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Steven E Kahn - One of the best experts on this subject based on the ideXlab platform.
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oral disposition index predicts the development of future diabetes above and beyond fasting and 2 h glucose levels
Diabetes Care, 2009Co-Authors: Kristina M Utzschneider, Ronald L Prigeon, Jenny Tong, Mirjam V Faulenbach, Darcy B Carr, Edward J Boyko, Donna L Leonetti, Marguerite J Mcneely, Wilfred Y Fujimoto, Steven E KahnAbstract:Objective: We sought to determine if an oral disposition index (DIO) predicts the development of diabetes over a 10 year period. First, we assessed the validity of DIO by demonstrating that a Hyperbolic Relationship exists between oral indices of insulin sensitivity and β-cell function. Research design and methods: 613 Japanese American subjects (322M/291F) underwent a 75-gram oral glucose tolerance test (OGTT) at baseline, 5 and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or HOMA-S. Insulin response was estimated as the change in insulin divided by change in glucose from 0-30 minutes (ΔI0-30/ΔG0-30). Results: ΔI0-30/ΔG0-30 demonstrated a curvilinear Relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the loge-transformed estimates included -1 for ΔI0-30/ΔG0-30 vs. 1/fasting insulin for all glucose tolerance groups, consistent with a Hyperbolic Relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included -1 only for subjects with NGT or IFG/IGT, but not diabetes. Based on this Hyperbolic Relationship, the product of ΔI0-30/ΔG0-30 and 1/fasting insulin was calculated (oral disposition index: DIO) and decreased from NGT to IFG/IGT to diabetes (p<0.001). Among non-diabetic subjects at baseline, baseline DIO predicted cumulative diabetes at 10-years (p<0.001) independent of age, sex, BMI, family history of diabetes and baseline fasting and 2-hour glucose. Conclusions: DIO provides a measure of β-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.
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impact of differences in fasting glucose and glucose tolerance on the Hyperbolic Relationship between insulin sensitivity and insulin responses
Diabetes Care, 2006Co-Authors: Kristina M Utzschneider, Ronald L Prigeon, Darcy B Carr, Rebecca L Hull, Jenny Tong, Jane B Shofer, Barbara M Retzlaff, Robert H Knopp, Steven E KahnAbstract:OBJECTIVE—To determine whether the Hyperbolic Relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH DESIGN AND METHODS—We studied 219 healthy subjects (88 male and 131 female subjects, aged 26–75 years) with fasting plasma glucose (FPG) RESULTS—Si and AIRg were inversely related for the entire cohort, and this Relationship was not significantly different from Hyperbolic. The inverse Relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG CONCLUSIONS—The inverse Relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a Hyperbolic Relationship, a decrease in β-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
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167 evidence for a Hyperbolic Relationship between insulin sensitivity and the insulin response derived from an oral glucose tolerance test
Journal of Investigative Medicine, 2005Co-Authors: Kristina M Utzschneider, Ronald L Prigeon, Darcy B Carr, Rebecca L Hull, Jenny Tong, Robert H Knopp, Steven E KahnAbstract:The Relationship between the insulin sensitivity index (SI) and the acute insulin response to glucose (AIRg) has been shown to be Hyperbolic for indices derived from an intravenous glucose tolerance test. Based on this Relationship, the disposition index (SI x AIRg) provides a measure of β-cell function and has been shown to be significantly lower in subjects at risk for diabetes (DM). We postulated that a similar Hyperbolic Relationship exists between measures of insulin sensitivity and insulin release derived from an oral glucose tolerance test (OGTT). 