Obesity and Type 2 DiabetesBCNCT06830096
Role of KATP Channel Loss in Type 2 Diabetes
A study testing 10 mg glipizide ingestion in people with Obesity and Type 2 Diabetes, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Insulin is a hormone that is made by β-cells in the pancreas and when released into the bloodstream helps control blood sugar levels. Insulin release is regulated by electrical activity in the β-cell which is generated by the ATP-sensitive potassium (KATP) channel. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity and Type 2 Diabetes
- What is being tested?
- 10 mg glipizide ingestion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2025to 31 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Lean-normoglycemic group (n=10): BMI ≥18.5 and <25.0 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
- Obesity-normoglycemic group (n=10): BMI ≥30 and <50 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
- Obesity-impaired fasting glucose group (n=10): BMI ≥30 and <50 kg/m², fasting plasma glucose concentration 100-125 mg/dl, and 2-hr oral glucose tolerance test plasma glucose concentration <200 mg/dl.
- Obesity-type 2 diabetes group (n=10): BMI ≥30 and <50 kg/m²; HbA1C 6.5-9.5%, fasting plasma glucose ≥126 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≥200 mg/dl and/or medical history of T2DM and currently using anti-diabetic medications.
Who cannot join
- Diabetes therapy with insulin at >0.5 units/kg/day.
- Any change in diabetes medication in previous 3 months.
- Unstable weight (>2% change during the last 2 months before entering the study).
- Evidence of significant organ system dysfunction or disease other than obesity and T2D.
- Regular use of tobacco products.
- Excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women).
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- Use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study.
- Anemia (Hemoglobin <10.0 g/dL).
- Pregnant or breastfeeding.
- Unable or unwilling to follow the study protocol or for any reason the research team believes the volunteer is not an appropriate candidate for this study, including non-compliance with screening appointments or previous medical visits.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University in St. Louis
St Louis, Missouri, 63110
Kyle Timmons, 314-362-8699, timmons@wustl.edu
Nathaniel York, PhD
About this study
Official title: Hyperglycemia Induced Hyperexcitability: A Novel Role for KATP in the Progression of Type 2 Diabetes
Insulin is a hormone that is made by β-cells in the pancreas and when released into the bloodstream helps control blood sugar levels. Insulin release is regulated by electrical activity in the β-cell which is generated by the ATP-sensitive potassium (KATP) channel. While reduced KATP activity is associated with increased insulin secretion, animals lacking KATP exhibit reduced secretion. This crossover from hypersecretion to undersecretion with KATP loss mirrors insulin secretion during type 2 diabetes. Intriguingly, evidence from cell and animal models suggest that chronically stimulated β-cells can lose KATP revealing a possible role for KATP loss in the failure of insulin secretion and poor control of blood sugar observed in type 2 diabetes. This study will therefore examine insulin responses following ingestion of a single dose of a sulfonylurea called glipizide that inhibits KATP channels in people with and without type 2 diabetes. The goal is to determine whether KATP channel activity is reduced during type 2 diabetes progression.
Read the detailed description
The worldwide epidemic of obesity has developed alongside, and is causally linked to, the epidemic of insulin resistance and type 2 diabetes mellitus (T2DM). Plasma insulin concentrations are typically elevated in people with insulin resistance attributable to an increase in insulin secretion rate by pancreatic β-cells; however, in people with T2DM, β-cells eventually fail to 'keep up' and there is a crossover from insulin hypersecretion to undersecretion.
In the β-cell, KATP channels serve as the link between rising glucose and insulin secretion. Unlike other cells in the body, the uptake of glucose by the β-cell is directly proportional to the amount of glucose in the blood, so increasing blood glucose results in increased metabolism and production of ATP. This ATP closes the KATP channel, depolarizing the cell and driving an increase in intracellular Ca2+, which stimulates the secretion of insulin. The critical role of KATP channels in control of insulin secretion is clearly demonstrated by Gain-of-function (GOF) mutations that increase channel activity, preventing glucose mediated depolarization and secretion of insulin. Such mutations underlie neonatal diabetes mellitus (NDM) in humans and severe diabetes in experimental NDM mice that express transgenic GOF mutant KATP channels. While this paradigm implies that loss of KATP should cause the opposite effect, i.e. hypersecretion of insulin, mice with complete knockout (KO) of KATP show little evidence of hyperinsulinism, instead developing reduced secretion and impaired glucose tolerance from a very early age. Intriguingly, loss of function (LOF) mutations in mice have been shown to result increased insulin secretion, but these "crossover" to the under secreting KO phenotype when challenged with a high fat diet, mirroring the progression of T2DM from hypersecretion to undersecretion. In humans, LOF mutations have been associated with congenital hyperinsulinism, characterized by hypersecretion of insulin and hypoglycemia from a young age. However, despite this early hyperinsulinism, children from with CHI generally remit, losing insulin secretion and even progressing to diabetes with time. Counter to the simple model directly coupling KATP inhibition to insulin secretion, these observations from humans and mouse models suggest a more complex regulation wherein acute depolarization induces insulin secretion but when prolonged, secretion begins to fail.
