Insulin ResistanceDESIRENCT02628301
Microvascular Dysfunction and the Development of Whole-body Insulin Resistance
A study testing Hypercaloric diet and Normocaloric diet in people with Insulin Resistance and Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
This study aims to elucidate the role of the microcirculation in the development of whole body insulin resistance. The investigators hypothesize that impaired insulin signaling in the vasculature is an early phenomenon in the development of whole body insulin resistance. Read more about this study
- Who is it for?
- Ages 18 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Type 2 Diabetes, Obesity
- What is being tested?
- Hypercaloric diet and Normocaloric diet
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2015to 30 May 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Caucasian
- BMI 22-25 kg/m2
- Normal insulin sensitivity as estimated by Homeostasis Model Assessment (HOMA-IR)
- Normoglycemia as defined by fasting plasma glucose (FPG) <6.1 mmol/l
- Normoglycemia as defined by 2 h glucose <7.8 mmol/l during oral glucose tolerance test (OGTT)
- Normal diet pattern according to the Dutch guidelines for a healthy diet 2006
- Stable body weight (<3% weight change) during 6 months before enrolment in the study
Who cannot join
- Presence of any relevant disease
- Use of any relevant medication
- First-degree relative with type 2 diabetes
- Smoking
- Shift work
- A history of chronic glucocorticoids (GC) use or GC use < 3 months ago
- Excessive sport activities (more often than 3 hours per week)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1081 HV
About this study
Official title: Is Microvascular Dysfunction an Early Phenomenon in the Development of Skeletal Muscle Insulin Resistance? A Dietary Intervention Study in Healthy Men
This study aims to elucidate the role of the microcirculation in the development of whole body insulin resistance. The investigators hypothesize that impaired insulin signaling in the vasculature is an early phenomenon in the development of whole body insulin resistance. Furthermore, the investigators aim to identify improvement of microvascular function as a potential target in diabetes prevention and treatment.
Read the detailed description
In today's society, food availability grossly exceeds our body's caloric demands. Excessive caloric intake causes weight gain and induces insulin resistance, a common characteristic of obesity and major risk factor for type 2 diabetes (T2DM) and cardiovascular disease.
The primary targets of insulin action are skeletal muscle, adipose tissue and the liver, but recent data point to the vascular endothelium as an important target. Insulin directly targets the endothelial cell where it activates phosphoinositide 3-kinase, resulting in Akt-mediated phosphorylation of endothelial nitric oxide synthase (eNOS). This leads to NO production - a potent vasodilator in the human body. Simultaneously insulin also activates the mitogen-activated protein kinase pathway in endothelial cells, which enhances the generation of the vasoconstrictor endothelin-1 via extracellular signal-regulated kinases 1/2 signaling. Via these two pathways insulin can regulate vascular tone.
In healthy individuals, insulin signaling in the endothelial cell leads to capillary recruitment in skeletal muscle tissue via vasodilatation of terminal arterioles. It has been proposed that insulin in this matter regulates the delivery of insulin and glucose to skeletal muscle by increasing endothelial surface area. In obese individuals and patients with T2DM, insulin-mediated capillary recruitment in skeletal muscle tissue is impaired and insulin-dependent glucose uptake is diminished. Whether these two processes are linked or occur in parallel remains unknown.
Interestingly, studies in rodents demonstrated that during obesity induced by high fat feeding, insulin resistance develops in the vasculature before these responses are detected in muscle, liver, or adipose tissue. Therefore, insulin signaling in endothelium might change in response to a positive energy balance to prevent nutrient overload in muscle and optimize nutrient storage in adipose tissue. Conversely, it has been hypothesized that early reversal of endothelial insulin resistance could prevent peripheral insulin resistance, assuming a cause-and-effect relationship between these processes. The most compelling evidence for this hypothesis came from studies in endothelial cell specific insulin receptor substrate-2 (IRS-2) knock-out mice. Kubota et al. demonstrated that impaired insulin signaling in endothelial cells, due to reduced IRS-2 expression and insulin-induced eNOS phosphorylation, caused attenuation of insulin-induced capillary recruitment and insulin delivery, which reduced glucose uptake by skeletal muscle. Moreover, restoration of insulin-induced eNOS phosphorylation in endothelial cells by infusion of beraprost sodium - a stable prostaglandin analogue - completely reversed the reduction in capillary recruitment and insulin delivery in tissue-specific knockout mice lacking IRS-2 in endothelial cells and fed a high-fat diet. As a result, glucose uptake by skeletal muscle was restored in these mice.