653 (276M/ 377F) first-degree relatives with no known history of DM underwent an OGTT. Of these, 242 were classified as being normal glucose tolerant (NGT), 292 as impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT) and 119 as DM. Insulin sensitivity was determined as 1/HOMA-IR and insulin release as the ratio of the incremental changes from 0-30 minutes in insulin and glucose (ΔI30/ΔG30). By regression analysis, the Relationship between 1/HOMA-IR and ΔI30/ΔG30 was Hyperbolic in all three groups. This was demonstrated with a linear fit between ln(1/HOMA-IR) and ln(ΔI30/ΔG30) having a slope not significantly different from -1 (mean±SD; NGT: slope = -1.12±0.08, r2 = 0.42; IFG/IGT: slope = -1.05±0.09, r2 =0.33; and DM: slope =-1.3±0.96, r2 =0.02). The curve fit for subjects with IFG/IGT fell below and to the left of NGT consistent with β-cell dysfunction. That for subjects with DM was below and to the left of that for IFG/IGT. When 1/HOMA-IR*ΔI30/ΔG30 was calculated to provide a measure of the adjusted insulin response, it was significantly lower in the IFG/IGT and DM groups (NGT:15.9±0.7 mM-2; IFG/IGT 8.5±0.4; DM 4.0±0.5; p≤0.001 for comparisons between each group). Based on the finding of this Hyperbolic Relationship, this adjusted insulin response (1/HOMA-IR*ΔI30/ΔG30) may be a useful tool to estimate β-cell function in large population studies based on an OGTT.
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the relative contributions of insulin resistance and beta cell dysfunction to the pathophysiology of type 2 diabetes
Diabetologia, 2003Co-Authors: Steven E KahnAbstract:The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the Hyperbolic Relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this Hyperbolic Relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.
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quantification of the Relationship between insulin sensitivity and β cell function in human subjects evidence for a Hyperbolic function
Diabetes, 1993Co-Authors: Steven E Kahn, Ronald L Prigeon, Edward J Boyko, David K Mcculloch, Richard N Bergman, Michael W Schwartz, J L Neifing, W K Ward, James C Beard, Jerry P PalmerAbstract:To determine the Relationship between insulin sensitivity and β-cell function, we quantified the insulin sensitivity index using the minimal model in 93 relatively young, apparently healthy human subjects of varying degrees of obesity (55 male, 38 female; 18–44 yr of age; body mass index 19.5–52.2 kg/m 2 ) and with fasting glucose levels I was compared with measures of body adiposity and β-cell function. Although lean individuals showed a wide range of S I , body mass index and S I were related in a curvilinear manner ( P I and the β-cell measures was more clearly curvilinear and reciprocal for fasting insulin ( P glucose ; P n = 56; P max ; n = 43; P I and the β-cell measures could not be distinguished from a hyperbola, i.e., S I × β-cell function = constant. This Hyperbolic Relationship described the data significantly better than a linear function ( P I , a proportionate reciprocal difference occurs in insulin levels and responses in subjects with similar carbohydrate tolerance. We conclude that in human subjects with normal glucose tolerance and varying degrees of obesity, β-cell function varies quantitatively with differences in insulin sensitivity. Because the function governing this Relationship is a hyperbola, when insulin sensitivity is high, large changes in insulin sensitivity produce relatively small changes in insulin levels and responses, whereas when insulin sensitivity is low, small changes in insulin sensitivity produce relatively large changes in insulin levels and responses. Percentile plots based on knowledge of this interaction are presented for evaluating β-cell function in populations and over time.
Yoshiyuki Fukuba - One of the best experts on this subject based on the ideXlab platform.
