The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index; 6 of the 73 sources its claims cite were checked for support.
Metabolic flexibility and insulin resistance
Open accessAbstract
Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” is mostly the consequence of impaired cellular glucose uptake. Indeed, after controlling for insulin-stimulated glucose disposal rate (amount of glucose available for oxidation), metabolic flexibility is not altered in obesity regardless of the presence of type 2 diabetes. To understand how intramyocellular lipids accumulate and cause insulin resistance, the assessment of metabolic flexibility to high-fat diets is more relevant than metabolic flexibility during a hyperinsulinemic clamp. An impaired capacity to upregulate muscle lipid oxidation in the face of high lipid supply may lead to increased muscle fat accumulation and insulin resistance. Surprisingly, very few studies have investigated the response to high-fat diets. In this review, we discuss the role of glucose disposal rate, adipose tissue lipid storage, and mitochondrial function on metabolic flexibility. Additionally, we emphasize the bias of using the change in respiratory quotient to calculate metabolic flexibility and propose novel approaches to assess metabolic flexibility. On the basis of current evidence, one cannot conclude that impaired metabolic flexibility is responsible for the accumulation of intramyocellular lipid and insulin resistance. We propose to study metabolic flexibility in response to high-fat diets in individuals having contrasting degree of insulin sensitivity and/or mitochondrial characteristics.
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TL;DR
This review argues that impaired metabolic flexibility during a hyperinsulinemic clamp in insulin-resistant subjects is largely a consequence of reduced insulin-stimulated glucose disposal, not a primary defect in fuel switching. It concludes that evidence linking impaired metabolic flexibility to intramyocellular lipid accumulation and insulin resistance is inconclusive, and calls for studies of metabolic flexibility to high-fat diets in individuals with contrasting insulin sensitivity and mitochondrial characteristics.
Key findings
- During a hyperinsulinemic clamp, the commonly reported metabolic inflexibility in insulin-resistant subjects is mostly explained by lower cellular glucose uptake: insulin-stimulated glucose disposal rate explained ∼50% of the variance in the change in respiratory quotient (ΔRQ). In quartile analysis, the insulin-sensitive group (n = 25) had about a fourfold higher glucose disposal rate, nonoxidative glucose disposal rate, and steady-state RQ than the insulin-resistant group (n = 25), but after adjustment for glucose disposal rate there was no longer any difference in nonoxidative glucose disposal rate or steady-state RQ (P > 0.44).
- The paper reports that after controlling for insulin-stimulated glucose disposal rate, metabolic flexibility is not altered in obesity regardless of type 2 diabetes, and no improvement in metabolic flexibility was observed after weight loss in type 2 diabetic individuals after controlling for glucose disposal rate.
- Evidence does not support the hypothesis that impaired mitochondrial function leads to lower metabolic flexibility to lipid; mitochondrial dysfunction may coexist with high fuel oxidation and enhanced insulin sensitivity. In one cited study, subjects with a family history of type 2 diabetes had on average 22% less mitochondrial DNA copy number, related to a higher decrease in sleeping RQ after a 3-day isoenergetic high-fat diet, but not to the change in 24-h RQ.
- The authors emphasize that using ΔRQ to calculate metabolic flexibility is biased by baseline RQ: in an illustrative example, two well-matched subjects both matched 24-h RQ to food quotient, yet one was classified as flexible (ΔRQ = −0.17) and the other as inflexible (ΔRQ = −0.07). They propose assessing the time to reach 50% of the expected change in RQ (ΔRQ50%) and studying responses to high-fat diets; based on RQ profiles, metabolically inflexible individuals could accumulate ∼200 g more fat than flexible subjects after 1 wk of a high-fat diet (60% of total energy).
Methods
- Narrative review; no primary experimental data are reported. The paper synthesizes human whole-body, skeletal muscle, and cultured myotube studies on metabolic flexibility, insulin resistance, obesity, type 2 diabetes, and family history of type 2 diabetes.
- It discusses assessment paradigms including fasting RQ, euglycemic-hyperinsulinemic clamp, high-carbohydrate and high-fat meals/diets, and in vitro myotube substrate switching.
- Main analysis is qualitative synthesis, with illustrative calculations and tables, including a table comparing steady-state RQ between subjects with high and low insulin-stimulated glucose disposal rate.