These data suggest that pharmacological stimulation of tissue perfusion may hold promise as a therapeutic strategy to increase whole body glucose disposal and thus prevent or reduce hyperglycaemia. In humans however, data linking improvement of capillary recruitment by pharmacological agents to restoration of whole-body glucose uptake are lacking. Low dose iloprost infusion - another stable prostaglandin analogue - has been shown to improve insulin-stimulated whole-body glucose uptake, but the mechanistic role of microvascular response was not assessed. Overall, it remains to be demonstrated whether improving capillary recruitment by endothelial insulin signaling or direct stimulation of smooth muscle tissue may serve as an attractive preventive or therapeutic approach to bypass cellular resistance to glucose disposal.
In conclusion, vascular insulin resistance leads to blunted capillary recruitment in the skeletal muscle and may lead to diminished glucose uptake due to a decreased capillary surface area for nutrient exchange. Up till now however it remains unclear if these processes are interrelated or occur in parallel. Evidence from animal studies suggest that vascular insulin resistance precedes diminished whole-body glucose uptake and myocellular impairments. This indicates a potential cause-effect relationship. In humans, however, this was never demonstrated. On the other hand, decreased capillary recruitment of skeletal muscle tissue could also protect muscle tissue from nutrient overload and shunt excess calories towards adipose tissue. Presently, it is unknown whether insulin redistributes blood flow from skeletal muscle to adipose tissue during hypercaloric conditions. Finally, it is unknown if stimulation of tissue perfusion with a pharmacological agent can restore whole-body glucose uptake is therefore an effective strategy in prevention or treatment of insulin resistance.
- Conditions
- Insulin Resistance, Type 2 Diabetes, Obesity
- Being tested
- Hypercaloric diet, Normocaloric diet
- Keywords
- Obesity, Type 2 Diabetes Mellitus, Hypercaloric diet, Microcirculation, Microvascular dysfunction, Insulin Resistance, Insulin Sensitivity, Insulin signaling
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypercaloric dietDietary supplement
Hypercaloric diet consisting of 60% excess calories based on resting energy expenditure (REE). Calories will be provided in the form of snacks in between the ad libitum meals. A subsequent hypocaloric diet will consist of 1.0x resting energy expenditure.
Normocaloric dietOther
Normocaloric diet
| Study group | Role | What they receive |
|---|---|---|
| Hypercaloric diet | Active comparator | Hypercaloric diet (1.6x REE) for 30 days Receives: Dietary Supplement: Hypercaloric diet |
| Normal diet | Placebo comparator | Normocaloric diet (1.0xREE) Receives: Other: Normocaloric diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular Insulin Sensitivity
Capillary recruitment by contrast-enhanced ultrasound.
Measured: Baseline, 7-10 days after initiation of the hypercaloric diet, after the hypercaloric diet, after the subsequent hypocaloric diet
Secondary outcomes (1)
Whole Body Insulin Sensitivity
M-value by euglycemic-hyperinsulinemic clamp
Measured: Baseline, 7-10 days after initiation of the hypercaloric diet, after the hypercaloric diet,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study startApr 2015
- Primary completion30 May 2017
- Study completion30 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erik Serne, Amsterdam UMC, location VUmc
- Investigators
- Erik Serne, MD PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02628301
- Sponsor's protocol ID
- DC2014DES001
- Acronym
- DESIRE
- Status last verified
- Jul 2017
- First submitted
- 10 Mar 2015
- Last updated
- 26 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001 Dec 13;414(6865):799-806. doi: 10.1038/414799a.
