The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; none of the 27 sources its claims cite is checked for support yet.
Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone
Open accessAbstract
Insulin resistance is associated with a decreased vasodilator response to insulin. Because insulin's vasodilator effect is nitric oxide dependent, this impairment may reflect endothelial dysfunction. Troglitazone, an insulin-sensitiser, might thus improve insulin-dependent and/or endothelium-dependent vascular function in insulin resistant obese subjects. For 8 weeks, fifteen obese subjects were treated with either 400 mg troglitazone once daily or placebo, in a randomised, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses (plethysmography) to intra-arterial administered acetylcholine and sodium nitroprusside; insulin sensitivity and insulin-induced vascular and neurohumoral responses (clamp); vasoconstrictor responses to NC-monomethyl-L-arginine (L-NMMA) during hyperinsulinaemia; and ambulatory 24-h blood pressure (ABPM). Baseline data (placebo) of obese subjects were compared with those obtained in lean control subjects. Obese subjects were insulin resistant compared with leans (whole-body glucose uptake: 26.8+/-3.0 vs. 53.9+/-4.3 [tmol kgl min-, p < 0.001). Troglitazone improved whole-body glucose uptake (to 31.9+/-3.3 micromol x kg(-1) x min(-1) , p=0.028), and forearm glucose uptake (from 1.09+/-0.54 to 2.31+/-0.69 micromol dL(-1) x min(-1), p=0.006). Insulin-induced vasodilatation was blunted in obese subjects (percent increase in forearm blood flow (FBF) in lean 66.5+/-23.0%, vs. 10.1+/-11.3% in obese, p=0.04), but did not improve during troglitazone. Vascular responses to acetylcholine, sodium nitroprusside and L-NMMA did not differ between the obese and lean group, nor between both treatment periods in the obese individuals. In conclusion, in insulin resistant obese subjects, endothelial vascular function is normal despite impaired vasodilator responses to insulin. Troglitazone improved insulin sensitivity but it had no effects on endothelium-dependent and -independent vascular responses. These data do not support an association between insulin resistance and endothelial function.
Overview
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Written from the paper’s full text.
TL;DR
In obese, insulin-resistant, normotensive adults, insulin-induced forearm vasodilatation was blunted compared with lean controls, but endothelium-dependent and endothelium-independent vascular responses were preserved. Troglitazone modestly improved insulin sensitivity without restoring insulin-mediated vasodilatation or altering endothelial function.
Key findings
- Obese subjects were insulin resistant: whole-body glucose uptake was 26.8 ± 3.0 vs 53.9 ± 4.3 mmol × kg⁻¹ × min⁻¹ in lean subjects (p < 0.001). Insulin-induced forearm blood flow increased 10.1 ± 11.3% in obese vs 66.5 ± 23.0% in lean subjects (p = 0.04).
- Vascular responses to acetylcholine, sodium nitroprusside, and L-NMMA were not different between lean and obese subjects and were not affected by troglitazone.
- Troglitazone improved whole-body glucose uptake to 31.9 ± 3.3 mmol × kg⁻¹ × min⁻¹ (p = 0.028) and insulin-induced forearm glucose uptake to 2.31 ± 0.69 mmol × dl⁻¹ × min⁻¹ (p = 0.006 vs placebo), but did not change insulin-induced vasodilatation (2.2 ± 4.9%, p = NS vs placebo).
- No significant correlation was observed between vascular responses to acetylcholine and insulin sensitivity (r = 0.20, p = NS); the correlation between insulin-induced change in blood flow and whole-body glucose uptake was r = 0.39 (p = 0.056).
Methods
- Randomized, placebo-controlled, double-blind crossover trial in 15 obese healthy volunteers (BMI 27–36 kg/m², age 25–50 years, normotensive) and 13 age- and sex-matched lean controls; treatment was troglitazone 400 mg/day or placebo for 8 weeks with a 2-week washout. Vascular responses were assessed in 13 obese subjects.
- Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial acetylcholine, sodium nitroprusside, and L-NMMA, plus a euglycaemic hyperinsulinaemic clamp (insulin 430 pmol × m⁻² × min⁻¹ for 120 min); 24-h ambulatory blood pressure was also monitored.
- Analyses used paired and unpaired t tests, repeated measures ANOVA, and Spearman correlations; significance was set at p < 0.05.
Limitations
- The paper states that it cannot exclude that a more pronounced increase in insulin sensitivity might result in greater insulin-mediated vasodilatation, and that no pharmacological therapy currently achieves this target.