Limitations
- Stated in paper: few studies have investigated metabolic flexibility to high-fat diets, and no studies have evaluated metabolic flexibility to lipid in subjects with contrasting degrees of insulin resistance; most studies used fasting RQ, which is not a reliable indicator of lipid oxidation capacity because it is strongly influenced by energy balance and dietary macronutrient composition.
- Stated in paper: the causal link between mitochondrial abnormalities and metabolic inflexibility/insulin resistance remains to be established, and evidence indicating mitochondrial defects as a driving factor is far from conclusive or even unavailable.
- Evident from text: as a narrative review, no systematic search or meta-analysis is described; conclusions depend on selected literature, and the paper notes that some cited comparisons failed to match groups for physical fitness, which could confound mitochondrial findings.
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Claims the paper makes
46 Not checked yet · 30 Own interpretation · 5 No basis given · 3 Partly supported · 1 Supported so far · 1 Own result · accuracy not yet measured
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In the paper
“However, after adjustment for differences in glucose disposal rates, there was no longer any difference in nonoxidative glucose disposal rate and steady-state RQ between groups (Ref. [14](#r14); [Table 2](#t2)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Results report that nonoxidative glucose disposal no longer differed after adjustment for glucose disposal rate (P = 0.87), and that the difference in ΔRQ was abolished (P = 0.19). The paper defines ΔRQ as the change from fasting to steady-state RQ, but does not report the adjusted comparison as a difference in steady-state RQ itself. Its groups were participants with type 2 diabetes and obesity-matched participants without diabetes, rather than groups defined solely by insulin sensitivity. (LLM, conf=0.83)
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In the paper
“Further support for these findings comes from studies in which glucose disposal rates were matched by increasing the glucose or insulin infusion rates ([27](#r27), [66](#r66)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Supportedcites [27] source
The Introduction describes studies that used hyperglycemia to match glucose disposal in people with NIDDM and controls. The Discussion says this paper likewise achieved comparable systemic glucose uptake by studying participants with NIDDM at their fasting hyperglycemia while controls remained euglycemic. This supports the glucose-based example; the sentence also cites another study for the insulin-based alternative. (LLM, conf=0.89)
- Not checked yetcites [66] source
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In the paper
“Such muscle mitochondrial dysfunction was suggested to be an intrinsic characteristic of muscle cells, since fat oxidation in response to palmitate was lower in myotubes from insulin-resistant vs. insulin-sensitive individuals ([16](#r16), [61](#r61)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Fatty acid oxidation results report 26% lower palmitate-derived CO₂ production in myotubes from people with type 2 diabetes than in control myotubes. The paper compared diabetic and control donors, not groups classified as insulin-resistant and insulin-sensitive, and it found no significant decrease in total palmitate oxidation. (LLM, conf=0.86)
- Supportedcites [61] source
The section “Metabolic adaptability is an intrinsic characteristic of muscle cells” reports that the increase in myotube fat oxidation after palmitate exposure was positively correlated with donors’ insulin sensitivity. Figure 4 interprets this as greater capacity to increase fat oxidation in subjects with higher insulin sensitivity. The evidence is a correlation across donors, rather than a categorical comparison of two groups; it supports the claim’s direction. (LLM, conf=0.88)
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In the paper
“As a consequence, data corrected for glucose disposal rate, a mechanism proximal to glucose oxidation, indicates no difference in metabolic flexibility and nonoxidative glucose disposal rate between subjects with or without type 2 diabetes and matched for body mass index, sex, and race.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
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In the paper
“For instance, patients with lipodystrophy (partial or total absence of subcutaneous adipose tissue) have similar fat oxidation than control individuals when fed a eucaloric, mixed diet ([51](#r51)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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- Not checked yetcites [51] source
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In the paper
“However, in response to excess energy as fat, lipodystrophic subjects have higher fat oxidation compared with control individuals ([51](#r51)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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- Not checked yetcites [51] source
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In the paper
“Furthermore, after controlling for glucose disposal rate, no improvement in metabolic flexibility is observed after weight loss in type 2 diabetic individuals subjected to a 1-yr intensive lifestyle intervention including energy restriction and increased physical activity ([14](#r14)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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- Not checked yetcites [14] source
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In the paper