PubMed 11742412Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006 Apr 18;113(15):1888-904. doi: 10.1161/CIRCULATIONAHA.105.563213.
PubMed 16618833De Boer MP, Meijer RI, Wijnstok NJ, Jonk AM, Houben AJ, Stehouwer CD, Smulders YM, Eringa EC, Serne EH. Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. Microcirculation. 2012 Jan;19(1):5-18. doi: 10.1111/j.1549-8719.2011.00130.x.
PubMed 21883642Kim F, Pham M, Maloney E, Rizzo NO, Morton GJ, Wisse BE, Kirk EA, Chait A, Schwartz MW. Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1982-8. doi: 10.1161/ATVBAHA.108.169722. Epub 2008 Sep 4.
PubMed 18772497Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, Liu Z. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia. 2009 May;52(5):752-64. doi: 10.1007/s00125-009-1313-z. Epub 2009 Mar 13.
PubMed 19283361Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005 Dec;54(12):3530-40. doi: 10.2337/diabetes.54.12.3530.
PubMed 16306372Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, Ezaki O, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab. 2011 Mar 2;13(3):294-307. doi: 10.1016/j.cmet.2011.01.018.
PubMed 21356519Paolisso G, Di Maro G, D'Amore A, Passariello N, Gambardella A, Varricchio M, D'Onofrio F. Low-dose iloprost infusion improves insulin action in aged healthy subjects and NIDDM patients. Diabetes Care. 1995 Feb;18(2):200-5. doi: 10.2337/diacare.18.2.200.
PubMed 7537193Emanuel AL, Meijer RI, Woerdeman J, van Raalte DH, Diamant M, Kramer MHH, Serlie MJ, Eringa EC, Serne EH. Effects of a Hypercaloric and Hypocaloric Diet on Insulin-Induced Microvascular Recruitment, Glucose Uptake, and Lipolysis in Healthy Lean Men. Arterioscler Thromb Vasc Biol. 2020 Jul;40(7):1695-1704. doi: 10.1161/ATVBAHA.120.314129. Epub 2020 May 14.
PubMed 32404008
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is Microvascular Dysfunction an Early Phenomenon in the Development of Skeletal Muscle Insulin Resistance? A Dietary Intervention Study in Healthy Men
- ClinicalTrials.gov ID
- NCT02628301
- Acronym / sponsor ID
- DESIRE / DC2014DES001
- Conditions
- Insulin Resistance, Type 2 Diabetes, Obesity
- Keywords
- Obesity, Type 2 Diabetes Mellitus, Hypercaloric diet, Microcirculation, Microvascular dysfunction, Insulin Resistance, Insulin Sensitivity, Insulin signaling
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- Apr 2015 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 30 May 2017 (actual)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to elucidate the role of the microcirculation in the development of whole body insulin resistance. The investigators hypothesize that impaired insulin signaling in the vasculature is an early phenomenon in the development of whole body insulin resistance. Furthermore, the investigators aim to identify improvement of microvascular function as a potential target in diabetes prevention and treatment.
Detailed description
In today's society, food availability grossly exceeds our body's caloric demands. Excessive caloric intake causes weight gain and induces insulin resistance, a common characteristic of obesity and major risk factor for type 2 diabetes (T2DM) and cardiovascular disease.
The primary targets of insulin action are skeletal muscle, adipose tissue and the liver, but recent data point to the vascular endothelium as an important target. Insulin directly targets the endothelial cell where it activates phosphoinositide 3-kinase, resulting in Akt-mediated phosphorylation of endothelial nitric oxide synthase (eNOS). This leads to NO production - a potent vasodilator in the human body. Simultaneously insulin also activates the mitogen-activated protein kinase pathway in endothelial cells, which enhances the generation of the vasoconstrictor endothelin-1 via extracellular signal-regulated kinases 1/2 signaling. Via these two pathways insulin can regulate vascular tone.
