DiabetesNCT00570154
Relation of White Blood Cell Function to Diabetes
An observational study of Diabetes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Patients who are pre-diabetic or have adult onset (type 2) diabetes have a significantly greater risk of developing heart, blood vessel, or kidney diseases. Recent studies have shown that abnormalities in white blood cell function may increase the chances of developing insulin resistance, the underlying… Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Nov 2007to 19 Oct 2009
- Phase
- Observational
- 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 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults older than 21 years and less than 40 years
- Subjects must either have:
- Insulin sensitivity with a fasting blood glucose less than 100 mg/dl and a 2-hour post oral glucose tolerance test blood glucose less than 140 mg/dl
- or
- Insulin resistance as defined by a fasting blood sugar of greater than or equal to 100mg/dl but less than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 140 mg/dl and less than 200 mg/dl.
- Subject understands protocol and provides written, informed consent.
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- Adults greater than or equal to 40 years and less than or equal to 60 years
- Subjects must either have:
- Insulin sensitivity with a fasting blood glucose less than 100 mg/dl and a 2-hour post oral glucose tolerance test blood glucose less than 140 mg/dl
- or
- Insulin resistance as defined by a fasting blood sugar of greater than or equal to 100mg/dl but less than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 140 mg/dl and less than 200 mg/dl.
- or
- Type II diabetes as defined by a fasting blood sugar of greater than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 200 mg/dl if untreated and/or if subjects are on oral hypoglycemic agent therapy where the HbA1c is greater than 6.7 percent.
- Subject understands protocol and provides written, informed consent.
Who cannot join
- Uncontrolled hypertension or therapy with a Beta-blocker
- History of heart failure (or ejection fraction less than 55 percent by echocardiogram), unstable coronary artery disease or symptomatic peripheral arterial disease requiring changes in medication or medical intervention in the preceding 3 months.
- Insulin-dependant diabetes mellitus or current use of thiazolidinediones
- Women of childbearing age unless recent pregnancy test is negative and you are not breast feeding.
- Serum creatinine greater than 2.5 mg/dl
- Liver transaminase levels greater than 2.5 times upper limit of normal
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- History of cancer in the last 5 years
- Active inflammatory disease, or infection, or abnormal white blood cell differential
- Enrollment in any drug studies within the last 30 days
- BMI greater than 35 for the middle age group and greater than 30 for the younger subjects
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Monocyte Biology in Insulin Sensitive, Resistant and Diabetic Subjects
Background:
Patients who are pre-diabetic or have adult onset (type 2) diabetes have a significantly greater risk of developing heart, blood vessel, or kidney diseases.
Read more
Recent studies have shown that abnormalities in white blood cell function may increase the chances of developing insulin resistance, the underlying problem in diabetic or pre-diabetic patients.
Objectives:
To determine levels of insulin sensitivity in selected volunteers.
To compare the white blood cells of non-diabetic, pre-diabetic, and type 2 (adult onset) diabetic volunteers to evaluate possible differences in white blood cell function.
Eligibility:
Individuals between 21 and 60 years of age who (1) are non-diabetic, (2) are pre-diabetic (glucose intolerant or insulin resistant), or (3) have type 2 diabetes that is controlled by diet and/or medications other than insulin.
Design:
Evaluations before treatment:
- Blood tests, including screening procedures for blood-transmitted diseases such as hepatitis B and C, insulin sensitivity and glucose tolerance tests, and liver and kidney function tests.
- Pregnancy tests for women of childbearing age.
Two tests will be performed during the study period:
- Glucose tolerance test to determine how well the body uses glucose.
- Blood drawn to study white blood cells.
Participants will be financially compensated for the time spent during the study.
Read the detailed description
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Interestingly, mitochondrial dysfunction in skeletal muscle and adipose tissue are early events in the development of type II diabetes mellitus and are proposed to play a role in exacerbating insulin resistance. The genetic disruption of macrophage mitochondrial biology in preclinical studies results in the development of insulin resistance and concurrent mitochondrial dysfunction in peripheral tissue including skeletal muscle and the liver. Whether this disruption of mitochondrial function is evident in human mononuclear cells is unknown. We propose that the disruption of mitochondrial function in circulating cells may contribute to not only peripheral insulin resistance but may also evoke the myriad of vascular complications associated with diabetes.
To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in circulating monocytes in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, gene expression and proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of monocytes with disease progression. To delineate these concepts we will evaluate study subjects' glucose tolerance and insulin sensitivity and draw blood to examine peripheral monocytes. Biological readouts will include: 1) the quantification of the mitochondrial genomic and electron transfer chain content; 2) the determination of mitochondrial reactive oxygen species capacity and defenses; 3) the pattern of monocyte differentiation and 4) the unbiased assessment of monocyte gene expression and proteome.
If the mitochondrial hypothesis is operational, this study will show that the mitochondrial disruption/dysfunction is a more generalized finding in type II diabetes. This would establish targeting the modification of mitochondrial function in various tissue/cell types as a novel strategy in the prevention and/or reversal of insulin resistance and diabetes.