“In fact, fasting RQ is inversely related to metabolic flexibility to carbohydrate during a clamp ([Fig. 3*A*](#f3)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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In the paper
“On the basis of the RQ profile for metabolically flexible and inflexible subjects shown in [Fig. 2*D*](#f2), and considering an energy intake of 2,500 kcal/day (protein intake 20% of total energy), the metabolically inflexible individuals would accumulate ∼200 g more fat than flexible subjects after 1 wk of a high-fat diet (60% of total energy).”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
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In the paper
“In addition, we observed that metabolic flexibility to glucose was directly related to plasma adiponectin concentration.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
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In the paper
“The former group had on average a 22% less mitochondrial DNA copy number (marker of mitochondrial number) than control subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [62] source
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In the paper
“Only glucose disposal rate and steady-state plasma FFA concentration (the latter explained 3% of the variance in metabolic flexibility) were independent determinants of the change in RQ (ΔRQ) during a euglycemic-hyperinsulinemic clamp accounting for half of its variance.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
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In the paper
“Increased mitochondrial number was related to a higher decrease in sleeping RQ in response to a 3-day isoenergetic high-fat diet.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [62] source
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In the paper
“Alternatively, elderly individuals matched for body mass and fat content to young volunteers showed on average 26% lower maximal aerobic consumption (vo2max) vs. young individuals ([6](#r6)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [6] source
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In the paper
“However, when mitochondrial number was related to 24-h RQ after the high-fat diet period, no association between mitochondrial number and the change in 24-h RQ was observed.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [62] source
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In the paper
“As expected, metabolic flexibility to glucose during a clamp was related to surrogate markers of insulin resistance such as fasting plasma glucose, FFA, and insulin concentrations.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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- Not checked yetcites [14] source
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In the paper
“However, after 4 days of intervention, both groups were similarly able to match whole body fuel oxidation to fuel intake.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [6] source
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In the paper
“Finally, the assessment of whole body RQ as a marker of metabolic flexibility can lead to erroneous conclusions about skeletal muscle metabolism, at least in people with type 2 diabetes.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
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- Not checked yetcites [23] source
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In the paper
“On the basis of current evidence, one cannot conclude that impaired metabolic flexibility is responsible for the accumulation of intramyocellular lipid and insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract
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In the paper
“The relationship between fasting RQ and insulin sensitivity, however, has not always been observed.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
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In the paper
“A reduced capacity of oxidative tissues and organs to adjust lipid oxidation to lipid availability can lead to tissue accumulation of lipids as triglycerides.”
§ Metabolic flexibility and insulin resistance > Abstract
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In the paper
“An impaired capacity to upregulate muscle lipid oxidation in the face of high lipid supply may lead to increased muscle fat accumulation and insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract
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In the paper
“The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” is mostly the consequence of impaired cellular glucose uptake.”
§ Metabolic flexibility and insulin resistance > Abstract
What the sources say
- Not checked yetcites [14] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As a consequence, the oxidative capacity of skeletal muscle may be of utmost importance to boost lipid oxidation to the level of lipid supply and therefore modulate insulin sensitivity.”
§ Metabolic flexibility and insulin resistance > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, after controlling for insulin-stimulated glucose disposal rate (amount of glucose available for oxidation), metabolic flexibility is not altered in obesity regardless of the presence of type 2 diabetes.”
§ Metabolic flexibility and insulin resistance > Abstract
What the sources say
- Not checked yetcites [14] source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” is mostly the consequence of impaired cellular glucose uptake.”
§ Metabolic flexibility and insulin resistance > Abstract
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, the ability to increase lipid oxidation as a function of their availability eventually reduces the formation of ceramides and diglycerides leading to improved insulin sensitivity.”