- The paper notes the study duration may have been relatively short, troglitazone effects were modest and variable between individuals, and a full dose-response curve of insulin on blood flow could not be constructed.
- Evident from the text: the sample was small (15 obese, 13 lean; vascular responses in 13 obese), one obese subject was excluded from the troglitazone portion after surgery/complications and 6.4 kg weight loss, and one subject had near syncope during a clamp but her data were included.
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37 Own result · 21 Not checked yet · 10 Own method · 7 Own interpretation · 4 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“responses to endothelium-dependent as well as independent vasodilators were absolutely similar with those in the lean group.”
§ Insulin > Discussion
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Troglitazone did not affect the absolute or relative vascular responses to nitroprusside (Fig. 2, lower panel).”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Acetylcholine induced a dose-dependent increase in FBF in the experimental arm.”
§ Insulin > Results
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Infusion of sodium nitroprusside induced a dosedependent increase in FBF in the experimental arm.”
§ Insulin > Results
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Responses in the obese group were not different from those in lean subjects and were not affected by troglitazone.”
§ Insulin > Haemodynamic parameters.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mean whole-body glucose uptake was 26.8 ± 3.0 (range 11.9±46.1),compared to 53.9 ± 4.3 (range 32.7±92.2) mmol × kg ±1 × min ±1 in lean subjects (p < 0.001).”
§ Insulin > Metabolic response to euglycaemic hyperinsulinaemic clamping.
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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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“L-NMMA infusion during systemic hyperinsulinaemia induced a dose-dependent vasoconstrictor response in the experimental arm in both groups.”
§ Insulin > Haemodynamic parameters.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insulin-induced vasodilatation was blunted in the obese group; FBF in the control arm from 1.87 ± 0.22 to 1.95 ± 0.19 ml × dl ±1 × min ±1 (p = NS vs. baseline), percentage increase in FBF 10.1 ± 11.3 % (p = 0.04 vs. lean group).”
§ Insulin > Haemodynamic parameters.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — 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 absolute or relative vascular responses were not different between lean and obese, nor were they affected by troglitazone (Fig. 2, upper panel).”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Body weight did not significantly change during both treatment periods (placebo: + 0.75 ± 0.46 kg, troglitazone: + 0.41 ± 0.48 kg, p = NS).”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 22
- The quote only partly states this claim. 2
- Probably not a substantial claim. 20
A result the paper reports from its own data — 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 absolute or relative vascular responses were not different between lean and obese, nor were they affected by troglitazone (Fig. 2, upper panel).”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“However the changes under these strictly double-blind placebo-controlled conditions were modest and largely variable between individuals.”
§ Insulin > Discussion
plain- Asserted: passes — The authors 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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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean ambulatory 24-h diastolic blood pressure decreased during treatment with troglitazone, mean ambulatory 24-h systolic blood pressure did not change (Table 2).”
§ Insulin > Haemodynamic parameters.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
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 number of subjects in our study was larger than in Steinberg's study.”
§ Insulin > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean plasma triglycerides (TG) and NEFA levels were higher, and HDL-cholesterol levels lower in the obese group.”
§ Insulin > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment with troglitazone did not change baseline arterial NE concentration nor the insulin-induced absolute or percentual increase in NE (all p = NS vs. placebo) (Table 3).”
§ Insulin > Haemodynamic parameters.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Troglitazone treatment was associated with slight decrements in NEFA (from 0.61 ± 0.07 to 0.47 ± 0.05 mmol × l ±1 , p = 0.06)”
§ Insulin > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“total cholesterol, HDL-cholesterol and TG concentrations did not significantly change.”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight weeks of treatment with Troglitazone improved total-body as well as forearm insulin-mediated glucose uptake and tended to lower fasting insulin concentration.”
§ Insulin > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Responses in blood pressure and heart rate to insulin were not different between the two groups and were not influenced by troglitazone.”
§ Insulin > Haemodynamic parameters.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a clear difference with respect to weight, fat percentage and waist/hip ratio.”
§ Insulin > Results
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, ambulatory diastolic blood pressure decreased slightly, and elevated NEFA lev-els showed a tendency to improve.”
§ Insulin > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insulin infusion increased systolic but not diastolic blood pressure in both groups.As a result, pulse pressure increased significantly (Table 3).”
§ Insulin > Haemodynamic parameters.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Obese subjects in our group exhibited well known features of the insulin resistance syndrome [38], with insulin sensitivity clearly different from lean subjects.”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [38]
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although all individuals were normotensive, mean office diastolic blood pressure was higher in the obese group.”