Electrical measurements from β-cells of isolated islets have demonstrated that incubation in high glucose results in a reduction in KATP activity, and mouse models of obesity and diabetes show increased electrical activity and a loss of KATP in proportion to their loss of glycemic control. These observations have led us to develop the hypothesis that β-cells subjected to chronic stimulation due to increased insulin resistance will progressively lose KATP, eventually causing the "crossover" to undersecretion that is observed in T2DM. In this study our goal is to test this hypothesis, administering a single dose of the KATP antagonist glipizide (10 mg) and using the resulting insulin secretion to indirectly assess KATP channel activity in the islets of volunteers from the following four cohorts, lean and normoglycemic (Lean NGT), obese with normoglycemia (Obesity NGT), obese with impaired fasting glucose (Obesity IFG) and obese type 2 diabetes (Obesity T2DM).
- Conditions
- Obesity and Type 2 Diabetes
- Being tested
- 10 mg glipizide ingestion
- Medical subject headings
- Obesity, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
10 mg glipizide ingestionDrug
A single dose of 10 mg glipizide will be ingested
| Study group | Role | What they receive |
|---|---|---|
| Lean with normal glucose tolerance | Experimental | Body mass index ≥18.5 and <25.0 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%. Receives: Drug: 10 mg glipizide ingestion |
| Obesity with normal glucose tolerance | Experimental | Body mass index ≥30 and <50 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%. Receives: Drug: 10 mg glipizide ingestion |
| Obesity with impaired fasting glucose | Experimental | Body mass index ≥30 and <50 kg/m², fasting plasma glucose concentration 100-125 mg/dl, and 2-hr oral glucose tolerance test plasma glucose concentration <200 mg/dl. Receives: Drug: 10 mg glipizide ingestion |
| Obesity with type 2 diabetes | Experimental | Body mass index ≥30 and <50 kg/m²; HbA1C 6.5-9.5%, fasting plasma glucose ≥126 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≥200 mg/dl and/or medical history of type 2 diabetes and currently using anti-diabetic medications. Receives: Drug: 10 mg glipizide ingestion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin secretion
Insulin secreted by pancreas into plasma measured over 90 minutes after glipizide ingestion. Insulin secretion will be calculated using a stepwise insulin secretion rate function to fit plasma C-peptide concentrations to a two-compartment model of C-peptide kinetics using population-based C-peptide model parameters.
Measured: 90 minutes after glipizide ingestion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2025
- Study start7 Mar 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity and Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06830096
- Sponsor's protocol ID
- 202406075
- Other IDs
- 5P30DK056341
- Acronym
- BC
- Status last verified
- Aug 2026
- First submitted
- 11 Feb 2025
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperglycemia Induced Hyperexcitability: A Novel Role for KATP in the Progression of Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT06830096
- Acronym / sponsor ID
- BC / 202406075
- Conditions
- Obesity and Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 7 Mar 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 17 Feb 2025 (actual)
- 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.
Insulin is a hormone that is made by β-cells in the pancreas and when released into the bloodstream helps control blood sugar levels. Insulin release is regulated by electrical activity in the β-cell which is generated by the ATP-sensitive potassium (KATP) channel. While reduced KATP activity is associated with increased insulin secretion, animals lacking KATP exhibit reduced secretion. This crossover from hypersecretion to undersecretion with KATP loss mirrors insulin secretion during type 2 diabetes. Intriguingly, evidence from cell and animal models suggest that chronically stimulated β-cells can lose KATP revealing a possible role for KATP loss in the failure of insulin secretion and poor control of blood sugar observed in type 2 diabetes. This study will therefore examine insulin responses following ingestion of a single dose of a sulfonylurea called glipizide that inhibits KATP channels in people with and without type 2 diabetes. The goal is to determine whether KATP channel activity is reduced during type 2 diabetes progression.
Detailed description
The worldwide epidemic of obesity has developed alongside, and is causally linked to, the epidemic of insulin resistance and type 2 diabetes mellitus (T2DM). Plasma insulin concentrations are typically elevated in people with insulin resistance attributable to an increase in insulin secretion rate by pancreatic β-cells; however, in people with T2DM, β-cells eventually fail to 'keep up' and there is a crossover from insulin hypersecretion to undersecretion.