§ Metabolic flexibility and insulin resistance > Abstract
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In the paper
“It is therefore only after short periods of time (one to a few days) that a difference in metabolic flexibility (switch from one type of fuel to another) can be observed.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility and Macronutrient Oxidative Regulation
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In the paper
“Contrary to expectations, in vitro suppressibility of fat oxidation was lower in subjects with higher whole body insulin sensitivity and higher metabolic flexibility to glucose.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [61] source
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In the paper
“The increase in fat oxidation in response to palmitate called in vitro “adaptability” was positively related to in vivo insulin sensitivity and metabolic flexibility.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [15] source
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In the paper
“The lower reliance on fat oxidation for energy supply in offspring from diabetic parents suggests that impaired fat oxidation might precede insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [20] source
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In the paper
“The commonly reported metabolic inflexibility and impaired glucose storage in insulin-resistant individuals is expected, since cellular glucose uptake is decreased and cellular glucose available for oxidation and storage is low ([8](#r8)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [8] source
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In the paper
“Together, these data suggest that intrinsic defects in fat oxidation are present in the skeletal muscle of insulin-resistant subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
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In the paper
“Therefore, differences in metabolic flexibility may be explained by insufficient control of such variables.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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In the paper
“Together, the results indicate that the impaired metabolic flexibility and glucose storage so often observed during a clamp in insulin-resistant individuals are the consequence of impaired glucose transport rather than a defective cellular glucose oxidative and nonoxidative metabolism.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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In the paper
“Subjects in negative energy balance or fed a high-fat diet have lower baseline RQ, increasing the potential to influence ΔRQ in response to energy macronutrients.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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In the paper
“Accordingly, a lesser decrease in RQ after a fat overload might be the result of enhanced adipose tissue lipid storage capacity rather than impaired lipid oxidative capacity.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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In the paper
“It is known that mitochondrial content and activity determine fatty acid oxidation in response to lipid.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [30] source
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In the paper
“These data and the evidence indicating multiple mitochondrial abnormalities in type 2 diabetic and insulin-resistant individuals ([3](#r3), [25](#r25), [36](#r36), [37](#r37), [40](#r40), [42](#r42), [43](#r43), [48](#r48), [59](#r59)) led to the hypothesis that lower mitochondrial capacity is associated with reduced resting lipid oxidation and therefore increased muscle lipid accumulation.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“However, subjects with higher metabolic flexibility will reach this equilibrium faster.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaindirectn = 2- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: After 7–10 days, all individuals will be in equilibrium between 24-h RQ and FQ.
In the paper
“On the other hand, the large difference in postprandial glycemia (∼2-fold) and lower skeletal muscle FFA uptake observed in diabetic vs. nondiabetic subjects likely drove the difference in leg RQ.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [28] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Since both subjects were able to match the 24-h RQ to FQ at the end of each week, both subjects should be considered similarly flexible.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
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None of the sources cited for this claim have been checked yet.
In the paper
“Just as intracellular glucose availability influences metabolic flexibility, higher plasma lipid concentration also drives fuel oxidation by increasing fat oxidation ([14](#r14), [33](#r33), [46](#r46), [52](#r52)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both studies suggest similar metabolic flexibility to carbohydrate- enriched diets in obese and lean individuals.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“In both groups, the changes in plasma glucose, FFA, and insulin concentrations were similar; however, individuals without a history of diabetes had larger decrease in RQ compared with offspring from diabetic parents.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [20] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, a lesser decrease in RQ was observed during the sleeping period in the offspring of diabetic parents compared with controls.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [62] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“After 3 days of a high-fat diet, both groups had a similar decrease in 24-h RQ and therefore a similar increase in fat oxidation.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [62] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Fat overload may represent a metabolic challenge for many individuals, even in energy balance conditions, who may indeed fail to appropriately upregulate skeletal muscle lipid oxidation, therefore causing intracellular lipid accumulation and insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
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In the paper