§ Insulin > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“in NIDDM [10,11] and hypertension [12], an impaired endothelial function has been reported.”
§ Insulin > Abstract
What the sources say
- Not checked yetcites [10]
- Not checked yetcites [11]
- Not checked yetcites [12]
plaincorrelational- Asserted: passes — The authors 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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It may state two separate claims as one.
In the paper
“Recent reports indeed claim a reduced vasodilator response to metacholine and not to sodium nitroprusside in insulin resistant obese individuals indicating a specific defect in endothelial-dependent vasodilatation [13].”
§ Insulin > Abstract
What the sources say
- Not checked yetcites [13]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Between both treatment periods there was a two week wash-out period.”
§ Insulin > Subjects.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
In the paper
“Statistical analyses were only performed after prior verification of appropriateness by exclusion of period or sequence effects [22].”
§ Insulin > Measurements.
What the sources say
- Not checked yetcites [22]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
In the paper
“In this study, obesity represents a situation of ªpureº insulin resistance, with the advantage that changes in insulin sensitivity are not confounded by changes in blood glucose concentrations (ªglucose toxicityº) [37].”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [37]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, in uncomplicated NIDDM, no correlation was observed between an index of in vivo NO generation and insulin sensitivity [32].”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [32]
plain- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Identical changes occurred when FVR instead of FBF was used for analyses.”
§ Insulin > Haemodynamic parameters.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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
“Troglitazone improves metabolic parameters related to insulin sensitivity, but it does not change the effect of insulin on vascular tone nor on endothelial function.”
§ Insulin > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Their study population (although strictly speaking normotensive), had higher blood pressure values (mean arterial pressure (MAP) » 100 mmHg) than ours (MAP » 92.5 mmHg), possibly explaining part of the observed differences [12].”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [12]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 absence of a specific defect in vascular endothelial function in obese, insulin-resistant subjects, despite a diminished insulin-induced vasodilatation, suggests that alternative mechanisms may be responsible for insulin-mediated vasodilatation.”
§ Insulin > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“hypercholesterolaemia, a disorder that is firmly associated with disturbed endothelial function [33]”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [33]
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Troglitazone was well tolerated, drug compliance was more than 95 %.”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“During infusion of acetylcholine, nitroprusside and L-NMMA infusions, intra-arterial blood pressure remained stable throughout (data not shown).”
§ Insulin > Haemodynamic parameters.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The subjects, pharmacists and investigators were not aware of the treatment code which was broken only after completion of all analyses.”
§ Insulin > Subjects.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Compliance was monitored by pill counts and diary records.”
§ Insulin > Subjects.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To avoid interference with the previously administered vasodilator drugs in the experimental arm (see Fig. 1, schedule of the protocol), changes in FBF in the control arm were used for statistical evaluation of the effect of insulin on blood flow.”
§ Insulin > Measurements.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“perhaps reflecting a specific beneficial drug effect on skeletal muscle glucose uptake.”
§ Insulin > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we performed a randomised, placebo-controlled, double-blind crossover trial with troglitazone in obese individuals characterised by insulin resistance.”
§ Insulin > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Steinberg et al. used metacholine instead of acetylcholine as endothelial-dependent vasodilator, which may not be purely nitric oxide dependent [30].”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [30]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These treatment results of troglitazone are consistent with earlier studies in humans [15±17].”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [15±17]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no sequence or period effects during the trial; mean weight change, fasting plasma glucose/insulin, lipid levels, insulin sensitivity and blood pressure were comparable during the first and second period of the trial.”
§ Insulin > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the role of ATP-dependent potassium channels [35] and Na + -K + -ATPase [36] has been reported as alternative mechanisms for insulin-induced vasodilatation”
§ Insulin > Discussion
What the sources say
- Not checked yetcites [35]
- Not checked yetcites [36]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Coefficients of plasma glucose variation during the last 30 min of the clamp were 3.1 ± 04 % in obese and 4.4 ± 0.7 % in lean subjects.”
§ Insulin > Measurements.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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. It may state two separate claims as one.
In the paper
“Although baseline FBF was not significantly different between both groups, FBF tended to be higher in the obese group.To compensate for these possible differences in baseline flow, responses to drugs were also expressed as percentage increase above baseline [23].”
§ Insulin > Measurements.
What the sources say
- Not checked yetcites [23]
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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. It may state two separate claims as one.
The authors state this as an assumption.
Whole blood glucose equals (1 - 0.3 × haematocrit) × plasma blood glucose.