- Conditions
- Diabetes
- Keywords
- Mitochondrial Function in Monocytes, Macrophages and Diabetes or Insulin Resistance, Peripheral Blood Mononuclear Cells, Diabetes, Monocyte, Macrophages, Proteome, Type 2 Diabetes, Insulin Resistance, Insulin Sensitivity, Pre-Diabetes, Healthy Volunteer, HV
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance, Diabetes Mellitus, Type 2, Glucose Intolerance
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2007 (estimated)
- Study start27 Nov 2007
- Primary completion19 Oct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 100 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00570154
- Sponsor's protocol ID
- 080028
- Other IDs
- 08-H-0028
- Status last verified
- 19 Oct 2009
- First submitted
- 7 Dec 2007
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007 Jul 10;116(2):151-7. doi: 10.1161/CIRCULATIONAHA.106.685628. Epub 2007 Jun 18.
PubMed 17576864Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 2006 Dec;55 Suppl 2(Suppl 2):S9-S15. doi: 10.2337/db06-S002.
PubMed 17130651Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan 21;307(5708):384-7. doi: 10.1126/science.1104343.
PubMed 15662004
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Monocyte Biology in Insulin Sensitive, Resistant and Diabetic Subjects
- ClinicalTrials.gov ID
- NCT00570154
- Acronym / sponsor ID
- 080028
- Conditions
- Diabetes
- Keywords
- Mitochondrial Function in Monocytes, Macrophages and Diabetes or Insulin Resistance, Peripheral Blood Mononuclear Cells, Diabetes, Monocyte, Macrophages, Proteome, Type 2 Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 27 Nov 2007
- Primary completion
- 19 Oct 2009 (actual)
- First posted
- 10 Dec 2007 (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.
Background:
Patients who are pre-diabetic or have adult onset (type 2) diabetes have a significantly greater risk of developing heart, blood vessel, or kidney diseases.
Recent studies have shown that abnormalities in white blood cell function may increase the chances of developing insulin resistance, the underlying problem in diabetic or pre-diabetic patients.
Objectives:
To determine levels of insulin sensitivity in selected volunteers.
To compare the white blood cells of non-diabetic, pre-diabetic, and type 2 (adult onset) diabetic volunteers to evaluate possible differences in white blood cell function.
Eligibility:
Individuals between 21 and 60 years of age who (1) are non-diabetic, (2) are pre-diabetic (glucose intolerant or insulin resistant), or (3) have type 2 diabetes that is controlled by diet and/or medications other than insulin.
Design:
Evaluations before treatment:
- Blood tests, including screening procedures for blood-transmitted diseases such as hepatitis B and C, insulin sensitivity and glucose tolerance tests, and liver and kidney function tests.
- Pregnancy tests for women of childbearing age.
Two tests will be performed during the study period:
- Glucose tolerance test to determine how well the body uses glucose.
- Blood drawn to study white blood cells.
Participants will be financially compensated for the time spent during the study.
Detailed description
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Interestingly, mitochondrial dysfunction in skeletal muscle and adipose tissue are early events in the development of type II diabetes mellitus and are proposed to play a role in exacerbating insulin resistance. The genetic disruption of macrophage mitochondrial biology in preclinical studies results in the development of insulin resistance and concurrent mitochondrial dysfunction in peripheral tissue including skeletal muscle and the liver. Whether this disruption of mitochondrial function is evident in human mononuclear cells is unknown. We propose that the disruption of mitochondrial function in circulating cells may contribute to not only peripheral insulin resistance but may also evoke the myriad of vascular complications associated with diabetes.
To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in circulating monocytes in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, gene expression and proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of monocytes with disease progression. To delineate these concepts we will evaluate study subjects' glucose tolerance and insulin sensitivity and draw blood to examine peripheral monocytes. Biological readouts will include: 1) the quantification of the mitochondrial genomic and electron transfer chain content; 2) the determination of mitochondrial reactive oxygen species capacity and defenses; 3) the pattern of monocyte differentiation and 4) the unbiased assessment of monocyte gene expression and proteome.
If the mitochondrial hypothesis is operational, this study will show that the mitochondrial disruption/dysfunction is a more generalized finding in type II diabetes. This would establish targeting the modification of mitochondrial function in various tissue/cell types as a novel strategy in the prevention and/or reversal of insulin resistance and diabetes.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Adults older than 21 years and less than 40 years
- Insulin sensitivity with a fasting blood glucose less than 100 mg/dl and a 2-hour post oral glucose tolerance test blood glucose less than 140 mg/dl
- or
- Insulin resistance as defined by a fasting blood sugar of greater than or equal to 100mg/dl but less than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 140 mg/dl and less than 200 mg/dl.
- Subject understands protocol and provides written, informed consent.
Key exclusion criteria (10 listed)
- Uncontrolled hypertension or therapy with a Beta-blocker
- History of heart failure (or ejection fraction less than 55 percent by echocardiogram), unstable coronary artery disease or symptomatic peripheral arterial disease requiring changes in medication or medical intervention in the preceding 3 months.
- Insulin-dependant diabetes mellitus or current use of thiazolidinediones
- Women of childbearing age unless recent pregnancy test is negative and you are not breast feeding.
- Serum creatinine greater than 2.5 mg/dl
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 17576864Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007 Jul 10;116(2):151-7. doi: 10.1161/CIRCULATIONAHA.106.685628. Epub 2007 Jun 18.
- Background: PubMed 17130651Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 2006 Dec;55 Suppl 2(Suppl 2):S9-S15. doi: 10.2337/db06-S002.
- Background: PubMed 15662004Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan 21;307(5708):384-7. doi: 10.1126/science.1104343.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
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 14 inclusion and 10 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 2 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 United States. 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. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00570154, which also lists 3 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 2 Jul 2017; AzTrials last refreshed its copy on 6 Nov 2026.