“This example clearly shows the relevance of having similar baseline RQ values when metabolic flexibility is assessed by the change in RQ.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
boostedcorrelationaln = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“In fact, a direct relationship between metabolic flexibility to glucose and glucose disposal rate is described ([14](#r14), [24](#r24), [61](#r61), [62](#r62)) ([Fig. 3*B*](#f3)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Since adipose tissue is the main source of plasma FFA, the capacity to store and release FFA from adipose tissue may influence metabolic flexibility ([11](#r11)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [11] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“For instance, frank mitochondrial dysfunction in humans (e.g., myopathies with impaired electron transport chain activity) is accompanied by increased fuel oxidation to compensate for the impaired mitochondrial ATP synthesis ([13](#r13)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [13] Gadian D , Radda G, Ross B, Hockaday J, Bore P, Taylor D, Styles P. Examination of a myopathy by phosphorus nuclear magnetic resonance. Lancet 2 : 774–775, 1981. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In conclusion, evidence indicating mitochondrial defects as a driving factor of metabolic inflexibility and insulin resistance are far from conclusive or even unavailable.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
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In the paper
“Furthermore, the mitochondrial capacity to oxidize acetyl-CoA coming from glucose is conserved in insulin-resistant subjects even if mitochondrial defects have been reported in those individuals ([3](#r3), [25](#r25), [36](#r36), [37](#r37), [40](#r40), [42](#r42), [43](#r43), [48](#r48), [59](#r59)).”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, under resting conditions, energy demand with concomitant fat oxidation requirement is hardly a metabolic challenge for muscle mitochondria.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, the difference in metabolic flexibility during the clamp in individuals with varying insulin sensitivity is mostly the consequence of variability in insulin-stimulated glucose disposal rate ([14](#r14)).”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
What the sources say
- Not checked yetcites [14] source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The rate at which fat oxidation adjusts to high fat intake is variable among individuals ([21](#r21), [53](#r53)), but only scarce evidence exists about which factors determine this variability.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, the literature does not support the hypothesis that impaired mitochondrial function leads to lower metabolic flexibility to lipid.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, mitochondrial dysfunction may well be associated with high fuel oxidation and enhanced insulin sensitivity.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“However, fasting RQ is not a reliable indicator of lipid oxidation capacity, since RQ under fasting conditions is mostly influenced by energy balance and dietary macronutrient composition ([22](#r22), [34](#r34), [54](#r54)).”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
What the sources say
- Not checked yetcites [22] source
- Not checked yetcites [34] McNeill G , Bruce AC, Ralph A, James WP. Inter-individual differences in fasting nutrient oxidation and the influence of diet composition. Int J Obes 12 : 455–463, 1988.
- Not checked yetcites [54] Schutz Y . The adjustment of energy expenditure and oxidation to energy intake: the role of carbohydrate and fat balance. Int J Obes Relat Metab Disord 17 , Suppl 3: S23–S27; discussion S41–S42, 1993.
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Furthermore, most studies have used fasting RQ as a marker of metabolic flexibility to lipid.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, since energy expenditure is minimal in resting conditions, the absolute lipid oxidative demand is hardly a metabolic challenge for muscle mitochondria.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As indicated in the previous section, a higher decrease in RQ after fat overload may well be a consequence of reduced adipose tissue lipid storage capacity.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, fuel oxidation may not necessarily be reduced in presence of mitochondrial dysfunction.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, an eventual defect in fat oxidation is unlikely to be evidenced in resting conditions.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
hedged- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The rate at which fat oxidation adjusts to high fat intake is variable among individuals ([21](#r21), [53](#r53)), but only scarce evidence exists about which factors determine this variability.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Surprisingly, there are no studies evaluating metabolic flexibility to lipid in subjects with contrasting degree of insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 16
- Probably not a substantial claim. 2
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Metabolic inflexibility to glucose and impaired glucose storage during a hyperinsulinemic clamp is consistently reported in insulin-resistant subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Supportedcites [14] source
The CONCLUSIONS section says insulin-resistant subjects have shown a blunted respiratory-quotient response during a hyperinsulinemic clamp. The RESULTS and DISCUSSION sections report lower insulin-stimulated nonoxidative glucose disposal—a measure that includes glucose storage—in the type 2 diabetes group. The paper also notes that both differences disappear after adjustment for glucose disposal rate; the claim describes the reported unadjusted findings. (LLM, conf=0.91)
- Not checked yetcites [24] source
- Partly supportedcites [61] sourceExperimental — accuracy not yet measured
The Introduction says insulin-resistant muscle does not switch to carbohydrate oxidation in response to insulin, and the results section reports that metabolic flexibility during a hyperinsulinemic clamp correlates with insulin sensitivity. The cited paper does not report impaired glucose storage during the clamp; its clamp measures glucose disposal and fuel switching, not storage. Page numbers are unavailable in our copy. (LLM, conf=0.87)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