“Assuming that whole blood glucose = (1±0.3´haematocrit) ´plasma blood glucose [20]”
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
“Despite a clear improvement in insulin sensitivity with treatment, no improvement in insulin-mediated or agonist-stimulated vasodilation was seen.”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [32]
Citations
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Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118709 · Cited by 1,687 · cited 2×
“Recent reports indeed claim a reduced vasodilator response to metacholine and not to sodium nitroprusside in insulin resistant obese individuals indicating a specific defect in endothelial-dependent vasodilatation [13].”
BackgroundThe two‐period cross‐over clinical trial.
Hills, M., & Armitage, P. (1979) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1979.tb05903.x · Cited by 1,399
Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. S., & Baron, A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117433 · Cited by 1,216
Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.
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Assessment of Insulin Sensitivityin Vivo*
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Thiazolidinediones in the Treatment of Insulin Resistance and Type II Diabetes
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Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114644 · Cited by 930
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Improvement in Glucose Tolerance and Insulin Resistance in Obese Subjects Treated with Troglitazone
Nolan, J. J., Ludvik, B. H., Beerdsen, P., Joyce, M., & Olefsky, J. M. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411033311803 · Cited by 914
Role of Insulin Resistance in Human Disease (Syndrome X): An Expanded Definition
Reaven, G. M. (1993) · Annual Review of Medicine · doi:10.1146/annurev.me.44.020193.001005 · Cited by 908
Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM
Laakso, M., Edelman, S. V., Brechtel, G., & Baron, A. D. (1992) · Diabetes · doi:10.2337/diab.41.9.1076 · Cited by 470
Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia
Chowienczyk, P. (1992) · The Lancet · doi:10.1016/0140-6736(92)92621-l · Cited by 466
Metabolic Effects of New Oral Hypoglycemic Agent CS-045 in NIDDM Subjects
Suter, S. L., Nolan, J. J., Wallace, P., Gumbiner, B. M., & Olefsky, J. M. (1992) · Diabetes Care · doi:10.2337/diacare.15.2.193 · Cited by 419
Measuring Forearm Blood Flow and Interpreting the Responses to Drugs and Mediators
Benjamin, N., Calver, A., Collier, J., Robinson, B. F., Vallance, P. J., & Webb, D. J. (1995) · Hypertension · doi:10.1161/01.hyp.25.5.918 · Cited by 399
Cardiac and Glycemic Benefits of Troglitazone Treatment in NIDDM
Ghazzi, M. N., Pérez, J. E., Antonucci, T. K., Driscoll, J. H., Huang, S. M., Faja, B. W., The Troglitazone Study Group, & Whitcomb, R. W. (1997) · Diabetes · doi:10.2337/diab.46.3.433 · Cited by 366
Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure.
Baron, A., Brechtel, G., Johnson, A., & Hardin, D. S. (1993) · Hypertension · doi:10.1161/01.hyp.21.2.129 · Cited by 362
Endothelial Nitric Oxide Production and Insulin Sensitivity
Petrie, J. R., Ueda, S., Webb, D. J., Elliott, H. L., & Connell, J. (1996) · Circulation · doi:10.1161/01.cir.93.7.1331 · Cited by 321
Thiazolidinediones in the treatment of insulin resistance and type II diabetes
Saltiel, A. R., & Olefsky, J. M. (1996) · Diabetes · doi:10.2337/diabetes.45.12.1661 · Cited by 303
̈kimattila, S. M., ̈ki, A. V., Groop, P., Cockcroft, J., Utriainen, T., Fagerudd, J. A., & ̈rvinen, H. Y.-J. (1996) · Circulation · doi:10.1161/01.cir.94.6.1276 · Cited by 286
Vollenweider, P., Randin, D., Tappy, L., Jéquier, E., Nicod, P., & Scherrer, U. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117242 · Cited by 285 · cited 1×
“Several investigators have reported that insulin induces vasodilatation in skeletal muscle [2±4], an effect that is impaired under conditions of insulin resistance [3, 6, 7, 24].”
