise (50% VO2 peak), and 1-h recovery. Body composition was evaluated using DEXA, MRI, and MRS, and 2-h oral glucose tolerance tests with insulin monitoring were used to evaluate glucose tolerance and insulin resistance. Lipolytic and FA oxidation rates were similar during rest and recovery in all groups; however, they were lower during moderate exercise in both HIV-infected groups [glycerol Ra: HIV+RTV 5.1+/-1.2 vs. HIV+no PI 5.9+/-2.8 vs. Control 7.4+/-2.2 micromol.kg fat-free mass (FFM)-1.min-1; palmitate oxidation: HIV+RTV 1.6+/-0.8 vs. HIV+no PI 1.6+/-0.8 vs. Control 2.5+/-1.7 micromol.kg FFM.min, P<0.01]. Fasting and orally-challenged glucose and insulin values were similar among groups. Lipolytic and FA oxidation rates were blunted during moderate exercise in HIV-positive subjects taking HAART. Lower FA oxidation during exercise was primarily due to impaired plasma FA oxidation, with a minor contribution from lower nonplasma FA oxidation. Regional differences in adipose tissue lipolysis during rest and moderate exercise may be important in HIV and warrant further study.     

Effect of 10 days of physical inactivity on glucose tolerance in master athletes

Master athletes who exercise regularly appear to avoid the development of insulin resistance and deterioration of glucose tolerance (GT) commonly seen with aging. To evaluate the possibility that exercise prevents rather than masks the aging-related changes responsible for development of insulin resistance, we investigated the effects of 10 days of physical inactivity in 14 master athletes aged 61 +/- 2 (SE) yr. The response of 10 of these men to inactivity was similar to that of young athletes, with an unchanged plasma glucose response and a significantly greater insulin response to an oral glucose tolerance test (OGTT) after 10 days of inactivity. These 10 athletes appeared to have been protected against the aging-related changes in GT because their plasma glucose and insulin levels during the OGTT after 10 days of inactivity were not significantly different from those of young lean sedentary men. In contrast, a deterioration in GT occurred in four of the master athletes during 10 days of inactivity; this was sufficiently marked in two of them to be classified as impaired GT. We conclude that regular exercise may 1) protect against the development of insulin resistance and decline in GT with aging in individuals with normal GT and 2) normalize GT by means of short-term effects of exercise in some individuals with abnormal GT.