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Relationship between the curvature constant parameter of the power duration curve and muscle cross sectional area of the thigh for cycle ergometry in humans
European Journal of Applied Physiology, 2002Co-Authors: Akira Miura, Masako Endo, Hironori Sato, Haruhiko Sato, Thomas J Barstow, Yoshiyuki FukubaAbstract:For high-intensity cycle ergometer exercise, the Relationship between power output (P) and its tolerable duration (t) has been well characterized by the Hyperbolic Relationship: (P–θ F)·t=W′, where θF has been termed the "critical power" or "fatigue threshold". The curvature constant (W′) reflects a constant amount of work which can be performed above θF, and it may be regarded as a muscle energy store. The Relationship of this energy store to muscle mass is not known. Therefore, the purpose of this study was to determine the Relationships among W′, accumulated peak oxygen deficit (accumulated peak O2-deficit), and muscle cross-sectional area (CSA) of the thigh for high-intensity cycle ergometry in humans. A group of 17 healthy male subjects (aged 21–41 years) participated in this study. The θF and W′ of the P-t Hyperbolic Relationship and the accumulated peak O2-deficit was calculated by standard procedures. The CSA of muscle, fat and bone in the right thigh were measured using ultrasonography. The mean (SD) of θF, W′, accumulated peak O2-deficit, and muscle CSA of the thigh were 200.0 (17.8) W, 12.60 (2.94) kJ, 2.29 (0.41) l, and 185.3 (22.6) cm2, respectively. The muscle CSA of the thigh was positively correlated with W′ (r=0.59, P<0.01) and with accumulated peak O2-deficit (r=0.54, P<0.05). The Relationship between W′ and accumulated peak O2-deficit also showed a positive correlation (r=0.63, P<0.005). Our results indicated that W′ derived from the P-t Hyperbolic curve as anaerobic working capacity is related to the CSA of muscle.
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Relationship between the curvature constant parameter of the power duration curve and muscle cross sectional area of the thigh for cycle ergometry in humans
European Journal of Applied Physiology, 2002Co-Authors: Akira Miura, Masako Endo, Hironori Sato, Haruhiko Sato, Thomas J Barstow, Yoshiyuki FukubaAbstract:For high-intensity cycle ergometer exercise, the Relationship between power output ( P) and its tolerable duration ( t) has been well characterized by the Hyperbolic Relationship: ( P- theta;(F)). t=W', where theta;(F) has been termed the "critical power" or "fatigue threshold". The curvature constant (W') reflects a constant amount of work which can be performed above theta;(F), and it may be regarded as a muscle energy store. The Relationship of this energy store to muscle mass is not known. Therefore, the purpose of this study was to determine the Relationships among W', accumulated peak oxygen deficit (accumulated peak O(2)-deficit), and muscle cross-sectional area (CSA) of the thigh for high-intensity cycle ergometry in humans. A group of 17 healthy male subjects (aged 21-41 years) participated in this study. The theta;(F) and W' of the P- t Hyperbolic Relationship and the accumulated peak O(2)-deficit was calculated by standard procedures. The CSA of muscle, fat and bone in the right thigh were measured using ultrasonography. The mean (SD) of theta;(F), W', accumulated peak O(2)-deficit, and muscle CSA of the thigh were 200.0 (17.8) W, 12.60 (2.94) kJ, 2.29 (0.41) l, and 185.3 (22.6) cm(2), respectively. The muscle CSA of the thigh was positively correlated with W' ( r=0.59, P<0.01) and with accumulated peak O(2)-deficit ( r=0.54, P<0.05). The Relationship between W' and accumulated peak O(2)-deficit also showed a positive correlation ( r=0.63, P<0.005). Our results indicated that W' derived from the P- t Hyperbolic curve as anaerobic working capacity is related to the CSA of muscle.
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the effect of glycogen depletion on the curvature constant parameter of the power duration curve for cycle ergometry
Ergonomics, 2000Co-Authors: Akira Miura, Hironori Sato, Haruhiko Sato, Brian J W Hipp, Yoshiyuki FukubaAbstract:For high-intensity cycle ergometer exercise, the relation between power (P) and its tolerable duration (t) has been well characterized by the Hyperbolic Relationship: (P-θF)t = W', or P = W'(1/t)+θF, where θF may be termed the ‘fatigue threshold’. The curvature constant (W') reflects a constant amount of work which is postulated to be equivalent to a finite energy store that relates to the oxygen-deficit: phosphagen pool, anaerobic glycolysis and oxygen stores. Compared to thetaF, the physiological nature of W' has received little consideration. The purpose of this study was therefore to establish the parameters of the power-duration curve (θF and W') for subjects in normal glycogen (NG) and glycogen depleted (GD) states. Seven healthy male subjects (aged 22 to 41 years) each performed four high-intensity square-wave exercise bouts on an electrically braked cycle ergometer under two different muscular glycogen content conditions, i.e. NG and GD states. Subjects performed the following exercise on the even...