BackgroundCarbohydrate Metabolism in Non-Insulin-Dependent Diabetes Mellitus
Dinneen, S., Gerich, J., & Rizza, R. (1992) · New England Journal of Medicine · doi:10.1056/nejm199209033271007 · Cited by 279
DISFUNCTION OF VASCULAR ENDOTHELIUM IN DIABETES MELLITUS
Cohen, R. A. (1993) · Cited by 252
Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM
Laakso, M., Edelman, S. V., Brechtel, G., et al. (1992) · Diabetes · doi:10.2337/diabetes.41.9.1076 · Cited by 145
Baron, A., Laakso, M., Brechtel, G., & Edelman, S. V. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115117 · Cited by 127
Effects of Insulin on Vascular Tone and Sympathetic Nervous System in NIDDM
Tack, C. J. J., Smits, P., Willemsen, J. J., Lenders, J. W. M., Thien, T., & Lutterman, J. A. (1996) · Diabetes · doi:10.2337/diab.45.1.15 · Cited by 117
Self-citationForearm Nitric Oxide Balance, Vascular Relaxation, and Glucose Metabolism in NIDDM Patients
Avogaro, A., Piarulli, F., Valerio, A., Miola, M., Calveri, M., Pavan, P., Vicini, P., Cobelli, C., Tiengo, A., Calò, L. A., et al. (1997) · Diabetes · doi:10.2337/diab.46.6.1040 · Cited by 97
Willemsen, J. J., Ross, H. A., Jacobs, M. C., Lenders, J. W. M., Thien, T., Swinkels, L. M. J. W., & Benraad, T. J. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.10.1455 · Cited by 91
Strain-gauge plethysmography; theoretical and practical notes on a new design.
Brakkee, A. J. M., & Vendrik, A. J. H. (1966) · Journal of Applied Physiology · doi:10.1152/jappl.1966.21.2.701 · Cited by 91
Importance of the Hematocrit in Interpretation of Blood Sugar
Dillon, R. S. (1965) · Diabetes · doi:10.2337/diab.14.10.672 · Cited by 89
Mimura, K., Umeda, F., Hiramatsu, S., Taniguchi, S., Ono, Y., Nakashima, N., Kobayashi, K., Masakado, M., Yoshiyasu, S. A. K. O., & Nawata, H. (1994) · Diabetic Medicine · doi:10.1111/j.1464-5491.1994.tb00333.x · Cited by 87
Forearm resistance vessel abnormalities and insulin resistance in obese adolescents.
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Role of Insulin Resistance in Human Disease (syndrome X): An Expanded Definition
Reaven, G. (1993) · Annual Review of Medicine · doi:10.1146/annurev.med.44.1.121 · Cited by 84
Activation of the Sodium-Potassium Pump Contributes to Insulin-Induced Vasodilation in Humans
Tack, C. J., Lutterman, J. A., Vervoort, G., Thien, T. A., & Smits, P. (1996) · Hypertension · doi:10.1161/01.hyp.28.3.426 · Cited by 78
Self-citationInsulin Sensitivity, Vascular Reactivity, and Clamp-Induced Vasodilatation in Essential Hypertension
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Effects of insulin on vascular tone and sympathetic nervous system in NIDDM
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Self-citationForearm nitric oxide balance, vascular relaxation, and glucose metabolism in NIDDM patients
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Self-citation
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Sorted by citations
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Cardiovascular Actions of Insulin
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Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome.
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Metadata
- Authors
- Tack, C. J. J., Ong, M. K. E., Lutterman, J. A., & Smits, P.
- Affiliations
- Radboud University Nijmegen (NL)
- ORCID
- Tack, C. J. J.
- Venue
- Diabetologia
- Published
- 1998-04-21
- Volume
- 41
- Issue
- 5
- Pages
- 569-576
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2040855107
- Semantic Scholar
- 9797f8f079c36c2855b3d263a5af040730aefdb6
- Cited by
- 177
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2015: 4 · 2014: 5 · 2013: 10 · 2012: 2
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- insulin resistance, obesity, troglitazone, endothelial function, nitric oxide, forearm blood flow, acetylcholine, sodium nitroprusside, L-NMMA, glucose uptake, blood pressure, neurohumoral response, hyperinsulinemia
- MeSH terms
- Troglitazone, Acetylcholine, Adult, Analysis of Variance, Blood Glucose, Cardiovascular System, Chromans, Dose-Response Relationship, Drug, Double-Blind Method, Endothelium, Vascular, Enzyme Inhibitors, Fasting, Female, Forearm, Hemodynamics, Humans, Hyperinsulinism, Hypoglycemic Agents, Insulin, Insulin Resistance, Lipids, Male, Middle Aged, Nitroprusside, Obesity, Reference Values, Regional Blood Flow, Thiazoles, Vasodilation, Vasodilator Agents, Glucose Clamp Technique, Biomarkers, Case-Control Studies, Cross-Over Studies, omega-N-Methylarginine, Thiazolidinediones
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 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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