NCT02628301

Brief 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. Furthermore, the investigators aim to identify improvement of microvascular function as a potential target in diabetes prevention and treatment.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 10, 2015

Completed
22 days until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
8 months until next milestone

First Posted

Study publicly available on registry

December 11, 2015

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2017

Completed
Last Updated

July 26, 2017

Status Verified

July 1, 2017

Enrollment Period

2.2 years

First QC Date

March 10, 2015

Last Update Submit

July 25, 2017

Conditions

Insulin ResistanceType 2 DiabetesObesity

Keywords

ObesityType 2 Diabetes MellitusHypercaloric dietMicrocirculationMicrovascular dysfunctionInsulin ResistanceInsulin SensitivityInsulin signaling

Outcome Measures

Primary Outcomes (1)

  • Microvascular Insulin Sensitivity

    Capillary recruitment by contrast-enhanced ultrasound.

    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

    Baseline, 7-10 days after initiation of the hypercaloric diet, after the hypercaloric diet,

Study Arms (2)

Hypercaloric diet

ACTIVE COMPARATOR

Hypercaloric diet (1.6x REE) for 30 days

Dietary Supplement: Hypercaloric diet

Normal diet

PLACEBO COMPARATOR

Normocaloric diet (1.0xREE)

Other: Normocaloric diet

Interventions

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.

Hypercaloric diet
Normocaloric dietOTHER

Normocaloric diet

Normal diet

Eligibility Criteria

Age18 Years - 30 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VU University Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Related Publications (9)

  • 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.

    PMID: 11742412BACKGROUND

  • Kim 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.

    PMID: 16618833BACKGROUND

  • De 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.

    PMID: 21883642BACKGROUND

  • Kim 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.

    PMID: 18772497BACKGROUND

  • Barrett 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.

    PMID: 19283361BACKGROUND

  • Park 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.

    PMID: 16306372BACKGROUND

  • Kubota 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.

    PMID: 21356519BACKGROUND

  • Paolisso 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.

    PMID: 7537193BACKGROUND

  • Emanuel 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.

    PMID: 32404008DERIVED

MeSH Terms

Conditions

Insulin ResistanceDiabetes Mellitus, Type 2Obesity

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesDiabetes MellitusEndocrine System DiseasesOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Erik Serne, MD PhD

    Amsterdam UMC, location VUmc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

March 10, 2015

First Posted

December 11, 2015

Study Start

April 1, 2015

Primary Completion

May 30, 2017

Study Completion

May 30, 2017

Last Updated

July 26, 2017

Record last verified: 2017-07

Locations

NL(1)