In the β-cell, KATP channels serve as the link between rising glucose and insulin secretion. Unlike other cells in the body, the uptake of glucose by the β-cell is directly proportional to the amount of glucose in the blood, so increasing blood glucose results in increased metabolism and production of ATP. This ATP closes the KATP channel, depolarizing the cell and driving an increase in intracellular Ca2+, which stimulates the secretion of insulin. The critical role of KATP channels in control of insulin secretion is clearly demonstrated by Gain-of-function (GOF) mutations that increase channel activity, preventing glucose mediated depolarization and secretion of insulin. Such mutations underlie neonatal diabetes mellitus (NDM) in humans and severe diabetes in experimental NDM mice that express transgenic GOF mutant KATP channels. While this paradigm implies that loss of KATP should cause the opposite effect, i.e. hypersecretion of insulin, mice with complete knockout (KO) of KATP show little evidence of hyperinsulinism, instead developing reduced secretion and impaired glucose tolerance from a very early age. Intriguingly, loss of function (LOF) mutations in mice have been shown to result increased insulin secretion, but these "crossover" to the under secreting KO phenotype when challenged with a high fat diet, mirroring the progression of T2DM from hypersecretion to undersecretion. In humans, LOF mutations have been associated with congenital hyperinsulinism, characterized by hypersecretion of insulin and hypoglycemia from a young age. However, despite this early hyperinsulinism, children from with CHI generally remit, losing insulin secretion and even progressing to diabetes with time. Counter to the simple model directly coupling KATP inhibition to insulin secretion, these observations from humans and mouse models suggest a more complex regulation wherein acute depolarization induces insulin secretion but when prolonged, secretion begins to fail.
Electrical measurements from β-cells of isolated islets have demonstrated that incubation in high glucose results in a reduction in KATP activity, and mouse models of obesity and diabetes show increased electrical activity and a loss of KATP in proportion to their loss of glycemic control. These observations have led us to develop the hypothesis that β-cells subjected to chronic stimulation due to increased insulin resistance will progressively lose KATP, eventually causing the "crossover" to undersecretion that is observed in T2DM. In this study our goal is to test this hypothesis, administering a single dose of the KATP antagonist glipizide (10 mg) and using the resulting insulin secretion to indirectly assess KATP channel activity in the islets of volunteers from the following four cohorts, lean and normoglycemic (Lean NGT), obese with normoglycemia (Obesity NGT), obese with impaired fasting glucose (Obesity IFG) and obese type 2 diabetes (Obesity T2DM).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lean with normal glucose tolerance | Experimental | Drug: 10 mg glipizide ingestionBody mass index ≥18.5 and <25.0 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%. |
| Obesity with normal glucose tolerance | Experimental | Drug: 10 mg glipizide ingestionBody mass index ≥30 and <50 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%. |
| Obesity with impaired fasting glucose | Experimental | Drug: 10 mg glipizide ingestionBody mass index ≥30 and <50 kg/m², fasting plasma glucose concentration 100-125 mg/dl, and 2-hr oral glucose tolerance test plasma glucose concentration <200 mg/dl. |
| Obesity with type 2 diabetes | Experimental | Drug: 10 mg glipizide ingestionBody mass index ≥30 and <50 kg/m²; HbA1C 6.5-9.5%, fasting plasma glucose ≥126 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≥200 mg/dl and/or medical history of type 2 diabetes and currently using anti-diabetic medications. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Lean-normoglycemic group (n=10): BMI ≥18.5 and <25.0 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
- Obesity-normoglycemic group (n=10): BMI ≥30 and <50 kg/m², fasting plasma glucose concentration <95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
- Obesity-impaired fasting glucose group (n=10): BMI ≥30 and <50 kg/m², fasting plasma glucose concentration 100-125 mg/dl, and 2-hr oral glucose tolerance test plasma glucose concentration <200 mg/dl.
- Obesity-type 2 diabetes group (n=10): BMI ≥30 and <50 kg/m²; HbA1C 6.5-9.5%, fasting plasma glucose ≥126 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≥200 mg/dl and/or medical history of T2DM and currently using anti-diabetic medications.
Key exclusion criteria (10 listed)
- Diabetes therapy with insulin at >0.5 units/kg/day.
- Any change in diabetes medication in previous 3 months.
- Unstable weight (>2% change during the last 2 months before entering the study).
- Evidence of significant organ system dysfunction or disease other than obesity and T2D.
- Regular use of tobacco products.
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 |
|---|---|---|
| 10 mg glipizide ingestionA single dose of 10 mg glipizide will be ingested | Drug | Lean with normal glucose tolerance, Obesity with impaired fasting glucose, Obesity with normal glucose tolerance, Obesity with type 2 diabetes |
Primary outcome
Insulin secretion
Time frame: 90 minutes after glipizide ingestion
Insulin secreted by pancreas into plasma measured over 90 minutes after glipizide ingestion. Insulin secretion will be calculated using a stepwise insulin secretion rate function to fit plasma C-peptide concentrations to a two-compartment model of C-peptide kinetics using population-based C-peptide model parameters.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 10 mg glipizide ingestion in people with Obesity and Type 2 Diabetes, run by Washington University School of Medicine 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 4 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: looking for participants now, as of the sponsor's last update on 10 Aug 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kyle Timmons (314-273-1879, nutritionresearch@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin secretion (time frame: 90 minutes after glipizide ingestion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Aug 2026.