Bernard Zinman - One of the best experts on this subject based on the ideXlab platform.
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Hyperbolic Relationship between insulin secretion and sensitivity on oral glucose tolerance test
Obesity, 2008Co-Authors: Ravi Retnakaran, Jill Hamilton, Sandy Shen, Anthony J G Hanley, Vladimir Vuksan, Bernard ZinmanAbstract:The utility of the disposition index as a measure of beta-cell compensatory capacity rests on the established Hyperbolic Relationship between its component insulin secretion and sensitivity measures as derived from the intravenous glucose tolerance test (IVGTT). If one is to derive an analogous measure of beta-cell compensation from the oral glucose tolerance test (OGTT), it is thus necessary to first establish the existence of this Hyperbolic Relationship between OGTT-based measures of insulin secretion and insulin sensitivity. In this context, we tested five OGTT-based measures of secretion (insulinogenic index, Stumvoll first phase, Stumvoll second phase, ratio of total area-under-the-insulin-curve to area-under-the-glucose-curve (AUC(ins/gluc)), and incremental AUC(ins/gluc)) with two measures of sensitivity (Matsuda index and 1/Homeostasis Model of Assessment for insulin resistance (HOMA-IR)). Using a model of log(secretion measure) = constant + beta x log(sensitivity measure), a Hyperbolic Relationship can be established if beta is approximately equal to -1, with 95% confidence interval (CI) excluding 0. In 277 women with normal glucose tolerance (NGT), the pairing of total AUC(ins/gluc) and Matsuda index was the only combination that satisfied these criteria (beta = -0.99, 95% CI (-1.66, -0.33)). This pairing also satisfied Hyperbolic criteria in 53 women with impaired glucose tolerance (IGT) (beta = -1.02, (-1.72, -0.32)). In a separate data set, this pairing yielded distinct hyperbolae for NGT (n = 245) (beta = -0.99, (-1.67, -0.32)), IGT (n = 116) (beta = -1.18, (-1.84, -0.53)), and diabetes (n = 43) (beta = -1.37, (-2.46, -0.29)). Moreover, the product of AUC(ins/gluc) and Matsuda index progressively decreased from NGT (212) to IGT (193) to diabetes (104) (P < 0.001), consistent with declining beta-cell function. In summary, a Hyperbolic Relationship can be demonstrated between OGTT-derived AUC(ins/gluc) and Matsuda index across a range of glucose tolerance. Based on these findings, the product of these two indices emerges as a potential OGTT-based measure of beta-cell function.
Jerry P Palmer - One of the best experts on this subject based on the ideXlab platform.