In healthy individuals, insulin signaling in the endothelial cell leads to capillary recruitment in skeletal muscle tissue via vasodilatation of terminal arterioles. It has been proposed that insulin in this matter regulates the delivery of insulin and glucose to skeletal muscle by increasing endothelial surface area. In obese individuals and patients with T2DM, insulin-mediated capillary recruitment in skeletal muscle tissue is impaired and insulin-dependent glucose uptake is diminished. Whether these two processes are linked or occur in parallel remains unknown.
Interestingly, studies in rodents demonstrated that during obesity induced by high fat feeding, insulin resistance develops in the vasculature before these responses are detected in muscle, liver, or adipose tissue. Therefore, insulin signaling in endothelium might change in response to a positive energy balance to prevent nutrient overload in muscle and optimize nutrient storage in adipose tissue. Conversely, it has been hypothesized that early reversal of endothelial insulin resistance could prevent peripheral insulin resistance, assuming a cause-and-effect relationship between these processes. The most compelling evidence for this hypothesis came from studies in endothelial cell specific insulin receptor substrate-2 (IRS-2) knock-out mice. Kubota et al. demonstrated that impaired insulin signaling in endothelial cells, due to reduced IRS-2 expression and insulin-induced eNOS phosphorylation, caused attenuation of insulin-induced capillary recruitment and insulin delivery, which reduced glucose uptake by skeletal muscle. Moreover, restoration of insulin-induced eNOS phosphorylation in endothelial cells by infusion of beraprost sodium - a stable prostaglandin analogue - completely reversed the reduction in capillary recruitment and insulin delivery in tissue-specific knockout mice lacking IRS-2 in endothelial cells and fed a high-fat diet. As a result, glucose uptake by skeletal muscle was restored in these mice.
These data suggest that pharmacological stimulation of tissue perfusion may hold promise as a therapeutic strategy to increase whole body glucose disposal and thus prevent or reduce hyperglycaemia. In humans however, data linking improvement of capillary recruitment by pharmacological agents to restoration of whole-body glucose uptake are lacking. Low dose iloprost infusion - another stable prostaglandin analogue - has been shown to improve insulin-stimulated whole-body glucose uptake, but the mechanistic role of microvascular response was not assessed. Overall, it remains to be demonstrated whether improving capillary recruitment by endothelial insulin signaling or direct stimulation of smooth muscle tissue may serve as an attractive preventive or therapeutic approach to bypass cellular resistance to glucose disposal.
In conclusion, vascular insulin resistance leads to blunted capillary recruitment in the skeletal muscle and may lead to diminished glucose uptake due to a decreased capillary surface area for nutrient exchange. Up till now however it remains unclear if these processes are interrelated or occur in parallel. Evidence from animal studies suggest that vascular insulin resistance precedes diminished whole-body glucose uptake and myocellular impairments. This indicates a potential cause-effect relationship. In humans, however, this was never demonstrated. On the other hand, decreased capillary recruitment of skeletal muscle tissue could also protect muscle tissue from nutrient overload and shunt excess calories towards adipose tissue. Presently, it is unknown whether insulin redistributes blood flow from skeletal muscle to adipose tissue during hypercaloric conditions. Finally, it is unknown if stimulation of tissue perfusion with a pharmacological agent can restore whole-body glucose uptake is therefore an effective strategy in prevention or treatment of insulin resistance.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypercaloric diet | Active comparator | Dietary Supplement: Hypercaloric dietHypercaloric diet (1.6x REE) for 30 days |
| Normal diet | Placebo comparator | Other: Normocaloric dietNormocaloric diet (1.0xREE) |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Caucasian
- BMI 22-25 kg/m2
- Normal insulin sensitivity as estimated by Homeostasis Model Assessment (HOMA-IR)
- Normoglycemia as defined by fasting plasma glucose (FPG) <6.1 mmol/l
- Normoglycemia as defined by 2 h glucose <7.8 mmol/l during oral glucose tolerance test (OGTT)
Key exclusion criteria (7 listed)
- Presence of any relevant disease
- Use of any relevant medication
- First-degree relative with type 2 diabetes
- Smoking
- Shift work
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypercaloric dietHypercaloric diet consisting of 60% excess calories based on resting energy expenditure (REE). Calories will be provided in the form of snacks in between the ad libitum meals. A subsequent hypocaloric diet will consist of 1.0x resting energy expenditure. | Dietary supplement | Hypercaloric diet |
| Normocaloric dietNormocaloric diet | Other | Normal diet |
Primary outcome
Microvascular Insulin Sensitivity
Time frame: Baseline, 7-10 days after initiation of the hypercaloric diet, after the hypercaloric diet, after the subsequent hypocaloric diet
Capillary recruitment by contrast-enhanced ultrasound.