In the paper
“We ([14](#r14)) recently described that insulin-stimulated glucose disposal rate is the main determinant of the change in RQ during a clamp, explaining ∼50% of its variance.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Using the ΔRQ as an index of metabolic flexibility, *subject A* will be characterized as flexible (ΔRQ = −0.17) and *subject B* as inflexible (ΔRQ = −0.07).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plainn = 2- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“However, in response to a high-carbohydrate meal (1,000 kcal, 76% energy from carbohydrate), individuals with a family history of diabetes had a higher plasma insulin concentration and a similar increase in RQ compared with control subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [20] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If skeletal muscle cannot match fat oxidation to lipid uptake, fat accumulation will ensue, which in turn will cause insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In addition, in vitro adaptability was positively related to aerobic capacity, suggesting that myotubes established from lean, fit, insulin-sensitive subjects are more metabolically flexible in response to palmitate exposure in vitro.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [15] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, such impaired mitochondrial lipid oxidation could simply be the result of reduced energy demand and not necessarily due to impaired substrate switching.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using the ΔRQ as an index of metabolic flexibility, *subject A* will be characterized as flexible (ΔRQ = −0.17) and *subject B* as inflexible (ΔRQ = −0.07).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, the assessment of metabolic flexibility should take into account the differences in baseline RQ and the timing required to match 24-h RQ to FQ.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“During postabsorptive conditions, diabetic individuals had higher RQ throughout the 6 h following the high-fat meal compared with nondiabetic subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [28] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, high plasma FFA concentration impairs insulin-stimulated glucose disposal rate and decreases intracellular glucose, which in turn reduces glucose oxidation and consequently enhances lipid oxidation ([2](#r2), [8](#r8)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, metabolic flexibility also depends on the rate at which nutrients are available to the cells, the ability of adipose tissue to handle fatty acids and even the method used for its calculation (i.e., ΔRQ).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, impaired metabolic flexibility may result from both a lower stimulated RQ and/or an elevated baseline RQ.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“However, comparisons among obese, diabetic, and lean individuals have failed to appropriately match the groups for physical fitness, opening up the possibility that mitochondrial dysfunction may be related to lower physical activity in metabolically inflexible subjects ([45](#r45)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [45] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“This is in line with the finding that high-fat diets increase mitochondrial biogenesis and fat oxidation in parallel with a decrease in insulin sensitivity ([18](#r18)), possibly as a consequence of increased partially oxidized lipid intermediates.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [18] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Similarly, mice with muscle-specific PGC1α (PPARγ coactivator-1α) deletion have defective mitochondrial function (e.g., lower staining for cytochrome *c* oxidase and succinate dehydrogenase); however, they have increased metabolic rate, lower RQ, and improved insulin-stimulated glucose uptake in skeletal muscle compared with wild-type animals ([19](#r19)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [19] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Individuals able to increase fat oxidation quickly in response to day-to-day changes in fat intake will eventually have lower muscle fat accumulation and be less prone to insulin resistance compared with slower adapters.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The answer is yes, since the speed of the adaptation will probably impact the amount of lipid accumulation in the muscle and therefore impact insulin sensitivity.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Since vo2max has been shown to be directly related to muscle mitochondrial density ([62](#r62), [63](#r63)), one could expect an improved metabolic flexibility in young vs. elderly individuals.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. The authors may not put it forward as true.
The paper relies on this without support.
The switch in fuel oxidation depends on the type and amount of nutrient available for oxidation at the cellular level.
“The switch in fuel oxidation will depend on the type and amount of nutrient available for oxidation at the cellular level.”
The paper relies on this without support.
Increased availability of carbohydrate rapidly increases carbohydrate oxidation and suppresses lipid oxidation.
“Increased availability of carbohydrate results in a rapid increase in carbohydrate oxidation associated with concomitant suppression of lipid oxidation.”
The paper relies on this without support.
When dietary fat intake increases, lipid oxidation increases slowly and progressively while carbohydrate oxidation is suppressed.
“However, when dietary fat intake increases, one observes a much slower progressive increase in lipid oxidation paralleled by suppression of carbohydrate oxidation.”
The paper relies on this without support.
After 7–10 days, all individuals will be in equilibrium between 24-h RQ and FQ.
“since after 7–10 days it is generally expected that all individuals will be in equilibrium between 24-h RQ and FQ.”
The paper relies on this without support.
