Role of KATP Channel Loss in Type 2 Diabetes
ConditionObesity and Type 2 Diabetes
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorWashington University School of Medicine
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
10 mg glipizide ingestion
DrugA single dose of 10 mg glipizide will be ingested
Treatment groups
40 Participants
are divided into 4 treatment groupsGroup A: Lean with normal glucose toleranceExperimental treatment 1 intervention
Group B: Obesity with normal glucose toleranceExperimental treatment 1 intervention
Group C: Obesity with impaired fasting glucoseExperimental treatment 1 intervention
Group D: Obesity with type 2 diabetesExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
90 minutes after glipizide ingestionSponsors and contacts
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Washington University School of Medicine
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Source ClinicalTrials.gov