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quantification of the Relationship between insulin sensitivity and β cell function in human subjects evidence for a Hyperbolic function
Diabetes, 1993Co-Authors: Steven E Kahn, Ronald L Prigeon, Edward J Boyko, David K Mcculloch, Richard N Bergman, Michael W Schwartz, J L Neifing, W K Ward, James C Beard, Jerry P PalmerAbstract:To determine the Relationship between insulin sensitivity and β-cell function, we quantified the insulin sensitivity index using the minimal model in 93 relatively young, apparently healthy human subjects of varying degrees of obesity (55 male, 38 female; 18–44 yr of age; body mass index 19.5–52.2 kg/m 2 ) and with fasting glucose levels I was compared with measures of body adiposity and β-cell function. Although lean individuals showed a wide range of S I , body mass index and S I were related in a curvilinear manner ( P I and the β-cell measures was more clearly curvilinear and reciprocal for fasting insulin ( P glucose ; P n = 56; P max ; n = 43; P I and the β-cell measures could not be distinguished from a hyperbola, i.e., S I × β-cell function = constant. This Hyperbolic Relationship described the data significantly better than a linear function ( P I , a proportionate reciprocal difference occurs in insulin levels and responses in subjects with similar carbohydrate tolerance. We conclude that in human subjects with normal glucose tolerance and varying degrees of obesity, β-cell function varies quantitatively with differences in insulin sensitivity. Because the function governing this Relationship is a hyperbola, when insulin sensitivity is high, large changes in insulin sensitivity produce relatively small changes in insulin levels and responses, whereas when insulin sensitivity is low, small changes in insulin sensitivity produce relatively large changes in insulin levels and responses. Percentile plots based on knowledge of this interaction are presented for evaluating β-cell function in populations and over time.
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quantification of the Relationship between insulin sensitivity and beta cell function in human subjects evidence for a Hyperbolic function
Diabetes, 1993Co-Authors: Steven E Kahn, Ronald L Prigeon, David K Mcculloch, Richard N Bergman, Michael W Schwartz, J L Neifing, W K Ward, James C Beard, E J Boyko, Jerry P PalmerAbstract:To determine the Relationship between insulin sensitivity and β-cell function, we quantified the insulin sensitivity index using the minimal model in 93 relatively young, apparently healthy human subjects of varying degrees of obesity (55 male, 38 female; 18–44 yr of age; body mass index 19.5–52.2 kg/m 2 ) and with fasting glucose levels I was compared with measures of body adiposity and β-cell function. Although lean individuals showed a wide range of S I , body mass index and S I were related in a curvilinear manner ( P I and the β-cell measures was more clearly curvilinear and reciprocal for fasting insulin ( P glucose ; P n = 56; P max ; n = 43; P I and the β-cell measures could not be distinguished from a hyperbola, i.e., S I × β-cell function = constant. This Hyperbolic Relationship described the data significantly better than a linear function ( P I , a proportionate reciprocal difference occurs in insulin levels and responses in subjects with similar carbohydrate tolerance. We conclude that in human subjects with normal glucose tolerance and varying degrees of obesity, β-cell function varies quantitatively with differences in insulin sensitivity. Because the function governing this Relationship is a hyperbola, when insulin sensitivity is high, large changes in insulin sensitivity produce relatively small changes in insulin levels and responses, whereas when insulin sensitivity is low, small changes in insulin sensitivity produce relatively large changes in insulin levels and responses. Percentile plots based on knowledge of this interaction are presented for evaluating β-cell function in populations and over time.
Akira Miura - One of the best experts on this subject based on the ideXlab platform.
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Relationship between the curvature constant parameter of the power duration curve and muscle cross sectional area of the thigh for cycle ergometry in humans
European Journal of Applied Physiology, 2002Co-Authors: Akira Miura, Masako Endo, Hironori Sato, Haruhiko Sato, Thomas J Barstow, Yoshiyuki FukubaAbstract:For high-intensity cycle ergometer exercise, the Relationship between power output (P) and its tolerable duration (t) has been well characterized by the Hyperbolic Relationship: (P–θ F)·t=W′, where θF has been termed the "critical power" or "fatigue threshold". The curvature constant (W′) reflects a constant amount of work which can be performed above θF, and it may be regarded as a muscle energy store. The Relationship of this energy store to muscle mass is not known. Therefore, the purpose of this study was to determine the Relationships among W′, accumulated peak oxygen deficit (accumulated peak O2-deficit), and muscle cross-sectional area (CSA) of the thigh for high-intensity cycle ergometry in humans. A group of 17 healthy male subjects (aged 21–41 years) participated in this study. The θF and W′ of the P-t Hyperbolic Relationship and the accumulated peak O2-deficit was calculated by standard procedures. The CSA of muscle, fat and bone in the right thigh were measured using ultrasonography. The mean (SD) of θF, W′, accumulated peak O2-deficit, and muscle CSA of the thigh were 200.0 (17.8) W, 12.60 (2.94) kJ, 2.29 (0.41) l, and 185.3 (22.6) cm2, respectively. The muscle CSA of the thigh was positively correlated with W′ (r=0.59, P<0.01) and with accumulated peak O2-deficit (r=0.54, P<0.05). The Relationship between W′ and accumulated peak O2-deficit also showed a positive correlation (r=0.63, P<0.005). Our results indicated that W′ derived from the P-t Hyperbolic curve as anaerobic working capacity is related to the CSA of muscle.