The ΔRQ50% is in the range of 1–2 days in response to high-carbohydrate diets and in the range of 3–5 days in response to high-fat diets.
“Such a ΔRQ50% may be in the range of 1–2 days in response to high-carbohydrate diets and in the range of 3–5 days in response to high-fat diets.”
The paper relies on this without support.
The adaptation of fat oxidation to high fat intake cannot take much more time than that required to deplete glycogen stores, i.e., a few days to a week.
“However, this adaptation cannot take much more time than that required to deplete the glycogen stores, i.e., a few days to a week.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As such, metabolic inflexibility is at the core of the pathophysiology of insulin resistance (146).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [146]
In the citing paper
“In turn, metabolically inflexible individuals fail to adapt their fuel preference to changes in carbohydrate or lipid supplies (Galgani et al, 2008).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
In the citing paper
“Metabolic inflexibility is defined as an impaired capacity to switch between different energy substrates and is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
In the citing paper
“Diverse mitochondrial parameters vary between insulin-resistant and insulin-sensitive subjects, such as mitochondrial number, structure, and function.”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
In the citing paper
“This suggests that mitochondrial dysfunction might contribute to metabolic inflexibility and insulin resistance (Galgani et al, 2008).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
Citations
Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193
Koves, T. R., Ussher, J. R., Noland, R. C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J. R. B., Newgard, C. B., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.013 · Cited by 1,990
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M. (1999) · Diabetologia · doi:10.1007/s001250051123 · Cited by 1,264
Kelley, D. E., Goodpaster, B., Wing, R. R., & Simoneau, J.-A. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.6.e1130 · Cited by 1,096
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
Kelley, D. E., & Mandarino, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.5.677 · Cited by 1,017
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Ritov, V. B., Menshikova, E. V., He, J., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E. (2005) · Diabetes · doi:10.2337/diabetes.54.1.8 · Cited by 887
Cited by
Sorted by citations
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,210
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787
The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility
Zhang, S., Hulver, M. W., McMillan, R. P., Cline, M. A., & Gilbert, E. R. (2014) · Nutrition & Metabolism · doi:10.1186/1743-7075-11-10 · Cited by 450
“The capacity for an organism to adapt fuel oxidation to fuel availability, that is, to preferentially utilize carbohydrate and lipid fuels and to be able to rapidly switch between them is termed metabolic flexibility [2,3].”
Correlation between Oxidative Stress, Nutrition, and Cancer Initiation
Saha, S. K., Lee, S. B., Won, J., Choi, H. Y., Kim, K., Yang, G., Dayem, A. A., & Cho, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071544 · Cited by 416
“The inability to shift from lipid to carbohydrate use (metabolic inflexibility) was investigated in obese patients and is accompanied with intra-myocellular lipid aggregation and insulin resistance (Figure 2) [84].”
BackgroundLipid-Induced Mitochondrial Stress and Insulin Action in Muscle
Muoio, D. M., & Neufer, P. D. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.010 · Cited by 343
“One viewpoint suggests that the inability to appropriately activate glucose oxidation in response to a meal simply reflects a secondary consequence of impaired insulin action (Galgani et al., 2008).”
Background
Metadata
- Authors
- Galgani, J. E., Moro, C., & Ravussin, E.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-11
- Volume
- 295
- Issue
- 5
- Pages
- E1009-E1017
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2584808
- OpenAlex
- W2168445785
- Cited by
- 532
- References
- 68
- Citations by year
- 2026: 36 · 2025: 40 · 2024: 17 · 2023: 22 · 2022: 38 · 2021: 36 · 2020: 46 · 2019: 34 · 2018: 32 · 2017: 38 · 2016: 21 · 2015: 28 · 2014: 39 · 2013: 40 · 2012: 17
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Universidad de Chile (submittedVersion)
- Funders
- National Institute on Aging (U01AG020478)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060412, R01-DK-60412)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metabolic flexibility, insulin resistance, intramyocellular lipid, glucose disposal rate, hyperinsulinemic-euglycemic clamp, respiratory quotient, high-fat diet, mitochondrial function, fuel oxidation, type 2 diabetes, obesity
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Humans, Insulin Resistance, Mitochondria, Obesity, Muscle, Skeletal, Carbohydrate Metabolism, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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