Diabetes Mellitus, Type 2NCT00753142
Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
A study testing Intralipid 20% and Glucose infusion in people with Diabetes Mellitus, Type 2, run by Emory University at 1 site in United States.
Trial summary
Obesity is common in African American (AA) patients with newly diagnosed diabetes who present with diabetic ketoacidosis (DKA). Despite the presentation with severe symptoms of insulinopenia and ketoacidosis, clinical and immunogenetic observations indicate that most obese AA patients with DKA have type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Intralipid 20% and Glucose infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Dec 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Obese African American subjects (body mass index (BMI) equal or greater than 30)
- Age 18-65
- Patients with a history of diabetic ketoacidosis as defined by the American Diabetes Association (ADA) criteria
- Patients admitted with hyperglycemia but without ketoacidosis (blood glucose greater than 400ml/dl without evidence of ketosis/ketones
- Obese nondiabetic controls (BMI >30; ruled out for diabetes with a 75g oral glucose tolerance test)
Who cannot join
- Patients with positive autoimmune markers (islet cell or glutamic acid decarboxylase (GAD) autoantibodies)
- Patients with significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes
- Patients with recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism
- Patients with bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies
- Patients with fasting hyperglycemia (blood glucose > 120 mg/dl) after discontinuation of insulin therapy
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Obesity is common in African American (AA) patients with newly diagnosed diabetes who present with diabetic ketoacidosis (DKA). Despite the presentation with severe symptoms of insulinopenia and ketoacidosis, clinical and immunogenetic observations indicate that most obese AA patients with DKA have type 2 diabetes. In such patients, previous studies reveal that: a) at presentation, obese AA patients with DKA have markedly decreased pancreatic insulin secretion, lower than in obese non-DKA patients admitted with comparable hyperglycemia, but significantly greater than in lean patients with DKA; b) aggressive diabetic management results in significant improvement in beta-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within 3 months of follow-up. Based on these observations the researchers conclude that similar to obese patients with hyperglycemia, most obese AA with DKA have type 2 diabetes, and that although defects in both insulin secretion and insulin action are present, transient b-cell failure is the primary defect in the development of ketoacidosis.
Read the detailed description
Obese AA patients with a history of DKA who later experience near-normoglycemia remission represent an ideal population in which to define the sequence of events that lead to b-cell dysfunction in type 2 diabetes. The researchers hypothesize that obese AA with DKA will prove particularly susceptible to beta-cells dysfunction due to sustained elevations of plasma glucose (glucose toxicity) and/or free fatty acid levels (lipotoxicity). This study will test beta-cell response by administering a glucose infusion to diabetic African Americans with a history of DKA, diabetic African Americans without a history of DKA, and non-diabetic African Americans.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Intralipid 20%, Glucose infusion
- Keywords
- Hyperglycemia
- Medical subject headings
- Diabetes Mellitus, Type 2, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid 20%Drug
Participants receive a 48-hour infusion with Intralipid at 40 milliliters per hour (mL/hr).
Glucose infusionDrug
Participants receive a glucose infusion consisting of 10% dextrose infused intravenously at a rate of 200 mg/m^2/min for 20 hours.
| Study group | Role | What they receive |
|---|---|---|
| Participants with ketosis-prone diabetes | Active comparator | Obese African Americans with type 2 diabetes with history of diabetic ketoacidosis (DKA) receiving Intralipid 20% and a glucose infusion. Receives: Drug: Intralipid 20%; Drug: Glucose infusion |
| Participants with ketosis-resistant diabetes | Active comparator | Obese African American with type 2 diabetes with hyperglycemia without ketosis receiving Intralipid 20% and a glucose infusion. Receives: Drug: Intralipid 20%; Drug: Glucose infusion |
| Non-diabetic control group | Active comparator | Obese African Americans without diabetes receiving a glucose infusion. Receives: Drug: Glucose infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
First-Phase Insulin Release (FPIR)
An arginine stimulation test was used to evaluate beta-cell function and insulin secretion. Increased glucose in the blood causes insulin to be released, beginning with a spike in insulin in the first 10 minutes and plateauing 2 to 3 later. Diminished first-phase insulin release is an early indicator of beta-cell dysfunction. Two sequential arginine stimulation tests were performed, the first set before and the second after completion of the 20-hour dextrose infusion. The first-phase insulin release (FPIR) was calculated as the sum of the insulin levels at 2, 3, 4, and 5 minutes after the arginine infusion. FPIR is expected to rise after the dextrose (glucose) infusion and FPIR generally rises less in persons with impaired glucose tolerance.
Measured: Hour 0, Hour 20
Secondary outcomes (1)
Number of Participants With Beta-cell Failure
Pancreatic beta-cells can adapt to insulin resistance during the early stages of diabetes but continuous exposure of beta-cells to prolonged hyperglycemia can cause irreversible damage due to glucotoxicity. This study aimed to evaluate whether hyperglycemia-induced reduced beta-cell failure was the result of beta-cell exhaustion or beta-cell desensitization, however, no participants experienced beta-cell failure so this original analysis could not be performed.
Measured: Hour 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2008 (estimated)
- Study startMar 2004
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Principal investigator, Guillermo Umpierrez, MD, Emory University
- Investigators
- Guillermo Umpierrez, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00753142
- Sponsor's protocol ID
- 898-2003
- Status last verified
- Sep 2018
- First submitted
- 12 Sep 2008
- Last updated
- 12 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gosmanov AR, Smiley D, Robalino G, Siqueira JM, Peng L, Kitabchi AE, Umpierrez GE. Effects of intravenous glucose load on insulin secretion in patients with ketosis-prone diabetes during near-normoglycemia remission. Diabetes Care. 2010 Apr;33(4):854-60. doi: 10.2337/dc09-1687. Epub 2010 Jan 12.