1 secondary outcome
Whole Body Insulin Sensitivity
Time frame: Baseline, 7-10 days after initiation of the hypercaloric diet, after the hypercaloric diet,
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2017.
- Background: PubMed 11742412Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001 Dec 13;414(6865):799-806. doi: 10.1038/414799a.
- Background: PubMed 16618833Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006 Apr 18;113(15):1888-904. doi: 10.1161/CIRCULATIONAHA.105.563213.
- Background: PubMed 21883642De Boer MP, Meijer RI, Wijnstok NJ, Jonk AM, Houben AJ, Stehouwer CD, Smulders YM, Eringa EC, Serne EH. Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. Microcirculation. 2012 Jan;19(1):5-18. doi: 10.1111/j.1549-8719.2011.00130.x.
- Background: PubMed 18772497Kim F, Pham M, Maloney E, Rizzo NO, Morton GJ, Wisse BE, Kirk EA, Chait A, Schwartz MW. Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1982-8. doi: 10.1161/ATVBAHA.108.169722. Epub 2008 Sep 4.
- Background: PubMed 19283361Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W, Liu Z. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia. 2009 May;52(5):752-64. doi: 10.1007/s00125-009-1313-z. Epub 2009 Mar 13.
- Background: PubMed 16306372Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005 Dec;54(12):3530-40. doi: 10.2337/diabetes.54.12.3530.
- Background: PubMed 21356519Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, Ezaki O, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab. 2011 Mar 2;13(3):294-307. doi: 10.1016/j.cmet.2011.01.018.
- Background: PubMed 7537193Paolisso G, Di Maro G, D'Amore A, Passariello N, Gambardella A, Varricchio M, D'Onofrio F. Low-dose iloprost infusion improves insulin action in aged healthy subjects and NIDDM patients. Diabetes Care. 1995 Feb;18(2):200-5. doi: 10.2337/diacare.18.2.200.
- Derived from this study: PubMed 32404008Emanuel AL, Meijer RI, Woerdeman J, van Raalte DH, Diamant M, Kramer MHH, Serlie MJ, Eringa EC, Serne EH. Effects of a Hypercaloric and Hypocaloric Diet on Insulin-Induced Microvascular Recruitment, Glucose Uptake, and Lipolysis in Healthy Lean Men. Arterioscler Thromb Vasc Biol. 2020 Jul;40(7):1695-1704. doi: 10.1161/ATVBAHA.120.314129. Epub 2020 May 14.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik Serne, MD PhD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypercaloric diet and Normocaloric diet in people with Insulin Resistance and Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microvascular Insulin Sensitivity (time frame: Baseline, 7-10 days after initiation of the hypercaloric diet, after the hypercaloric diet, after the subsequent hypocaloric diet). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02628301, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017; AzTrials last refreshed its copy on 6 Nov 2026.