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Relationship between the curvature constant parameter of the power duration curve and muscle cross sectional area of the thigh for cycle ergometry in humans
European Journal of Applied Physiology, 2002Co-Authors: Akira Miura, Masako Endo, Hironori Sato, Haruhiko Sato, Thomas J Barstow, Yoshiyuki FukubaAbstract:For high-intensity cycle ergometer exercise, the Relationship between power output ( P) and its tolerable duration ( t) has been well characterized by the Hyperbolic Relationship: ( P- theta;(F)). t=W', where theta;(F) has been termed the "critical power" or "fatigue threshold". The curvature constant (W') reflects a constant amount of work which can be performed above theta;(F), and it may be regarded as a muscle energy store. The Relationship of this energy store to muscle mass is not known. Therefore, the purpose of this study was to determine the Relationships among W', accumulated peak oxygen deficit (accumulated peak O(2)-deficit), and muscle cross-sectional area (CSA) of the thigh for high-intensity cycle ergometry in humans. A group of 17 healthy male subjects (aged 21-41 years) participated in this study. The theta;(F) and W' of the P- t Hyperbolic Relationship and the accumulated peak O(2)-deficit was calculated by standard procedures. The CSA of muscle, fat and bone in the right thigh were measured using ultrasonography. The mean (SD) of theta;(F), W', accumulated peak O(2)-deficit, and muscle CSA of the thigh were 200.0 (17.8) W, 12.60 (2.94) kJ, 2.29 (0.41) l, and 185.3 (22.6) cm(2), respectively. The muscle CSA of the thigh was positively correlated with W' ( r=0.59, P<0.01) and with accumulated peak O(2)-deficit ( r=0.54, P<0.05). The Relationship between W' and accumulated peak O(2)-deficit also showed a positive correlation ( r=0.63, P<0.005). Our results indicated that W' derived from the P- t Hyperbolic curve as anaerobic working capacity is related to the CSA of muscle.
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the effect of glycogen depletion on the curvature constant parameter of the power duration curve for cycle ergometry
Ergonomics, 2000Co-Authors: Akira Miura, Hironori Sato, Haruhiko Sato, Brian J W Hipp, Yoshiyuki FukubaAbstract:For high-intensity cycle ergometer exercise, the relation between power (P) and its tolerable duration (t) has been well characterized by the Hyperbolic Relationship: (P-θF)t = W', or P = W'(1/t)+θF, where θF may be termed the ‘fatigue threshold’. The curvature constant (W') reflects a constant amount of work which is postulated to be equivalent to a finite energy store that relates to the oxygen-deficit: phosphagen pool, anaerobic glycolysis and oxygen stores. Compared to thetaF, the physiological nature of W' has received little consideration. The purpose of this study was therefore to establish the parameters of the power-duration curve (θF and W') for subjects in normal glycogen (NG) and glycogen depleted (GD) states. Seven healthy male subjects (aged 22 to 41 years) each performed four high-intensity square-wave exercise bouts on an electrically braked cycle ergometer under two different muscular glycogen content conditions, i.e. NG and GD states. Subjects performed the following exercise on the even...