PubMed 20067967
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
- ClinicalTrials.gov ID
- NCT00753142
- Acronym / sponsor ID
- 898-2003
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Hyperglycemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- American Diabetes Association
- Study start
- Mar 2004
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 16 Sep 2008 (estimated)
- Results
- Posted 1 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obesity is common in African American (AA) patients with newly diagnosed diabetes who present with diabetic ketoacidosis (DKA). Despite the presentation with severe symptoms of insulinopenia and ketoacidosis, clinical and immunogenetic observations indicate that most obese AA patients with DKA have type 2 diabetes. In such patients, previous studies reveal that: a) at presentation, obese AA patients with DKA have markedly decreased pancreatic insulin secretion, lower than in obese non-DKA patients admitted with comparable hyperglycemia, but significantly greater than in lean patients with DKA; b) aggressive diabetic management results in significant improvement in beta-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within 3 months of follow-up. Based on these observations the researchers conclude that similar to obese patients with hyperglycemia, most obese AA with DKA have type 2 diabetes, and that although defects in both insulin secretion and insulin action are present, transient b-cell failure is the primary defect in the development of ketoacidosis.
Detailed description
Obese AA patients with a history of DKA who later experience near-normoglycemia remission represent an ideal population in which to define the sequence of events that lead to b-cell dysfunction in type 2 diabetes. The researchers hypothesize that obese AA with DKA will prove particularly susceptible to beta-cells dysfunction due to sustained elevations of plasma glucose (glucose toxicity) and/or free fatty acid levels (lipotoxicity). This study will test beta-cell response by administering a glucose infusion to diabetic African Americans with a history of DKA, diabetic African Americans without a history of DKA, and non-diabetic African Americans.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Participants with ketosis-prone diabetes | Active comparator | Drug: Intralipid 20%, Drug: Glucose infusionObese African Americans with type 2 diabetes with history of diabetic ketoacidosis (DKA) receiving Intralipid 20% and a glucose infusion. |
| Participants with ketosis-resistant diabetes | Active comparator | Drug: Intralipid 20%, Drug: Glucose infusionObese African American with type 2 diabetes with hyperglycemia without ketosis receiving Intralipid 20% and a glucose infusion. |
| Non-diabetic control group | Active comparator | Drug: Glucose infusionObese African Americans without diabetes receiving a glucose infusion. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Obese African American subjects (body mass index (BMI) equal or greater than 30)
- Age 18-65
- Patients with a history of diabetic ketoacidosis as defined by the American Diabetes Association (ADA) criteria
- Patients admitted with hyperglycemia but without ketoacidosis (blood glucose greater than 400ml/dl without evidence of ketosis/ketones
- Obese nondiabetic controls (BMI >30; ruled out for diabetes with a 75g oral glucose tolerance test)
Key exclusion criteria (6 listed)
- Patients with positive autoimmune markers (islet cell or glutamic acid decarboxylase (GAD) autoantibodies)
- Patients with significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes
- Patients with recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism
- Patients with bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies
- Patients with fasting hyperglycemia (blood glucose > 120 mg/dl) after discontinuation of insulin therapy
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 |
|---|---|---|
| Intralipid 20%Participants receive a 48-hour infusion with Intralipid at 40 milliliters per hour (mL/hr). | Drug | Participants with ketosis-prone diabetes, Participants with ketosis-resistant diabetes |
| Glucose infusionParticipants receive a glucose infusion consisting of 10% dextrose infused intravenously at a rate of 200 mg/m^2/min for 20 hours. | Drug | Non-diabetic control group, Participants with ketosis-prone diabetes, Participants with ketosis-resistant diabetes |
Primary outcome
First-Phase Insulin Release (FPIR)
Time frame: Hour 0, Hour 20
An arginine stimulation test was used to evaluate beta-cell function and insulin secretion. Increased glucose in the blood causes insulin to be released, beginning with a spike in insulin in the first 10 minutes and plateauing 2 to 3 later. Diminished first-phase insulin release is an early indicator of beta-cell dysfunction. Two sequential arginine stimulation tests were performed, the first set before and the second after completion of the 20-hour dextrose infusion. The first-phase insulin release (FPIR) was calculated as the sum of the insulin levels at 2, 3, 4, and 5 minutes after the arginine infusion. FPIR is expected to rise after the dextrose (glucose) infusion and FPIR generally rises less in persons with impaired glucose tolerance.
1 secondary outcome
Number of Participants With Beta-cell Failure
Time frame: Hour 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20067967Gosmanov AR, Smiley D, Robalino G, Siqueira JM, Peng L, Kitabchi AE, Umpierrez GE. Effects of intravenous glucose load on insulin secretion in patients with ketosis-prone diabetes during near-normoglycemia remission. Diabetes Care. 2010 Apr;33(4):854-60. doi: 10.2337/dc09-1687. Epub 2010 Jan 12.
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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.
Guillermo Umpierrez, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intralipid 20% and Glucose infusion in people with Diabetes Mellitus, Type 2, run by Emory University 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 5 inclusion and 6 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 12 Oct 2018. 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?
Yes. Results are posted in the registry (first posted 1 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
First-Phase Insulin Release (FPIR) (time frame: Hour 0, Hour 20). 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 NCT00753142, which also lists 1 linked publication.
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 12 Oct 2018.